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Fractionated busulfan myeloablative conditioning improves survival in older patients with acute myeloid leukemia and myelodysplastic syndrome
Author(s) -
Oran Betül,
Saliba Rima M.,
Mehta Rohtesh S.,
Alousi Amin M.,
Marin David,
Valdez Ben C.,
Chen Julianne,
Bashir Qaiser,
Ciurea Stefan O.,
Olson Amanda L.,
Hosing Chitra,
Kebriaei Partow,
Rezvani Katy,
Shpall Elizabeth J.,
Champlin Richard E.,
Andersson Borje S.,
Popat Uday R.
Publication year - 2021
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.33383
Subject(s) - medicine , busulfan , hazard ratio , myelodysplastic syndromes , fludarabine , gastroenterology , myeloid leukemia , regimen , surgery , hematopoietic stem cell transplantation , transplantation , chemotherapy , cyclophosphamide , confidence interval , bone marrow
Background A myeloablative conditioning regimen can be safely given to older patients and those with comorbidities without increasing nonrelapse mortality (NRM) by fractionating the dose of intravenous busulfan. How this approach compares in efficacy with traditional, nonfractionated, lower dose regimens is unknown. Methods Outcomes were compared in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome who received either myeloablative, fractionated busulfan (f‐Bu) dosed to achieve an area under the curve of 20,000 μmol per minute (f‐Bu20K) over 2 weeks (n = 84) or a standard, nonfractionated, lower busulfan dose regimen of 16,000 μmol per minute (Bu16K) over 4 days (n = 78). Both groups also received fludarabine 40 mg/m 2 intravenously for 4 days. Graft‐versus‐host disease prophylaxis was tacrolimus and methotrexate. Patients in the Bu16K group who had unrelated donors also received antithymocyte globulin. The primary endpoint was progression‐free survival. Results Roughly one‐half of the patients were aged >65 years, approximately 40% had poor‐risk cytogenetics, approximately 40% of those with AML were not in complete remission, and approximately 40% had a comorbidity index >3. At 2 years, progression‐free survival was significantly improved in the f‐Bu20K group compared with the Bu16K group (45% vs 24%, respectively; hazard ratio [HR], 0.6; 95% CI, 0.4‐0.8; P = .004). This was because of a significant reduction in progression (34% vs 59%, respectively; HR, 0.5; 95% CI, 0.3‐0.8; P = .003) without any increase in NRM (21% vs 15%, respectively; HR, 1.4; 95% CI, 0.7‐3; P = .3), which resulted in improved overall survival (51% vs 31%, respectively; HR, 0.6; 95% CI, 0.3‐0.9; P = .01). Conclusions A myeloablative, fractionated busulfan regimen reduces relapse and improves survival without increasing NRM in older patients with AML and myelodysplastic syndrome.