Shwachman-Diamond syndrome: early bone marrow transplantation in a high risk patient and new clues to pathogenesis

Abstract

Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterised by exocrine pancreas insufficiency, metaphyseal dysostosis and bone marrow dysfunction. Recurrent severe bacterial infections and susceptibility to leukaemia are the major causes of morbidity and mortality occurring preferentially in patients with pancytopenia and features of myelodysplasia. Here we report a patient with SDS leading to recurrent bacterial infections and a deteriorating condition since early infancy. Extensive investigations disclosed severe pancytopenia, myelodysplasia and a clonal cytogenetic abnormality, inv(14)(q11q32), as risk factors of leukaemic transformation. He therefore underwent allogeneic geno-identical bone marrow transplantation which resulted in correction of all haematological and immunological abnormalities within an 18-month follow up period. Conclusion Bone marrow transplantation may be considered early as a valuable treatment option especially in high risk Schwachman-Diamond syndrome patients anticipating malignant transformation, life-threatening severe infections or further organ damage.

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.…”

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

“…13,28 However as summarized in Table 4 several patients have been successfully transplanted with cyclophosphamide containing regimens. 29,30 Although our series was limited to three patients, several other SDS patients have also been transplanted with the preparative regimen of Melphalan, VP16, TLI and ATG (personal communications) and no cardiac complications have been reported. Careful pre-transplant evaluation is important in planning the preparative regimen as some SDS patients could have pre-existing organ dysfunction (hepatic, cardiac, renal).…”

“…Faber et al 29 suggested that transplantation at an earlier age might result in favorable outcomes prior to the development of leukemic transformation or organ dysfunction that may impact tolerance of the myeloablative preparative regimen.…”

Successful unrelated bone marrow transplantation for Shwachman–Diamond syndrome

“…Including this report, only 11 cases of allogeneic transplant have been reported in the literature. 3,4,[9][10][11][12][13][14] Indications for transplantation were marrow aplasia (five cases), myelodysplastic syndrome (three cases) and acute myeloid leukemia (three cases). Only five of 11 were alive at follow up, and four of them were disease-free survivors with follow-ups ranging from 9 months to 5 years.…”

“…2 Supportive treatment with antibiotics and transfusion, and correction of malabsorption with oral pancreatic enzymes, currently allow prolonged survival without modifying the natural evolution of the disease. 1,2 Allogeneic stem cell transplantation is a valuable option when clonal disorders such as leukemic transformation, myelodysplasia or severe marrow aplasia develop 3,4 but experience in this field is very limited due to the rarity of the disease and the lack of clear-cut indications concerning the optimum timing of transplantation. We report a successful unrelated identical bone marrow transplant (BMT) in a 5-year-old boy who developed marrow aplasia after initial marrow dysplasia.…”