TY - JOUR
T1 - Reduced-Intensity Conditioning with Fludarabine, Melphalan, and Total Body Irradiation for Allogeneic Hematopoietic Cell Transplantation
T2 - The Effect of Increasing Melphalan Dose on Underlying Disease and Toxicity
AU - Chen, George L.
AU - Hahn, Theresa
AU - Wilding, Gregory E.
AU - Groman, Adrienne
AU - Hutson, Alan
AU - Zhang, Yali
AU - Khan, Usman
AU - Liu, Hong
AU - Ross, Maureen
AU - Bambach, Barbara
AU - Higman, Meghan
AU - Neppalli, Vishala
AU - Sait, Sheila
AU - Block, Anne Marie W.
AU - Wallace, Paul K.
AU - Singh, Anurag K.
AU - McCarthy, Philip L.
N1 - Publisher Copyright:
© 2018 American Society for Blood and Marrow Transplantation
PY - 2019/4
Y1 - 2019/4
N2 - Disease relapse and toxicity are the shortcomings of reduced-intensity conditioning (RIC) for allogeneic hematopoietic cell transplantation (alloHCT). We hypothesized that adding total body irradiation (TBI) to and decreasing melphalan (Mel) from a base RIC regimen of fludarabine (Flu) and Mel would increase cytoreduction and improve disease control while decreasing toxicity. We performed a phase II trial of Flu 160 mg/m 2 , Mel 50 mg/m 2 , and TBI 400 cGy (FluMelTBI-50, n = 61), followed by a second phase II trial of Flu 160 mg/m 2 , Mel 75 mg/m 2 , and TBI 400cGy (FluMelTBI-75, n = 94) as RIC for alloHCT. Outcomes were compared with a contemporaneous cohort of 162 patients who received Flu 125 mg/m 2 and Mel 140 mg/m 2 . Eligibility criteria were equivalent for all 3 regimens. All patients were ineligible for myeloablative/intensive conditioning. The median (range) follow-up for all patients was 51 (15 to 103) months. Day 100 donor lymphoid chimerism and transplant-related mortality, neutrophil and platelet engraftment, acute and chronic graft versus host disease incidence, overall survival (OS), and progression-free survival (PFS) were equivalent between FluMel, FluMelTBI-50, and FluMelTBI-75. Stomatitis wasdecreased for FluMelTBI versus FluMel (P <.01). PFS for patients not in complete remission on alloHCT was improved for FluMelTBI-75 versus FluMel (P =.03). On multivariate analysis, OS (P =.05) and PFS (P =.05) were significantly improved for FluMelTBI-75 versus FluMel. FluMelTBI-75 is better tolerated than FluMel, with improved survival and disease control.
AB - Disease relapse and toxicity are the shortcomings of reduced-intensity conditioning (RIC) for allogeneic hematopoietic cell transplantation (alloHCT). We hypothesized that adding total body irradiation (TBI) to and decreasing melphalan (Mel) from a base RIC regimen of fludarabine (Flu) and Mel would increase cytoreduction and improve disease control while decreasing toxicity. We performed a phase II trial of Flu 160 mg/m 2 , Mel 50 mg/m 2 , and TBI 400 cGy (FluMelTBI-50, n = 61), followed by a second phase II trial of Flu 160 mg/m 2 , Mel 75 mg/m 2 , and TBI 400cGy (FluMelTBI-75, n = 94) as RIC for alloHCT. Outcomes were compared with a contemporaneous cohort of 162 patients who received Flu 125 mg/m 2 and Mel 140 mg/m 2 . Eligibility criteria were equivalent for all 3 regimens. All patients were ineligible for myeloablative/intensive conditioning. The median (range) follow-up for all patients was 51 (15 to 103) months. Day 100 donor lymphoid chimerism and transplant-related mortality, neutrophil and platelet engraftment, acute and chronic graft versus host disease incidence, overall survival (OS), and progression-free survival (PFS) were equivalent between FluMel, FluMelTBI-50, and FluMelTBI-75. Stomatitis wasdecreased for FluMelTBI versus FluMel (P <.01). PFS for patients not in complete remission on alloHCT was improved for FluMelTBI-75 versus FluMel (P =.03). On multivariate analysis, OS (P =.05) and PFS (P =.05) were significantly improved for FluMelTBI-75 versus FluMel. FluMelTBI-75 is better tolerated than FluMel, with improved survival and disease control.
KW - Fludarabine
KW - Melphalan
KW - Minimal residual disease
KW - Reduced-intensity conditioning
KW - Total body irradiation
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U2 - 10.1016/j.bbmt.2018.09.042
DO - 10.1016/j.bbmt.2018.09.042
M3 - Article
C2 - 30300731
AN - SCOPUS:85056320469
SN - 1083-8791
VL - 25
SP - 689
EP - 698
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 4
ER -