Clofarabine and Treosulfan as Conditioning for Matched Related and Unrelated Hematopoietic Stem Cell Transplantation: Results from the Clo3o Phase II Trial: Biology of Blood and Marrow Transplantation

J. Peccatori, S. Mastaglio, F. Giglio, R. Greco, R. Crocchiolo, F. Patriarca, B. Forno, S. Deola, A. Assanelli, M.T. Lupo Stanghellini, M. Marcatti, M. Zecca, S. Cortelazzo, R. Fanin, F. Fagioli, F. Locatelli, F. Ciceri

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be curative for patients with hematologic malignancies. The ideal conditioning regimen before allo-HSCT has not been established. We conducted a Phase II study to evaluate the tolerability and efficacy of clofarabine and treosulfan as conditioning regimen before allo-HSCT. The primary objective was to evaluate the cumulative incidence of nonrelapse mortality (NRM) on day +100. Forty-four patients (36 with acute myelogenous leukemia, 5 with acute lymphoblastic leukemia, 3 with myelodysplastic syndromes) were enrolled. The median patient age was 47 years, and the median duration of follow-up was 27 months. The conditioning regimen was based on clofarabine 40 mg/m2 (days -6 to -2) and treosulfan 14 g/m2 (days -6 to -4). Allogeneic hematopoietic stem cells were derived from a sibling (n = 22) or a well-matched unrelated donor (n = 22). Graft-versus-host disease (GVHD) prophylaxis consisted of antithymocyte globulin, rituximab, cyclosporine, and a short-course of methotrexate. The regimen allowed for rapid engraftment and a 100-day NRM of 18%, due mainly to bacterial infections. The incidences of grade II-IV acute GVHD and chronic GVHD were 16% and 19%, respectively. The rates of overall survival (OS), progression-free survival, and relapse at 2 years were 51%, 31%, and 50%, respectively. Significantly different outcomes were observed between patients with low-intermediate and patients with high-very high Disease Risk Index (DRI) scores (1-year OS, 78% and 24%, respectively). Our findings show that the use of treosulfan and clofarabine as a conditioning regimen for allo-HSCT is feasible, with a 78% 1-year OS in patients with a low-intermediate DRI score. However, 1-year NRM was 18%, and despite the intensified conditioning regimen, relapse incidence remains a major issue in patients with poor prognostic risk factors. © 2019 American Society for Transplantation and Cellular Therapy
Original languageEnglish
Pages (from-to)316-322
Number of pages7
JournalBiol. Blood Marrow Transplant.
Issue number2
Publication statusPublished - 2020


  • Allogeneic hematopoietic stem cell transplantation
  • Clofarabine
  • Treosulfan
  • clofarabine
  • cyclosporine
  • folinic acid
  • ganciclovir
  • methotrexate
  • rituximab
  • thymocyte antibody
  • treosulfan
  • acute graft versus host disease
  • acute lymphoblastic leukemia
  • acute myeloid leukemia
  • adolescent
  • adult
  • aged
  • allogeneic hematopoietic stem cell transplantation
  • Article
  • brain hemorrhage
  • central nervous system infection
  • chimera
  • chronic graft versus host disease
  • cystitis
  • cytomegalovirus infection
  • deep vein thrombosis
  • disease risk assessment
  • drug efficacy
  • drug tolerability
  • engraftment
  • erythroderma
  • febrile neutropenia
  • female
  • follow up
  • heart arrhythmia
  • hematuria
  • human
  • hypertransaminasemia
  • hypocalcemia
  • incidence
  • major clinical study
  • male
  • matched related donor
  • matched unrelated donor
  • microangiopathy
  • mortality
  • mucosa inflammation
  • multicenter study
  • myeloablative conditioning
  • nausea
  • overall survival
  • phase 2 clinical trial
  • pleura effusion
  • pneumonia
  • progression free survival
  • rash
  • relapse
  • scoring system
  • septic shock
  • single drug dose
  • skin defect
  • treatment outcome
  • ulcer


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