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Page editor		Section editor
	Francesca Montanari, MD Yale University New Haven, CT, USA LinkedIn		Tarsheen Sethi, MD, MSCI Yale University New Haven, CT, USA LinkedIn

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.

7 regimens on this page 9 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 contains dosing details in manuscript PubMed

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 contains dosing details in abstract PubMed
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 dosing details in abstract PubMed
1. 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 PubMed
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 dosing details in abstract PubMed
1. 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 PubMed
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 dosing details in manuscript PubMed
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 contains dosing details in manuscript PubMed NCT01458548
1. 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 contains dosing details in manuscript PubMed

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 contains dosing details in manuscript PubMed 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 contains dosing details in manuscript link to PMC article PubMed NCT00066469

Reduction of immunosuppression

RIS: Reduction of ImmunoSuppression

Regimen

Study	Evidence
Starzl et al. 1984	Case series
Reshef et al. 2011	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 PubMed
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 PubMed

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 contains dosing details in manuscript PubMed
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 contains dosing details in manuscript PubMed NCT01458548
1. 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 contains dosing details in manuscript PubMed

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 contains dosing details in manuscript PubMed NCT01458548
1. 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 contains dosing details in manuscript PubMed

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 contains dosing details in abstract PubMed NCT03394365

@@ Line 3: / Line 3: @@
 [[#top|Back to Top]]
 </div>
-{{#lst:Section editor transclusions|ptld}}
+{{#lst:Editorial board transclusions|ptld}}
 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|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.
 {| class="wikitable" style="float:right; margin-right: 5px;"
@@ Line 11: / Line 11: @@
 |}
 {{TOC limit|limit=3}}
+=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 [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480 NCCN Guidelines - B-cell Lymphomas].''
 =Induction=
 ==ACVBP, dose-adjusted {{#subobject:bb17b2|Regimen=1}}==
 ACVBP: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''indesine, '''<u>B</u>'''leomycin, '''<u>P</u>'''rednisone
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:1cd335|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 25%"|Study
+!style="width: 33%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2006.06228.x Fohrer et al. 2006]
+|[https://doi.org/10.1111/j.1365-2141.2006.06228.x Fohrer et al. 2006]
+|1989-2003
 |style="background-color:#91cf61"|Phase 2
 |-
 |}
-''Of historical interest, only.''
+''Note: This is of historical interest, only.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Doxorubicin (Adriamycin)]]
+*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
-*[[Cyclophosphamide (Cytoxan)]]
+*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1
-*[[Vindesine (Eldisine)]]
+*[[Vindesine (Eldisine)]] 2 mg/m<sup>2</sup> (maximum dose of 4 mg) IV once on day 1
-*[[Bleomycin (Blenoxane)]]
+*[[Bleomycin (Blenoxane)]] 15 mg IV once on day 1
 ====Glucocorticoid therapy====
-*[[Prednisone (Sterapred)]]
+*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> (route not specified) once per day on days 1 to 5
+'''14-day cycle for 6 cycles'''
+</div></div>
 ===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. [https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2006.06228.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/16889621 PubMed]
+# 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. [https://doi.org/10.1111/j.1365-2141.2006.06228.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16889621/ PubMed]
 ==Rituximab monotherapy {{#subobject:514479|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-===Protocol variant #1, 4-week course {{#subobject:513282|Variant=1}}===
+===Regimen variant #1, 4-week course {{#subobject:513282|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
+!style="width: 33%"|Dates of enrollment
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://onlinelibrary.wiley.com/doi/10.1111/j.1600-6143.2005.01098.x Oertel et al. 2005]
+|[https://doi.org/10.1111/j.1600-6143.2005.01098.x Oertel et al. 2005]
 |1999-2002
-|style="background-color:#ffffbe"|Phase 2, <20 pts
+|style="background-color:#ffffbe"|Phase 2, fewer than 20 pts
 |-
 |[http://www.bloodjournal.org/content/107/8/3053.long Choquet et al. 2005]
@@ Line 62: / Line 69: @@
 |-
 |}
-''This regimen is intended for B-cell PTLD. Note that this is a modification of the original PTLD-1 trial schema.''
+''Note: This regimen was intended for B-cell PTLD. Note that this was a modification of the original PTLD-1 trial schema.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
-*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+'''7-day cycle for 4 cycles'''
-'''4-week course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
 *González-Barca et al. 2007: Patients underwent interim staging 4 to 8 weeks later
-**Those achieving CR: no further treatment
+**González-Barca et al. 2007, patients achieving CR: [[#Observation_888|no further treatment]]
-**Those achieving PR: [[#Rituximab_monotherapy_2|Rituximab consolidation]]
+**González-Barca et al. 2007, patients achieving PR: [[#Rituximab_monotherapy_2|Rituximab]] consolidation
 *PTLD-1: Patients underwent interim staging by CT between days 40 and 50
-**Those achieving CR: [[#Rituximab_monotherapy_2|Rituximab consolidation]]
+**PTLD-1, patients achieving CR: [[#Rituximab_monotherapy_2|Rituximab]] consolidation
-**All others: [[#R-CHOP|R-CHOP]]
+**PTLD-1, patients not achieving CR: Salvage [[#R-CHOP|R-CHOP]]
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, q6mo blocks {{#subobject:9f729f|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 25%"|Study
+!style="width: 33%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://onlinelibrary.wiley.com/doi/10.1002/cncr.21391 Blaes et al. 2005]
+|[https://doi.org/10.1002/cncr.21391 Blaes et al. 2005]
-|style="background-color:#ffffbe"|Phase 2, <20 pts
+|1999-2001
+|style="background-color:#ffffbe"|Phase 2, fewer than 20 pts
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 '''6-month cycle for up to 4 cycles (2 years)'''
+</div></div>
 ===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. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.21391 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16149091 PubMed]
+# 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. [https://doi.org/10.1002/cncr.21391 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16149091/ PubMed]
-# 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. [https://onlinelibrary.wiley.com/doi/10.1111/j.1600-6143.2005.01098.x link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16303003 PubMed]
+# 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. [https://doi.org/10.1111/j.1600-6143.2005.01098.x link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16303003/ PubMed]
-## '''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. [https://doi.org/10.1007/s00277-007-0298-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17522862 PubMed]
+## '''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. [https://doi.org/10.1007/s00277-007-0298-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17522862/ PubMed]
-# 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. [http://www.bloodjournal.org/content/107/8/3053.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16254143 PubMed]
+# 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. [http://www.bloodjournal.org/content/107/8/3053.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16254143/ PubMed]
-## '''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. [https://doi.org/10.1007/s00277-007-0298-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17522862 PubMed]
+## '''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. [https://doi.org/10.1007/s00277-007-0298-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17522862/ PubMed]
-# 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. [http://www.haematologica.org/content/92/11/1489.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18024397 PubMed]
+# 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. [http://www.haematologica.org/content/92/11/1489.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18024397/ PubMed]
-# '''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. [https://doi.org/10.1016/S1470-2045(11)70300-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22173060 PubMed] NCT01458548
+# '''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. [https://doi.org/10.1016/S1470-2045(11)70300-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22173060/ PubMed] [https://clinicaltrials.gov/study/NCT01458548 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 [https://doi.org/10.1200/JCO.2016.69.3564 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27992268 PubMed]
+## '''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 [https://doi.org/10.1200/JCO.2016.69.3564 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27992268/ PubMed]
 ==R, then CHOP {{#subobject:f84777|Regimen=1}}==
 R, then CHOP: '''<u>R</u>'''ituximab followed by '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''redniso(lo)ne
-===Protocol {{#subobject:a97899|Variant=1}}===
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:a97899|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
+!style="width: 33%"|Dates of enrollment
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
@@ Line 113: / Line 124: @@
 |-
 |}
-====Targeted therapy====
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy, R portion (cycle 1)====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+====Chemotherapy, CHOP portion (cycles 2 to 5)====
-'''4-week course, followed in 4 weeks by:'''
-====Chemotherapy====
 *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
-====Glucocorticoid therapy====
+====Glucocorticoid therapy, CHOP portion (cycles 2 to 5)====
 *[[Prednisone (Sterapred)]] 50 mg/m<sup>2</sup> PO once per day on days 1 to 5
+====Supportive therapy, CHOP portion (cycles 2 to 5)====
-====Supportive medications====
 *[[:Category:Granulocyte colony-stimulating factors|G-CSF]] was required
 *[[:Category:PCP prophylaxis|PJP prophylaxis]] was recommended
+'''8-week course, then 21-day cycle for 4 cycles'''
-'''21-day cycle for 4 cycles'''
+</div></div>
 ===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. [https://doi.org/10.1016/S1470-2045(11)70300-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22173060 PubMed] NCT01458548
+# '''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. [https://doi.org/10.1016/S1470-2045(11)70300-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22173060/ PubMed] [https://clinicaltrials.gov/study/NCT01458548 NCT01458548]
 ==R-CP {{#subobject:2de85f|Regimen=1}}==
 R-CP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisone or Prednisolone
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:affa46|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
+!style="width: 33%"|Dates of enrollment
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
@@ Line 148: / Line 154: @@
 |-
 |}
-''This regimen was intended for patients less than 30 years of age.''
+''Note: This regimen was intended for patients less than 30 years of age.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Rituximab (Rituxan)]] as follows:
@@ Line 158: / Line 165: @@
 **[[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'''
+</div></div>
 ===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. [https://onlinelibrary.wiley.com/doi/10.1111/j.1600-6143.2012.04206.x link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484187/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22883417 PubMed] NCT00066469
+# '''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. [https://doi.org/10.1111/j.1600-6143.2012.04206.x link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484187/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22883417/ PubMed] [https://clinicaltrials.gov/study/NCT00066469 NCT00066469]
 ==Reduction of immunosuppression {{#subobject:1d45b7|Regimen=1}}==
 RIS: '''<u>R</u>'''eduction of '''<u>I</u>'''mmuno'''<u>S</u>'''uppression
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:7b1583|Variant=1}}===
 {| class="wikitable" style="width: 40%; text-align:center;"
@@ Line 180: / Line 186: @@
 |}
 ''No antineoplastic therapy, treatment consists of reduction or discontinuation (a.k.a., "withdrawal") of immunosuppressive medications.''
+</div></div>
 ===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. [https://doi.org/10.1016/S0140-6736(84)90994-2 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987704/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/6142304 PubMed]
+# '''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. [https://doi.org/10.1016/S0140-6736(84)90994-2 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987704/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/6142304/ PubMed]
-# '''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. [https://onlinelibrary.wiley.com/doi/10.1111/j.1600-6143.2010.03387.x link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079420/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21219573 PubMed]
+# '''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. [https://doi.org/10.1111/j.1600-6143.2010.03387.x link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079420/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21219573/ PubMed]
 =Consolidation after upfront therapy=
 ==Rituximab monotherapy {{#subobject:57gy79|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-===Protocol variant #1, q3wk x 4 {{#subobject:51ajbc2|Variant=1}}===
+===Regimen variant #1, q3wk x 4 {{#subobject:51ajbc2|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
+!style="width: 33%"|Dates of enrollment
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
@@ Line 200: / Line 205: @@
 |-
 |}
-''This regimen is intended for B-cell PTLD. Note that this is a modification of the original PTLD-1 trial schema.''
+''Note: This regimen was intended for B-cell PTLD. Note that this was a modification of the original PTLD-1 trial schema.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-*[[#Rituximab_monotherapy|Rituximab]] x 4, with CR
+*[[#Rituximab_monotherapy|Rituximab]] induction x 4, with CR
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 '''21-day cycle for 4 cycles'''
+</div></div><br>
-===Protocol variant #2, 4-week course {{#subobject:7euba9|Variant=1}}===
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 4-week course {{#subobject:7euba9|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
+!style="width: 33%"|Dates of enrollment
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
@@ Line 219: / Line 227: @@
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-*[[#Rituximab_monotherapy|Rituximab]] x 4, with PR
+*[[#Rituximab_monotherapy|Rituximab]] induction x 4, with PR
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
-*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+'''7-day cycle for 4 cycles'''
-'''4-week course'''
+</div></div>
 ===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. [http://www.haematologica.org/content/92/11/1489.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18024397 PubMed]
+# 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. [http://www.haematologica.org/content/92/11/1489.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18024397/ PubMed]
-# '''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. [https://doi.org/10.1016/S1470-2045(11)70300-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22173060 PubMed] NCT01458548
+# '''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. [https://doi.org/10.1016/S1470-2045(11)70300-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22173060/ PubMed] [https://clinicaltrials.gov/study/NCT01458548 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 [https://doi.org/10.1200/JCO.2016.69.3564 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27992268 PubMed]
+## '''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 [https://doi.org/10.1200/JCO.2016.69.3564 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27992268/ PubMed]
 ==R-CHOP {{#subobject:32c6a1|Regimen=1}}==
 R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:84bd21|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
+!style="width: 33%"|Dates of enrollment
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
@@ Line 245: / Line 254: @@
 |-
 |}
-''This regimen is intended for B-cell PTLD. Note that this is a modification of the original PTLD-1 trial schema.''
+''Note: This regimen was intended for B-cell PTLD. Note that this was a modification of the original PTLD-1 trial schema.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-*[[#Rituximab_monotherapy|Rituximab]] x 4, without achievement of CR
+*[[#Rituximab_monotherapy|Rituximab]] induction x 4, without achievement of CR
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
 *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
@@ Line 256: / Line 268: @@
 ====Glucocorticoid therapy====
 *[[Prednisone (Sterapred)]] 50 mg/m<sup>2</sup> PO once per day on days 1 to 5
+====Supportive therapy====
-====Supportive medications====
 *[[:Category:Granulocyte colony-stimulating factors|G-CSF]] was required
 *[[:Category:PCP prophylaxis|PJP prophylaxis]] was recommended
 '''21-day cycle for 4 cycles'''
+</div></div>
+===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. [https://doi.org/10.1016/S1470-2045(11)70300-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22173060/ PubMed] [https://clinicaltrials.gov/study/NCT01458548 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 [https://doi.org/10.1200/JCO.2016.69.3564 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27992268/ PubMed]
+=Subsequent lines of therapy=
+==Tabelecleucel monotherapy {{#subobject:32c6a1|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:84bd21|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1016/s1470-2045(23)00649-6 Mahadeo et al. 2024 (ALLELE)]
+|2018-06-27 to 2021-11-05
+|style="background-color:#91cf61"|Non-randomized Phase 3
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Immunotherapy====
+*[[Tabelecleucel (Ebvallo)]] 2 x 10<sup>6</sup> cells/kg IV once per day on days 1, 8, 15
+'''35-day cycles'''
+</div></div>
 ===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. [https://doi.org/10.1016/S1470-2045(11)70300-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22173060 PubMed] NCT01458548
+#'''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. [https://doi.org/10.1016/s1470-2045(23)00649-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/38309282/ PubMed] [https://clinicaltrials.gov/study/NCT03394365 NCT03394365]
-## '''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 [https://doi.org/10.1200/JCO.2016.69.3564 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27992268 PubMed]
 [[Category:Post-transplant lymphoproliferative disorder regimens]]
 [[Category:Disease-specific pages]]
 [[Category:Lymphoproliferative disorders]]

Difference between revisions of "Post-transplant lymphoproliferative disorder"

Revision as of 23:37, 30 May 2024

Guidelines

NCCN

Induction

ACVBP, dose-adjusted

Regimen

Chemotherapy

Glucocorticoid therapy

References

Rituximab monotherapy

Regimen variant #1, 4-week course

Targeted therapy

Subsequent treatment

Regimen variant #2, q6mo blocks

Targeted therapy

References

R, then CHOP

Regimen

Targeted therapy, R portion (cycle 1)

Chemotherapy, CHOP portion (cycles 2 to 5)

Glucocorticoid therapy, CHOP portion (cycles 2 to 5)

Supportive therapy, CHOP portion (cycles 2 to 5)

References

R-CP

Regimen

Targeted therapy

Chemotherapy

Glucocorticoid therapy

References

Reduction of immunosuppression

Regimen

References

Consolidation after upfront therapy

Rituximab monotherapy

Regimen variant #1, q3wk x 4

Preceding treatment

Targeted therapy

Regimen variant #2, 4-week course

Preceding treatment

Targeted therapy

References

R-CHOP

Regimen

Preceding treatment

Targeted therapy

Chemotherapy

Glucocorticoid therapy

Supportive therapy

References

Subsequent lines of therapy

Tabelecleucel monotherapy

Regimen

Immunotherapy

References

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