title: Clofarabine versus fludarabine-based reduced-intensity conditioning regimen prior to allogeneic transplantation in adults with AML/MDS.
abstract: We have retrospectively compared survivals between acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) patients who received either a clofarabine/busulfan (CloB2A2) or a fludarabine/busulfan (FB2A2) RIC regimen for allogeneic stem cell transplantation. Between 2009 and 2014, 355 allotransplanted cases were identified from the SFGM-TC registry as having received either the FB2A2 (n = 316, 56% males, median age: 59.2 years, AML 78.5%, first complete remission [CR1] 72%, median follow-up: 20 months) or the CloB2A2 (n = 39, 62% males, median age: 60.8 years, AML 62%, CR1 69%, median follow-up: 22.4 months) RIC regimen. In multivariate analysis, FB2A2 was associated with significant lower overall survival (OS, HR: 2.14; 95%CI: 1.05-4.35, P = 0.04) and higher relapse incidence (RI, HR: 2.17; 95%CI: 1.02-4.61, P = 0.04) and a trend for lower leukemia-free survival (LFS, HR: 1.75; 95%CI: 0.94-3.26, P = 0.08). These results were confirmed using a propensity score-matching strategy. However, when considering AML and MDS patients separately, the benefit of the CLOB2A2 regimen was restricted to AML patients (2-year OS FB2A2: 38% [14.5-61.6] vs. CloB2A2: 79.2% [62.9-95.4], P = 0.01; 2-year LFS FB2A2: 38% [16-59.9] vs. CloB2A2: 70.8% [52.6-89], P = 0.03). The better survivals were due to the lower risk of relapse in this CloB2A2 AML subgroup (2-year RI FB2A2: 41.2% [19-62.4] vs. CloB2A2: 16.7% [5-34.2], P = 0.05). This retrospective comparison suggests that the CloB2A2 RIC regimen can likely provide longer survival than that awarded by a FB2A2 RIC regimen and may become a new standard of care RIC regimen for allotransplanted AML patients. A prospective phase 3 randomized study is warranted.
authors.affiliation: Hematology Department, CHU Hotel-Dieu, Nantes, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Chevallier
authors.affiliation: Université Pierre & Marie Curie, Paris, France.|INSERM, UMRs 938, Paris, France.|Hôpital Saint-Antoine, AP-HP, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.affiliation: Hematology Department, Hôpital Saint-Louis, Paris, France.
authors.forename: Regis Peffault
authors.initials: RP
authors.lastname: de La Tour
authors.affiliation: Hematology Department, CHRU Hautepierre, Strasbourg, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lioure
authors.affiliation: Hematology Department, CHU, Grenoble, France.
authors.forename: Claude-Eric
authors.initials: CE
authors.lastname: Bulabois
authors.affiliation: Hematology Department, Centre Anti-cancéreux, Toulouse, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Huynh
authors.affiliation: Hematology Department, Institut Paoli-Calmette, Marseille, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Blaise
authors.affiliation: Hematology Department, CHU, Limoges, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Turlure
authors.affiliation: Hematology Department, CHU, Besançon, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Daguindau
authors.affiliation: Hematology Department, CHU, Poitiers, France.
authors.forename: Natacha
authors.initials: N
authors.lastname: Maillard
authors.affiliation: CHU de Lille, LIRIC INSERM U995, Université Lille2, Lille, France.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yakoub-Agha
authors.affiliation: Hematology Department, CHU, Brest, France.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Guillerm
authors.affiliation: Hematology Department, CHU, Montpellier, France.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Delage
authors.affiliation: Hematology Department, CHU, Rouen, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Contentin
authors.affiliation: Hematology Department, CHU, Clermont-Ferrand, France.
authors.forename: Jacques-Olivier
authors.initials: JO
authors.lastname: Bay
authors.affiliation: Hematology Department, CHU Henri Mondor, Creteil, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Beckerich
authors.affiliation: Hematology Department, IGR, Villejuif, France.
authors.forename: Jean-Henri
authors.initials: JH
authors.lastname: Bourhis
authors.affiliation: Hematology Department, CHU, Lyon, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Detrait
authors.affiliation: Hematology Department, CHU, Bordeaux, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Vigouroux
authors.affiliation: Hematology Department, CHU, Angers, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: François
authors.affiliation: Hematology Department, CHU, Nice, France.
authors.forename: Faezeh
authors.initials: F
authors.lastname: Legrand
authors.affiliation: Hematology Department, CHU Hotel-Dieu, Nantes, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Guillaume
authors.affiliation: Université Pierre & Marie Curie, Paris, France.|INSERM, UMRs 938, Paris, France.|Hôpital Saint-Antoine, AP-HP, Paris, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000008:administration & dosage; D000077866:Clofarabine; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D000077866:Clofarabine; D014740:Vidarabine; C024352:fludarabine
keywords: Acute myeloid leukemia; allogeneic stem cell transplantation; clofarabine; fludarabine; myelodysplastic syndrome; reduced-toxicity conditioning regimen