Post-transplant lymphoproliferative disorder

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Post-transplant lymphoproliferative disorder (PTLD) of the monomorphic variety is typically treated as per the histologic subtype, which is usually diffuse large B-cell lymphoma (DLBCL). However, some regimens specific to PTLD have been developed, primarily due to concern of excess infectious toxicities in the setting of immunosuppression, and are included here.
Last updated on 2024-07-23:8 regimens on this page
10 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - B-cell Lymphomas.
=Induction=
==ACVBP, dose-adjusted==
ACVBP: Adriamycin (Doxorubicin), Cyclophosphamide, Vindesine, Bleomycin, Prednisone
===Regimen===
Study 	Dates of enrollment	Evidence
Fohrer et al. 2006	1989-2003 	Phase 2
Note: This is of historical interest, only.
====Chemotherapy====
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
*Vindesine (Eldisine) 2 mg/m2 (maximum dose of 4 mg) IV once on day 1
*Bleomycin (Blenoxane) 15 mg IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 60 mg/m2 (route not specified) once per day on days 1 to 5
14-day cycle for 6 cycles
===References===
# Fohrer C, Caillard S, Koumarianou A, Ellero B, Woehl-Jaeglé ML, Meyer C, Epailly E, Chenard MP, Lioure B, Natarajan-Ame S, Maloisel F, Lutun P, Kessler R, Moulin B, Bergerat JP, Wolf P, Herbrecht R. Long-term survival in post-transplant lymphoproliferative disorders with a dose-adjusted ACVBP regimen. Br J Haematol. 2006 Sep;134(6):602-12. Epub 2006 Aug 2. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Rituximab monotherapy==
===Regimen variant #1, 4-week course===
Study 	Dates of enrollment	Evidence
Oertel et al. 2005 	1999-2002 	Phase 2, fewer than 20 pts
Choquet et al. 2005 	2000-2001 	Phase 2
González-Barca et al. 2007 	2000-2005 	Phase 2
Trappe et al. 2011 (PTLD-1)	2002-2008 	Phase 2
Note: This regimen was intended for B-cell PTLD. Note that this was a modification of the original PTLD-1 trial schema.
====Targeted therapy====
*Rituximab (Rituxan) 375 mg/m2 IV once on day 1
7-day cycle for 4 cycles
====Subsequent treatment====
*González-Barca et al. 2007: Patients underwent interim staging 4 to 8 weeks later
**González-Barca et al. 2007, patients achieving CR: no further treatment
**González-Barca et al. 2007, patients achieving PR: Rituximab consolidation
*PTLD-1: Patients underwent interim staging by CT between days 40 and 50
**PTLD-1, patients achieving CR: Rituximab consolidation
**PTLD-1, patients not achieving CR: Salvage R-CHOP
===Regimen variant #2, q6mo blocks===
Study 	Dates of enrollment	Evidence
Blaes et al. 2005	1999-2001 	Phase 2, fewer than 20 pts
====Targeted therapy====
*Rituximab (Rituxan) 375 mg/m2 IV once per day on days 1, 8, 15, 22
6-month cycle for up to 4 cycles (2 years)
===References===
# Blaes AH, Peterson BA, Bartlett N, Dunn DL, Morrison VA. Rituximab therapy is effective for posttransplant lymphoproliferative disorders after solid organ transplantation: results of a phase II trial. Cancer. 2005 Oct 15;104(8):1661-7. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# Oertel SH, Verschuuren E, Reinke P, Zeidler K, Papp-Váry M, Babel N, Trappe RU, Jonas S, Hummel M, Anagnostopoulos I, Dörken B, Riess HB. Effect of anti-CD 20 antibody rituximab in patients with post-transplant lymphoproliferative disorder (PTLD). Am J Transplant. 2005 Dec;5(12):2901-6. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
## Pooled update: Choquet S, Oertel S, LeBlond V, Riess H, Varoqueaux N, Dörken B, Trappe RU. Rituximab in the management of post-transplantation lymphoproliferative disorder after solid organ transplantation: proceed with caution. Ann Hematol. 2007 Aug;86(8):599-607. Epub 2007 May 24. link to original article EuroPMC
# Choquet S, Leblond V, Herbrecht R, Socié G, Stoppa AM, Vandenberghe P, Fischer A, Morschhauser F, Salles G, Feremans W, Vilmer E, Peraldi MN, Lang P, Lebranchu Y, Oksenhendler E, Garnier JL, Lamy T, Jaccard A, Ferrant A, Offner F, Hermine O, Moreau A, Fafi-Kremer S, Morand P, Chatenoud L, Berriot-Varoqueaux N, Bergougnoux L, Milpied N. Efficacy and safety of rituximab in B-cell post-transplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study. Blood. 2006 Apr 15;107(8):3053-7. Epub 2005 Oct 27. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
## Pooled update: Choquet S, Oertel S, LeBlond V, Riess H, Varoqueaux N, Dörken B, Trappe RU. Rituximab in the management of post-transplantation lymphoproliferative disorder after solid organ transplantation: proceed with caution. Ann Hematol. 2007 Aug;86(8):599-607. Epub 2007 May 24. link to original article EuroPMC
# González-Barca E, Domingo-Domenech E, Capote FJ, Gómez-Codina J, Salar A, Bailen A, Ribera JM, López A, Briones J, Muñoz A, Encuentra M, de Sevilla AF; GEL/TAMO (Grupo Español de Linfomas); GELCAB (Grupo para el Estudio de los Linfomas Catalano-Balear); GOTEL (Grupo Oncológico para el Tratamiento y Estudio de los Linfomas). Prospective phase II trial of extended treatment with rituximab in patients with B-cell post-transplant lymphoproliferative disease. Haematologica. 2007 Nov;92(11):1489-94. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# PTLD-1: Trappe RU, Oertel S, Leblond V, Mollee P, Sender M, Reinke P, Neuhaus R, Lehmkuhl H, Horst HA, Salles G, Morschhauser F, Jaccard A, Lamy T, Leithäuser M, Zimmermann H, Anagnostopoulos I, Raphael M, Riess H, Choquet S; German PTLD Study Group.; European PTLD Network. Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial. Lancet Oncol. 2012 Feb;13(2):196-206. Epub 2011 Dec 13. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01458548
## Update: Trappe RU, Dierickx D, Zimmermann H, Morschhauser F, Mollee P, Zaucha JM, Dreyling MH, Dührsen U, Reinke P, Verhoef G, Subklewe M, Hüttmann A, Tousseyn T, Salles G, Kliem V, Hauser IA, Tarella C, Van Den Neste E, Gheysens O, Anagnostopoulos I, Leblond V, Riess H, Choquet S. Response to rituximab induction is a predictive marker in B-cell post-transplant lymphoproliferative disorder and allows successful stratification into rituximab or R-CHOP consolidation in an international, prospective, multicenter phase II trial. J Clin Oncol. 2017 Feb 10;35(5):536-43. Epub 2016 Dec 19. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==R, then CHOP==
R, then CHOP: Rituximab followed by Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne
===Regimen===
Study 	Dates of enrollment	Evidence
Trappe et al. 2011 (PTLD-1)	2002-2008 	Phase 2
====Targeted therapy, R portion (cycle 1)====
*Rituximab (Rituxan) 375 mg/m2 IV once per day on days 1, 8, 15, 22
====Chemotherapy, CHOP portion (cycles 2 to 5)====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
====Glucocorticoid therapy, CHOP portion (cycles 2 to 5)====
*Prednisone (Sterapred) 50 mg/m2 PO once per day on days 1 to 5
====Supportive therapy, CHOP portion (cycles 2 to 5)====
*G-CSF was required
*PJP prophylaxis was recommended
8-week course, then 21-day cycle for 4 cycles
===References===
# PTLD-1: Trappe RU, Oertel S, Leblond V, Mollee P, Sender M, Reinke P, Neuhaus R, Lehmkuhl H, Horst HA, Salles G, Morschhauser F, Jaccard A, Lamy T, Leithäuser M, Zimmermann H, Anagnostopoulos I, Raphael M, Riess H, Choquet S; German PTLD Study Group.; European PTLD Network. Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial. Lancet Oncol. 2012 Feb;13(2):196-206. Epub 2011 Dec 13. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01458548
==R-CP==
R-CP: Rituximab, Cyclophosphamide, Prednisone or Prednisolone
===Regimen===
Study 	Dates of enrollment	Evidence
Gross et al. 2012 (COG ANHL0221)	2004-2008 	Phase 2
Note: This regimen was intended for patients less than 30 years of age.
====Targeted therapy====
*Rituximab (Rituxan) as follows:
**Cycles 1 & 2: 375 mg/m2 IV once per day on days 1, 8, 15
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*ONE of the following steroids:
**Prednisone (Sterapred) 1 mg/kg PO twice per day on days 1 to 5
**Methylprednisolone (Solumedrol) 0.8 mg/kg IV every 12 hours on days 1 to 5
21-day cycle for 6 cycles
===References===
# COG ANHL0221: Gross TG, Orjuela MA, Perkins SL, Park JR, Lynch JC, Cairo MS, Smith LM, Hayashi RJ. Low-dose chemotherapy and rituximab for posttransplant lymphoproliferative disease (PTLD): a Children's Oncology Group Report. Am J Transplant. 2012 Nov;12(11):3069-75. Epub 2012 Aug 6. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00066469
==Reduction of immunosuppression==
RIS: Reduction of ImmunoSuppression
===Regimen===
Study 	Dates of enrollment 	Evidence
Starzl et al. 1984	1979-12 to 1983-06-01	Case series
Reshef et al. 2011	1988-08 to 2008-06 	Retrospective
No antineoplastic therapy, treatment consists of reduction or discontinuation (a.k.a., "withdrawal") of immunosuppressive medications.
===References===
# Case series: Starzl TE, Nalesnik MA, Porter KA, Ho M, Iwatsuki S, Griffith BP, Rosenthal JT, Hakala TR, Shaw BW Jr, Hardesty RL, Jaffe R, Bahnson HT. Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy. Lancet. 1984 Mar 17;1(8377):583-7. link to original article link to PMC article EuroPMC
# Retrospective: Reshef R, Vardhanabhuti S, Luskin MR, Heitjan DF, Hadjiliadis D, Goral S, Krok KL, Goldberg LR, Porter DL, Stadtmauer EA, Tsai DE. Reduction of immunosuppression as initial therapy for posttransplantation lymphoproliferative disorder. Am J Transplant. 2011 Feb;11(2):336-47. Epub 2011 Jan 10. link to original article link to PMC article EuroPMC
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=Consolidation after upfront therapy=
==Rituximab monotherapy==
===Regimen variant #1, q3wk x 4===
Study 	Dates of enrollment	Evidence
Trappe et al. 2011 (PTLD-1)	2002-2008 	Phase 2
Note: This regimen was intended for B-cell PTLD. Note that this was a modification of the original PTLD-1 trial schema.
====Preceding treatment====
*Rituximab induction x 4, with CR
====Targeted therapy====
*Rituximab (Rituxan) 375 mg/m2 IV once on day 1
21-day cycle for 4 cycles
===Regimen variant #2, 4-week course===
Study 	Dates of enrollment	Evidence
González-Barca et al. 2007	2000-2005 	Phase 2
====Preceding treatment====
*Rituximab induction x 4, with PR
====Targeted therapy====
*Rituximab (Rituxan) 375 mg/m2 IV once on day 1
7-day cycle for 4 cycles
===References===
# González-Barca E, Domingo-Domenech E, Capote FJ, Gómez-Codina J, Salar A, Bailen A, Ribera JM, López A, Briones J, Muñoz A, Encuentra M, de Sevilla AF; GEL/TAMO (Grupo Español de Linfomas).; GELCAB (Grupo para el Estudio de los Linfomas Catalano-Balear).; GOTEL (Grupo Oncológico para el Tratamiento y Estudio de los Linfomas). Prospective phase II trial of extended treatment with rituximab in patients with B-cell post-transplant lymphoproliferative disease. Haematologica. 2007 Nov;92(11):1489-94. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# PTLD-1: Trappe RU, Oertel S, Leblond V, Mollee P, Sender M, Reinke P, Neuhaus R, Lehmkuhl H, Horst HA, Salles G, Morschhauser F, Jaccard A, Lamy T, Leithäuser M, Zimmermann H, Anagnostopoulos I, Raphael M, Riess H, Choquet S; German PTLD Study Group.; European PTLD Network. Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial. Lancet Oncol. 2012 Feb;13(2):196-206. Epub 2011 Dec 13. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01458548
## Update: Trappe RU, Dierickx D, Zimmermann H, Morschhauser F, Mollee P, Zaucha JM, Dreyling MH, Dührsen U, Reinke P, Verhoef G, Subklewe M, Hüttmann A, Tousseyn T, Salles G, Kliem V, Hauser IA, Tarella C, Van Den Neste E, Gheysens O, Anagnostopoulos I, Leblond V, Riess H, Choquet S. Response to rituximab induction is a predictive marker in B-cell post-transplant lymphoproliferative disorder and allows successful stratification into rituximab or R-CHOP consolidation in an international, prospective, multicenter phase II trial. J Clin Oncol. 2017 Feb 10;35(5):536-43. Epub 2016 Dec 19. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==R-CHOP==
R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
===Regimen===
Study 	Dates of enrollment	Evidence
Trappe et al. 2011 (PTLD-1)	2002-2008 	Phase 2
Note: This regimen was intended for B-cell PTLD. Note that this was a modification of the original PTLD-1 trial schema.
====Preceding treatment====
*Rituximab induction x 4, without achievement of CR
====Targeted therapy====
*Rituximab (Rituxan) 375 mg/m2 IV once on day 1
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 50 mg/m2 PO once per day on days 1 to 5
====Supportive therapy====
*G-CSF was required
*PJP prophylaxis was recommended
21-day cycle for 4 cycles
===References===
# PTLD-1: Trappe RU, Oertel S, Leblond V, Mollee P, Sender M, Reinke P, Neuhaus R, Lehmkuhl H, Horst HA, Salles G, Morschhauser F, Jaccard A, Lamy T, Leithäuser M, Zimmermann H, Anagnostopoulos I, Raphael M, Riess H, Choquet S; German PTLD Study Group.; European PTLD Network. Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial. Lancet Oncol. 2012 Feb;13(2):196-206. Epub 2011 Dec 13. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01458548
## Update: Trappe RU, Dierickx D, Zimmermann H, Morschhauser F, Mollee P, Zaucha JM, Dreyling MH, Dührsen U, Reinke P, Verhoef G, Subklewe M, Hüttmann A, Tousseyn T, Salles G, Kliem V, Hauser IA, Tarella C, Van Den Neste E, Gheysens O, Anagnostopoulos I, Leblond V, Riess H, Choquet S. Response to rituximab induction is a predictive marker in B-cell post-transplant lymphoproliferative disorder and allows successful stratification into rituximab or R-CHOP consolidation in an international, prospective, multicenter phase II trial. J Clin Oncol. 2017 Feb 10;35(5):536-43. Epub 2016 Dec 19. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
=Subsequent lines of therapy=
==Tabelecleucel monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence
Mahadeo et al. 2024 (ALLELE)	2018-06-27 to 2021-11-05	Non-randomized Phase 3
====Immunotherapy====
*Tabelecleucel (Ebvallo) 2 x 106 cells/kg IV once per day on days 1, 8, 15
35-day cycles
===References===
#ALLELE: Mahadeo KM, Baiocchi R, Beitinjaneh A, Chaganti S, Choquet S, Dierickx D, Dinavahi R, Duan X, Gamelin L, Ghobadi A, Guzman-Becerra N, Joshi M, Mehta A, Navarro WH, Nikiforow S, O'Reilly RJ, Reshef R, Ruiz F, Spindler T, Prockop S. Tabelecleucel for allogeneic haematopoietic stem-cell or solid organ transplant recipients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease after failure of rituximab or rituximab and chemotherapy (ALLELE): a phase 3, multicentre, open-label trial. Lancet Oncol. 2024 Mar;25(3):376-387. Epub 2024 Jan 31. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT03394365
Category:Post-transplant lymphoproliferative disorder regimens
Category:Disease-specific pages
Category:Lymphoproliferative disorders