Liposomal daunorubicin, fludarabine, and cytarabine (FLAD) as bridge therapy to stem cell transplant in relapsed and refractory acute leukemia

Enrico De Astis, Marino Clavio, Anna Maria Raiola, Anna Ghiso, Fabio Guolo, Paola Minetto, Federica Galaverna, Maurizio Miglino, Carmen Di Grazia, Filippo Ballerini, Carlo Marani, Giordana Pastori, Laura Mitscheunig, Fabio Cruciani, Davide Lovera, Riccardo Varaldo, Chiara Ghiggi, Roberto Massimo Lemoli, Andrea Bacigalupo, Marco Gobbi

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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.

Original languageEnglish
Pages (from-to)2011-2018
Number of pages8
JournalAnnals of Hematology
Volume93
Issue number12
DOIs
Publication statusPublished - 2014

Fingerprint

Daunorubicin
Cytarabine
Leukemia
Stem Cells
Transplants
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Acute Myeloid Leukemia
Hematopoietic Stem Cell Transplantation
Therapeutics
Blast Crisis
fludarabine
Survival
Siblings
Unrelated Donors

Keywords

  • ALL
  • AML
  • Cytarabine
  • Fludarabine
  • HSCT
  • Liposomal daunorubicin
  • Relapsed-refractory acute leukemias
  • Stem cell transplant

ASJC Scopus subject areas

  • Hematology
  • Medicine(all)

Cite this

Liposomal daunorubicin, fludarabine, and cytarabine (FLAD) as bridge therapy to stem cell transplant in relapsed and refractory acute leukemia. / De Astis, Enrico; Clavio, Marino; Raiola, Anna Maria; Ghiso, Anna; Guolo, Fabio; Minetto, Paola; Galaverna, Federica; Miglino, Maurizio; Di Grazia, Carmen; Ballerini, Filippo; Marani, Carlo; Pastori, Giordana; Mitscheunig, Laura; Cruciani, Fabio; Lovera, Davide; Varaldo, Riccardo; Ghiggi, Chiara; Lemoli, Roberto Massimo; Bacigalupo, Andrea; Gobbi, Marco.

In: Annals of Hematology, Vol. 93, No. 12, 2014, p. 2011-2018.

Research output: Contribution to journalArticle

De Astis, E, Clavio, M, Raiola, AM, Ghiso, A, Guolo, F, Minetto, P, Galaverna, F, Miglino, M, Di Grazia, C, Ballerini, F, Marani, C, Pastori, G, Mitscheunig, L, Cruciani, F, Lovera, D, Varaldo, R, Ghiggi, C, Lemoli, RM, Bacigalupo, A & Gobbi, M 2014, 'Liposomal daunorubicin, fludarabine, and cytarabine (FLAD) as bridge therapy to stem cell transplant in relapsed and refractory acute leukemia', Annals of Hematology, vol. 93, no. 12, pp. 2011-2018. https://doi.org/10.1007/s00277-014-2143-8
De Astis, Enrico ; Clavio, Marino ; Raiola, Anna Maria ; Ghiso, Anna ; Guolo, Fabio ; Minetto, Paola ; Galaverna, Federica ; Miglino, Maurizio ; Di Grazia, Carmen ; Ballerini, Filippo ; Marani, Carlo ; Pastori, Giordana ; Mitscheunig, Laura ; Cruciani, Fabio ; Lovera, Davide ; Varaldo, Riccardo ; Ghiggi, Chiara ; Lemoli, Roberto Massimo ; Bacigalupo, Andrea ; Gobbi, Marco. / Liposomal daunorubicin, fludarabine, and cytarabine (FLAD) as bridge therapy to stem cell transplant in relapsed and refractory acute leukemia. In: Annals of Hematology. 2014 ; Vol. 93, No. 12. pp. 2011-2018.
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AU - De Astis, Enrico

AU - Clavio, Marino

AU - Raiola, Anna Maria

AU - Ghiso, Anna

AU - Guolo, Fabio

AU - Minetto, Paola

AU - Galaverna, Federica

AU - Miglino, Maurizio

AU - Di Grazia, Carmen

AU - Ballerini, Filippo

AU - Marani, Carlo

AU - Pastori, Giordana

AU - Mitscheunig, Laura

AU - Cruciani, Fabio

AU - Lovera, Davide

AU - Varaldo, Riccardo

AU - Ghiggi, Chiara

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AU - Bacigalupo, Andrea

AU - Gobbi, Marco

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