Difference between revisions of "Post-transplant lymphoproliferative disorder"

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'''Use of this site is subject to you reading and agreeing with the terms set forth in the [[HemOnc.org_-_A_Hematology_Oncology_Wiki:General_disclaimer|disclaimer]].'''
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Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are [[How_to_contribute|invited to contribute to the site]].
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[[#top|Back to Top]]
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</div>
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{{#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;"
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
|-
 
|-
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|<div style="background-color: #66FF66; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} regimens on this page</b></font></div>
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
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<div style="background-color: #66CCFF; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} variants on this page</b></font></div>
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
|}
 
|}
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
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+
=Guidelines=
−
=All lines of therapy=
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'''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==
−
==Rituximab (Rituxan) {{#subobject:514479|Regimen=1}}==
+
*''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].''
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
=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 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]]
 
|-
 
|-
−
|[[#top|back to top]]
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|[https://doi.org/10.1111/j.1365-2141.2006.06228.x Fohrer et al. 2006]
−
|}
+
|1989-2003
−
===Regimen #1 {{#subobject:513282|Variant=1}}===
+
|style="background-color:#91cf61"|Phase 2
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
−
|-
 
−
|[http://ascopubs.org/doi/full/10.1200/JCO.2016.69.3564 Trappe et al. 2016 (PTLD-1)]
 
−
|style="background-color:#eeee00"|Phase II
 
 
|-
 
|-
 
|}
 
|}
−
''This regimen is intended for B-cell PTLD.''
+
''Note: This is of historical interest, only.''
−
====Chemotherapy, part one====
+
<div class="toccolours" style="background-color:#b3e2cd">
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+
====Chemotherapy====
−
 
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
−
'''4-week course'''
+
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1
−
 
+
*[[Vindesine (Eldisine)]] 2 mg/m<sup>2</sup> (maximum dose of 4 mg) IV once on day 1
−
''Patients underwent interim staging by CT between days 40 and 50; those achieving CR proceeded to part two; all others proceeded to [[#R-CHOP|R-CHOP]].''
+
*[[Bleomycin (Blenoxane)]] 15 mg IV once on day 1
−
 
+
====Glucocorticoid therapy====
−
====Chemotherapy, part two====
+
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> (route not specified) once per day on days 1 to 5
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
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'''14-day cycle for 6 cycles'''
−
 
+
</div></div>
−
'''21-day cycle for 4 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. [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]
  
−
===Regimen #2 {{#subobject:513282|Variant=1}}===
+
==Rituximab monotherapy {{#subobject:514479|Regimen=1}}==
−
{| border="1" style="text-align:center;" !align="left"  
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<div class="toccolours" style="background-color:#eeeeee">
−
|'''Study'''
+
===Regimen variant #1, 4-week course {{#subobject:513282|Variant=1}}===
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+
{| 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]]
 
|-
 
|-
−
|[http://onlinelibrary.wiley.com/doi/10.1111/j.1600-6143.2005.01098.x/abstract;jsessionid=4E716335857389072519829FA0027067.f04t04 Oertel et al. 2005]
+
|[https://doi.org/10.1111/j.1600-6143.2005.01098.x Oertel et al. 2005]
−
|style="background-color:#ff0000"|Phase II, <20 pts
+
|1999-2002
 +
|style="background-color:#ffffbe"|Phase 2, fewer than 20 pts
 
|-
 
|-
−
|}
+
|[https://doi.org/10.1182/blood-2005-01-0377 Choquet et al. 2005]
−
''This regimen is intended for B-cell PTLD.''
+
|2000-2001
−
====Chemotherapy, part one====
+
|style="background-color:#91cf61"|Phase 2
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
 
 
−
'''4-week course'''
 
−
 
 
−
===References===
 
−
# 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. [http://onlinelibrary.wiley.com/doi/10.1111/j.1600-6143.2005.01098.x/abstract;jsessionid=4E716335857389072519829FA0027067.f04t04 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16303003 PubMed]
 
−
# 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 [http://ascopubs.org/doi/full/10.1200/JCO.2016.69.3564 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23545991 PubMed]
 
−
 
 
−
==R-CHOP {{#subobject:32c6a1|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
 
|-
 
|-
−
|[[#top|back to top]]
+
|[https://doi.org/10.3324/haematol.11360 González-Barca et al. 2007]
−
|}
+
|2000-2005
−
R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
+
|style="background-color:#91cf61"|Phase 2
−
===Regimen {{#subobject:84bd21|Variant=1}}===
 
−
{| border="1" style="text-align:center;" !align="left"
 
−
|'''Study'''
 
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
 
|-
 
|-
−
|[http://ascopubs.org/doi/full/10.1200/JCO.2016.69.3564 Trappe et al. 2016 (PTLD-1)]
+
|[https://doi.org/10.1016/S1470-2045(11)70300-X Trappe et al. 2011 (PTLD-1)]
−
|style="background-color:#eeee00"|Phase II
+
|2002-2008
 +
|style="background-color:#91cf61"|Phase 2
 
|-
 
|-
 
|}
 
|}
−
''This regimen is intended for B-cell PTLD, and is for patients not achieving CR after [[#Rituximab_.28Rituxan.29|rituximab]] x 4.''
+
''Note: This regimen was intended for B-cell PTLD. Note that this was a modification of the original PTLD-1 trial schema.''
−
====Chemotherapy====
+
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
+
'''7-day cycle for 4 cycles'''
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+
</div>
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg per cycle) IV once on day 1
+
<div class="toccolours" style="background-color:#cbd5e7">
−
*[[Prednisone (Sterapred)]] 50 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
====Subsequent treatment====
−
 
+
*González-Barca et al. 2007: Patients underwent interim staging 4 to 8 weeks later
−
====Supportive medications====
+
**González-Barca et al. 2007, patients achieving CR: [[#Observation_888|no further treatment]]
−
*G-CSF was required
+
**González-Barca et al. 2007, patients achieving PR: [[#Rituximab_monotherapy_2|Rituximab]] consolidation
−
*PJP prophylaxis was recommended
+
*PTLD-1: Patients underwent interim staging by CT between days 40 and 50
−
 
+
**PTLD-1, patients achieving CR: [[#Rituximab_monotherapy_2|Rituximab]] consolidation
−
'''21-day cycle for 4 cycles'''
+
**PTLD-1, patients not achieving CR: Salvage [[#R-CHOP|R-CHOP]]
−
 
+
</div></div><br>
−
===References===
+
<div class="toccolours" style="background-color:#eeeeee">
−
# 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 [http://ascopubs.org/doi/full/10.1200/JCO.2016.69.3564 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23545991 PubMed]
+
===Regimen variant #2, q6mo blocks {{#subobject:9f729f|Variant=1}}===
−
 
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
−
==R -> CHOP {{#subobject:f84777|Regimen=1}}==
+
!style="width: 33%"|Study
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1002/cncr.21391 Blaes et al. 2005]
 +
|1999-2001
 +
|style="background-color:#ffffbe"|Phase 2, fewer than 20 pts
 
|-
 
|-
−
|[[#top|back to top]]
 
 
|}
 
|}
−
R -> CHOP: '''<u>R</u>'''ituximab followed by '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
+
<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://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://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]
 +
# 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]
 +
# 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] [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]
 +
==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
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:a97899|Variant=1}}===
 
===Regimen {{#subobject:a97899|Variant=1}}===
−
{| border="1" style="text-align:center;" !align="left"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
−
|'''Study'''
+
!style="width: 33%"|Study
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[http://www.sciencedirect.com/science/article/pii/S147020451170300X Trappe et al. 2011 (PTLD-1)]
+
|[https://doi.org/10.1016/S1470-2045(11)70300-X Trappe et al. 2011 (PTLD-1)]
−
|style="background-color:#eeee00"|Phase II
+
|2002-2008
 +
|style="background-color:#91cf61"|Phase 2
 
|-
 
|-
 
|}
 
|}
−
====Chemotherapy, rituximab portion====
+
<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
 
*[[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, CHOP portion====
 
 
*[[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 per cycle) 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, 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, CHOP portion (cycles 2 to 5)====
−
====Supportive medications====
+
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] was required
−
*G-CSF was required
+
*[[:Category:PCP prophylaxis|PJP prophylaxis]] was recommended
−
*PJP prophylaxis was recommended
+
'''8-week course, then 21-day cycle for 4 cycles'''
−
 
+
</div></div>
−
'''21-day cycle for 4 cycles'''
 
−
 
 
 
===References===
 
===References===
−
# Trappe R, Oertel S, Leblond V, Mollee P, Sender M, Reinke P, Neuhaus R, Lehmkuhl H, Horst HA, Salles G, Morschhauser F, Jaccard A, Lamy T, Leithäuser M, Zimmermann H, Anagnostopoulos I, Raphael M, Riess H, Choquet S; German PTLD Study Group.; European PTLD Network. Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial. Lancet Oncol. 2012 Feb;13(2):196-206. Epub 2011 Dec 13. [http://www.sciencedirect.com/science/article/pii/S147020451170300X link to SD article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22173060 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] [https://clinicaltrials.gov/study/NCT01458548 NCT01458548]
−
 
 
 
==R-CP {{#subobject:2de85f|Regimen=1}}==
 
==R-CP {{#subobject:2de85f|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
 
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
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:affa46|Variant=1}}===
 
===Regimen {{#subobject:affa46|Variant=1}}===
−
{| border="1" style="text-align:center;" !align="left"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
−
|'''Study'''
+
!style="width: 33%"|Study
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[http://ascopubs.org/doi/full/10.1200/JCO.2016.69.3564 Trappe et al. 2016 (PTLD-1)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484187/ Gross et al. 2012 (COG ANHL0221)]
−
|style="background-color:#eeee00"|Phase II
+
|2004-2008
 +
|style="background-color:#91cf61"|Phase 2
 
|-
 
|-
 
|}
 
|}
−
''This regimen was intended for patients <30 years of age.''
+
''Note: This regimen was intended for patients less than 30 years of age.''
−
====Chemotherapy====
+
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 
*[[Rituximab (Rituxan)]] as follows:
 
*[[Rituximab (Rituxan)]] as follows:
 
**Cycles 1 & 2: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
**Cycles 1 & 2: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
====Chemotherapy====
 
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 +
====Glucocorticoid therapy====
 
*ONE of the following steroids:
 
*ONE of the following steroids:
−
**[[Prednisone (Sterapred)]] 1 mg/kg PO BID on days 1 to 5
+
**[[Prednisone (Sterapred)]] 1 mg/kg PO twice per day on days 1 to 5
−
**[[Methylprednisolone (Solumedrol)]] 0.8 mg/kg IV q12h 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. 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]
  
−
'''21-day cycle for 6 cycles'''
+
==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;"
 +
!style="width: 25%"|Study
 +
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987704/ Starzl et al. 1984]
 +
|style="background-color:#ffffbe"|Case series
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079420/ Reshef et al. 2011]
 +
|style="background-color:#ffffbe"|Retrospective
 +
|-
 +
|}
 +
''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]
 +
# '''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">
 +
===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%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(11)70300-X Trappe et al. 2011 (PTLD-1)]
 +
|2002-2008
 +
|style="background-color:#91cf61"|Phase 2
 +
|-
 +
|}
 +
''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]] 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>
 +
<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%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.3324/haematol.11360 González-Barca et al. 2007]
 +
|2000-2005
 +
|style="background-color:#91cf61"|Phase 2
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*[[#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 on day 1
 +
'''7-day cycle for 4 cycles'''
 +
</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. [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] [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]
 +
==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%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(11)70300-X Trappe et al. 2011 (PTLD-1)]
 +
|2002-2008
 +
|style="background-color:#91cf61"|Phase 2
 +
|-
 +
|}
 +
''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]] 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
 +
====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====
 +
*[[Prednisone (Sterapred)]] 50 mg/m<sup>2</sup> PO once per day on days 1 to 5
 +
====Supportive therapy====
 +
*[[: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===
 
===References===
−
# 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://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484187/ link to PMC article] '''contains verified protcol''' [https://www.ncbi.nlm.nih.gov/pubmed/22883417 PubMed]
+
#'''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:Chemotherapy regimens]]
+
[[Category:Post-transplant lymphoproliferative disorder regimens]]
−
[[Category:Malignant hematology regimens]]
+
[[Category:Disease-specific pages]]
−
[[Category:Lymphoma regimens]]
+
[[Category:Lymphoproliferative disorders]]

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Page editor Section editor
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 Francesca Montanari, MD
Yale University
New Haven, CT, USA
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 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

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

Glucocorticoid therapy

14-day cycle for 6 cycles

References

  1. Fohrer C, Caillard S, Koumarianou A, Ellero B, Woehl-Jaeglé ML, Meyer C, Epailly E, Chenard MP, Lioure B, Natarajan-Ame S, Maloisel F, Lutun P, Kessler R, Moulin B, Bergerat JP, Wolf P, Herbrecht R. Long-term survival in post-transplant lymphoproliferative disorders with a dose-adjusted ACVBP regimen. Br J Haematol. 2006 Sep;134(6):602-12. Epub 2006 Aug 2. link to original article 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

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

6-month cycle for up to 4 cycles (2 years)

References

  1. Blaes AH, Peterson BA, Bartlett N, Dunn DL, Morrison VA. Rituximab therapy is effective for posttransplant lymphoproliferative disorders after solid organ transplantation: results of a phase II trial. Cancer. 2005 Oct 15;104(8):1661-7. link to original article contains dosing details in abstract PubMed
  2. Oertel SH, Verschuuren E, Reinke P, Zeidler K, Papp-Váry M, Babel N, Trappe RU, Jonas S, Hummel M, Anagnostopoulos I, Dörken B, Riess HB. Effect of anti-CD 20 antibody rituximab in patients with post-transplant lymphoproliferative disorder (PTLD). Am J Transplant. 2005 Dec;5(12):2901-6. link to original article contains 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
  3. Choquet S, Leblond V, Herbrecht R, Socié G, Stoppa AM, Vandenberghe P, Fischer A, Morschhauser F, Salles G, Feremans W, Vilmer E, Peraldi MN, Lang P, Lebranchu Y, Oksenhendler E, Garnier JL, Lamy T, Jaccard A, Ferrant A, Offner F, Hermine O, Moreau A, Fafi-Kremer S, Morand P, Chatenoud L, Berriot-Varoqueaux N, Bergougnoux L, Milpied N. Efficacy and safety of rituximab in B-cell post-transplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study. Blood. 2006 Apr 15;107(8):3053-7. Epub 2005 Oct 27. link to original article contains 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
  4. González-Barca E, Domingo-Domenech E, Capote FJ, Gómez-Codina J, Salar A, Bailen A, Ribera JM, López A, Briones J, Muñoz A, Encuentra M, de Sevilla AF; GEL/TAMO (Grupo Español de Linfomas); GELCAB (Grupo para el Estudio de los Linfomas Catalano-Balear); GOTEL (Grupo Oncológico para el Tratamiento y Estudio de los Linfomas). Prospective phase II trial of extended treatment with rituximab in patients with B-cell post-transplant lymphoproliferative disease. Haematologica. 2007 Nov;92(11):1489-94. link to original article contains dosing details in manuscript PubMed
  5. 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)

Chemotherapy, CHOP portion (cycles 2 to 5)

Glucocorticoid therapy, CHOP portion (cycles 2 to 5)

Supportive therapy, CHOP portion (cycles 2 to 5)

8-week course, then 21-day cycle for 4 cycles

References

  1. 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

Chemotherapy

Glucocorticoid therapy

21-day cycle for 6 cycles

References

  1. 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

  1. 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
  2. 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

Targeted therapy

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

Targeted therapy

7-day cycle for 4 cycles

References

  1. 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
  2. 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

Chemotherapy

Glucocorticoid therapy

Supportive therapy

21-day cycle for 4 cycles

References

  1. 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

35-day cycles

References

  1. 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
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