Combination of fludarabine, amsacrine, and cytarabine followed by reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation in patients with high-risk acute myeloid leukemia
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Sequential use of chemotherapy and reduced-intensity conditioning (RIC) with allogeneic stem cell transplantation (SCT) has been proposed to improve the treatment outcomes in patients with high-risk acute myeloid leukemia (AML). Here, we present our experience with this procedure in a cohort of 60 AML patients with primary induction failure (n = 9); early, refractory, or ≥ second relapse (n = 41); or unfavorable cytogenetics (n = 10). A combination of fludarabine (30 mg/m2/day), cytarabine (2 g/m2/day), and amsacrine (100 mg/m2/day) for 4 days was used. After 3 days of rest, RIC was carried out, consisting of 4 Gy total body irradiation, antithymocyte globulin (ATG-Fresenius), and cyclophosphamide (fludarabine, amsacrine, and cytarabine (FLAMSA)-RIC protocol). Prophylactic donor lymphocyte infusions (pDLIs) were given in patients with complete remission (CR) and without evidence of graft-versus-host disease ≥120 days after SCT. The median time of neutrophil engraftment was 17 days. CR was achieved in 47 of 60 patients (78 %). Eleven patients received pDLIs resulting in long-term CR in eight of them. Non-relapse mortality after 1 and 3 years was 25 and 28 %, respectively. With a median follow-up of 37 months (range, 10–69), 3-year overall survival and 3-year progression-free survival were 42 and 33 %, respectively. In a multivariate analysis, dose of CD34(+) cells >5 × 106/kg (p = 0.005; hazard ratio (HR) = 0.276), remission of AML before SCT (p = 0.044; HR = 0.421), and achievement of complete chimerism after SCT (p = 0.001; HR = 0.205) were significant factors of better overall survival. The use of the FLAMSA-RIC protocol in suitable high-risk AML patients results in a long-term survival rate of over 40 %.
KeywordsAcute myeloid leukemia Reduced-intensity conditioning Fludarabine Cytarabine Amsacrine Allogeneic transplantation
The work was supported in part by Research Grants MSMT CR CZ.1.05/1.1.00/02.0068 (CEITEC), MSMT CR CZ.1.07/2.3.00/20.0045 (SuPReMMe), and by the Czech Leukemia Study Group – for Life (CELL), and by MH CZ – DRO (FNBr, 65269705).
Conflict of interest
The authors declare no conflict of interest.
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