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
| Authors | |
|---|---|
| Year of publication | 2013 |
| Type | Article in Periodical |
| Magazine / Source | Annals of hematology |
| MU Faculty or unit | |
| Citation | |
| Web | http://dx.doi.org/10.1007/s00277-013-1790-5 |
| Doi | http://dx.doi.org/10.1007/s00277-013-1790-5 |
| Field | Oncology and hematology |
| Keywords | Acute myeloid leukemia; Reduced-intensity conditioning; Fludarabine; Cytarabine; Amsacrine; Allogeneic transplantation |
| Attached files | |
| Description | 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/m(2)/day), cytarabine (2 g/m(2)/day), and amsacrine (100 mg/m(2)/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 longterm 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 >5x10(6)/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 %. |
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