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Familial Haploidentical (FHI) T-Cell Depleted (TCD) with T-Cell Addback Stem Cell Transplantation for Patients with High-Risk Sickle Cell Disease (SCD) (IND 14359)

Track: Poster Abstracts
Wednesday, February 26, 2014, 6:45 PM-7:45 PM
Longhorn Hall E (Exhibit Level 1) (Gaylord Texan)
Julie-An Talano, MD , Pediatric Hematology/Oncology and BMT, Children's Hospital of Wisconsin, Milwaukee, WI
Carolyn Keever-Taylor, PhD , Medicine, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI
Mark Walters, MD , Hematology/Oncology, Children's Hospital & Research Center, Oakland, Oakland, CA
Shalini Shenoy, MD , Pediatrics, Washington University, St. Louis Children's Hospital, St. Louis, MO
Theodore B Moore, MD , Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA
Susan K. Parsons, MD, MRP , Tufts Medical Center, Boston, MA
Cori Abikoff, MD , Pediatrics, New York Medical College, Valhalla, NY
Allen J Dozor, MD , Pediatrics, New York Medical College, Valhalla, NY
Deborah Friedman, MD , Pediatrics, New York Medical College, Valhalla, NY
Ramanamoorthy Chitti, MD , Radiation Oncology, New York Medical College, Valhalla, NY
Qiuhu Shi, PhD , Biostatistics, New York Medical College, Valhalla, NY
Brenda Grossman, MD , Pathology & Immunology, Washington University, St. Louis, MO
Rona Weinberg, PhD , New York Blood Center, New York, NY
Erin Morris, RN, BSN , Pediatrics, New York Medical College, Valhalla, NY
Phyllis Brand, RN, MPH , Pediatrics, New York Medical College, Valhalla, NY
Daniel Mangan, BS , Pediatrics, New York Medical College, Valhalla, NY
Sandra Foley, RN, MSN, CPNP , Pediatrics, New York Medical College, Valhalla, NY
Olga Militano, PharmD , Pediatrics, New York Medical College, Valhalla, NY
Janet Ayello, MS, MT(ASCP) , Pediatrics, New York Medical College, Valhalla, NY
Mildred Semidei-Pomales, MS , Pediatrics, New York Medical College, Valhalla, NY
Lee Ann Baxter-Lowe, PhD , Immunogentics and Transplantation Lab, UCSF, San Francsico, CA
Mitchell S. Cairo, MD , Pediatrics, New York Medical College, Valhalla, NY

Allogeneic stem cell transplantation (AlloSCT) from HLA-matched unaffected sibling donors (MSD) has been successful for high-risk SCD, but only 14-18% of patients have such a donor (Freed/Cairo et al, BMT, 2012). Alternate donors include unrelated adult donors (URD) and umbilical cord blood (UCB) donors (Cairo et al., BBMT, 2008). URD are limited and unrelated UCB transplant results are poor (Radhakrishnan K/Cairo et al., BBMT 2013, Kamani et al., BBMT, 2012). In a high-risk FHI TCD thalassemia study, 16/22 cases engrafted without acute GVHD (aGVHD) and with 90% overall survival. (Sodani et al., Blood, 2010). FHI TCD AlloSCT, could expand the donor pool and improve outcomes for SCD.

This SCD consortium trial is investigating the safety, feasibility, EFS, donor chimerism, graft failure, acute and chronic GVHD, and infectious mortality after FHI TCD AlloSCT in high-risk SCD patients (Figure 1).

 

Patients (2-20.99 yrs) without an 8/8 HLA MSD or URD and who have ≥1 high-risk SCD feature are eligible. Patients receive hydroxyurea (60mg/kg/d) and azathioprine (3mg/kg/d x50d), fludarabine (30mg/m2/d x5d), busulfan (3.2mg/kg/d x4d), thiotepa (10mg/kg x1d), cyclophosphamide (50mg/kg x4d), R-ATG (2mg/kg/d x4d), and TLI (500cGy) followed by FHI T-cell depleted AlloSCT. Acute GVHD prophylaxis is tacrolimus. The CliniMACS (IND 14359) collects HPC, Apheresis- CD34-enriched cells; target dose of 10.0 x 106 CD34+ cells/kg with 2.0 x 105 CD3+ T cells/kg added back.

Two patients have received AlloSCTs to date. Pt. 1 is a 10yr ♂ with a history of abnormal Transcranial Dopplers and multiple Vaso occlusive Crises. Pt. 2 is a 13yr ♀ with two previous strokes, hypertransfusion and Moyamoya.  Both utilized maternal donors without complications, and had early myeloid engraftment, ≥92% whole blood and ≥ 85%RBC donor chimerism, no aGVHD or cGVHD, and are alive with NED (Figure 2). Two more patients are undergoing conditioning.

Early results indicate FHI TCD AlloSCT is feasible in high-risk SCD patients who lack MSD or URD.  A larger cohort is needed to assess long-term safety and outcomes (Supported by FDA 5R01FD004090-02 and a grant from Otsuka) (IND #14359 and NCT 01461837).

Figure1.

 

Figure 2.

 

Disclosures:
M. S. Cairo, Otsuka Pharmaceutical, Grantee: Grant
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