Radiation-free, alternative-donor HCT for Fanconi anemia patients: Results from a prospective multi-institutional study Journal Article

Authors: Mehta, P. A.; Davies, S. M.; Leemhuis, T.; Myers, K.; Kernan, N. A.; Prockop, S. E.; Scaradavou, A.; O'Reilly, R. J.; Williams, D. A.; Lehmann, L.; Guinan, E.; Margolis, D.; Baker, K. S.; Lane, A.; Boulad, F.
Article Title: Radiation-free, alternative-donor HCT for Fanconi anemia patients: Results from a prospective multi-institutional study
Abstract: Fanconi anemia (FA) is an inherited bone marrow failure syndrome characterized by chromosomal fragility, progressive marrow failure, and cancer predisposition. Hematopoietic cell transplantation (HCT) is curative for FA-related marrow failure or leukemia, but both radiation exposure during transplant and graft-versus-host disease (GVHD) may increase risk of later malignancies of the head and neck and anogenital area. In this study, we tested a radiation-free conditioning regimen with a T-cell-depleted graft to eliminate radiation exposure and minimize early and late toxicities of transplant. Forty-five patients (median age, 8.2 years; range 4.3-44) with FA underwent HCT between June 2009 and May 2014. The preparative regimen included busulfan, cyclophosphamide, fludarabine, and rabbit anti-thymocyte globulin. Busulfan levels were monitored to avoid excess toxicity. All grafts were CD34-selected/T-cell-depleted using the CliniMacs CD34 columns (Miltenyi). Thirty-four patients (75.6%) with marrow failure and 11 (24.4%) with myelodysplastic syndrome underwent HCT using matched unrelated (n = 25, 55.5%), mismatched unrelated (n = 14, 31.1%), or mismatched related donors (n = 6, 13.4%). One year probabilities of overall and disease-free survival for the entire cohort, including patients with myeloid malignancy and those receiving mismatched related/haploidentical grafts, were 80% (+/- 6%) and 77.7% (+/- 6.2%), respectively (median follow-up 41 months). All young children (<10 years of age) undergoing HCT for marrow failure using low-dose busulfan-containing regimen survived. No patients developed acute grade 3-4 GVHD. Sequential reduction of busulfan dose was successfully achieved per study design. Our results show excellent outcomes in patients with FA undergoing alternative donor HCT without radiation exposure. The study is registered to www.clinicaltrials.gov as #NCT01082133.
Keywords: busulfan; stem-cell transplantation; versus-host-disease; bone-marrow-transplantation; malignancies; secondary; conditioning regimen; antithymocyte globulin; aplastic-anemia; intravenous; cytoreductive regimen; low-dose busulfan
Journal Title: Blood
Volume: 129
Issue: 16
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2017-04-20
Start Page: 2308
End Page: 2315
Language: English
ACCESSION: WOS:000399565300016
DOI: 10.1182/blood-2016-09-743112
PUBMED: 28179273
PMCID: PMC5766838
Notes: Article -- Source: Wos
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MSK Authors
  1. Nancy Kernan
    382 Kernan
  2. Farid Boulad
    255 Boulad
  3. Susan E Prockop
    161 Prockop
  4. Richard O'Reilly
    487 O'Reilly