Reduced-intensity transplantation for lymphomas using haploidentical related donors versus HLA-matched sibling donors: A center for international blood and marrow transplant research analysis

Nilanjan Ghosh; Reem Karmali; Vanderson Rocha; Kwang Woo Ahn; Alyssa DiGilio; Parameswaran N. Hari; Veronika Bachanova; Ulrike Bacher; Parastoo Dahi; Marcos De Lima; Anita D'Souza; Timothy S. Fenske; Siddhartha Ganguly; Mohamed A. Kharfan-Dabaja; Tim D. Prestidge; Bipin N. Savani; Sonali M. Smith; Anna M. Sureda; Edmund K. Waller; Samantha Jaglowski; Alex F. Herrera; Philippe Armand; Rachel B. Salit; Nina D. Wagner-Johnston; Ephraim Fuchs; Javier Bolaños-Meade; Mehdi Hamadani

doi:10.1200/JCO.2015.66.3476

Reduced-intensity transplantation for lymphomas using haploidentical related donors versus HLA-matched sibling donors: A center for international blood and marrow transplant research analysis

Nilanjan Ghosh, Reem Karmali, Vanderson Rocha, Kwang Woo Ahn, Alyssa DiGilio, Parameswaran N. Hari, Veronika Bachanova, Ulrike Bacher, Parastoo Dahi, Marcos De Lima, Anita D'Souza, Timothy S. Fenske, Siddhartha Ganguly, Mohamed A. Kharfan-Dabaja, Tim D. Prestidge, Bipin N. Savani, Sonali M. Smith, Anna M. Sureda, Edmund K. Waller, Samantha JaglowskiAlex F. Herrera, Philippe Armand, Rachel B. Salit, Nina D. Wagner-Johnston, Ephraim Fuchs, Javier Bolaños-Meade, Mehdi Hamadani

Medicine - Hematology, Oncology, Transplant

Research output: Contribution to journal › Article › peer-review

176 Scopus citations

Abstract

Purpose: Related donor haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry. Materials and Methods: We evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versushost disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor-based GVHD prophylaxis. Results: Median follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P < .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P < .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34). Conclusion: Haplo-HCT with PT-Cy provides survival outcomes comparable to MSD-HCT, with a significantly lower risk of chronic GVHD.

Original language	English (US)
Pages (from-to)	3141-3149
Number of pages	9
Journal	Journal of Clinical Oncology
Volume	34
Issue number	26
DOIs	https://doi.org/10.1200/JCO.2015.66.3476
State	Published - Sep 10 2016

Bibliographical note

Funding Information:
The Center for International Blood and Marrow Transplant Research is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute, the National Heart, Lung, and Blood Institute, and the National Institute of Allergy and Infectious Diseases; Grant/Cooperative Agreement 5U10HL069294 from the National Heart, Lung, and Blood Institute and National Cancer Institute; contract HHSH250201200016C with Health Resources and Services Administration; two grants, N00014-13- 1-0039 and N00014-14-1-0028, from the Office of Naval Research; and grants from ∗Actinium Pharmaceuticals, Allos Therapeutics, ∗Amgen, Anonymous donation to the Medical College of Wisconsin, Ariad, Be the Match Foundation, ∗Blue Cross and Blue Shield Association, ∗Celgene Corporation, Chimerix, Inc, Fred Hutchinson Cancer Research Center, Fresenius-Biotech North America, ∗Gamida Cell Teva Joint Venture, Genentech,∗Gentium SpA, Genzyme Corporation, GlaxoSmithKline, Health Research, Roswell Park Cancer Institute, HistoGenetics, Incyte Corporation, Jeff Gordon Children's Foundation, Kiadis Pharma, The Leukemia and Lymphoma Society, Medac, The Medical College of Wisconsin, Merck and Co, Millennium: Takeda Oncology, ∗Milliman USA, ∗Miltenyi Biotec, National Marrow Donor Program, Onyx Pharmaceuticals, Optum Healthcare Solutions, Osiris Therapeutics, Otsuka America Pharmaceutical, Perkin Elmer, ∗Remedy Informatics, ∗Sanofi US, Seattle Genetics, Sigma-Tau Pharmaceuticals, Soligenix, St. Baldrick's Foundation, StemCyte, A Global Cord Blood Therapeutics, Stemsoft Software, Swedish Orphan Biovitrum, ∗Tarix Pharmaceuticals, ∗TerumoBCT, ∗Teva Neuroscience, ∗THERAKOS, University of Minnesota, University of Utah, and ∗Wellpoint. Asterisks denote corporate members. We thank Morgan Geronime for administrative support and Mary Eapen for her valuable scientific input.

Publisher Copyright:
© 2016 by American Society of Clinical Oncology.

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Ghosh, N., Karmali, R., Rocha, V., Ahn, K. W., DiGilio, A., Hari, P. N., Bachanova, V., Bacher, U., Dahi, P., De Lima, M., D'Souza, A., Fenske, T. S., Ganguly, S., Kharfan-Dabaja, M. A., Prestidge, T. D., Savani, B. N., Smith, S. M., Sureda, A. M., Waller, E. K., ... Hamadani, M. (2016). Reduced-intensity transplantation for lymphomas using haploidentical related donors versus HLA-matched sibling donors: A center for international blood and marrow transplant research analysis. Journal of Clinical Oncology, 34(26), 3141-3149. https://doi.org/10.1200/JCO.2015.66.3476

Reduced-intensity transplantation for lymphomas using haploidentical related donors versus HLA-matched sibling donors : A center for international blood and marrow transplant research analysis. / Ghosh, Nilanjan; Karmali, Reem; Rocha, Vanderson et al.

In: Journal of Clinical Oncology, Vol. 34, No. 26, 10.09.2016, p. 3141-3149.

Research output: Contribution to journal › Article › peer-review

Ghosh, N, Karmali, R, Rocha, V, Ahn, KW, DiGilio, A, Hari, PN, Bachanova, V, Bacher, U, Dahi, P, De Lima, M, D'Souza, A, Fenske, TS, Ganguly, S, Kharfan-Dabaja, MA, Prestidge, TD, Savani, BN, Smith, SM, Sureda, AM, Waller, EK, Jaglowski, S, Herrera, AF, Armand, P, Salit, RB, Wagner-Johnston, ND, Fuchs, E, Bolaños-Meade, J & Hamadani, M 2016, 'Reduced-intensity transplantation for lymphomas using haploidentical related donors versus HLA-matched sibling donors: A center for international blood and marrow transplant research analysis', Journal of Clinical Oncology, vol. 34, no. 26, pp. 3141-3149. https://doi.org/10.1200/JCO.2015.66.3476

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title = "Reduced-intensity transplantation for lymphomas using haploidentical related donors versus HLA-matched sibling donors: A center for international blood and marrow transplant research analysis",

abstract = "Purpose: Related donor haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry. Materials and Methods: We evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versushost disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor-based GVHD prophylaxis. Results: Median follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P < .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P < .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34). Conclusion: Haplo-HCT with PT-Cy provides survival outcomes comparable to MSD-HCT, with a significantly lower risk of chronic GVHD.",

author = "Nilanjan Ghosh and Reem Karmali and Vanderson Rocha and Ahn, {Kwang Woo} and Alyssa DiGilio and Hari, {Parameswaran N.} and Veronika Bachanova and Ulrike Bacher and Parastoo Dahi and {De Lima}, Marcos and Anita D'Souza and Fenske, {Timothy S.} and Siddhartha Ganguly and Kharfan-Dabaja, {Mohamed A.} and Prestidge, {Tim D.} and Savani, {Bipin N.} and Smith, {Sonali M.} and Sureda, {Anna M.} and Waller, {Edmund K.} and Samantha Jaglowski and Herrera, {Alex F.} and Philippe Armand and Salit, {Rachel B.} and Wagner-Johnston, {Nina D.} and Ephraim Fuchs and Javier Bola{\~n}os-Meade and Mehdi Hamadani",

note = "Funding Information: The Center for International Blood and Marrow Transplant Research is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute, the National Heart, Lung, and Blood Institute, and the National Institute of Allergy and Infectious Diseases; Grant/Cooperative Agreement 5U10HL069294 from the National Heart, Lung, and Blood Institute and National Cancer Institute; contract HHSH250201200016C with Health Resources and Services Administration; two grants, N00014-13- 1-0039 and N00014-14-1-0028, from the Office of Naval Research; and grants from ∗Actinium Pharmaceuticals, Allos Therapeutics, ∗Amgen, Anonymous donation to the Medical College of Wisconsin, Ariad, Be the Match Foundation, ∗Blue Cross and Blue Shield Association, ∗Celgene Corporation, Chimerix, Inc, Fred Hutchinson Cancer Research Center, Fresenius-Biotech North America, ∗Gamida Cell Teva Joint Venture, Genentech,∗Gentium SpA, Genzyme Corporation, GlaxoSmithKline, Health Research, Roswell Park Cancer Institute, HistoGenetics, Incyte Corporation, Jeff Gordon Children's Foundation, Kiadis Pharma, The Leukemia and Lymphoma Society, Medac, The Medical College of Wisconsin, Merck and Co, Millennium: Takeda Oncology, ∗Milliman USA, ∗Miltenyi Biotec, National Marrow Donor Program, Onyx Pharmaceuticals, Optum Healthcare Solutions, Osiris Therapeutics, Otsuka America Pharmaceutical, Perkin Elmer, ∗Remedy Informatics, ∗Sanofi US, Seattle Genetics, Sigma-Tau Pharmaceuticals, Soligenix, St. Baldrick's Foundation, StemCyte, A Global Cord Blood Therapeutics, Stemsoft Software, Swedish Orphan Biovitrum, ∗Tarix Pharmaceuticals, ∗TerumoBCT, ∗Teva Neuroscience, ∗THERAKOS, University of Minnesota, University of Utah, and ∗Wellpoint. Asterisks denote corporate members. We thank Morgan Geronime for administrative support and Mary Eapen for her valuable scientific input. Publisher Copyright: {\textcopyright} 2016 by American Society of Clinical Oncology.",

year = "2016",

month = sep,

day = "10",

doi = "10.1200/JCO.2015.66.3476",

language = "English (US)",

volume = "34",

pages = "3141--3149",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "American Society of Clinical Oncology",

number = "26",

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TY - JOUR

T1 - Reduced-intensity transplantation for lymphomas using haploidentical related donors versus HLA-matched sibling donors

T2 - A center for international blood and marrow transplant research analysis

AU - Ghosh, Nilanjan

AU - Karmali, Reem

AU - Rocha, Vanderson

AU - Ahn, Kwang Woo

AU - DiGilio, Alyssa

AU - Hari, Parameswaran N.

AU - Bachanova, Veronika

AU - Bacher, Ulrike

AU - Dahi, Parastoo

AU - De Lima, Marcos

AU - D'Souza, Anita

AU - Fenske, Timothy S.

AU - Ganguly, Siddhartha

AU - Kharfan-Dabaja, Mohamed A.

AU - Prestidge, Tim D.

AU - Savani, Bipin N.

AU - Smith, Sonali M.

AU - Sureda, Anna M.

AU - Waller, Edmund K.

AU - Jaglowski, Samantha

AU - Herrera, Alex F.

AU - Armand, Philippe

AU - Salit, Rachel B.

AU - Wagner-Johnston, Nina D.

AU - Fuchs, Ephraim

AU - Bolaños-Meade, Javier

AU - Hamadani, Mehdi

N1 - Funding Information: The Center for International Blood and Marrow Transplant Research is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute, the National Heart, Lung, and Blood Institute, and the National Institute of Allergy and Infectious Diseases; Grant/Cooperative Agreement 5U10HL069294 from the National Heart, Lung, and Blood Institute and National Cancer Institute; contract HHSH250201200016C with Health Resources and Services Administration; two grants, N00014-13- 1-0039 and N00014-14-1-0028, from the Office of Naval Research; and grants from ∗Actinium Pharmaceuticals, Allos Therapeutics, ∗Amgen, Anonymous donation to the Medical College of Wisconsin, Ariad, Be the Match Foundation, ∗Blue Cross and Blue Shield Association, ∗Celgene Corporation, Chimerix, Inc, Fred Hutchinson Cancer Research Center, Fresenius-Biotech North America, ∗Gamida Cell Teva Joint Venture, Genentech,∗Gentium SpA, Genzyme Corporation, GlaxoSmithKline, Health Research, Roswell Park Cancer Institute, HistoGenetics, Incyte Corporation, Jeff Gordon Children's Foundation, Kiadis Pharma, The Leukemia and Lymphoma Society, Medac, The Medical College of Wisconsin, Merck and Co, Millennium: Takeda Oncology, ∗Milliman USA, ∗Miltenyi Biotec, National Marrow Donor Program, Onyx Pharmaceuticals, Optum Healthcare Solutions, Osiris Therapeutics, Otsuka America Pharmaceutical, Perkin Elmer, ∗Remedy Informatics, ∗Sanofi US, Seattle Genetics, Sigma-Tau Pharmaceuticals, Soligenix, St. Baldrick's Foundation, StemCyte, A Global Cord Blood Therapeutics, Stemsoft Software, Swedish Orphan Biovitrum, ∗Tarix Pharmaceuticals, ∗TerumoBCT, ∗Teva Neuroscience, ∗THERAKOS, University of Minnesota, University of Utah, and ∗Wellpoint. Asterisks denote corporate members. We thank Morgan Geronime for administrative support and Mary Eapen for her valuable scientific input. Publisher Copyright: © 2016 by American Society of Clinical Oncology.

PY - 2016/9/10

Y1 - 2016/9/10

N2 - Purpose: Related donor haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry. Materials and Methods: We evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versushost disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor-based GVHD prophylaxis. Results: Median follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P < .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P < .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34). Conclusion: Haplo-HCT with PT-Cy provides survival outcomes comparable to MSD-HCT, with a significantly lower risk of chronic GVHD.

AB - Purpose: Related donor haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry. Materials and Methods: We evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versushost disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor-based GVHD prophylaxis. Results: Median follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P < .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P < .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34). Conclusion: Haplo-HCT with PT-Cy provides survival outcomes comparable to MSD-HCT, with a significantly lower risk of chronic GVHD.

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JO - Journal of Clinical Oncology

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ER -

Reduced-intensity transplantation for lymphomas using haploidentical related donors versus HLA-matched sibling donors: A center for international blood and marrow transplant research analysis

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