Successful unrelated umbilical cord blood transplantation in children with Shwachman-Diamond syndrome

Abstract

Summary:Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterized by pancreatic insufficiency and variable degrees of neutropenia. SDS patients are at risk of developing myelodysplasia, aplastic anemia, and leukemic transformation. The role and timing of allogeneic hematopoietic stem cell transplantation (HSCT) in SDS remain controversial. We report three SDS patients with severe aplasia transplanted using unrelated umbilical cord blood (UCB). Patients received melphalan (180 mg/m 2 ), etoposide (1200 mg/m 2 ), antithymocyte globulin (90 mg/kg), and total lymphoid irradiation (500 cGy); graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and prednisone. Myeloid engraftment occurred promptly with absolute neutrophil count 4500 cells/mm 3 on day 1575 and all patients displayed 100% donor chimerism by 2 months post transplant. The major complication of transplant was GVHD, with all patients developing grade II or III acute GVHD, one progressing to chronic extensive GVHD. Patients are alive 309, 623, and 2029 days post transplant. Factors important in HSCT outcome for SDS may include transplantation at a young age, avoidance of cyclophosphamide, and adequate GVHD prophylaxis. Importantly, these cases also suggest that unrelated UCB, in the absence of a matched family member, is an excellent alternative stem cell source for SDS patients undergoing HSCT. Bone Marrow Transplantation (2005) 36, 855-861.

Substitution of cyclophosphamide and busulfan by fludarabine, treosulfan and melphalan in a preparative regimen for children and adolescents with Shwachman–Diamond syndrome

“…More recently, a single report described three patients transplanted with UCB. 15 Unfortunately, long-term outcome data are not available for most of the patients. At the time of reporting, o50% of cases were noted to be alive.…”

Reduced-intensity conditioning is effective and safe for transplantation of patients with Shwachman–Diamond syndrome

“…The available literature on HSCT in SDS patients is limited and consists mainly of case reports. [19][20][21][22][23][24][25][26][27][28][29] Vibhakar et al 30 recently reviewed the published experience with HSCT in SDS patients and reported a total of 28 patients, including their own. All but four patients received ablative conditioning regimens containing CY with or without TBI/ TLI.…”

Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome

“…[17][18][19][20][21][22][23] The terminology non-malignant SC was preferred to aplastic anemia, because routine bone marrow samples from SDS patients exhibited dysgranulopoietic features or abnormalities of granulopoietic maturation. As in Fanconi anemia, the dyserythropoiesis, hyposegmentation or condensed chromatin should not be considered as a sign of myelodysplasia, 37 unless it is observed in more than 50% of the neutrophils.…”