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The safety and efficacy of clofarabine in combination with high-dose cytarabine and total body irradiation myeloablative conditioning and allogeneic stem cell transplantation in children, adolescents, and young adults (CAYA) with poor-risk acute leukemia

Bone Marrow Transplantation (2018) | Download Citation


Acute leukemias in children with CR3, refractory relapse, or induction failure (IF) have a poor prognosis. Clofarabine has single agent activity in relapsed leukemia and synergy with cytarabine. We sought to determine the safety and overall survival in a Phase I/II trial of conditioning with clofarabine (doses 40 – 52 mg/m2), cytarabine 1000 mg/m2, and 1200 cGy TBI followed by alloSCT in children, adolescents, and young adults with poor-risk leukemia. Thirty-seven patients; Age 12 years (1–22 years); ALL/AML: 34:3 (18 IF, 10 CR3, 13 refractory relapse); 15 related, 22 unrelated donors. Probabilities of neutrophil, platelet engraftment, acute GvHD, and chronic GvHD were 94%, 84%, 49%, and 30%, respectively. Probability of day 100 TRM was 8.1%. 2-year EFS (event free survival) and OS (overall survival) were 38.6% (CI95: 23–54%), and 41.3% (CI95: 25–57%). Multivariate analysis demonstrated overt disease at time of transplant (relative risk (RR) 3.65, CI95: 1.35–9.89, P = 0.011) and umbilical cord blood source (RR 2.17, CI95: 1.33–4.15, P = 0.019) to be predictors of worse EFS/OS. This novel myeloablative conditioning regimen followed by alloSCT is safe and well tolerated in CAYA with very poor-risk ALL or AML. Further investigation in CAYA with better risk ALL and AML undergoing alloSCT is warranted.

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We would like to thank Erin Morris, RN, and Virginia Davenport, RN for their expert editorial assistance, the PBMTC chair, Michael Pulsipher, MD, and the PBMTC Oncology Committee for their support and all the patients and families that participated in this study. We would also like to thank the external Data Safety Monitoring Board members for their expert advice and review of this clinical trial (Chair, Sima Jeha, MD; Roger Giller, MD and Koen Van Biesen, MD). This research was supported in part by grants from the Pediatric Cancer Research Foundation, Doris Duke Charitable Foundation and Genzyme.

Author information


  1. Departments of Pediatrics, Valhalla, NY, USA

    • Jessica Hochberg
    • , Nan Chen
    • , Lauren Harrison
    • , Olga Militano
    • , M. Fevzi Ozkaynak
    •  & Mitchell S. Cairo
  2. Pediatric Institute, Cleveland Clinic Children’s, Cleveland, Ohio, USA

    • Stacey Zahler
  3. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    • Mark B. Geyer
  4. Department of Pediatrics, Hackensack University Medical Center, Hackensack, NJ, USA

    • Jennifer Krajewski
    •  & Alfred P. Gillio
  5. Department of Pediatrics, University of Louisville, Louisville, KY, USA

    • Alexandra C. Cheerva
  6. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA

    • Julie Talano
  7. Department of Pediatrics, University of California at Los Angeles, Los Angeles, CA, USA

    • Theodore B. Moore
  8. Department of Hematology/Oncology, Children’s Hospital and Research Center of Oakland, Oakland, CA, USA

    • Mark C. Walters
  9. Department of Pathology and Laboratory Medicine, Children’s Hospital Los Angeles, Los Angeles, CA, USA

    • Lee Ann Baxter-Lowe
  10. Departments of Microbiology and Immunology, Valhalla, NY, USA

    • Carl Hamby
    •  & Mitchell S. Cairo
  11. Departments of Medicine, Valhalla, NY, USA

    • Mitchell S. Cairo
  12. Departments of Pathology, Valhalla, NY, USA

    • Mitchell S. Cairo
  13. Departments of Cell Biology and Anatomy, New York Medical College, Valhalla, NY, USA

    • Mitchell S. Cairo


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Conflict of interest

M.B.G. reports grants and non-financial support from Doris Duke Charitable Foundation, during the conduct of the study; and grants from Lymphoma Research Foundation, grants from NIH/National Center for Advancing Translational Sciences, outside the submitted work. The remaining authors declare that they have no conflict of interest.

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Correspondence to Mitchell S. Cairo.

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