Successful Unrelated Donor Bone Marrow Transplantation for Shwachman-Diamond Syndrome with Leukemia

Abstract

Shwachman-Diamond syndrome (SDS) is a rare congenital disorder featuring exocrine pancreatic insufficiency, growth retardation, and bone marrow dysfunction. Reports suggest that nearly 25% of all cases are complicated with leukemia. Although stem cell transplantation is the sole option for these patients, successful results are rarely obtained. Poor outcomes are often related to graft failure and cardiac and other organ toxicities. We describe in this report successful unrelated donor bone marrow transplantation for a patient with SDS who progressed to acute myelogenous leukemia. The patient received attenuated intensified chemotherapy because of his intolerance to ordinary chemotherapy and went into remission. Sustained unrelated donor bone marrow engraftment was accomplished after treatment with a reduced amount of cyclophosphamide and antithymocyte globulin with 12 Gy of total body irradiation as a conditioning regimen. To the best of our knowledge, this report is the first to describe unrelated donor bone marrow transplantation with complete engraftment for an SDS patient with myelogenous leukemia.

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.…”

“…15,23,28,31 Savilahti and Rapola 31 reported significant cardiac dysfunction in patients with SDS even without exposure to CY. In their series of 16 Finnish patients, 8 had cardiac abnormalities on necropsy including cardiac fibrosis and areas of necrosis.…”

Genetic Analysis of Shwachman-Diamond Syndrome: Phenotypic Heterogeneity in Patients Carrying Identical SBDS Mutations

“…All patients except cases 4 and 5 were unrelated. Case 1 developed de novo AML at 18 years old and underwent successful unrelated bone marrow transplantation three years prior to the current study (Mitsui et al 2004). Case 2 had an affected elder brother who died of sepsis at 5 years of age.…”

“…Approximately 25% of cases have been reported to develop aplastic anemia, myelodysplastic syndrome or leukemia (Dror and Freedman 2002;Smith 2002;Mitsui et al 2004).…”

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

“…11 Allogeneic bone marrow transplantation has been reported as a curative modality for hematological disturbances in patients with SDS. 12,13 Unfortunately allogeneic bone marrow transplantation in SDS has been poorly tolerated due to excessive organ toxicities (ie cardiac toxicity). 13 Owing to the rarity of this syndrome and the lack of consensus regarding transplant indications, there are no standardized transplant regimens.…”