Objective: To explore the effectiveness of allogeneic hematopoietic stem cell transplantation(allo-HSCT) for Shwachman-Diamond Syndrome(SDS) complicated with severe hemocytopenia, myelodysplastic syndrome(MDS) and acute myeloid leukemia(AML).

Methods: A total of 25 patients with SDS who underwent allo-HSCT in Beijing JingDu Children's Hospital from July 2015 to July 2025 were enrolled. The clinical manifestations and details about allo-HSCT were summarized.

Results: There were 17 males and 8 females enrolled. The male/female ratio was 2.125. All the patients were clinically and genetically diagnosed as SDS. The median age at diagnosis was 8 months(ranging from 1 day to 158 months) old. The patients' median age at HSCT was 28 months (ranging from 7 to 162) old. The patients' median weight and height was 9.7kg (ranging from 5.2 to 38.2) and 80cm(ranging from 60 to 160). All cases had neutropenia, 9 cases complicated with anemia or thrombopenia, 9 cases had pancytopenia. 1 case was diagnosed with AML, 5 cases were diagnosed with myelodysplastic syndrome(MDS) with low balsts. 2 cases complicated with complex karyotypes. 5 cases had mutated Tp53. 6 girls had their ovaries frozen before HSCT. The donors consisted of 14 cases of unrelated cord blood(UCB), 6 cases of mismatched related donors(MMRD) and 5 cases of mismatched unrelated donors(MMUD). All patients used myeloablating conditioning.The regimen of the case with AML consisted of busulfan, fludarabine, cytarabine, cyclophosphamide and anti-thymocyte globulin(ATG). Other patients' regimens consisted of busulfan, fludarabine, ATG with or without cyclophosphamide. All were given cyclosporine and mycophenolate mofetil to prevent graft-versus- host disease(GVHD). Balliximab was given at +1 day to the patients whose donor was MMRD and methotrexate was given at +1,+4,+7,+11 days to the patients whose donor was MMUD or UCB. 24 cases achieved engraftment, the other case underwent haploid HSCT following failure of cord blood transplantation, currently at day +6 post-infusion, and the engraftment rate was 96%. The median time to neutrophil engraftment and platelet engraftment was 12 (ranging from 9 to 22)days and 16.5 (ranging from 11 to 66)days, respectively. There were 0/13, 3/6, 2/5 cases with acute GVHD (grades II to IV) and 1/13, 2/6, 1/5 mild chronic GVHD in UCB, MMRD and MMUD groups. There was no middle and severe chronic GVHD. Within the follow-up of 10.5(ranging from 0 to 119) months, 2 patients died and 1 patient with MDS relapsed. The patient with complex karyotype and Tp53 mutation experienced MDS recurrence with increased blasts after cord blood transplantation. Then he got chemotherapy and second transplantation(haploid), but failed to achieve negative MRD. Melphalan was administered before donor peripheral blood stem cell infusion, resulting in negative MRD. But he subsequently developed grade IV acute GVHD and thrombotic microangiopath. Finally, another relapse occurred at +29 months post-second transplant, and he is currently receiving palliative care. The OS and EFS rate was 92% and 88%.

Conclusions: Allo-HSCT is an effective treatment for SDS complicated with severe hematological abnormalities.Compared with MMRD and MMUD HSCT, the incidence of GVHD in CBT is lower. MDS complicated with both complex karyotype and Tp53 mutation was associated with an extremely poor prognosis.

This content is only available as a PDF.
2025
Sign in via your Institution