309 Reduced Intensity Transplantation for Inherited Bone Marrow Failure Syndromes

Track: Poster Abstracts
Wednesday, February 11, 2015, 6:45 PM-7:45 PM
Grand Hall CD (Manchester Grand Hyatt)
Alok Kothari, MD , Department of Pediatrics, Washington University School of Medicine, Saint Louis, MO
Shalini Shenoy, MD , Pediatrics, Washington University, St. Louis Children's Hospital, St. Louis, MO
Robert J. Hayashi, MD , St. Louis Children's Hospital, University of Washington, St. Louis, MO
Paul Haut, MD , Pediatric Hematology/Oncology, Riley Hospital for Children/Indiana University, Indianapolis, IN
Jeffrey H Davis, MD , Pediatrics, British Columbia Children's Hospital, Vancouver, BC, Canada
Alexander Ngwube , Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Lisa Murray, MA , Pediatric Hematology/ Oncology, Washington University, St. Louis, MO
Brett Loechelt, MD , Blood and Marrow Transplantation, Children's National Medical Center, Washington, DC
Presentation recording not available for download or distribution as requested by the presenting author.

Background

Inherited bone marrow failure syndromes (IBMFS) include genetic disorders with hematopoietic cytopenias due to mutations in genes supporting normal hematopoiesis. Transformation to myeloid leukemia or myelodysplastic syndrome occurs in 4-25% by adulthood. Allogeneic hematopoietic cell transplantation (HCT) is curative but has been largely limited to sibling donor HCT due to toxicities of alternative donor transplants. The development of successful HCT strategies is necessary in this setting to benefit more patients. This includes optimizing transplant conditioning, reducing mortality, late effects, and GVHD so HCT can benefit more patients.

Hypothesis

A reduced intensity conditioning regimen (RIC) and HCT from matched marrow or matched/one-antigen mismatched cord will result in high overall survival (OS) and event-free survival (EFS) in patients (<21 years) with IBMFS (excluding Fanconi Anemia).

Methods

IBMFS patients (3 Diamond-Blackfan Anemia, 1 Congenital Dyserythropoietic Anemia, 1 Shwachman-Diamond Syndrome, 2 Congenital Amegakaryocytic Thrombocytopenia, 1 Congenital BM Failure, 1 X-linked Thrombocytopenia, 1 Severe Congenital Neutropenia, 1 X- Chromosome Deletion) received alemtuzumab intravenously for 3 days (dose 33 mg if <10kg; 45 mg if >10kg) (day -21 to -19), fludarabine (30 mg/m2/day) (day -8 to -4) and melphalan (140 mg/m2) on day -3.  All received a calcineurin inhibitor as GVHD prophylaxis. Marrow recipients received short course methotrexate and steroids, and cord recipients received mycophenolate.

 

Results

Eleven patients between 2 months and 14 years of age (median 23 months) underwent HCT. Nine were from unrelated donors; ten received BM; one received UCB. Ten had full donor chimerism by 30 days. OS and EFS were 82% with median follow up of 62 months (range 12-186). Two deaths (BM recipients for DBA and Congenital BMF) at day 45 and 346 were due to aGVHD and graft rejection followed by mortality after a second transplant resepctively. The cumulative incidence of acute (grade II-IV) and chronic GVHD was 9 and 0% repsectively.  Eight of the 9 survivors had successfully discontinued systemic immunosuppression by one year post HCT. Robust immune reconstitution was noted at 1 year in survivors.

Conclusions

This RIC regimen was tolerated well by this very young recipient group. The regimen had a high success rate (also previously described in HCT for Shwachman-Diamond syndrome: Bhatla, BMT 2008) and is expected to have fewer late toxicities. Though the numbers are small, outcomes are encouraging in these rare disorders supporting a HCT consideration early during the course of the disease prior to marrow related complications.

Disclosures:
Nothing To Disclose
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