Sequential allogeneic hematopoietic stem cell transplantation for active refractory/relapsed myeloid malignancies: results of a reduced-intensity conditioning preceded by clofarabine and cytosine arabinoside, a retrospective study on behalf of the SFGM-TC

• Published in: Annals of hematology 2020-08, Vol.99 (8), p.1855-1862
• Main Authors: Le Bourgeois, Amandine, Labopin, Myriam, Marçais, Ambroise, de Latour, Regis Peffault, Blaise, Didier, Chantepie, Sylvain, N’Guyen, Stéphanie, Maillard, Natacha, Forcade, Edouard, Yakoub-Agha, Ibrahim, Huynh, Anne, Marchand, Tony, Bilger, Karin, Ceballos, Patrice, Charbonnier, Amandine, Turlure, Pascal, Rubio, Marie-Thérese, Béné, Marie Christine, Guillaume, Thierry, Mohty, Mohamad, Chevallier, Patrice
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Allografts; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Blood cancer; Cancer; Clofarabine - administration & dosage; Cytarabine - administration & dosage; Disease-Free Survival; Female; Hematology; Hematopoietic Stem Cell Transplantation; Human health and pathology; Humans; Immunology; Leukemia, Myeloid, Acute - mortality; Leukemia, Myeloid, Acute - therapy; Life Sciences; Male; Medicine; Medicine & Public Health; Middle Aged; Myelodysplastic Syndromes - mortality; Myelodysplastic Syndromes - therapy; Oncology; Original Article; Retrospective Studies; Stem cell transplantation; Stem cells; Survival Rate; Transplantation Conditioning; Transplants & implants
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-020-04074-7

Allogeneic stem cell transplantation (allo-SCT) represents the most beneficial treatment for patients with active relapsed/refractory (R/R) hematologic malignancies. Recently, sequential regimens combining debulking chemotherapy followed by reduced-intensity conditioning (RIC) have shown encouraging results for these patients. In this retrospective study, we report the extended results of a sequential regimen of clofarabine, cytosine arabinoside, and RIC in 131 adults with active R/R myeloid disease at transplant. Conditioning consisted of clofarabine (30 mg/m 2 /day) and cytosine arabinoside (1 g/m 2 /day) for 5 days, followed, after a rest of 3 days, by an RIC combining cyclophosphamide (60 mg/kg) for 1 day, iv busulfan (3.2 mg/kg/day) for 2 days, and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Between 2007 and 2016, 131 patients (males n  = 75, median age: 52.6 years) were identified from the SFGM-TC registry. There were 111 acute myeloid leukemia (AML) patients and 20 cases with myelodysplastic or myeloproliferative syndrome. Status at transplant was known for all but 4 patients and was primary refractory ( n  = 81) and 1st or 2nd relapse ( n  = 46). All patients received allo-SCT from a matched donor (sibling n  = 64, unrelated n  = 67). Engraftment was observed in 105/122 (86%) evaluable cases and 63% of the patients achieved complete remission (CR) after transplant. The 1-year overall survival, disease-free survival, relapse incidence, non-relapse mortality, and graft-versus-host disease-free/relapse-free survival were 39.2%, 28.1%, 41.0%, 30.8%, and 22.2%, respectively. This study confirms that this sequential clofarabine-based regimen provides a high CR rate in this critical population, although relapse remains a matter of concern.