A Reduced-Toxicity Regimen Is Associated with Durable Engraftment and Clinical Cure of Nonmalignant Genetic Diseases among Children Undergoing Blood and Marrow Transplantation with an HLA-Matched Related Donor

Kris Michael Mahadeo, Kenneth I. Weinberg, Hisham Abdel-Azim, David B. Miklos, Renna Killen, Donald Kohn, Gay M. Crooks, Ami J. Shah, Sandhya Kharbanda, Rajni Agarwal, Neena Kapoor

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3 Scopus citations

Abstract

Blood and marrow transplantation (BMT) is a standard curative therapy for patients with nonmalignant genetic diseases. Myeloablative conditioning has been associated with significant regimen-related toxicity (RRT), whereas reduced-intensity conditioning regimens have been associated with graft failure. In this prospective pilot trial conducted at 2 centers between 2006 and 2013, we report the outcome of 22 patients with nonmalignant genetic diseases who were conditioned with a novel reduced-toxicity regimen: i.v. busulfan (16 mg/kg), alemtuzumab (52 mg/m2), fludarabine (140 mg/m2), and cyclophosphamide (105 mg/kg). The median age of the study population was 3.5 years (range, 5 months to 26 years). No cases of sinusoidal obstruction syndrome, severe or chronic graft-versus-host disease (GVHD), or primary graft failure were reported. Median time to neutrophil engraftment (>500 cells/μL) and platelet engraftment (>20K cells/μL) were 19 (range, 12 to 50) and 23.5 (range, 14 to 134) days, respectively. The median length of follow-up was 3 years (range, .2 to 6.3). The overall survival rates were 95% at 100 days (95% confidence interval, .72 to .99) and 90% at 6 years (95% confidence interval, .68 to .98). RRT and chronic GVHD are significant barriers to BMT for patients with nonmalignant genetic diseases. This alemtuzumab-based reduced-toxicity regimen appears to be promising with durable engraftment, effective cure of clinical disease, low rates of RRT, and no observed chronic GVHD.

Original languageEnglish (US)
Pages (from-to)440-444
Number of pages5
JournalBiology of Blood and Marrow Transplantation
Volume21
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

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Keywords

  • Alemtuzumab
  • Nonmalignant diseases
  • Pediatrics
  • Reduced toxicity

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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