Successful Unrelated Umbilical Cord Blood Transplantation for Shwachman-Diamond Syndrome.

Shwachman-Diamond Syndrome (SDS) is an autosomal recessive disorder characterized by pancreatic insufficiency and variable degrees of neutropenia. Additional clinical features include short stature, skeletal abnormalities and bone marrow dysfunction. SDS patients are at increased risk of developing myelodysplasia, aplastic anemia and leukemic transformation. The role and timing of allogeneic hematopoietic stem cell transplantation (HSCT) in SDS remains controversial due to a poorly defined predisposition toward peri-transplant complications and overall poor survival. Here we report three SDS patients (age 13 mo, 16 mo and 8 yr) with severe aplasia successfully transplanted using 5/6 HLA matched unrelated umbilical cord blood. All patients received a previously described “cardiac sparing” conditioning regimen consisting of Melphalan (180 mg/m²), Etoposide (1200 mg/m²), anti-thymocyte globulin (90 mg/kg), and low dose total lymphoid irradiation (500 cGy) with graft versus host disease (GVHD) prophylaxis consisting of cyclosporine and prednisone. Patients received grafts containing 6.7 – 9.1 x 10⁵ CD34+ cells/kg. Myeloid engraftment occurred promptly with the ANC > 500 cells/mm³ on day 15 ± 5. Platelet recovery (>20k without transfusion) occurred on day 20, 30 and 140 days post transplant. All patients displayed 100% donor chimerism by 2 months post transplant. Patients were discharged between 25 – 60 days post transplant without severe complications, though all patients displayed grade II or III acute GVHD, and one developed chronic GVHD. The patients are alive 85, 390 and 850 days post transplant. Factors that may be important in HSCT outcome for SDS include transplantation at a relatively young age prior to malignant transformation, avoidance of cyclophosphamide in the preparative regimen, and adequate GVHD prophylaxis. Importantly, these cases also suggest that unrelated umbilical cord blood, in the absence of a matched family member, should be considered as the preferred source of donor stem cells in SDS patients undergoing HSCT.