title: Fludarabine, cytarabine, and mitoxantrone (FLAM) for the treatment of relapsed and refractory adult acute lymphoblastic leukemia. A phase study by the Polish Adult Leukemia Group (PALG).
abstract: Outcome of adults with acute lymphoblastic leukemia (ALL) who fail to achieve complete remission (CR) or who relapse soon after initial response is poor. The goal of this phase II study by the Polish Adult Leukemia Group (PALG) was to evaluate safety and efficacy of a new salvage regimen (FLAM) consisting of sequential fludarabine, cytarabine, and mitoxantrone. Fifty patients were included with primary (n = 13) or secondary (n = 5) refractoriness, early (<12 months) first relapse (n = 15), first relapse after hematopoietic cell transplantation (HCT) regardless CR duration (n = 13), and second or subsequent relapse (n = 4). Median age was 31(18-60) years, 28% of patients were bcr/abl-positive. CR rate equaled 50% and was significantly higher for patients in whom FLAM was administered as a second-line therapy compared to those more heavily pre-treated (66 vs 13%, p = 0.02). Seventeen patients had leukemia regrowth after initial cytoreduction, whereas, eight patients died in aplasia. The incidence of early death was higher in patients aged > or =40 years compared to the younger subgroup (33 vs 8%, p=0.03). Septic infections were the most frequent severe complication. At 3 years, the probability of disease-free survival for patients who achieved CR equaled 16%. Seven patients underwent allogeneic HCT. FLAM regimen is feasible for relapsed and refractory adults with ALL and could be recommended in particular for younger patients as a second-line treatment. However, as the remission duration is short, allogeneic HCT (alloHCT) should be considered as soon as possible.
authors.affiliation: Department of Haematology and BMT, Silesian Medical University, Reymonta 8 St., 40-038, Katowice, Poland. sgiebel@poczta.onet.pl
authors.forename: Sebastian
authors.initials: S
authors.lastname: Giebel
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Krawczyk-Kulis
authors.forename: Maria
authors.initials: M
authors.lastname: Adamczyk-Cioch
authors.forename: Beata
authors.initials: B
authors.lastname: Jakubas
authors.forename: Grazyna
authors.initials: G
authors.lastname: Palynyczko
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Lewandowski
authors.forename: Anna
authors.initials: A
authors.lastname: Dmoszynska
authors.forename: Aleksander
authors.initials: A
authors.lastname: Skotnicki
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Nowak
authors.forename: Jerzy
authors.initials: J
authors.lastname: Holowiecki
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D011044:Poland; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000628:therapy*; D012008:Recurrence; D012074:Remission Induction; D018805:Sepsis / Q000209:etiology; D013997:Time Factors; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D003561:Cytarabine; D008942:Mitoxantrone; D014740:Vidarabine