title: Liposomal daunorubicin, fludarabine, and cytarabine (FLAD) as bridge therapy to stem cell transplant in relapsed and refractory acute leukemia.
abstract: Therapeutic options for patients with relapsed or refractory acute leukemia are still undefined and often unsatisfactory. We report the outcome of 79 patients with relapsed-refractory acute leukemia treated with fludarabine, cytarabine, and liposomal daunorubicin (FLAD regimen) followed by hematopoietic stem cell transplantation (HSCT), when clinically indicated, between May 2000 and January 2013. Forty-one patients had acute myeloid leukemia (AML), and 38 had acute lymphoblastic leukemia (ALL). Two patients with myeloid blast crises of CML and three with lymphoid blast crises were included in the AML and ALL subgroups, respectively. Median age was 48 years (range 13-77). FLAD was well tolerated with negligible, nonhematological toxicity. Six patients (7.5 %) died before response evaluation. Forty-seven patients achieved hematologic complete response (CR). Complete remission rate was 53 and 65 % among AML and ALL patients, respectively. No CR was recorded among 11 refractory AML patients. Twenty-four patients (30 %) underwent HSCT. Nine patients received stem cells from an HLA identical sibling, and 15 from an alternative donor (3 unrelated matched, 12 haploidentical sibling). Median overall survival in AML and ALL patients receiving FLAD therapy was 9 and 8 months, respectively. A 5-year projected OS for patients receiving the whole program (FLAD + HSCT) was 24 % for AML patients (median survival 43 months), 28 % for ALL patients treated in relapse (median survival 15 months), and 0 % for ALL patients treated for refractory disease. In this paper, we show that FLAD seems to be an effective bridge therapy to HSCT for a part of poor prognosis acute leukemia patients. However, prospective studies are needed to confirm our results.
authors.affiliation: Division of Clinical Hematology and Division of Hematology and Hematopoietic Stem Cell Transplantation, IRCCS S Martino-IST, Viale Benedetto XV, N 6, 16132, Genova, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: De Astis
authors.forename: Marino
authors.initials: M
authors.lastname: Clavio
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Raiola
authors.forename: Anna
authors.initials: A
authors.lastname: Ghiso
authors.forename: Fabio
authors.initials: F
authors.lastname: Guolo
authors.forename: Paola
authors.initials: P
authors.lastname: Minetto
authors.forename: Federica
authors.initials: F
authors.lastname: Galaverna
authors.forename: Maurizio
authors.initials: M
authors.lastname: Miglino
authors.forename: Carmen
authors.initials: C
authors.lastname: Di Grazia
authors.forename: Filippo
authors.initials: F
authors.lastname: Ballerini
authors.forename: Carlo
authors.initials: C
authors.lastname: Marani
authors.forename: Giordana
authors.initials: G
authors.lastname: Pastori
authors.forename: Laura
authors.initials: L
authors.lastname: Mitscheunig
authors.forename: Fabio
authors.initials: F
authors.lastname: Cruciani
authors.forename: Davide
authors.initials: D
authors.lastname: Lovera
authors.forename: Riccardo
authors.initials: R
authors.lastname: Varaldo
authors.forename: Chiara
authors.initials: C
authors.lastname: Ghiggi
authors.forename: Roberto Massimo
authors.initials: RM
authors.lastname: Lemoli
authors.forename: Andrea
authors.initials: A
authors.lastname: Bacigalupo
authors.forename: Marco
authors.initials: M
authors.lastname: Gobbi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016913:Blood Component Transfusion; D003131:Combined Modality Therapy; D060830:Consolidation Chemotherapy; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000628:therapy; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000628:therapy; D016016:Proportional Hazards Models; D012074:Remission Induction; D012189:Retrospective Studies; D016879:Salvage Therapy; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D008081:Liposomes; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D014740:Vidarabine; C024352:fludarabine; D003630:Daunorubicin