Surgical splenectomy is not practised anymore in the current era. It is now replaced by …. medical splenectomy (using a rituximab – Anti CD20 antibody)
I agree with my colleagues that surgical splenectomy was replaced by Rituximab.
References:
1) Macklin PS, Morris PJ, Knight SR. A systematic review of the use of rituximab for desensitization in renal transplantation. Transplantation. 2014 Oct;98(8):794-805.
2) Lo P, Sharma A, Craig JC, et al. Preconditioning Therapy in ABO-Incompatible Living Kidney Transplantation: A Systematic Review and Meta-Analysis. Transplantation. 2016 Apr;100(4):933-942.
I think replaced by B cell depletion (anti CD 20) rituximab.
In addition, splenectomy is considered plasma cell debulking maneuver so can be replaced be bortezomib.
We can use rituximab to block naive B lymphocytes (CD20), simulating splenectomy. However, if there are many plasma cells already circulating (CD19), this treatment will be insufficient, and bortezomib should be added to block plasma cells or evaluate plasma exchange associated with IVIg.
Using a CD20 depleting agents e.g. Rituximab : medical splenectomy
Jamila Elamouri
2 years ago
surgical splenectomy has no role nowadays, as the advancement in immunosuppressive medications allows for the depletion of the antibody-producing cells without the need to remove a spleen. Rituximab is a monoclonal antibody directed against CD20 cells. can be used to treat ABMR
dina omar
2 years ago
Surgical splenectomy was done in :desensitization in high immunological risk recipients, refractory ABMR. But surgical splenectomy may be complicated with serious life threatening infections especially encapsulated organism. so, now replaced by : anti-CD20 antibody rituximab.
Nazik Mahmoud
2 years ago
Splenectomy is last option in desensitisation but Surgical splenectomy not done any more Replaced by rituximab
Wee Leng Gan
2 years ago
IV RITUXIMAB
Ahmed Fouad Omar
2 years ago
What is the role of surgical splenectomy in transplantation?
Surgical splenectomy was used in the past based on the fact that it reduces B cells load and AB production. It was used as part of the desensitization protocols (ABO incompatible or HLA incompatible transplantation) or as a rescue therapy in refractory antibody mediated rejection when added to standard therapy (PP+IVIG).However, this was associated with increased risk of infections with encapsulated organisms, sepsis and increased mortality rates.
In the modern transplantation era, surgical splenectomy is replaced by medical splenectomy through the use of the more specific and safer medications like Rituximab (anti CD 20- B cell depletion) and Bortezomib (antiCD19- plasma cell depletion).
References:
1.zvetanov I., Spaggiar M., John H., et al. The role of splenectomy in the setting of refractory humoral rejection after kidney transplantation. Transplant Proc. 2012; 44(5):1254.
2. Locke JE, Zachary AA, Haas M, Melancon JK, Warren DS, Simpkins CE, Segev DL, Montgomery RA. The utility of splenectomy as rescue treatment for severe acute antibody mediated rejection. Am J Transplant. 2007 Apr;7(4)
3.DR Tarek Abbas Lecture
Akram Abdullah
2 years ago
surgical splenectomy is not practiced any more for treatment of recurrent AMR, for removing antibodies , it is now replaced by rituximab ( anti CD 20 antibody)
Hamdy Hegazy
2 years ago
Surgical splenectomy many years ago was proposed as a treatment option for ABMR based on theory that splenectomy reduces memory B-cells and decrease Ab Production.
However, in the new era of modern IS it is replaced by plasmapheresis and rituximab.
Nandita Sugumar
2 years ago
Role of surgical splenectomy in transplant
Surgical splenectomy was indicated in severe thrombocytopenia. Pre transplant Splenectomy also played a major role in cadaveric kidney transplant.
Splenectomy was thought to have a mild long term effect on post transplant infection rates particularly in ABO incompatible kidney transplant patients. However, vaccines against infection are essential for an assured effect.
However, it is important to recognize that simultaneous splenectomy and renal transplant can lead to over immunosuppression, resulting in possibility of sepsis and CMV activation, which could lead to death of the patient in adverse cases due to the immunosuppression. Case reports reveal this happening and blame surgical splenectomy done at the same time as kidney transplant for this fatal outcome.
Surgical splenectomy was done previously as part of desensitization for highly sensitized patients or patients with a HLA mismatched donor to avoid rejection outcomes in order to improve graft and patient outcome.
The role of splenectomy in kidney transplant is close to negligible at present. It has been substituted by medical splenectomy, which is rituximab which is an anti CD20 antibody.
Manal Malik
2 years ago
splenectomy in the past used in ABOi transplantation and targeting CD20 of B cells which produce antibodies because of high risk of infection and thrombosis substitute by Rituximab which is humanized mouse monoclonal antibody targeting CD20 in B cell .
some studies done prior to transplant ,result shows no decrease in number of rejection postrenal transplant.
referenc
-the spleen is the site of antibodies production through cells .so removal of spleen leads to depletion of these cell. Splendtomy remove a major source of lymphocytes including antibodies secreting B cells , B cell precursor cells and plasma cells.
– Surgical splenctomy was used In :
* highly sensitized patients .
* ABO incompatibility.
* treatment of refractoryABMR.
– the effect of splenectomy on immune system is permanent and may put patients at risk of development life threatening infection especially encapsulated bacteria.
-now days we use rituximab as medical splenctomy.
– rituximam is chimeric/ human monoclonal antibody binds to CD20 on pre B and mature B lymphocyte .
-FDA Rituximab for treatment of refractory or relapsedB cell lymphomas and also For treatment of post-transplant lymphoproliferative diseases.
MICHAEL Farag
3 years ago
1. Splenectomy was used initially as a part of desensitization protocols in high risk transplant recipient as (HLA incompatible or ABO incompatible transplantation) in order to remove B cell and abolish the main site for destruction of antibody bounded cells.
2. Also it can be used in treatment of resistant AMR ( last resort after failure of standard of care therapy as PEX and IVIg).
3. However, high mortality secondary to post splenectomy overwhelming infections and sepsis made it obsolete now. In addition, the advances and availability of many pharmacological therapeutics which can act as medical splenectomy and can replace it as rituximab ( B cell depletion) and bortezomib ( plasma cell depletion).
Balaji Kirushnan
3 years ago
The role of surgical splenectomy has now become obsolete in renal transplantation.
The spleen is the site of antibody production by B cells. Alloreactive dendritic T cells from the donor traverse the blood stream and reach the spleen where they are primed to initiate an allo immune response.
It has been used in desensitized patients and ABO incompatible renal transplant recipients for antibody removal purposes. The morbid nature of the splenectomy surgery and the high risk of infections with encapsulated organisms (eg Pneumococcus and Meningcoccus) has put splenectomy behind the cards for antibody removal.
In studies which used splenectomy for ABO incompatible desensitization, comparable results have been produced in those patients with plasmaphresis + Rituximab and those with plasmaphresis + splenectomy.
There are case reports and small studies where splenectomy was used as a rescue therapy for severe antibody rejection. The mortality after renal transplant in splnectomized patients were reported to be higher than non splenectomized patients.
Splenectomy was replaced by rituximab which is medical splenectomy
ahmed saleeh
3 years ago
*Splenectomy was used as a part of desensitization protocols in high risk transplant recipient as (HLA incompatible or ABO incompatible transplantation) in order to remove B cell and abort the main site for destruction of antibody bounded cells.
*Also it can be used in treatment of resistant AMR ( after failure of standard of care therapy as PEX and IVIg).
Last edited 3 years ago by ahmed saleeh
CARLOS TADEU LEONIDIO
3 years ago
Splenectomy was used in cases of ABO incompatibility as a way to avoid hyperacute rejection. However, we have had pre-conditioning regimens that included anti-CD20 monoclonal antibody (rituximab)
kumar avijeet
3 years ago
Surgical splenectomy removes spleen which is the production house of antibody, as this procedure has multiple morbidities with total paralysis of humoral immunity on longterm puts patients life in life-threatening infections, hence now a days, not practiced.
But it has definite role in-
1.treatment refractory ABMR.
2.desensitization of highly sensitized.
Murad Hemadneh
3 years ago
Spleen plays an important immunological role as it produces B lymphocytes and plasma cells. For that reason it participates in antibody production. Surgical Splenectomy results in depletion of Plasma cells and reduction of antibody production which leads to state of tolerance. It was used in the past.
In current practice, medical splenectomy replaced surgical splenectomy with Rituximab as this drug attacks CD20 B cells.
Reference:
Kamar, N., Milioto, O., Puissant-Lubrano, B., Esposito, L., Pierre, M. C., Mohamed, A. O., Lavayssière, L., Cointault, O., Ribes, D., Cardeau, I., Nogier, M. B., Durand, D., Abbal, M., Blancher, A., & Rostaing, L. (2010). Incidence and predictive factors for infectious disease after rituximab therapy in kidney-transplant patients. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 10(1), 89–98. https://doi.org/10.1111/j.1600-6143.2009.02785.x 3- Davidson RN, Wall RA. Prevention and management of infections in patients without a spleen. Clin Microbiol Infect 2001;7: 657–60 [PubMed] [Google Scholar]
Thuraya Salim
3 years ago
surgical splenectomy indicated in those pt having ABO and HLAincompatible KT and pt who are refractory to post – transplant plasmaphresis it may be indicated.
rituximab
Shereen Yousef
3 years ago
Splenectomy offers removal of the sources of Ab production
Many Studied was done evaluating the benifts of splenectomy and risk of infection
One study was done to evaluate long-term effect of rituximab and splenectomy on de novo HLA antibody production and chronic antibody-mediated rejection after renal transplantation 92 ABO-incompatible and 228 ABO-identical/compatible consecutive renal transplant patients and determined their de novo HLA antibody production and graft outcome.
Patients with pretransplant donor-specific antibodies had been excluded.
ABO-incompatible transplants included 30 recipients treated with rituximab, 51 by splenectomy, or 11 with neither, due to low anti-A or -B antibody titer. Graft survival in ABO-identical/compatible patients (97.7% at 5 years) was significantly higher than in ABO-incompatible (87.0% at 5 years), rituximab (96.7% at 3 years), or splenectomy (85.7% at 5 years) patients.
Only four patients had clinical chronic antibody-mediated rejection (two each identical/compatible and incompatible). There was no significant difference in prevalence of de novo HLA antibody, including donor-specific and nondonor-specific antibodies among ABO-identical/compatible patients (13.9%), patients receiving rituximab (14.3%) or splenectomy (13.2%), or among those receiving cyclosporine, tacrolimus, mycophenolate mofetil, mizoribine, and everolimus.
Renal function remained stable in most recipients with de novo HLA antibody. Thus, neither pretransplant splenectomy nor rituximab treatment has an inhibitory effect on de novo HLA antibody production during medium-term follow-up. Further study on long-term effects is needed.
Rituximab is a chimeric anti-CD20 monoclonal antibody that leads to B cell depletion.
It is an effective treatment for post-transplant lymphoproliferative disorder, and is also used in both HLA antibody incompatible renal transplantation and the treatment of acute rejection. Recent evidence suggests rituximab may prevent the development of chronic antibody mediated rejection. The mechanisms underlying its effects are likely to relate both to long-term effects on plasma cell development and to the impact on B cell modulation of T cell responses.
Reference;
Satoshi Ashimine et al. Kidney Int. 2014 Feb.
Neither pre-transplant rituximab nor splenectomy affects de novo HLA antibody production after renal transplantation.
Rituximab in renal transplantation
A Nicholas R Barnett et al. Transpl Int. 2013 Jun.
Surgical splenectomy was done before in the following situations:
-desensitization in high immunological risk transplants.
– in ABO incompatible transplants.
-treatment in refractory antibody mediated rejection.
But surgical splenectomy may be complicated with serious life threatening infections especially encapsulated organism (pneumococcal infections)
It has been replaced with ‘medical splenectomy’ involving use of anti-CD20 antibody rituximab.
Asmaa Khudhur
3 years ago
The spleen is the site of antibodies production through B cells , so removal of the spleen will lead to depletion of these cells .
Surgical splenectomy was used for :
Highly sensitized recipients
ABO incompatibility
As last option in treatment of refractory ABMR
In the modern era surgical splenectomy was replaced by medical splenectomy ( Rituximab) because of the risk of overwhelming infection by encapsulated pneumococcal bacteria and sepsis.
fakhriya Alalawi
3 years ago
Several studies had prescribed the role and advantages of Splenectomy, most dating back to the 1980s. One of those was published by Okiye SE et al in 1983, where he analysed the effect of splenectomy in One hundred eight patients versus 57 who did not. They reported that Splenectomy improved cadaver donor renal allograft survival (p = 0.001) in the diabetic patients (p = 0.015) and in those 50 years of age or older (p = 0.026) but it did not improve survival in those who received living related donor kidneys. The incidence of infection and sepsis was comparable in both groups and was responsible for death in 34% of the patients who underwent splenectomy compared with 22% of those who did not (no significant difference).
Surgical splenectomy is not practised anymore in our current era. Yet, In 2014 Orandi et al, described rescuing therapy to preserve allograft function for patients with early & severe AMR. He reported a better graft survival in patients treated with both splenectomy plus eculizumab compared to those treated with eculizumab alone or splenectomy alone.
References:
· Orandi BJ, Zachary AA, Dagher NN, et al. Eculizumab and splenectomy as salvage therapy for severe antibody-mediated rejection after HLA-incompatible kidney transplantation. Transplantation. 2014 Oct 27;98(8):857-863.
· Okiye SE, Zincke H, Engen DE, Sterioff S, Offord KP, Frohnert PP, Johnson WJ. Splenectomy in high-risk primary renal transplant recipients. Am J Surg. 1983 Nov;146(5):594-601.
Dalia Ali
3 years ago
Splenectomy
Splenectomy has been used in desensitization protocols of ABO-incompatible kidney transplant recipients. Splenectomy removes a major source of lymphocytes, including antibody-secreting B cells, B cell precursor cells, and plasma cells. It has also been used in the treatment of refractory AMR
However, the effect of splenectomy on the immune system is permanent, which may place the patients at risk for the development of life-threat- ening sepsis, especially from encapsulated bacteria
So use rituximab as medical spleenectomy is better approach
Rituximab (Anti-CD20). Rituximab is a chimeric murine/human monoclonal antibody that binds to CD20 on pre-B and mature B lymphocytes
It is FDA approved for treatment of refractory or relapsed B cell lymphomas and is also used for treatment of posttransplant lym- phoproliferative disease (PTLD).
Reference
Kwaku Marfo,* Amy Lu,* Min Ling*† and Enver Akalin*‡ Desensitization Protocols and Their Outcome. Clin J Am Soc Nephrol 6: 922–936, 2011. doi: 10.2215/CJN.08140910.
Abdulrahman Ishag
3 years ago
The spleen is not only the principle site of antibody synthesis, but also is a source of specific alloreactive host lymphocytes . It has been suggested that transient post transplant migration of dendritic cells from the transplanted graft to the spleen may be responsible for initiation of graft rejection . On the contrary the spleen may play a major role in prolongation of graft survival in different species , perhaps by generation of specific suppressor cells .
1-Some have reported a beneficial effect of splenectomy either pre- or peri transplantation and have attributed this benefit to a reduction in antibody production or improved leukocyte count and therefore tolerance to azathioprine (AZA) .
2– Earlier studies suggested that splenectomy appeared to reduce the incidence of early rejection .
3- Some studies found that splenectomy was associated with allograft survival .
4- Others have shown no benefit, discouraging the routine use of this
procedure because of its potentially lethal complications due to delayed infection and thromboembolic events .
Surgical splenectomy is not practised anymore in the current era. It is now replaced by …. medical splenectomy (using a rituximab – Anti CD20 antibody)
Reference ;
1-Kaplan B, Gangemi A, Thielke J, Oberholzer J, Sankary H, Benedetti E. Successful rescue of refractory, severe antibody mediated rejection with splenectomy. Transplantation. 2007 Jan 15;83(1):99-100. doi: 10.1097/01.tp.0000243739.31440.2b. PMID: 17220802
2–Iwai T.et al. Splenectomy for ABO-Incompatible Kidney Transplantation and Very Late-Onset Cytomegalovirus Disease .Urol Int 2020;104:651–656
Professor Ahmed Halawa
Admin
3 years ago
Thanks All for the excellent answer. Yes Rituximab has replaced surgical splenectomy
Mahmud Islam
3 years ago
splenectomy is not indicated but may be useful in liver transplantation to improve thrombocytopenia maybe, also maybe used in ABO-incompatible cases but now we have desensitization protocols plasmapheresis and also depleting agents like Rituximab
mai shawky
3 years ago
1. Splenectomy was used initially as a part of desensitization protocols in high risk transplant recipient as (HLA incompatible or ABO incompatible transplantation) in order to remove B cell and abolish the main site for destruction of antibody bounded cells.
2. Also it can be used in treatment of resistant AMR ( last resort after failure of standard of care therapy as PEX and IVIg).
3. However, high mortality secondary to post splenectomy overwhelming infections and sepsis made it obsolete now. In addition, the advances and availability of many pharmacological therapeutics which can act as medical nephrectomy and can replace it as rituximab ( B cell depletion) and bortezomib ( plasma cell depletion).
References;
Salvadori M, Tsalouchos A. Current protocols and outcomes of ABO-incompatible kidney transplantation. World Journal of Transplantation. 2020 Jul 29;10(7):191.
Schinstock CA, Mannon RB, Budde K, Chong AS, Haas M, Knechtle S, Lefaucheur C, Montgomery RA, Nickerson P, Tullius SG, Ahn C. Recommended treatment for antibody-mediated rejection after kidney transplantation: the 2019 expert consensus from the transplantion society working group. Transplantation. 2020 May;104(5):911.
Theepa Mariamutu
3 years ago
Splenectomy is not practised anymore in the current era. It is now replaced by rituximab
ABO-Incompatible Recipients
Waigankar et al
reported improved patient (85.7% vs. 78.9%) and graft survival (unadjusted, 85.7% vs. 68.4%; death-censored, 100.0% vs. 89.4%) among seven patients receiving rituximab, plasmapheresis, and IVIg compared to 19 patients who underwent splenectomy with plasmapheresis and IVIg. but low Downs and Black score (10/32)
Hyodo et al.
compared 29 patients desensitized with rituximab and MMF with 31 patients who underwent splenectomy with MMF and 62 patients who underwent splenectomy with azathioprine.
statistically significant decrease among those receiving rituximab compared to the other groups. Graft survival at 5 years was equivalent between the rituximab and splenectomy plus MMF groups.
Tokyo Women’s Medical University study
recipients desensitized with rituximab and plasmapheresis were compared to 45 patients who underwent splenectomy with plasmapheresis
patient survival, graft survival, rejection-free survival, and median serum creatinine seem to be comparable across the three groups
Splenectomy as Rescue Treatment
Splenectomy as Rescue Treatment for Severe Acute Antibody Mediated Rejection
Alexander et al.
retrospectively analyzed 351 transplant recipients and found a 25% greater mortality among patients that were splenectomized. More than half the mortality among splenectomized transplant recipients was secondary to post splenectomy sepsis
References
Montgomery RA, Locke JE, King KE, Segev DL, Warren DS, Kraus ES, Cooper M, Simpkins CE, Singer AL, Stewart ZA, Melancon JK, Ratner L, Zachary AA, Haas M. ABO incompatible renal transplantation: a paradigm ready for broad implementation. Transplantation. 2009 Apr 27;87(8):1246-55. doi: 10.1097/TP.0b013e31819f2024. PMID: 19384174.
Kaplan B, Gangemi A, Thielke J, Oberholzer J, Sankary H, Benedetti E. Successful rescue of refractory, severe antibody mediated rejection with splenectomy. Transplantation. 2007 Jan 15;83(1):99-100. doi: 10.1097/01.tp.0000243739.31440.2b. PMID: 17220802
Locke JE, Zachary AA, Haas M, Melancon JK, Warren DS, Simpkins CE, Segev DL, Montgomery RA. The utility of splenectomy as rescue treatment for severe acute antibody mediated rejection. Am J Transplant. 2007 Apr;7(4):842-6. doi: 10.1111/j.1600-6143.2006.01709.x. PMID: 17391127.
Last edited 3 years ago by Theepa Mariamutu
Weam Elnazer
3 years ago
Splenectomy as a method of desensitization:
Splenectomy combined with plasmapheresis, rituximab and low-dose IVIG was shown to be less effective than utilizing just plasmapheresis, rituximab, and low-dose IVIG alone
Renal transplantation in the presence of ABO incompatibility
Plasmapheresis, IVIG, and either Rituximab or, less typically, splenectomy are all part of the desensitization strategy for patients getting ABO-incompatible kidney transplants.
Although the addition of Rituximab or splenectomy to plasmapheresis and IVIG has been shown to be ineffective, it is still controversial whether they should be included. Splenectomy as a therapy for ABMR is discussed.
When ABMR is refractory, splenectomy may be indicated. Based on case reports, nine patients in two distinct trials who had failed standard therapy for ABMR had splenectomy after failing to react to it and responded well.
-Kwaku Marfo, et al Desensitization Protocols and Their Outcome. CJASN April 2011
Drtalib Salman
3 years ago
What is the role of surgical splenectomy in transplantation?
Splenectomy used for refractory AB mediated rejection if there is no response to IV Ig and plasma exchange but after discovery of modern immunosuppressive drug (rituximab) now days no longer used for for following :
-it cause over immunosuppression which may lead to fatal infection so we should out weigh risk and benefit.
-the efficacy of splenectomy if we compare with antiCD20 rituximab there is no much difference , although laparoscopic splenectomy used by some centers and it has good response for treatment of Ab mediated rejection but no longer used for primary prevention in highly sensitized patient or ABO incompatible transplant .
Abdul Rahim Khan
3 years ago
Splenectomy has no role in renal transplantation in modern era though it has been used in the past in highly sensitized patients to decrease denovo antibody production by removing B cells ,ABO incompatible renal transplantation and also as rescue therapy in resistant ABMR Alternative options are now available with less side effects as compared to Splenectomy which was associated with higher incidence of significant sepsis. Currently anti CD20 -Rituximab is available as alternative to Splenectomy.
Reference;
Mark Haas et al. The Utility of Splenectomy as Rescue Treatment for Severe Acute Antibody Mediated Rejection. American Journal of transplantation. April 2007. 7(4):842-6
Ben Lomatayo
3 years ago
Role of surgical splenectomy in transplantation ;
Spleen produces B lymphocytes
Surgical splenectomy results in depletion of the anti-body producing B lymphocytes resulting in a state of tolerance
This was a common practice in Japan for ABO incompatible transplants
They found that splenectomy + immuno-suppressive therapy was associated excellent graft survival rate > 90% at 5 years.
Limitations of surgical splenectomy ;
Recent studies revealed that spleen is important for induction and maintenance of regulatory CD4+ CD25+ T lymphocytes
These regulatory T cells are importance for self-tolerance
MOHAMED Elnafadi
3 years ago
The spleen has been shown to be an important site of proliferation and maturation of immunocompetent cells reactive against an allograft
hence may be before there was aconcept that by doing surgical splenectomy it will remove suppressor t cells and other cells as memory B cells and plasma cells hence resposible for ab production after faliure of plasmapharesis and other immune suppressant medications .
nowdays it is replaced by medical splenectomy by ritxumab to avoid hazards of surgery and there is no more beneficial add to patient
Dalia Eltahir
3 years ago
In ABO-incompatible renal transplantation
, splenectomy was done to reduce B cell pool ,patients undergoing splenectomy may have a lifelong susceptibility to infection and mortality.
and then replaced by induction of rituximab, a monoclonal antibody against B cell surface molecule CD20 .Also used in acute AMR in addition to slandered protocol .
Amit Sharma
3 years ago
What is the role of surgical splenectomy in transplantation?
Surgical splenectomy has been used in transplantation in following conditions:
1) As part of pre-operative desensitization in high immunological risk transplants. (1)
2) Pre-operatively in ABO incompatible transplants. (2)
3) As part of treatment in refractory antibody mediated rejection. (3,4)
It has been replaced with ‘medical splenectomy’ involving use of anti-CD20 antibody rituximab, due to morbidity and mortality associated with surgical splenectomy- including increased risk of infections, especially pneumococcal infections. (5)
In ABO incompatible transplants, even rituximab has been shown to have doubtful value with no rise in antibody mediated rejection incidence seen in patients not given rituximab. (2)
References:
1) Okiye SE, Zincke H, Engen DE, Sterioff S, Offord KP, Frohnert PP, Johnson WJ. Splenectomy in high-risk primary renal transplant recipients. Am J Surg. 1983 Nov;146(5):594-601. doi: 10.1016/0002-9610(83)90295-7. PMID: 6356949.
2) Montgomery RA, Locke JE, King KE, Segev DL, Warren DS, Kraus ES, Cooper M, Simpkins CE, Singer AL, Stewart ZA, Melancon JK, Ratner L, Zachary AA, Haas M. ABO incompatible renal transplantation: a paradigm ready for broad implementation. Transplantation. 2009 Apr 27;87(8):1246-55. doi: 10.1097/TP.0b013e31819f2024. PMID: 19384174.
3) Locke JE, Zachary AA, Haas M, Melancon JK, Warren DS, Simpkins CE, Segev DL, Montgomery RA. The utility of splenectomy as rescue treatment for severe acute antibody mediated rejection. Am J Transplant. 2007 Apr;7(4):842-6. doi: 10.1111/j.1600-6143.2006.01709.x. PMID: 17391127.
4) Kaplan B, Gangemi A, Thielke J, Oberholzer J, Sankary H, Benedetti E. Successful rescue of refractory, severe antibody mediated rejection with splenectomy. Transplantation. 2007 Jan 15;83(1):99-100. doi: 10.1097/01.tp.0000243739.31440.2b. PMID: 17220802.
5) Sonnenday CJ, Warren DS, Cooper M, Samaniego M, Haas M, King KE, Shirey RS, Simpkins CE, Montgomery RA. Plasmapheresis, CMV hyperimmune globulin, and anti-CD20 allow ABO-incompatible renal transplantation without splenectomy. Am J Transplant. 2004 Aug;4(8):1315-22. doi: 10.1111/j.1600-6143.2004.00507.x. PMID: 15268734.
Last edited 3 years ago by Amit Sharma
Doaa Elwasly
3 years ago
Splenectomy was performed in ABO-incompatible kidney transplantation to lower the B cell burden. Studies demonstrated that patients undergoing splenectomy can be subjected to infection and mortality for lifelong as it increase the incidence of cytomegalovirus (CMV) disease even at a very late stage after transplantation in ABO-incompatible recipients.(1)
Splenectomy was used as an adjuvant therapy to current AMR protocol, which includes PP/IVIg and in some cases anti-CD20.
Since plasma cells reside in the spleen before migrating to the bone marrow. These cells do not express CD20 and are not liable to ablation with anti-CD20 monoclonal antibodies.
Splenectomy was effective in debulking plasma cells, thereby decreasing antibody production to a level that can be controlled with PP. In Locke JE etal studyit was demonstrated that splenectomy, in some cases, is associated with return of renal function, and this can start before the reinitiation of PP. (2)
2-Locke JE etal.The Utility of Splenectomy as Rescue Treatment for Severe Acute Antibody Mediated Rejection. American journal of trasnplanation 2007 :7;4;842-846
Heba Wagdy
3 years ago
Splenectomy was initially used in ABO incompatible kidney transplantation as pre transplant desensitization protocol.
It was used as B cell depletion therapy to prevent rapid generation of B cells in highly sensitized recipients and before ABO incompatible kidney transplantation.
It was also used as salvage procedure for severe early antibody mediated rejection
It was gradually replaced by Rituximab, the drug used now to obtain B cell depletion.
It was associated with surgical risk and long-term risks as overwhelming post splenectomy infection.
Morath C, Zeier M, Döhler B, Opelz G, Süsal C. ABO-incompatible kidney transplantation. Frontiers in immunology. 2017 Mar 6;8:234.
Salvadori M, Tsalouchos A. Current protocols and outcomes of ABO-incompatible kidney transplantation. World Journal of Transplantation. 2020 Jul 29;10(7):191.
Schinstock CA, Mannon RB, Budde K, Chong AS, Haas M, Knechtle S, Lefaucheur C, Montgomery RA, Nickerson P, Tullius SG, Ahn C. Recommended treatment for antibody-mediated rejection after kidney transplantation: the 2019 expert consensus from the transplantion society working group. Transplantation. 2020 May;104(5):911.
Innocent lule segamwenge
3 years ago
Surgical splenectomy has been previously used in ABO incomplete transplants as a way of reducing the B cell pool. The spleen is considered a major source of anti-A and anti-B antibodies(Salamon et al., 1985).
Splenectomy is effective in removing anti-blood group producing plasma cells. This can be done pre-transplant or at the time of transplantation.
It used when transplanting non-A2 blood group ABOI kidney transplants.
This approach however, is associated with post-transplant infections like late onset CMV infection(Iwai et al., 2020).
Current protocols have abandoned this approach preferring to use plasmapheresis, Iv Ig and rituximab(Gloor et al., 2005).
GLOOR, J. M., LAGER, D. J., FIDLER, M. E., GRANDE, J. P., MOORE, S. B., WINTERS, J. L., KREMERS, W. K. & STEGALL, M. D. 2005. A Comparison of Splenectomy versus Intensive Posttransplant Antidonor Blood Group Antibody Monitoring without Splenectomy in ABO-Incompatible Kidney Transplantation. Transplantation, 80, 1572-1577.
IWAI, T., UCHIDA, J., KOSOKU, A., KABEI, K., NISHIDE, S., NAGANUMA, T., MAEDA, K., YOSHIKAWA, Y., KUMADA, N., TAKEMOTO, Y. & NAKATANI, T. 2020. Splenectomy for ABO-Incompatible Kidney Transplantation and Very Late-Onset Cytomegalovirus Disease. Urologia Internationalis, 104, 651-656.
SALAMON, D. J., RAMSEY, G., NUSBACHER, J., YANG, S., STARZL, T. E. & ISRAEL, L. 1985. Anti-A production by a group O spleen transplanted to a group A recipient. Vox sanguinis, 48, 309-312.
Mohammed Sobair
3 years ago
Therapeutic splenectomy in transplant : Human leukocyte antigen (HLA) and/or ABOi desensitization for renal
transplantation . pharmacological treatments (e.g., rituximab) are now used in
place of splenectomy to achieve complete depletion of B-cells in peripheral blood.. Some centers consider splenectomy in treating ABMR refractory to
plasmapheresis and/or IVIG .
General medical and surgical indication in transplant patient:
Splenic abscess.
Splenic lymphoma in PTLD.
Tumors ,metastasis. And cyst
Bleeding disorders .e.g ITP.
Ibrahim Omar
3 years ago
the spleen is a major lymphoid organ and it is responsible for immunity and resistance to infection. the main indication of splenectomy is hypersplenism for managing related pancytopenia. the main complication of splenectomy is the increased risk of infection, sometimes overwhelming sepsis.
because of the role of spleen in immunity, splenectomy was tried for treatment of several immune related disorders as ITP and others.
in transplantation, the spleen is involved in the allo-immune responce, mostly the antibody mediated one. therefore, splenectomy was tried in treatment of severe anti-body mediated rejection.
splenectomy was also tried in desensitization protocols in high risk patients including those with ABO incompatible donors.
Mohamed Saad
3 years ago
The role of surgical splenectomy in transplantation?====================================== Splenectomy may revers AMR by debulking plasma cell.Patients with a very high load of plasma cells may not be rescued by splenectomy alone and may need additional treatments.(1,2). 1-Prof .Tarek Abbas lecture.(Renal allograft rejection part II).2-Ivo Tzvetanov et al.(Cell population in spleens during antibody-mediated rejection: pathologic and clinical findings) 2012 Aug 15;94(3):255-62
Zahid Nabi
3 years ago
Splenectomy has been considered as part of desensitization protocol and as a rescue therapy for resistant ABMR but has not shown promising results. Rituximab does the same job so it is no more considered as a safe option but desperate situation at times need desperate measures and in such a scenario none can always think of it.
Alaa eddin salamah
3 years ago
The spleen acts as a repository for memory B cells and plasma cells, thus playing an important role in the alloantibody response.
Splenectomy used to reduce the pool of B-lymphocytes in patients with ABO-incompatibility to decrease the risk of graft rejection. Nowadays, Medical splenectomy with Rituximab has the same role and it is mainly used instead of surgical splenectomy.
A study by Kamar et al on 77 kidney transplant patients who received Rituximab with a median follow-up of 16.5 (1-55) months for rituximab patients and 60.9 (1.25-142.7) months for control patients, the incidence of infectious disease was 45.45% and 53.9% (ns), respectively. (1)
Patients who have undergone splenectomy are at risk of overwhelming post splenectomy infection, which is characterized by sepsis, meningitis or both, and carries a fatality rate of 50%–70%. These episodes occur in patients who have had splenectomy at a rate of 0.2%–0.5% per year, with a lifetime risk of about 5%. (2)
Rescue splenectomy has been proposed as a last salvage option for cases where conventional therapy failed (PE, IVIG and rituximab). (3)
1- Tzvetanov M.Spaggiari H. Jeon R.G. Roca C.Bhati J.Oberholzer E. Benedetti Division of Transplantation, Department of Surgery, University of Illinois at Chicago (UIC), Chicago, Illinois, USA https://doi.org/10.1016/j.transproceed.2012.01.109
2- Kamar, N., Milioto, O., Puissant-Lubrano, B., Esposito, L., Pierre, M. C., Mohamed, A. O., Lavayssière, L., Cointault, O., Ribes, D., Cardeau, I., Nogier, M. B., Durand, D., Abbal, M., Blancher, A., & Rostaing, L. (2010). Incidence and predictive factors for infectious disease after rituximab therapy in kidney-transplant patients. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 10(1), 89–98. https://doi.org/10.1111/j.1600-6143.2009.02785.x 3- Davidson RN, Wall RA. Prevention and management of infections in patients without a spleen. Clin Microbiol Infect 2001;7: 657–60 [PubMed] [Google Scholar]
3- Michael Latzko, Sakshi Jasra, Sana Akbar, Harry Sun, Sadanand Palekar, “Laparoscopic Splenectomy to Salvage Renal Transplants from Severe Acute Antibody-Mediated Rejection”, Case Reports in Transplantation, vol. 2012, Article ID 253173, 3 pages, 2012. https://doi.org/10.1155/2012/253173
Fatima AlTaher
3 years ago
Indications for surgical splenectomy in transplantation1- Rescue therapy for ABMR , if conventional therapy failed ( PE, IVIG and rituximab ) 2- In ABO incompitable transplantations to decrease B lymphocyte pool
Latzko M, Jasra S, Akbar S, Sun H, Palekar S. Laparoscopic splenectomy to salvage renal transplants from severe acute antibody-mediated rejection. Case Rep Transplant. 2012;2012:253173. doi:10.1155/2012/253173
Iwai T, Uchida J, Kosoku A, Kabei K, Nishide S, Naganuma T, Maeda K, Yoshikawa Y, Kumada N, Takemoto Y, Nakatani T: Splenectomy for ABO-
saja Mohammed
3 years ago
What is the role of surgical splenectomy in transplantation?
1-Surgical splenectomy was used as part of desensitization protocal(antibodies removal )in ABOItransplantaion with low quilty of evdience from case series and small cohort studies which have been replaced by rituximab anti cd20 in the recent updated desensitization protocals (1,2).
2- refractory AMBR as rescue therapy afterfailed first line therapy( pp,IVIG, rituximab in previously highly sensitized patients , the evidence from case series and case reports(3,4).
references:
1-Current protocols and outcomes of ABO-incompatible kidney
transplantation,World J Transplant 2020 July 29; 10(7): 191-205.
2-Sonnenday CJ, Warren DS, Cooper M, Samaniego M, Haas M, King KE, Shirey RS, Simpkins CE, Montgomery RA. Plasmapheresis, CMV hyperimmune globulin, and anti-CD20 allow ABO-incompatible renal transplantation without splenectomy. Am J Transplant. 2004;4:1315–1322
3-Successful rescue of refractory, severe antibody mediated rejection with splenectomy.
Kaplan B, Gangemi A, Thielke J, Oberholzer J, Sankary H, Benedetti E
Transplantation. 2007;83(1):99.Uptodate.
4- The utility of splenectomy as rescue treatment for severe acute antibody mediated rejection.Locke JE, Zachary AA, Haas M, Melancon JK, Warren DS, Simpkins CE, Segev DL, Montgomery RA SO,Am J Transplant. 2007;7(4):842.
Tahani Ashmaig
3 years ago
The role of splenectomy in transplantation:
______________________________________________
▪︎ Splenectomy has been used in desensitization protocols of ABO-incompatible kidney transplant recipients. It removes a major source of lymphocytes, including antibody-secreting B cells, B cell precursor cells, and plasma cells[1].
▪︎It has also been used in the treatment of refractory AMR. However, the effect of splenectomy on the immune system is permanent, which may place the patients at risk for the development of life-threatening sepsis, especially from encapsulated bacteria [1].
▪︎splenectomy plus ecluzimab may provide an effective intervention for rescuing and preserving allograft function in pt with early severe AMR [2]
____________________
References:
[1] Kwaku Marfo, et al “Desensitization Protocols and Their Outcome”. CJASN April 2011, 6 (4) 922-936; DOI: https://doi.org/10.2215/CJN.08140910
[2] Jorge Carlos. et al ” Antibody- Mediated Rejection. Ochsner Journal 17:46-55, 2017.
Reem Younis
3 years ago
-Splenectomy has been proposed as a last salvage option for AMR.One study showed that splenectomy can be successfully performed alone or in association with other treatments like bortezomib or rituximab to overcome severe AMR.
-Splenectomy has been used in desensitization protocols of ABO-incompatible kidney transplant recipients. Splenectomy removes a major source of lymphocytes, including antibody-secreting B cells, B cell precursor cells, and plasma cells, but it places the patient at risk of life-threatening infections
-Splenectomy may affect the incidence of cytomegalovirus (CMV) disease even at a very late stage after transplantation in ABO-incompatible. One study showed seven patients received their graft from an ABO-incompatible living donor and underwent splenectomy for B cell reduction. Among them, 3 recipients experienced very late-onset CMV disease approximately 10 years after their transplant and were enrolled in this study.
-Rituximab has become a recognized treatment in induction therapy for ABOi renal transplantation instead of splenectomy.
References:
I. Tzvetanov, M. Spaggiari, H. Jeon and et al.
The Role of Splenectomy in the Setting of Refractory Humoral Rejection After Kidney Transplantation. Transplantation ProceedingsVolume 44, Issue 5June 2012
-A. Nicholas R. Barnett, Vassilis G. Hadjianastassiou,and Nizam Mamode .Rituximab in renal transplantation.Transplant International ISSN 0934-0874
-lwai T.a · Uchida J.a · Kosoku A.a and et al. Splenectomy for ABO-Incompatible Kidney Transplantation and Very Late-Onset Cytomegalovirus Disease. Urol Int 2020;104:651–656
Mohamed Fouad
3 years ago
Splenectomy in general of two types:
Surgical splenectomy either laparoscopic or open and medical splenectomy by transcatheter embolization of the splenic artery or splenic radiation.
Splenectomy in renal transplantation can be used in some cases:
1-As a rescue therapy in severe ABMR with high antibodies load not responding to conventional anti-rejection therapy of plasmapheresis (PP), IVIg and rituximab .The magnitude of antibody burden must be controlled to prevent renal thrombosis or cortical necrosis. There are several case series of surgical splenectomy, splenic embolization, and splenic radiation used as a salvage procedure for severe early AMR.It must be performed rapidly after the onset of early AMR to be effective.
2- Splenectomy used in desensitization protocols of ABO-incompatible kidney transplant recipients. Splenectomy removes a major source of lymphocytes, including antibody secreting B cells and plasma cells.
2- Medical splenectomy as a part of posttransplant lymphoid irradiation in mixed chimerism in living fully matched renal transplant.
Referrences 89. Locke JE, Zachary AA, Haas M, et al. The utility of splenectomy as rescue treatment for severe acute antibody mediated rejection.Am J Transplant20077842–846
Kaplan B, Gangemi A, Thielke J, Oberholzer J, Sankary H, Benedetti E: Successful rescue of refractory, severe antibody mediated rejection with splenectomy. Transplantation 83: 99 –100, 2007
Woodley SL, Gurley KE, Hoffmann SL, Nicolls MR, Hagberg R, Clayberger C, Holm B, Wang X, Hall BM, Strober S, Induction of tolerance to heart allografts in rats using posttransplant total lymphoid irradiation and anti-T cell antibodies. Transplantation 56, 1443–1447 (1993).
amiri elaf
3 years ago
Plasmapheresis, CMV hyperimmune globulin, and anti‐CD20 allow ABO‐incompatible renal transplantation without splenectomy
# Majority of protocols developed to allow ABO incompatible (ABOi) renal transplantation include concurrent splenectomy as a prerequisite to successful transplantion.
# In this study they use low dose of plasmapheresis, CMV hyperimmune globulin , and anti‐CD20 monoclonal antibody (rituximab) to allow ABOi renal transplantation without splenectomy.
# The result is that:
* ABO antibody titers have remained below pretreatment levels.
* Absence of AMR and stable allograft function in this series show the potential of this preconditioning protocol to increase ABOi renal transplantation.
* Use of rituximab, allowing avoidance of splenectomy, may further remove one of the significant disincentives to ABOi transplantation, and eliminate the risk of post‐splenectomy infections.
Christopher J Sonnenday, Daniel S Warren, Mathew Cooper, Milagros Samaniego, Mark Haas, Karen E King, R Sue Shirey, Christopher E Simpkins, Robert A Montgomery
American Journal of Transplantation 4 (8), 1315-1322, 2004
Mohamed Mohamed
3 years ago
4. What is the role of surgical splenectomy in transplantation?
The role of splenectomy, as a part of desensitization protocol, has largely been replaced by medicalsplenectomy(e.g.anti-CD20(RITUXIMAB)).
Splenectomy had been done as a rescue procedure due tofailure of standard rejection treatments in presensitized patientswho developed AMR after living donor kidney transplantation [1].
Splenectomy was tried in the past to reduce B cell pool but was associated with higher rate of sepsis and mortality
Currently splenectomy has no rule in renal transplantation due to lack of the evidence that this is more effective than other safer medical options like Rituximab
Splenectomy was found to be associated with an increase in the risk of infection with encapsulated microorganisms, recently it was found that splenectomy may be linked to late onset (> 10 years post-transplant) CMV disease (1)
The benefit of splenectomy was assessed in three indications in renal transplantation :
Splenectomy in desensitization:
Addition of splenectomy to plasmapheresis, rituximaband low dose IVIG was inferior to using PP + Rituximab and low dose IVIG alone (2)
ABO incompatible renal transplantation
Desensitization protocol for patients receiving ABO incompatible kidney includes plasmapharesis, IVIG and either Rituximab or less commonly splenectomy.
The addition of Rituximab or splenectomy to plasmapheresis and IVIG is debatable since it was found that they add no benefit. (3)
Splenectomy in treatment of ABMR
Indication of splenectomy in refractory ABMR based on case reports, 9 patients in 2 different studies underwent splenectomy after failure of conventional treatment of ABMR, all responded well with good uop and decrease of serum creatinine within 48 hours of the operation. (4, 5)
REFERANCES
1- Iwai T.a, Uchida J.a, Kosoku A.a, Kabei K.a , et al. Splenectomy for ABO-Incompatible Kidney Transplantation and Very Late-Onset Cytomegalovirus Disease. Urol Int 2020;104:651–656
2- Magee CC, Felgueiras J, Tinckam K, Malek S, Mah H, Tullius S. Renal transplantation in patients with positive lymphocytotoxicity crossmatches: one center’s experience. Transplantation 2008; 86: 96.
3- Montgomery RA, Locke JE, King KE, et al. ABO incompatible renal transplantation: a paradigm ready for broad implementation. Transplantation 2009; 87:1246
4- Kaplan B, Gangemi A, Thielke J, et al. Successful rescue of refractory, severe antibody mediated rejection with splenectomy. Transplantation 2007; 83:99.
5- Locke JE, Zachary AA, Haas M, et al. The utility of splenectomy as rescue treatment for severe acute antibody mediated rejection. Am J Transplant 2007; 7:842.)
Splenectomy is not routinely performed in patients with ABMR, given the lack of evidence that this intervention is safer or more efficacious than available medical therapy. However, some centers consider splenectomy in treating ABMR refractory to plasmapheresis and/or IVIG.
Reference:
Kidney trsnsplantation in adult, :prevention and treatment of Antibody mediated rejection, Arjang Djamali. http://www.uptodate.com
Dear All
Surgical splenectomy is not practised anymore in the current era. It is now replaced by…………………. (Please complete the sentence)
Surgical splenectomy is not practised anymore in the current era. It is now replaced by …. medical splenectomy (using a rituximab – Anti CD20 antibody)
medical splenectomy by rituximab
Rituximab, a monoclonal antibody against B cell surface molecule CD20
I think replaced by PEX , Rituximab, and also IVIG.
I agree with my colleagues that surgical splenectomy was replaced by Rituximab.
References:
1) Macklin PS, Morris PJ, Knight SR. A systematic review of the use of rituximab for desensitization in renal transplantation. Transplantation. 2014 Oct;98(8):794-805.
2) Lo P, Sharma A, Craig JC, et al. Preconditioning Therapy in ABO-Incompatible Living Kidney Transplantation: A Systematic Review and Meta-Analysis. Transplantation. 2016 Apr;100(4):933-942.
Anti CD20 monoclonal Ab (Rituximab).
Rituximab
I think replaced by B cell depletion (anti CD 20) rituximab.
In addition, splenectomy is considered plasma cell debulking maneuver so can be replaced be bortezomib.
Surgical splenectomy is not practised anymore in the current era. It is now replaced by: plasmapheresis and Rituximab
We can use rituximab to block naive B lymphocytes (CD20), simulating splenectomy. However, if there are many plasma cells already circulating (CD19), this treatment will be insufficient, and bortezomib should be added to block plasma cells or evaluate plasma exchange associated with IVIg.
Rituximab
Rituximab
Rituximab
Medical splenectomy by using Rituximab.
Rituximab help in B cell depletion which is the same effect of splenectomy with similar ridk of infection
medical splenectomy ( Rituximab)
Rituximab anti CD 20
Medical splenectomy
Surgical splenectomy is not practised anymore in the current era. It is now replaced by rituximab
surgicalsplenctomy account for 45% infection among the patient and replace by Rituximab
Using a CD20 depleting agents e.g. Rituximab : medical splenectomy
surgical splenectomy has no role nowadays, as the advancement in immunosuppressive medications allows for the depletion of the antibody-producing cells without the need to remove a spleen. Rituximab is a monoclonal antibody directed against CD20 cells. can be used to treat ABMR
Surgical splenectomy was done in :desensitization in high immunological risk recipients, refractory ABMR.
But surgical splenectomy may be complicated with serious life threatening infections especially encapsulated organism. so, now replaced by : anti-CD20 antibody rituximab.
Splenectomy is last option in desensitisation but Surgical splenectomy not done any more Replaced by rituximab
IV RITUXIMAB
What is the role of surgical splenectomy in transplantation?
References:
1.zvetanov I., Spaggiar M., John H., et al. The role of splenectomy in the setting of refractory humoral rejection after kidney transplantation. Transplant Proc. 2012; 44(5):1254.
2. Locke JE, Zachary AA, Haas M, Melancon JK, Warren DS, Simpkins CE, Segev DL, Montgomery RA. The utility of splenectomy as rescue treatment for severe acute antibody mediated rejection. Am J Transplant. 2007 Apr;7(4)
3.DR Tarek Abbas Lecture
surgical splenectomy is not practiced any more for treatment of recurrent AMR, for removing antibodies , it is now replaced by rituximab ( anti CD 20 antibody)
Surgical splenectomy many years ago was proposed as a treatment option for ABMR based on theory that splenectomy reduces memory B-cells and decrease Ab Production.
However, in the new era of modern IS it is replaced by plasmapheresis and rituximab.
Role of surgical splenectomy in transplant
Surgical splenectomy was indicated in severe thrombocytopenia. Pre transplant Splenectomy also played a major role in cadaveric kidney transplant.
Splenectomy was thought to have a mild long term effect on post transplant infection rates particularly in ABO incompatible kidney transplant patients. However, vaccines against infection are essential for an assured effect.
However, it is important to recognize that simultaneous splenectomy and renal transplant can lead to over immunosuppression, resulting in possibility of sepsis and CMV activation, which could lead to death of the patient in adverse cases due to the immunosuppression. Case reports reveal this happening and blame surgical splenectomy done at the same time as kidney transplant for this fatal outcome.
Surgical splenectomy was done previously as part of desensitization for highly sensitized patients or patients with a HLA mismatched donor to avoid rejection outcomes in order to improve graft and patient outcome.
The role of splenectomy in kidney transplant is close to negligible at present. It has been substituted by medical splenectomy, which is rituximab which is an anti CD20 antibody.
splenectomy in the past used in ABOi transplantation and targeting CD20 of B cells which produce antibodies because of high risk of infection and thrombosis substitute by Rituximab which is humanized mouse monoclonal antibody targeting CD20 in B cell .
some studies done prior to transplant ,result shows no decrease in number of rejection postrenal transplant.
referenc
-the spleen is the site of antibodies production through cells .so removal of spleen leads to depletion of these cell. Splendtomy remove a major source of lymphocytes including antibodies secreting B cells , B cell precursor cells and plasma cells.
– Surgical splenctomy was used In :
* highly sensitized patients .
* ABO incompatibility.
* treatment of refractoryABMR.
– the effect of splenectomy on immune system is permanent and may put patients at risk of development life threatening infection especially encapsulated bacteria.
-now days we use rituximab as medical splenctomy.
– rituximam is chimeric/ human monoclonal antibody binds to CD20 on pre B and mature B lymphocyte .
-FDA Rituximab for treatment of refractory or relapsedB cell lymphomas and also For treatment of post-transplant lymphoproliferative diseases.
1. Splenectomy was used initially as a part of desensitization protocols in high risk transplant recipient as (HLA incompatible or ABO incompatible transplantation) in order to remove B cell and abolish the main site for destruction of antibody bounded cells.
2. Also it can be used in treatment of resistant AMR ( last resort after failure of standard of care therapy as PEX and IVIg).
3. However, high mortality secondary to post splenectomy overwhelming infections and sepsis made it obsolete now. In addition, the advances and availability of many pharmacological therapeutics which can act as medical splenectomy and can replace it as rituximab ( B cell depletion) and bortezomib ( plasma cell depletion).
The role of surgical splenectomy has now become obsolete in renal transplantation.
The spleen is the site of antibody production by B cells. Alloreactive dendritic T cells from the donor traverse the blood stream and reach the spleen where they are primed to initiate an allo immune response.
It has been used in desensitized patients and ABO incompatible renal transplant recipients for antibody removal purposes. The morbid nature of the splenectomy surgery and the high risk of infections with encapsulated organisms (eg Pneumococcus and Meningcoccus) has put splenectomy behind the cards for antibody removal.
In studies which used splenectomy for ABO incompatible desensitization, comparable results have been produced in those patients with plasmaphresis + Rituximab and those with plasmaphresis + splenectomy.
There are case reports and small studies where splenectomy was used as a rescue therapy for severe antibody rejection. The mortality after renal transplant in splnectomized patients were reported to be higher than non splenectomized patients.
Splenectomy was replaced by rituximab which is medical splenectomy
*Splenectomy was used as a part of desensitization protocols in high risk transplant recipient as (HLA incompatible or ABO incompatible transplantation) in order to remove B cell and abort the main site for destruction of antibody bounded cells.
*Also it can be used in treatment of resistant AMR ( after failure of standard of care therapy as PEX and IVIg).
Splenectomy was used in cases of ABO incompatibility as a way to avoid hyperacute rejection. However, we have had pre-conditioning regimens that included anti-CD20 monoclonal antibody (rituximab)
Surgical splenectomy removes spleen which is the production house of antibody, as this procedure has multiple morbidities with total paralysis of humoral immunity on longterm puts patients life in life-threatening infections, hence now a days, not practiced.
But it has definite role in-
1.treatment refractory ABMR.
2.desensitization of highly sensitized.
Spleen plays an important immunological role as it produces B lymphocytes and plasma cells. For that reason it participates in antibody production. Surgical Splenectomy results in depletion of Plasma cells and reduction of antibody production which leads to state of tolerance. It was used in the past.
In current practice, medical splenectomy replaced surgical splenectomy with Rituximab as this drug attacks CD20 B cells.
Reference:
surgical splenectomy indicated in those pt having ABO and HLAincompatible KT and pt who are refractory to post – transplant plasmaphresis it may be indicated.
rituximab
Splenectomy offers removal of the sources of Ab production
Many Studied was done evaluating the benifts of splenectomy and risk of infection
One study was done to evaluate long-term effect of rituximab and splenectomy on de novo HLA antibody production and chronic antibody-mediated rejection after renal transplantation 92 ABO-incompatible and 228 ABO-identical/compatible consecutive renal transplant patients and determined their de novo HLA antibody production and graft outcome.
Patients with pretransplant donor-specific antibodies had been excluded.
ABO-incompatible transplants included 30 recipients treated with rituximab, 51 by splenectomy, or 11 with neither, due to low anti-A or -B antibody titer. Graft survival in ABO-identical/compatible patients (97.7% at 5 years) was significantly higher than in ABO-incompatible (87.0% at 5 years), rituximab (96.7% at 3 years), or splenectomy (85.7% at 5 years) patients.
Only four patients had clinical chronic antibody-mediated rejection (two each identical/compatible and incompatible). There was no significant difference in prevalence of de novo HLA antibody, including donor-specific and nondonor-specific antibodies among ABO-identical/compatible patients (13.9%), patients receiving rituximab (14.3%) or splenectomy (13.2%), or among those receiving cyclosporine, tacrolimus, mycophenolate mofetil, mizoribine, and everolimus.
Renal function remained stable in most recipients with de novo HLA antibody. Thus, neither pretransplant splenectomy nor rituximab treatment has an inhibitory effect on de novo HLA antibody production during medium-term follow-up. Further study on long-term effects is needed.
Rituximab is a chimeric anti-CD20 monoclonal antibody that leads to B cell depletion.
It is an effective treatment for post-transplant lymphoproliferative disorder, and is also used in both HLA antibody incompatible renal transplantation and the treatment of acute rejection. Recent evidence suggests rituximab may prevent the development of chronic antibody mediated rejection. The mechanisms underlying its effects are likely to relate both to long-term effects on plasma cell development and to the impact on B cell modulation of T cell responses.
Reference;
Satoshi Ashimine et al. Kidney Int. 2014 Feb.
Neither pre-transplant rituximab nor splenectomy affects de novo HLA antibody production after renal transplantation.
Rituximab in renal transplantation
A Nicholas R Barnett et al. Transpl Int. 2013 Jun.
Surgical splenectomy was done before in the following situations:
-desensitization in high immunological risk transplants.
– in ABO incompatible transplants.
-treatment in refractory antibody mediated rejection.
But surgical splenectomy may be complicated with serious life threatening infections especially encapsulated organism (pneumococcal infections)
It has been replaced with ‘medical splenectomy’ involving use of anti-CD20 antibody rituximab.
The spleen is the site of antibodies production through B cells , so removal of the spleen will lead to depletion of these cells .
Surgical splenectomy was used for :
Highly sensitized recipients
ABO incompatibility
As last option in treatment of refractory ABMR
In the modern era surgical splenectomy was replaced by medical splenectomy ( Rituximab) because of the risk of overwhelming infection by encapsulated pneumococcal bacteria and sepsis.
Several studies had prescribed the role and advantages of Splenectomy, most dating back to the 1980s. One of those was published by Okiye SE et al in 1983, where he analysed the effect of splenectomy in One hundred eight patients versus 57 who did not. They reported that Splenectomy improved cadaver donor renal allograft survival (p = 0.001) in the diabetic patients (p = 0.015) and in those 50 years of age or older (p = 0.026) but it did not improve survival in those who received living related donor kidneys. The incidence of infection and sepsis was comparable in both groups and was responsible for death in 34% of the patients who underwent splenectomy compared with 22% of those who did not (no significant difference).
Surgical splenectomy is not practised anymore in our current era. Yet, In 2014 Orandi et al, described rescuing therapy to preserve allograft function for patients with early & severe AMR. He reported a better graft survival in patients treated with both splenectomy plus eculizumab compared to those treated with eculizumab alone or splenectomy alone.
References:
· Orandi BJ, Zachary AA, Dagher NN, et al. Eculizumab and splenectomy as salvage therapy for severe antibody-mediated rejection after HLA-incompatible kidney transplantation. Transplantation. 2014 Oct 27;98(8):857-863.
· Okiye SE, Zincke H, Engen DE, Sterioff S, Offord KP, Frohnert PP, Johnson WJ. Splenectomy in high-risk primary renal transplant recipients. Am J Surg. 1983 Nov;146(5):594-601.
Splenectomy
Splenectomy has been used in desensitization protocols of ABO-incompatible kidney transplant recipients. Splenectomy removes a major source of lymphocytes, including antibody-secreting B cells, B cell precursor cells, and plasma cells. It has also been used in the treatment of refractory AMR
However, the effect of splenectomy on the immune system is permanent, which may place the patients at risk for the development of life-threat- ening sepsis, especially from encapsulated bacteria
So use rituximab as medical spleenectomy is better approach
Rituximab (Anti-CD20). Rituximab is a chimeric murine/human monoclonal antibody that binds to CD20 on pre-B and mature B lymphocytes
It is FDA approved for treatment of refractory or relapsed B cell lymphomas and is also used for treatment of posttransplant lym- phoproliferative disease (PTLD).
Reference
Kwaku Marfo,* Amy Lu,* Min Ling*† and Enver Akalin*‡ Desensitization Protocols and Their Outcome. Clin J Am Soc Nephrol 6: 922–936, 2011. doi: 10.2215/CJN.08140910.
The spleen is not only the principle site of antibody synthesis, but also is a source of specific alloreactive host lymphocytes . It has been suggested that transient post transplant migration of dendritic cells from the transplanted graft to the spleen may be responsible for initiation of graft rejection . On the contrary the spleen may play a major role in prolongation of graft survival in different species , perhaps by generation of specific suppressor cells .
1-Some have reported a beneficial effect of splenectomy either pre- or peri transplantation and have attributed this benefit to a reduction in antibody production or improved leukocyte count and therefore tolerance to azathioprine (AZA) .
2– Earlier studies suggested that splenectomy appeared to reduce the incidence of early rejection .
3- Some studies found that splenectomy was associated with allograft survival .
4- Others have shown no benefit, discouraging the routine use of this
procedure because of its potentially lethal complications due to delayed infection and thromboembolic events .
Surgical splenectomy is not practised anymore in the current era. It is now replaced by …. medical splenectomy (using a rituximab – Anti CD20 antibody)
Reference ;
1-Kaplan B, Gangemi A, Thielke J, Oberholzer J, Sankary H, Benedetti E. Successful rescue of refractory, severe antibody mediated rejection with splenectomy. Transplantation. 2007 Jan 15;83(1):99-100. doi: 10.1097/01.tp.0000243739.31440.2b. PMID: 17220802
2–Iwai T.et al. Splenectomy for ABO-Incompatible Kidney Transplantation and Very Late-Onset Cytomegalovirus Disease .Urol Int 2020;104:651–656
Thanks All for the excellent answer. Yes Rituximab has replaced surgical splenectomy
splenectomy is not indicated but may be useful in liver transplantation to improve thrombocytopenia maybe, also maybe used in ABO-incompatible cases but now we have desensitization protocols plasmapheresis and also depleting agents like Rituximab
1. Splenectomy was used initially as a part of desensitization protocols in high risk transplant recipient as (HLA incompatible or ABO incompatible transplantation) in order to remove B cell and abolish the main site for destruction of antibody bounded cells.
2. Also it can be used in treatment of resistant AMR ( last resort after failure of standard of care therapy as PEX and IVIg).
3. However, high mortality secondary to post splenectomy overwhelming infections and sepsis made it obsolete now. In addition, the advances and availability of many pharmacological therapeutics which can act as medical nephrectomy and can replace it as rituximab ( B cell depletion) and bortezomib ( plasma cell depletion).
References;
Salvadori M, Tsalouchos A. Current protocols and outcomes of ABO-incompatible kidney transplantation. World Journal of Transplantation. 2020 Jul 29;10(7):191.
Schinstock CA, Mannon RB, Budde K, Chong AS, Haas M, Knechtle S, Lefaucheur C, Montgomery RA, Nickerson P, Tullius SG, Ahn C. Recommended treatment for antibody-mediated rejection after kidney transplantation: the 2019 expert consensus from the transplantion society working group. Transplantation. 2020 May;104(5):911.
Splenectomy is not practised anymore in the current era. It is now replaced by rituximab
ABO-Incompatible Recipients
Waigankar et al
Hyodo et al.
Tokyo Women’s Medical University study
Splenectomy as Rescue Treatment
Splenectomy as Rescue Treatment for Severe Acute Antibody Mediated Rejection
Alexander et al.
References
Splenectomy as a method of desensitization:
Splenectomy combined with plasmapheresis, rituximab and low-dose IVIG was shown to be less effective than utilizing just plasmapheresis, rituximab, and low-dose IVIG alone
Renal transplantation in the presence of ABO incompatibility
Plasmapheresis, IVIG, and either Rituximab or, less typically, splenectomy are all part of the desensitization strategy for patients getting ABO-incompatible kidney transplants.
Although the addition of Rituximab or splenectomy to plasmapheresis and IVIG has been shown to be ineffective, it is still controversial whether they should be included. Splenectomy as a therapy for ABMR is discussed.
When ABMR is refractory, splenectomy may be indicated. Based on case reports, nine patients in two distinct trials who had failed standard therapy for ABMR had splenectomy after failing to react to it and responded well.
-Kwaku Marfo, et al Desensitization Protocols and Their Outcome. CJASN April 2011
What is the role of surgical splenectomy in transplantation?
Splenectomy used for refractory AB mediated rejection if there is no response to IV Ig and plasma exchange but after discovery of modern immunosuppressive drug (rituximab) now days no longer used for for following :
-it cause over immunosuppression which may lead to fatal infection so we should out weigh risk and benefit.
-the efficacy of splenectomy if we compare with antiCD20 rituximab there is no much difference , although laparoscopic splenectomy used by some centers and it has good response for treatment of Ab mediated rejection but no longer used for primary prevention in highly sensitized patient or ABO incompatible transplant .
Splenectomy has no role in renal transplantation in modern era though it has been used in the past in highly sensitized patients to decrease denovo antibody production by removing B cells ,ABO incompatible renal transplantation and also as rescue therapy in resistant ABMR Alternative options are now available with less side effects as compared to Splenectomy which was associated with higher incidence of significant sepsis. Currently anti CD20 -Rituximab is available as alternative to Splenectomy.
Reference;
Mark Haas et al. The Utility of Splenectomy as Rescue Treatment for Severe Acute Antibody Mediated Rejection. American Journal of transplantation. April 2007. 7(4):842-6
Role of surgical splenectomy in transplantation ;
Limitations of surgical splenectomy ;
The spleen has been shown to be an important site of
proliferation and maturation of immunocompetent cells
reactive against an allograft
hence may be before there was aconcept that by doing surgical splenectomy it will remove suppressor t cells and other cells as memory B cells and plasma cells hence resposible for ab production after faliure of plasmapharesis and other immune suppressant medications .
In ABO-incompatible renal transplantation
, splenectomy was done to reduce B cell pool ,patients undergoing splenectomy may have a lifelong susceptibility to infection and mortality.
and then replaced by induction of rituximab, a monoclonal antibody against B cell surface molecule CD20 .Also used in acute AMR in addition to slandered protocol .
What is the role of surgical splenectomy in transplantation?
Surgical splenectomy has been used in transplantation in following conditions:
1) As part of pre-operative desensitization in high immunological risk transplants. (1)
2) Pre-operatively in ABO incompatible transplants. (2)
3) As part of treatment in refractory antibody mediated rejection. (3,4)
It has been replaced with ‘medical splenectomy’ involving use of anti-CD20 antibody rituximab, due to morbidity and mortality associated with surgical splenectomy- including increased risk of infections, especially pneumococcal infections. (5)
In ABO incompatible transplants, even rituximab has been shown to have doubtful value with no rise in antibody mediated rejection incidence seen in patients not given rituximab. (2)
References:
1) Okiye SE, Zincke H, Engen DE, Sterioff S, Offord KP, Frohnert PP, Johnson WJ. Splenectomy in high-risk primary renal transplant recipients. Am J Surg. 1983 Nov;146(5):594-601. doi: 10.1016/0002-9610(83)90295-7. PMID: 6356949.
2) Montgomery RA, Locke JE, King KE, Segev DL, Warren DS, Kraus ES, Cooper M, Simpkins CE, Singer AL, Stewart ZA, Melancon JK, Ratner L, Zachary AA, Haas M. ABO incompatible renal transplantation: a paradigm ready for broad implementation. Transplantation. 2009 Apr 27;87(8):1246-55. doi: 10.1097/TP.0b013e31819f2024. PMID: 19384174.
3) Locke JE, Zachary AA, Haas M, Melancon JK, Warren DS, Simpkins CE, Segev DL, Montgomery RA. The utility of splenectomy as rescue treatment for severe acute antibody mediated rejection. Am J Transplant. 2007 Apr;7(4):842-6. doi: 10.1111/j.1600-6143.2006.01709.x. PMID: 17391127.
4) Kaplan B, Gangemi A, Thielke J, Oberholzer J, Sankary H, Benedetti E. Successful rescue of refractory, severe antibody mediated rejection with splenectomy. Transplantation. 2007 Jan 15;83(1):99-100. doi: 10.1097/01.tp.0000243739.31440.2b. PMID: 17220802.
5) Sonnenday CJ, Warren DS, Cooper M, Samaniego M, Haas M, King KE, Shirey RS, Simpkins CE, Montgomery RA. Plasmapheresis, CMV hyperimmune globulin, and anti-CD20 allow ABO-incompatible renal transplantation without splenectomy. Am J Transplant. 2004 Aug;4(8):1315-22. doi: 10.1111/j.1600-6143.2004.00507.x. PMID: 15268734.
Splenectomy was performed in ABO-incompatible kidney transplantation to lower the B cell burden. Studies demonstrated that patients undergoing splenectomy can be subjected to infection and mortality for lifelong as it increase the incidence of cytomegalovirus (CMV) disease even at a very late stage after transplantation in ABO-incompatible recipients.(1)
Splenectomy was used as an adjuvant therapy to current AMR protocol, which includes PP/IVIg and in some cases anti-CD20.
Since plasma cells reside in the spleen before migrating to the bone marrow. These cells do not express CD20 and are not liable to ablation with anti-CD20 monoclonal antibodies.
Splenectomy was effective in debulking plasma cells, thereby decreasing antibody production to a level that can be controlled with PP. In Locke JE etal studyit was demonstrated that splenectomy, in some cases, is associated with return of renal function, and this can start before the reinitiation of PP. (2)
Reference
1-Iwai T.et al. Splenectomy for ABO-Incompatible Kidney Transplantation and Very Late-Onset Cytomegalovirus Disease .Urol Int 2020;104:651–656
2- Locke JE etal. The Utility of Splenectomy as Rescue Treatment for Severe Acute Antibody Mediated Rejection. American journal of trasnplanation 2007 :7;4;842-846
Splenectomy was initially used in ABO incompatible kidney transplantation as pre transplant desensitization protocol.
It was used as B cell depletion therapy to prevent rapid generation of B cells in highly sensitized recipients and before ABO incompatible kidney transplantation.
It was also used as salvage procedure for severe early antibody mediated rejection
It was gradually replaced by Rituximab, the drug used now to obtain B cell depletion.
It was associated with surgical risk and long-term risks as overwhelming post splenectomy infection.
Morath C, Zeier M, Döhler B, Opelz G, Süsal C. ABO-incompatible kidney transplantation. Frontiers in immunology. 2017 Mar 6;8:234.
Salvadori M, Tsalouchos A. Current protocols and outcomes of ABO-incompatible kidney transplantation. World Journal of Transplantation. 2020 Jul 29;10(7):191.
Schinstock CA, Mannon RB, Budde K, Chong AS, Haas M, Knechtle S, Lefaucheur C, Montgomery RA, Nickerson P, Tullius SG, Ahn C. Recommended treatment for antibody-mediated rejection after kidney transplantation: the 2019 expert consensus from the transplantion society working group. Transplantation. 2020 May;104(5):911.
Surgical splenectomy has been previously used in ABO incomplete transplants as a way of reducing the B cell pool. The spleen is considered a major source of anti-A and anti-B antibodies(Salamon et al., 1985).
Splenectomy is effective in removing anti-blood group producing plasma cells. This can be done pre-transplant or at the time of transplantation.
It used when transplanting non-A2 blood group ABOI kidney transplants.
This approach however, is associated with post-transplant infections like late onset CMV infection(Iwai et al., 2020).
Current protocols have abandoned this approach preferring to use plasmapheresis, Iv Ig and rituximab(Gloor et al., 2005).
GLOOR, J. M., LAGER, D. J., FIDLER, M. E., GRANDE, J. P., MOORE, S. B., WINTERS, J. L., KREMERS, W. K. & STEGALL, M. D. 2005. A Comparison of Splenectomy versus Intensive Posttransplant Antidonor Blood Group Antibody Monitoring without Splenectomy in ABO-Incompatible Kidney Transplantation. Transplantation, 80, 1572-1577.
IWAI, T., UCHIDA, J., KOSOKU, A., KABEI, K., NISHIDE, S., NAGANUMA, T., MAEDA, K., YOSHIKAWA, Y., KUMADA, N., TAKEMOTO, Y. & NAKATANI, T. 2020. Splenectomy for ABO-Incompatible Kidney Transplantation and Very Late-Onset Cytomegalovirus Disease. Urologia Internationalis, 104, 651-656.
SALAMON, D. J., RAMSEY, G., NUSBACHER, J., YANG, S., STARZL, T. E. & ISRAEL, L. 1985. Anti-A production by a group O spleen transplanted to a group A recipient. Vox sanguinis, 48, 309-312.
Therapeutic splenectomy in transplant :
Human leukocyte antigen (HLA) and/or ABOi desensitization for renal
transplantation . pharmacological treatments (e.g., rituximab) are now used in
place of splenectomy to achieve complete depletion of B-cells in peripheral blood..
Some centers consider splenectomy in treating ABMR refractory to
plasmapheresis and/or IVIG .
General medical and surgical indication in transplant patient:
Splenic abscess.
Splenic lymphoma in PTLD.
Tumors ,metastasis. And cyst
Bleeding disorders .e.g ITP.
The role of surgical splenectomy in transplantation?======================================
Splenectomy may revers AMR by debulking plasma cell.Patients with a very high load of plasma cells may not be rescued by splenectomy alone and may need additional treatments.(1,2).
1-Prof .Tarek Abbas lecture.(Renal allograft rejection part II).2-Ivo Tzvetanov et al.( Cell population in spleens during antibody-mediated rejection: pathologic and clinical findings) 2012 Aug 15;94(3):255-62
Splenectomy has been considered as part of desensitization protocol and as a rescue therapy for resistant ABMR but has not shown promising results. Rituximab does the same job so it is no more considered as a safe option but desperate situation at times need desperate measures and in such a scenario none can always think of it.
The spleen acts as a repository for memory B cells and plasma cells, thus playing an important role in the alloantibody response.
Splenectomy used to reduce the pool of B-lymphocytes in patients with ABO-incompatibility to decrease the risk of graft rejection. Nowadays, Medical splenectomy with Rituximab has the same role and it is mainly used instead of surgical splenectomy.
A study by Kamar et al on 77 kidney transplant patients who received Rituximab with a median follow-up of 16.5 (1-55) months for rituximab patients and 60.9 (1.25-142.7) months for control patients, the incidence of infectious disease was 45.45% and 53.9% (ns), respectively. (1)
Patients who have undergone splenectomy are at risk of overwhelming post splenectomy infection, which is characterized by sepsis, meningitis or both, and carries a fatality rate of 50%–70%. These episodes occur in patients who have had splenectomy at a rate of 0.2%–0.5% per year, with a lifetime risk of about 5%. (2)
Rescue splenectomy has been proposed as a last salvage option for cases where conventional therapy failed (PE, IVIG and rituximab). (3)
1- Tzvetanov M.Spaggiari H. Jeon R.G. Roca C.Bhati J.Oberholzer E. Benedetti Division of Transplantation, Department of Surgery, University of Illinois at Chicago (UIC), Chicago, Illinois, USA https://doi.org/10.1016/j.transproceed.2012.01.109
2- Kamar, N., Milioto, O., Puissant-Lubrano, B., Esposito, L., Pierre, M. C., Mohamed, A. O., Lavayssière, L., Cointault, O., Ribes, D., Cardeau, I., Nogier, M. B., Durand, D., Abbal, M., Blancher, A., & Rostaing, L. (2010). Incidence and predictive factors for infectious disease after rituximab therapy in kidney-transplant patients. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 10(1), 89–98. https://doi.org/10.1111/j.1600-6143.2009.02785.x 3- Davidson RN, Wall RA. Prevention and management of infections in patients without a spleen. Clin Microbiol Infect 2001;7: 657–60 [PubMed] [Google Scholar]
3- Michael Latzko, Sakshi Jasra, Sana Akbar, Harry Sun, Sadanand Palekar, “Laparoscopic Splenectomy to Salvage Renal Transplants from Severe Acute Antibody-Mediated Rejection”, Case Reports in Transplantation, vol. 2012, Article ID 253173, 3 pages, 2012. https://doi.org/10.1155/2012/253173
Indications for surgical splenectomy in transplantation1- Rescue therapy for ABMR , if conventional therapy failed ( PE, IVIG and rituximab )
2- In ABO incompitable transplantations to decrease B lymphocyte pool
Latzko M, Jasra S, Akbar S, Sun H, Palekar S. Laparoscopic splenectomy to salvage renal transplants from severe acute antibody-mediated rejection. Case Rep Transplant. 2012;2012:253173. doi:10.1155/2012/253173
Iwai T, Uchida J, Kosoku A, Kabei K, Nishide S, Naganuma T, Maeda K, Yoshikawa Y, Kumada N, Takemoto Y, Nakatani T: Splenectomy for ABO-
What is the role of surgical splenectomy in transplantation?
1-Surgical splenectomy was used as part of desensitization protocal(antibodies removal )in ABOItransplantaion with low quilty of evdience from case series and small cohort studies which have been replaced by rituximab anti cd20 in the recent updated desensitization protocals (1,2).
2- refractory AMBR as rescue therapy afterfailed first line therapy( pp,IVIG, rituximab in previously highly sensitized patients , the evidence from case series and case reports(3,4).
references:
1-Current protocols and outcomes of ABO-incompatible kidney
transplantation,World J Transplant 2020 July 29; 10(7): 191-205.
2-Sonnenday CJ, Warren DS, Cooper M, Samaniego M, Haas M, King KE, Shirey RS, Simpkins CE, Montgomery RA. Plasmapheresis, CMV hyperimmune globulin, and anti-CD20 allow ABO-incompatible renal transplantation without splenectomy. Am J Transplant. 2004;4:1315–1322
3-Successful rescue of refractory, severe antibody mediated rejection with splenectomy.
Kaplan B, Gangemi A, Thielke J, Oberholzer J, Sankary H, Benedetti E
Transplantation. 2007;83(1):99.Uptodate.
4- The utility of splenectomy as rescue treatment for severe acute antibody mediated rejection.Locke JE, Zachary AA, Haas M, Melancon JK, Warren DS, Simpkins CE, Segev DL, Montgomery RA SO,Am J Transplant. 2007;7(4):842.
The role of splenectomy in transplantation:
______________________________________________
▪︎ Splenectomy has been used in desensitization protocols of ABO-incompatible kidney transplant recipients. It removes a major source of lymphocytes, including antibody-secreting B cells, B cell precursor cells, and plasma cells[1].
▪︎It has also been used in the treatment of refractory AMR. However, the effect of splenectomy on the immune system is permanent, which may place the patients at risk for the development of life-threatening sepsis, especially from encapsulated bacteria [1].
▪︎splenectomy plus ecluzimab may provide an effective intervention for rescuing and preserving allograft function in pt with early severe AMR [2]
____________________
References:
[1] Kwaku Marfo, et al “Desensitization Protocols and Their Outcome”. CJASN April 2011, 6 (4) 922-936; DOI: https://doi.org/10.2215/CJN.08140910
[2] Jorge Carlos. et al ” Antibody- Mediated Rejection. Ochsner Journal 17:46-55, 2017.
-Splenectomy has been proposed as a last salvage option for AMR.One study showed that splenectomy can be successfully performed alone or in association with other treatments like bortezomib or rituximab to overcome severe AMR.
-Splenectomy has been used in desensitization protocols of ABO-incompatible kidney transplant recipients. Splenectomy removes a major source of lymphocytes, including antibody-secreting B cells, B cell precursor cells, and plasma cells, but it places the patient at risk of life-threatening infections
-Splenectomy may affect the incidence of cytomegalovirus (CMV) disease even at a very late stage after transplantation in ABO-incompatible. One study showed seven patients received their graft from an ABO-incompatible living donor and underwent splenectomy for B cell reduction. Among them, 3 recipients experienced very late-onset CMV disease approximately 10 years after their transplant and were enrolled in this study.
-Rituximab has become a recognized treatment in induction therapy for ABOi renal transplantation instead of splenectomy.
References:
I. Tzvetanov, M. Spaggiari, H. Jeon and et al.
The Role of Splenectomy in the Setting of Refractory Humoral Rejection After Kidney Transplantation. Transplantation ProceedingsVolume 44, Issue 5June 2012
-A. Nicholas R. Barnett, Vassilis G. Hadjianastassiou,and Nizam Mamode .Rituximab in renal transplantation.Transplant International ISSN 0934-0874
-lwai T.a · Uchida J.a · Kosoku A.a and et al. Splenectomy for ABO-Incompatible Kidney Transplantation and Very Late-Onset Cytomegalovirus Disease. Urol Int 2020;104:651–656
Splenectomy in general of two types:
Surgical splenectomy either laparoscopic or open and medical splenectomy by transcatheter embolization of the splenic artery or splenic radiation.
Splenectomy in renal transplantation can be used in some cases:
1-As a rescue therapy in severe ABMR with high antibodies load not responding to conventional anti-rejection therapy of plasmapheresis (PP), IVIg and rituximab .The magnitude of antibody burden must be controlled to prevent renal thrombosis or cortical necrosis.
There are several case series of surgical splenectomy, splenic embolization, and splenic radiation used as a salvage procedure for severe early AMR.It must be performed rapidly after the onset of early AMR to be effective.
2- Splenectomy used in desensitization protocols of ABO-incompatible kidney transplant recipients. Splenectomy removes a major source of lymphocytes, including antibody secreting B cells and plasma cells.
2- Medical splenectomy as a part of posttransplant lymphoid irradiation in mixed chimerism in living fully matched renal transplant.
Referrences
89. Locke JE, Zachary AA, Haas M, et al. The utility of splenectomy as rescue treatment for severe acute antibody mediated rejection.Am J Transplant20077842–846
Kaplan B, Gangemi A, Thielke J, Oberholzer J, Sankary H, Benedetti E: Successful rescue of refractory, severe antibody mediated rejection with splenectomy. Transplantation 83: 99 –100, 2007
Woodley SL, Gurley KE, Hoffmann SL, Nicolls MR, Hagberg R, Clayberger C, Holm B, Wang X, Hall BM, Strober S, Induction of tolerance to heart allografts in rats using posttransplant total lymphoid irradiation and anti-T cell antibodies. Transplantation 56, 1443–1447 (1993).
Plasmapheresis, CMV hyperimmune globulin, and anti‐CD20 allow ABO‐incompatible renal transplantation without splenectomy
# Majority of protocols developed to allow ABO incompatible (ABOi) renal transplantation include concurrent splenectomy as a prerequisite to successful transplantion.
# In this study they use low dose of plasmapheresis, CMV hyperimmune globulin , and anti‐CD20 monoclonal antibody (rituximab) to allow ABOi renal transplantation without splenectomy.
# The result is that:
* ABO antibody titers have remained below pretreatment levels.
* Absence of AMR and stable allograft function in this series show the potential of this preconditioning protocol to increase ABOi renal transplantation.
* Use of rituximab, allowing avoidance of splenectomy, may further remove one of the significant disincentives to ABOi transplantation, and eliminate the risk of post‐splenectomy infections.
Christopher J Sonnenday, Daniel S Warren, Mathew Cooper, Milagros Samaniego, Mark Haas, Karen E King, R Sue Shirey, Christopher E Simpkins, Robert A Montgomery
American Journal of Transplantation 4 (8), 1315-1322, 2004
4. What is the role of surgical splenectomy in transplantation?
The role of splenectomy, as a part of desensitization protocol, has largely been replaced by medical splenectomy(e.g.anti-CD20(RITUXIMAB)).
Splenectomy had been done as a rescue procedure due to failure of standard rejection treatments in presensitized patients who developed AMR after living donor kidney transplantation [1].
Splenectomy plus eculizumab has been used as salvage therapy for severe AMR after HLA–incompatible kidney transplantation[2].
Neither pre-transplant rituximab nor splenectomy affects de novo HLA antibody production after renal transplantation[3]
Reference:
I.TzvetanovM.SpaggiariH.JeonR.G.RocaC.BhatiJ.OberholzerE.Benedetti
Division of Transplantation, Department of Surgery, University of Illinois at Chicago (UIC), Chicago, Illinois, USA
https://doi.org/10.1016/j.transproceed.2012.01.109
2.Orandi, Babak J.1; Zachary, Andrea A.2; Dagher, Nabil N.1; Bagnasco, Serena M.3; Garonzik-Wang, Jacqueline M.1; Van Arendonk, Kyle J.1; Gupta, Natasha1; Lonze, Bonnie E.1; Alachkar, Nada2; Kraus, Edward S.2; Desai, Niraj M.1; Locke, Jayme E.4; Racusen, Lorraine C.3; Segev, Dorry L.1Transplantation: October 27, 2014 – Volume 98 – Issue 8 – p 857-863: 10.1097/TP.0000000000000298
SatoshiAshimine1YoshihikoWatarai1TakayukiYamamoto1TakahisaHiramitsu1MakotoTsujita1KojiNanmoku1NorihikoGoto1AsamiTakeda2AkioKatayama3KazuharuUchida4TakaakiKobayashi56 https://doi.org/10.1038/ki.2013.291
Splenectomy was tried in the past to reduce B cell pool but was associated with higher rate of sepsis and mortality
Currently splenectomy has no rule in renal transplantation due to lack of the evidence that this is more effective than other safer medical options like Rituximab
Splenectomy was found to be associated with an increase in the risk of infection with encapsulated microorganisms, recently it was found that splenectomy may be linked to late onset (> 10 years post-transplant) CMV disease (1)
The benefit of splenectomy was assessed in three indications in renal transplantation :
Splenectomy in desensitization:
ABO incompatible renal transplantation
Splenectomy in treatment of ABMR
REFERANCES
1- Iwai T.a, Uchida J.a, Kosoku A.a, Kabei K.a , et al. Splenectomy for ABO-Incompatible Kidney Transplantation and Very Late-Onset Cytomegalovirus Disease. Urol Int 2020;104:651–656
2- Magee CC, Felgueiras J, Tinckam K, Malek S, Mah H, Tullius S. Renal transplantation in patients with positive lymphocytotoxicity crossmatches: one center’s experience. Transplantation 2008; 86: 96.
3- Montgomery RA, Locke JE, King KE, et al. ABO incompatible renal transplantation: a paradigm ready for broad implementation. Transplantation 2009; 87:1246
4- Kaplan B, Gangemi A, Thielke J, et al. Successful rescue of refractory, severe antibody mediated rejection with splenectomy. Transplantation 2007; 83:99.
5- Locke JE, Zachary AA, Haas M, et al. The utility of splenectomy as rescue treatment for severe acute antibody mediated rejection. Am J Transplant 2007; 7:842.)
Excellent response
Splenectomy is not routinely performed in patients with ABMR, given the lack of evidence that this intervention is safer or more efficacious than available medical therapy. However, some centers consider splenectomy in treating ABMR refractory to plasmapheresis and/or IVIG.
Reference:
Kidney trsnsplantation in adult, :prevention and treatment of Antibody mediated rejection, Arjang Djamali. http://www.uptodate.com