Gemcitabine, Fludarabine, and Melphalan for Reduced-Intensity Conditioning and Allogeneic Stem Cell Transplantation for Relapsed and Refractory Hodgkin Lymphoma.

Abstract

Forty patients (median age, 31 years; range, 20 to 63) with Hodgkin lymphoma underwent an allogeneic stem cell transplant with the gemcitabine-fludarabine-melphalan reduced-intensity conditioning regimen. Thirty-one patients (77%) had undergone a prior autologous stem cell transplant, with a median time to progression after transplant of 6 months (range, 1 to 68). Disease status at transplant was complete remission/complete remission, undetermined (n = 23; 57%), partial remission (n = 14; 35%), and other (n = 3; 8%). Twenty-six patients (65%) received brentuximab vedotin before allotransplant. The overall complete response rate before allotransplant was 65% in brentuximab-treated patients versus 42% in brentuximab-naive patients (P = .15). At the latest follow-up (October 2015) 31 patients were alive. The median follow-up was 41 months (range, 5 to 87). Transplant-related mortality rate at 3 years was 17%. Pulmonary, skin toxicities, and nausea were seen in 13 (33%), 11 (28%), and 37 (93%) patients, respectively. At 3 years, estimates for overall and progression-free survival were 75% (95% CI, 57% to 86%) and 54% (95% CI, 36% to 70%). Overall incidence for disease progression was 28% (95% CI, 16% to 50%). We believe the gemcitabine-fludarabine-melphalan regimen allows moderate dose intensification with acceptable morbidity and mortality. The inclusion of gemcitabine affected nausea, pulmonary, and likely skin toxicity. Exposure to brentuximab vedotin allowed more patients to reach allogeneic stem cell transplantation in complete remission. With over 50% of patients progression-free at 3 years, allogeneic stem cell transplantation with reduced-intensity conditioning remains an effective and relevant treatment option for Hodgkin lymphoma in the brentuximab vedotin era.

• Authors: Paolo Anderlini, Rima M Saliba, Celina Ledesma, Tamera Plair, Amin M Alousi, Chitra M Hosing, Issa F Khouri, Yago Nieto, Uday R Popat, Elizabeth J Shpall, Michelle A Fanale, Frederick B Hagemeister, Yasuhiro Oki, Saatva Neelapu, Jorge E Romaguera, Anas Younes, Richard E Champlin
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 22 Issue 7 Pg. 1333-1337 (07 2016) ISSN: 1523-6536 [Electronic] United States
• PMID: 27064056 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Immunoconjugates
• Deoxycytidine
• Brentuximab Vedotin
• Vidarabine
• fludarabine
• Melphalan
• Gemcitabine

Topics

• Adult
• Brentuximab Vedotin
• Deoxycytidine (analogs & derivatives, therapeutic use)
• Female
• Hematopoietic Stem Cell Transplantation (adverse effects, methods, mortality)
• Hodgkin Disease (complications, mortality, therapy)
• Humans
• Immunoconjugates (therapeutic use)
• Lung Diseases (chemically induced)
• Male
• Melphalan (therapeutic use)
• Middle Aged
• Nausea (chemically induced)
• Remission Induction
• Salvage Therapy (adverse effects, methods, mortality)
• Skin Diseases (chemically induced)
• Survival Analysis
• Transplantation Conditioning (adverse effects, methods, mortality)
• Transplantation, Homologous
• Vidarabine (analogs & derivatives, therapeutic use)
• Young Adult
• Gemcitabine