title: Efficacy of a 3-day, low-dose treatment with 5-azacytidine followed by donor lymphocyte infusions in older patients with acute myeloid leukemia or chronic myelomonocytic leukemia relapsed after allografting.
abstract: We have piloted a low-dose schedule of 5-azacytidine followed by donor lymphocyte infusions (DLIs) in patients with relapse of AML or chronic myelomonocytic leukemia (CMMoL) after allografting. Of the 26 patients (median age 62 years, range 28-75) with relapsed AML (n=24) or CMMoL (n=2), 11 (42%) had poor-risk cytogenetics. Twenty-three patients had received fludarabine-based reduced-toxicity conditioning regimens, and three had received conventional myeloablative conditioning. Patients received 5-azacytidine s.c., at a total daily dose of 100 mg, on days 1-3, to be followed by DLI on day 10, with the next course of treatment to be started on day 22. A total of 60 courses of 5-azacytidine were administered, with a median of 2 courses (range: 1-10). In 44 courses, 5-azacytidine was followed by DLI, and thus 19/26 (73%) patients received at least one course of this combined treatment. Clinically relevant neutropenic infections not associated with progressive disease developed in four patients, one of them succumbing to sepsis. Only two patients developed de novo acute GvHD after the combination of 5-azacytidine and DLI. Overall, 66% of the patients benefited from this treatment, with continued CRs achieved in 4 (16%) patients, lasting a median of 525 days (range: 450+ to 820+), and a 50% rate of temporary disease control with stable mixed chimerism (median duration 72 days). The median survival from the start of 5-azacytidine treatment was 136 days (range: 23 to 873+), with an estimated 2-year survival probability of 16%. In conclusion, this non-intensive outpatient regimen of 5-azacytidine followed by DLI is feasible, with a very low aGVHD rate. Objective responses, including continuous complete donor chimerism, occurred also in patients with poor-risk cytogenetics.
authors.affiliation: Division Hematology and Oncology, University of Freiburg Medical Center, Freiburg, Germany. Michael.luebbert@uniklinik-freiburg.de
authors.forename: M
authors.initials: M
authors.lastname: Lübbert
authors.forename: H
authors.initials: H
authors.lastname: Bertz
authors.forename: R
authors.initials: R
authors.lastname: Wäsch
authors.forename: R
authors.initials: R
authors.lastname: Marks
authors.forename: B
authors.initials: B
authors.lastname: Rüter
authors.forename: R
authors.initials: R
authors.lastname: Claus
authors.forename: J
authors.initials: J
authors.lastname: Finke
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D001374:Azacitidine / Q000008:administration & dosage*; D019175:DNA Methylation; D004334:Drug Administration Schedule; D044127:Epigenesis, Genetic; D005260:Female; D006086:Graft vs Host Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D015477:Leukemia, Myelomonocytic, Chronic / Q000628:therapy*; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D010865:Pilot Projects; D033581:Stem Cell Transplantation; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine