Difference between revisions of "Post-transplant lymphoproliferative disorder"
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[[#top|Back to Top]] | [[#top|Back to Top]] | ||
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− | {{#lst: | + | {{#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. | 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;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
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|} | |} | ||
{{TOC limit|limit=3}} | {{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= | =Induction= | ||
==ACVBP, dose-adjusted {{#subobject:bb17b2|Regimen=1}}== | ==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 | 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:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:1cd335|Variant=1}}=== | ===Regimen {{#subobject:1cd335|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
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<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====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==== | ====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> | </div></div> | ||
===References=== | ===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://doi.org/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}}== | ==Rituximab monotherapy {{#subobject:514479|Regimen=1}}== | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | === | + | ===Regimen variant #1, 4-week course {{#subobject:513282|Variant=1}}=== |
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
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|[https://doi.org/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 | |1999-2002 | ||
− | |style="background-color:#ffffbe"|Phase 2, | + | |style="background-color:#ffffbe"|Phase 2, fewer than 20 pts |
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2005-01-0377 Choquet et al. 2005] |
|2000-2001 | |2000-2001 | ||
|style="background-color:#91cf61"|Phase 2 | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.3324/haematol.11360 González-Barca et al. 2007] |
|2000-2005 | |2000-2005 | ||
|style="background-color:#91cf61"|Phase 2 | |style="background-color:#91cf61"|Phase 2 | ||
Line 66: | Line 72: | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once | + | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1 |
− | '''4 | + | '''7-day cycle for 4 cycles''' |
</div> | </div> | ||
<div class="toccolours" style="background-color:#cbd5e7"> | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
*González-Barca et al. 2007: Patients underwent interim staging 4 to 8 weeks later | *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 CR: [[#Observation_888|no further treatment]] |
**González-Barca et al. 2007, patients 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 | *PTLD-1: Patients underwent interim staging by CT between days 40 and 50 | ||
**PTLD-1, patients achieving CR: [[#Rituximab_monotherapy_2|Rituximab]] consolidation | **PTLD-1, patients achieving CR: [[#Rituximab_monotherapy_2|Rituximab]] consolidation | ||
− | **PTLD-1, patients not achieving CR: [[#R-CHOP|R-CHOP]] | + | **PTLD-1, patients not achieving CR: Salvage [[#R-CHOP|R-CHOP]] |
</div></div><br> | </div></div><br> | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
Line 87: | Line 93: | ||
|[https://doi.org/10.1002/cncr.21391 Blaes et al. 2005] | |[https://doi.org/10.1002/cncr.21391 Blaes et al. 2005] | ||
|1999-2001 | |1999-2001 | ||
− | |style="background-color:#ffffbe"|Phase 2, | + | |style="background-color:#ffffbe"|Phase 2, fewer than 20 pts |
|- | |- | ||
|} | |} | ||
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# 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] | # 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. [ | + | # 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. [https://doi.org/10.1182/blood-2005-01-0377 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. [ | + | # 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. [https://doi.org/10.3324/haematol.11360 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 {{#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 | 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 | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | === | + | ===Regimen {{#subobject:a97899|Variant=1}}=== |
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
Line 119: | Line 125: | ||
|} | |} | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
− | ====Targeted therapy==== | + | ====Targeted therapy, R portion (cycle 1)==== |
*[[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 per day on days 1, 8, 15, 22 | ||
− | + | ====Chemotherapy, CHOP portion (cycles 2 to 5)==== | |
− | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1 | *[[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 | *[[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 | *[[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 | *[[Prednisone (Sterapred)]] 50 mg/m<sup>2</sup> PO once per day on days 1 to 5 | ||
− | ====Supportive therapy==== | + | ====Supportive therapy, CHOP portion (cycles 2 to 5)==== |
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] was required | *[[:Category:Granulocyte colony-stimulating factors|G-CSF]] was required | ||
*[[:Category:PCP prophylaxis|PJP prophylaxis]] was recommended | *[[:Category:PCP prophylaxis|PJP prophylaxis]] was recommended | ||
− | '''21-day cycle for 4 cycles''' | + | '''8-week course, then 21-day cycle for 4 cycles''' |
</div></div> | </div></div> | ||
===References=== | ===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 {{#subobject:2de85f|Regimen=1}}== | ||
R-CP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisone or Prednisolone | R-CP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisone or Prednisolone | ||
Line 163: | Line 168: | ||
</div></div> | </div></div> | ||
===References=== | ===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://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] 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}}== | ==Reduction of immunosuppression {{#subobject:1d45b7|Regimen=1}}== | ||
RIS: '''<u>R</u>'''eduction of '''<u>I</u>'''mmuno'''<u>S</u>'''uppression | RIS: '''<u>R</u>'''eduction of '''<u>I</u>'''mmuno'''<u>S</u>'''uppression | ||
Line 184: | Line 190: | ||
# '''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://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] | # '''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= | =Consolidation after upfront therapy= | ||
==Rituximab monotherapy {{#subobject:57gy79|Regimen=1}}== | ==Rituximab monotherapy {{#subobject:57gy79|Regimen=1}}== | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | === | + | ===Regimen variant #1, q3wk x 4 {{#subobject:51ajbc2|Variant=1}}=== |
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
Line 201: | Line 208: | ||
<div class="toccolours" style="background-color:#cbd5e8"> | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Rituximab_monotherapy|Rituximab]] x 4, with CR | + | *[[#Rituximab_monotherapy|Rituximab]] induction x 4, with CR |
</div> | </div> | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
Line 209: | Line 216: | ||
</div></div><br> | </div></div><br> | ||
<div class="toccolours" style="background-color:#eeeeee"> | <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;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
Line 215: | Line 222: | ||
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.3324/haematol.11360 González-Barca et al. 2007] |
|2000-2005 | |2000-2005 | ||
|style="background-color:#91cf61"|Phase 2 | |style="background-color:#91cf61"|Phase 2 | ||
Line 222: | Line 229: | ||
<div class="toccolours" style="background-color:#cbd5e8"> | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Rituximab_monotherapy|Rituximab]] x 4, with PR | + | *[[#Rituximab_monotherapy|Rituximab]] induction x 4, with PR |
</div> | </div> | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once | + | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1 |
− | '''4 | + | '''7-day cycle for 4 cycles''' |
</div></div> | </div></div> | ||
===References=== | ===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. [ | + | # 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. [https://doi.org/10.3324/haematol.11360 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 {{#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 | R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone | ||
Line 250: | Line 257: | ||
<div class="toccolours" style="background-color:#cbd5e8"> | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Rituximab_monotherapy|Rituximab]] x 4, without achievement of CR | + | *[[#Rituximab_monotherapy|Rituximab]] induction x 4, without achievement of CR |
</div> | </div> | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
Line 267: | Line 274: | ||
</div></div> | </div></div> | ||
===References=== | ===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] |
− | ## '''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] |
=Subsequent lines of therapy= | =Subsequent lines of therapy= | ||
==Tabelecleucel monotherapy {{#subobject:32c6a1|Regimen=1}}== | ==Tabelecleucel monotherapy {{#subobject:32c6a1|Regimen=1}}== | ||
Line 278: | Line 285: | ||
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[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 | |style="background-color:#91cf61"|Non-randomized Phase 3 | ||
|- | |- | ||
Line 285: | Line 292: | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunotherapy==== | ====Immunotherapy==== | ||
− | *[[Tabelecleucel (Ebvallo)]] | + | *[[Tabelecleucel (Ebvallo)]] 2 x 10<sup>6</sup> cells/kg IV once per day on days 1, 8, 15 |
+ | '''35-day cycles''' | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | #'''ALLELE:''' NCT03394365 | + | #'''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] |
+ | |||
[[Category:Post-transplant lymphoproliferative disorder regimens]] | [[Category:Post-transplant lymphoproliferative disorder regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Lymphoproliferative disorders]] | [[Category:Lymphoproliferative disorders]] |
Latest revision as of 01:27, 27 June 2024
Page editor | Section editor | ||
---|---|---|---|
Francesca Montanari, MD Yale University New Haven, CT, USA |
Tarsheen Sethi, MD, MSCI Yale University New Haven, CT, USA |
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.
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
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
- 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
- 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
- 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
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
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
- 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
- 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