title: 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.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas. Electronic address: panderli@mdanderson.org.
authors.forename: Paolo
authors.initials: P
authors.lastname: Anderlini
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Rima M
authors.initials: RM
authors.lastname: Saliba
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Celina
authors.initials: C
authors.lastname: Ledesma
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Tamera
authors.initials: T
authors.lastname: Plair
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Amin M
authors.initials: AM
authors.lastname: Alousi
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Chitra M
authors.initials: CM
authors.lastname: Hosing
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Issa F
authors.initials: IF
authors.lastname: Khouri
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Yago
authors.initials: Y
authors.lastname: Nieto
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Uday R
authors.initials: UR
authors.lastname: Popat
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
authors.affiliation: Department of Lymphoma, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Fanale
authors.affiliation: Department of Lymphoma, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Frederick B
authors.initials: FB
authors.lastname: Hagemeister
authors.affiliation: Department of Lymphoma, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Oki
authors.affiliation: Department of Lymphoma, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Saatva
authors.initials: S
authors.lastname: Neelapu
authors.affiliation: Department of Lymphoma, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Romaguera
authors.affiliation: Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Anas
authors.initials: A
authors.lastname: Younes
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
mesh_terms: D000328:Adult; D000079963:Brentuximab Vedotin; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006689:Hodgkin Disease / Q000150:complications / Q000401:mortality / Q000628:therapy*; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D008171:Lung Diseases / Q000139:chemically induced; D008297:Male; D008558:Melphalan / Q000627:therapeutic use*; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D012074:Remission Induction; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D012871:Skin Diseases / Q000139:chemically induced; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D018796:Immunoconjugates; D003841:Deoxycytidine; D000079963:Brentuximab Vedotin; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan; D000093542:Gemcitabine
keywords: Allogeneic stem cell transplantation; Bone marrow transplantation; Brentuximab vedotin; Hodgkin lymphoma