277 Hematopoietic Cell Transplantation (HCT) for Treatment of Genetic Lymphohematopoietic Diseases for Patients Lacking a Fully Matched Sibling Donor Using a Novel Conditioning Regimen

Track: Contributed Abstracts
Wednesday, February 13, 2013, 6:45 PM-7:45 PM
Hall 1 (Salt Palace Convention Center)
Sandhya Kharbanda, MD , Pediatric Stem Cell Transplant, Stanford University, Palo Alto, CA
Rajni Agarwal, MD , Pediatric Stem Cell Transplantation, Stanford University, Palo Alto, CA
David B. Miklos, MD, PhD , Division of Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, CA
Matthew Porteus, MD, PhD , Stanford University
Michael Amylon, MD , Dept. of Pediatrics, Stanford University Medical Center, Stanford, CA
Jennifer R Willert, MD , Children's Hosp San Diego, San Diego, CA
Kenneth I Weinberg, MD , Stanford University School of Medicine, Palo Alto, CA

The genetic lymphohematopoietic diseases have been effectively treated and cured by performing allogeneic HCT from a histocompatible sibling donor following a standard conditioning regimen with busulfan (BU), cyclophosphamide (CY), and antithymocyte globulin, and recently with  reduced intensity conditioning (RIC) regimens. With the use of either conventional conditioning or RIC, the biggest limitation of these approaches is the lack of a fully HLA-matched sibling donor. Higher risks of graft rejection and graft-versus-host disease (GVHD) with the use of non-matched sibling donors – including unrelated donors (URD) or mismatched related donors (mMRD) makes these transplants high risk with high rates of treatment related mortality (TRM). We report preliminary results (table below) on six patients with genetic lymphohematological disorders lacking fully matched sibling donors who were transplanted using a novel conditioning regimen. The regimen consisted of conventional myeloablative, targeted dose of IV BU (16 doses), reduced dose of CY (105 mg/kg), Fludarabine (FLU) 140 mg/m2, and Alemtuzumab 52mg/m2 total pre-transplant in 3 doses. GVHD prophylaxis consisted of alemtuzumab 10mg/m2 on Days+1 and +2, cyclosporine (or tacrolimus), and mycophenolate mofetil. All patients engrafted and survive without severe GVHD. The prolonged immune deficiency with intensive alemtuzumab was complicated by a high risk of viral infection, requiring both intensive antiviral prophylaxis and treatment. We conclude that this regimen significantly decreases immediate post-transplant morbidity, maintains engraftment potential, and decreases the risk of GVHD. The use of FLU and intensive alemtuzumab conditioning to permit decreased CY dosing, along with post-transplant alemtuzumab, can overcome the major obstacles (TRM, non-engraftment, GVHD) to successful HCT for patients with genetic diseases lacking a conventional donor.

                                                                                                           

Disease (age in years)

Stem cell donor/source,

HLA match

Day of WBC engraft

ment

Acute/Chronic GvHD

Viral infections

Outcome (length of f/up)

WAS (2)

URD/marrow, 10/10

+26

Stage III  skin/skin

None

Alive (6 yrs), off immunosuppression (IS)

Hunter Syndrome (5)

URD/marrow, 10/10

+28

None

CMV

Alive (5 yrs), off IS

Hurler Syndrome (1)

URD/marrow, 10/10

+27

Stage 1 skin/none

None

Alive ( 3 yrs),  off IS

Sickle beta-thalassemia (24)

mMRD/marrow8/10

+17

None

CMV

Alive (3 yrs), off IS

Sickle Cell (11)

mMRD/marrow8/10

+16

Stage 1 skin, stage 1 gut/none

CMV, HHV-6, Adeno, and BK

Alive (11 mo), off IS

Sickle Cell (8)

URD/marrow,  10/10

+18

Stage1 skin/none to date

HHV-6 and Adeno

Alive (110 days), on IS

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