316 Improved Outcomes in Patients with Dyskeratosis Congenita (DC) Undergoing Allogeneic Hematopoietic Cell Transplantation (HCT) Using Reduced Intensity Conditioning

Track: Poster Abstracts
Wednesday, February 11, 2015, 6:45 PM-7:45 PM
Grand Hall CD (Manchester Grand Hyatt)
Adam S Nelson, MBBS , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
Stella M. Davies, MBBS, PhD, MRCP , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
Kasiani C. Myers, MD , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
Rebecca A. Marsh, MD , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
Sonata Jodele, MD , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
Leann Mount , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
Tracey A O'Brien, MD , Kids Cancer Centre, Sydney Children's Hospital, Sydney, Australia
Parinda A. Mehta, MD , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
Presentation recording not available for download or distribution as requested by the presenting author.

Background

HCT is the only curative option for progressive marrow failure and/or myelosdysplastic syndrome or leukemia associated with DC.  HCT for DC is limited by a high incidence of treatment-related mortality; related to underlying chromosomal instability resulting in sensitivity to chemotherapy and radiation.  We report our experience using a reduced intensity conditioning (RIC) regimen without radiation for HCT in patients with DC.

Methods

Retrospective chart review was performed with IRB approval. 

Results

7 patients with DC underwent HSCT using a RIC regimen consisting of alemtuzumab, fludarabine, and lower dose melphalan between September 2010 and April 2014.  Patient demographics and disease characteristics are shown in Table 1.

1 patient with MDS and DC did not receive alemtuzumab to avoid mixed chimerism.  The remaining 6 patients all received Alemtuzumab at age appropriate dosing (on Day -22 to -18, or day -14 to 10 or day -6 to -2).  All patients received fludarabine from days -8 to -4 (30-40mg/m2/dose).  Melphalan dose was reduced by 50% to 70mg/m2/dose, to avoid excessive toxicity related to baseline chemo-sensitivity.  GVHD prophylaxis consisted of cyclosporine and steroids or MMF.  None of the patients had pre-existing hepatic dysfunction.

All patients engrafted and none developed mixed chimerism.  See Table 2 for additional results. 2 patients developed acute GVHD, one with grade 2 skin GVHD that evolved in to limited chronic skin GVHD and the second patient developed grade 3 gut GVHD in the setting of pre-existing colitis.  

5 patients remain alive and well (100% engrafted) at a median follow up of 28 months (range 5- 47.6). 

Conclusion

A RIC regimen containing alemtuzumab, fludarabine, and lower dose melphalan (without radiation) results in durable engraftment rates, acceptable toxicity and improved overall survival in patients with DC undergoing HCT.

Disclosures:
Nothing To Disclose
See more of: Poster Session 1: Pediatric Disorders
See more of: Poster Abstracts
<< Previous Presentation | Next Presentation >>