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Outcomes of matched sibling donor hematopoietic stem cell transplantation for severe sickle cell disease with myeloablative conditioning and intermediate-dose of rabbit anti-thymocyte globulin

Authors

  • Sandeep Soni MD,

    Corresponding author
    1. Division of Hematology/Oncology/BMT, Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University, Columbus, Ohio
    • Correspondence to: Sandeep Soni, Director of Hematology/BMT bluebird bio, Inc., 150 Second St., Cambridge, MA 02141.

      E-mail: ssoni@bluebirdbio.com

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  • Thomas G. Gross MD, PhD,

    1. Division of Hematology/Oncology/BMT, Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University, Columbus, Ohio
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  • Hemalatha Rangarajan MD,

    1. Division of Hematology/Oncology/BMT, Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University, Columbus, Ohio
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  • K. Scott Baker MD,

    1. Clinical Research Division, Fred Hutchison Cancer Research Center, Seattle, Washington
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  • Mollie Sturm MPH,

    1. Division of Hematology/Oncology/BMT, Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University, Columbus, Ohio
    2. Division of Biostatistics, Nationwide Children's Hospital, Columbus, Ohio
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  • Melissa Rhodes MD

    1. Division of Hematology/Oncology/BMT, Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University, Columbus, Ohio
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  • Conflict of Interest: Nothing to declare.

Abstract

Background

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for sickle cell disease (SCD) in children. Despite excellent outcomes of matched sibling donor (MSD) HSCT, there is still 5–10% chance of rejection and transplant related mortality (TRM) with 12–23% incidence of graft versus host disease (GVHD). We postulated that an intermediate dose of rabbit anti-thymocyte globulin (r-ATG, 10 mg/kg cumulative) would be effective in preventing both rejection and GVHD.

Patients and Methods

Fifteen patients, median age 5 (range 1.5–18) years, underwent MSD HSCT using busulfan (≥12.8 mg/kg with first dose pharmacokinetics), cyclophosphamide (total 200 mg/kg) and r-ATG. Bone marrow was the stem cell source; tacrolimus and methotrexate were given for GVHD prophylaxis.

Results

All patients achieved donor engraftment and there was no TRM. One patient rejected donor cells at 2 months post-transplant. Majority of the patients had high and sustained level of donor chimerism. None of the patients developed ≥Grade II GVHD. Incidence of CMV (10%) and EBV (9%) reactivations was low with rapid immune-reconstitution. Overall survival was 100% with event free survival of 93%.

Conclusions

Eliminating the risks of TRM and GVHD by optimizing the regimen may lead to further acceptance of HSCT for SCD. Pediatr Blood Cancer 2014;61:1685–1689. © 2014 Wiley Periodicals, Inc.

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