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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.
- Source :
-
Annals of hematology [Ann Hematol] 2013 Oct; Vol. 92 (10), pp. 1397-403. Date of Electronic Publication: 2013 Jun 01. - Publication Year :
- 2013
-
Abstract
- 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%.
- Subjects :
- Adult
Antineoplastic Combined Chemotherapy Protocols
Female
Graft vs Host Disease prevention & control
Humans
Male
Middle Aged
Vidarabine therapeutic use
Young Adult
Amsacrine therapeutic use
Antimetabolites, Antineoplastic therapeutic use
Cytarabine therapeutic use
Hematopoietic Stem Cell Transplantation methods
Leukemia, Myeloid, Acute drug therapy
Leukemia, Myeloid, Acute therapy
Vidarabine analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0584
- Volume :
- 92
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Annals of hematology
- Publication Type :
- Academic Journal
- Accession number :
- 23728608
- Full Text :
- https://doi.org/10.1007/s00277-013-1790-5