NYMC Faculty Publications

Pilot Trial of Risk-Adapted Cyclophosphamide Intensity Based Conditioning and HLA Matched Sibling and Unrelated Cord Blood Stem Cell Transplantation in Newly Diagnosed Pediatric and Adolescent Recipients With Acquired Severe Aplastic Anemia

Author Type(s)

Faculty

DOI

10.1002/pbc.24976

Journal Title

Pediatric Blood & Cancer

First Page

1289

Last Page

1294

Document Type

Article

Publication Date

7-1-2014

Department

Pediatrics

Keywords

Adolescent, Allografts, Anemia, Aplastic, Child, Child, Preschool, Cord Blood Stem Cell Transplantation, Cyclophosphamide, Disease-Free Survival, Female, Graft Rejection, Humans, Immunosuppressive Agents, Male, Pilot Projects, Risk Assessment, Risk Factors, Survival Rate, Transplantation Conditioning, Unrelated Donors

Disciplines

Medicine and Health Sciences

Abstract

BACKGROUND: Cyclophosphamide-based conditioning regimens and allogeneic hematopoietic stem cell transplantation (AlloHSCT) from matched related donors (MRD) has resulted in the highest survival rates in children and adolescents with acquired severe aplastic anemia (SAA). Time to transplant has consistently been associated with decreased overall survival. Reduced toxicity conditioning and AlloHSCT has been used successfully in other pediatric non-malignant diseases.

PROCEDURE: We piloted a risk-adapted AlloHSCT approach, using fludarabine and anti-thymocyte globulin based conditioning with high (200 mg/kg) and low (60 mg/kg) dose cyclophosphamide as upfront treatment in newly diagnosed pediatric patients with acquired SAA incorporating alternative donor sources, including cord blood. Average risk for non-engraftment patients with(60 mg/kg); High Risk, those with ≥10 transfusions received conditioning regimen with higher intensity cyclophosphamide (200 mg/kg).

RESULTS: Seventeen patients were enrolled and underwent AlloHSCT including 12 males and 5 females with mean age of 8 years (range 3-16), and median follow-up time of 39 months (range 1-135). Donor sources included MRD BM (6/6 [n = 9], 5/6 [n = 2]) and unrelated CB (5/6 [n = 4], 4/6 [n = 2]). Five year OS was 67.6% (37.9-85.4). Three secondary graft failures (17.6%) occurred in the low dose cyclophosphamide arm.

CONCLUSIONS: Upfront treatment with risk-adapted cyclophosphamide conditioning AlloSCT is well tolerated for the management of newly diagnosed pediatric and adolescent patients with acquired SAA. However, the increased risk of graft rejection in the lower dose arm warrants additional research regarding the optimal intensity of cyclophosphamide-based conditioning regimen to reduce toxicity without increasing graft failure.

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