Post-transplant lymphoproliferative disorder

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6 regimens on this page
8 variants on this page


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.

All lines of therapy

ACVBP, dose-adjusted

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ACVBP: Adriamycin (Doxorubicin), Cyclophosphamide, Vindesine, Bleomycin, Prednisone

Regimen

Study Evidence
Fohrer et al. 2006 Phase II

Of historical interest, only.

Chemotherapy

References

  1. 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 PubMed

Rituximab (Rituxan)

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Regimen #1

Study Evidence
Trappe et al. 2016 (PTLD-1) Phase II

This regimen is intended for B-cell PTLD.

Chemotherapy, part one

4-week course

Patients underwent interim staging by CT between days 40 and 50; those achieving CR proceeded to part two; all others proceeded to R-CHOP.

Chemotherapy, part two

21-day cycle for 4 cycles

Regimen #2

Study Evidence
Oertel et al. 2005 Phase II, <20 pts
Choquet et al. 2005 Phase II
González-Barca et al. 2007 Phase II

This regimen is intended for B-cell PTLD.

Chemotherapy, part one

4-week course

Regimen #3

Study Evidence
González-Barca et al. 2007 Phase II

This regimen is intended for patients not achieving CR after the first 4 doses of rituximab.

Chemotherapy, part one

4-week course

Patients underwent interim staging 4 to 8 weeks later; those achieving CR received no further treatment, while those achieving PR received:

Chemotherapy, part two

4-week course

Regimen #4

Study Evidence
Blaes et al. 2005 Phase II, <20 pts

Chemotherapy, part one

6-month cycle for up to 2 years

References

  1. 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 contains protocol PubMed
  2. 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 contains protocol PubMed
    1. Update: Choquet S, Oertel S, LeBlond V, Riess H, Varoqueaux N, Dörken B, Trappe R. 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 PubMed
  3. 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 contains protocol PubMed
    1. Update: Choquet S, Oertel S, LeBlond V, Riess H, Varoqueaux N, Dörken B, Trappe R. 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 PubMed
  4. 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 contains verified protocol PubMed
  5. 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 contains verified protocol PubMed

R-CHOP

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R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen

Study Evidence
Trappe et al. 2016 (PTLD-1) Phase II

This regimen is intended for B-cell PTLD, and is for patients not achieving CR after rituximab x 4.

Chemotherapy

Supportive medications

  • G-CSF was required
  • PJP prophylaxis was recommended

21-day cycle for 4 cycles

References

  1. 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 contains verified protocol PubMed

R -> CHOP

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R -> CHOP: Rituximab followed by Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen

Study Evidence
Trappe et al. 2011 (PTLD-1) Phase II

Chemotherapy, rituximab portion

4-week course, followed in 4 weeks by:

Chemotherapy, CHOP portion

Supportive medications

  • G-CSF was required
  • PJP prophylaxis was recommended

21-day cycle for 4 cycles

References

  1. Trappe R, 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 SD article contains verified protocol PubMed

R-CP

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R-CP: Rituximab, Cyclophosphamide, Prednisone or Prednisolone

Regimen

Study Evidence
Gross et al. 2012 Phase II

This regimen was intended for patients <30 years of age.

Chemotherapy

21-day cycle for 6 cycles

References

  1. 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. link to original article contains verified protcol PubMed

Reduction of immunosuppression (RIS)

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Regimen

Study Evidence
Starzl et al. 1984 Case series, <20 pts
Reshef et al. 2011 Retrospective

No antineoplastic therapy, treatment consists of reduction or discontinuation (a.k.a., "withdrawal") of immunosuppressive medications.

References

  1. Starzl TE, Nalesnik MA, Porter KA, Ho M, Iwatsuki S, Griffith BP, Rosenthal JT, Hakala TR, Shaw BW Jr, Hardesty RL, et al. Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy. Lancet. 1984 Mar 17;1(8377):583-7. link to PMC article PubMed
  2. 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 PMC article PubMed