Unrelated donor bone marrow transplantation for children and adolescents with aplastic anaemia or myelodysplasia

Summary:The purpose of this study was to evaluate the role of allogeneic bone marrow transplantation (BMT) in children with myelodysplastic syndrome (MDS). In total, 94 consecutive pediatric patients with MDS received an allogeneic BMT from 1976 to 2001 for refractory anemia (RA) (n ¼ 25), RA with ringed sideroblasts (RARS) (n ¼ 2), RA with excess blasts (RAEB) (n ¼ 20), RAEB in transformation (RAEB-T) (n ¼ 14), juvenile myelomonocytic leukemia (JMML) (n ¼ 32) or chronic myelomonocytic leukemia (CMML) (n ¼ 1). The estimated 3-year probabilities of survival, event-free survival (EFS), nonrelapse mortality and relapse were 50, 41, 28 and 29%, respectively. Patients with RA/RARS had an estimated 3-year survival of 74% compared to 68% in those with RAEB and 33% in patients with JMML/CMML. In multivariable analysis, patients with RAEB-T or JMML were 3.9 and 3.7 times more likely to die compared to those with RA/RARS and RAEB (P ¼ 0.005 and 0.004, respectively). Patients with RAEB-T were 5.5 times more likely to relapse (P ¼ 0.01). The median follow-up among the 43 surviving patients is 10 years (range 1-25). We conclude that allogeneic BMT for children with MDS is well tolerated and can be curative.

Section: Discussionmentioning

confidence: 82%

Allogeneic bone marrow transplantation in children with myelodysplastic syndrome or juvenile myelomonocytic leukemia: the Seattle experience

Yusuf

Frangoul

Gooley

et al. 2004

“…Graft rejection and GVHD account for significant morbidity and mortality in these patients. 19 In the study by Davies et al, 20 seven SAA children underwent BMT with URD; three survived, and grades III-IV acute GVHD were 37% with T-replete bone marrow. The series from Japan noted 11% early or late rejection, with grades III-IV acute GVHD 20%, and chronic GVHD 30%.…”

Section: Discussionmentioning

confidence: 99%

Unrelated donor bone marrow transplantation for children with severe aplastic anemia: minimal GVHD and durable engraftment with partial T cell depletion

Bunin

Aplenc

Iannone

et al. 2005

Summary:Both increased graft rejection and increased graft vs host disease (GVHD) remain obstacles to success for unrelated donor (URD) BMT for patients with SAA. Partial T cell depletion (PTCD) may decrease the risk of severe GVHD, while still maintaining sufficient donor T lymphocytes to ensure engraftment. We report on 12 patients with SAA who underwent PTCD URD BMT. All patients had failed medical therapy or relapsed following initial responses, and were transfusion dependent. The median age was 6 years, and there were five males. Donors were matched for four patients, and mismatched for eight. All patients received total body irradiation with either Ara-C or thiotepa and cyclophosphamide. PTCD was accomplished using monoclonal antibody T10B9 or OKT3 and complement. All patients engrafted, with a median time of 18 days to ANC 4500. Only one patient had greater than grade II acute GVHD; two patients had limited and one patient extensive chronic GVHD. Nine patients are alive and transfusion independent at a median months post BMT. Three patients died from infection or renal failure. This series suggests that an aggressive immunosuppressive conditioning regimen with PTCD results in successful engraftment and minimal GVHD in pediatric patients with SAA, even with HLA mismatched donors.

“…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.…”

Section: Discussionmentioning

confidence: 99%

Successful unrelated bone marrow transplantation for Shwachman–Diamond syndrome

Cesaro

Guariso

Calore

et al. 2001

Summary:A 5-year-old boy with Shwachman-Diamond syndrome underwent unrelated HLA-identical bone marrow transplantation for severe pancytopenia. Conditioning was with busulfan, thiotepa and cyclophosphamide plus rabbit anti-lymphocyte serum. Engraftment for neutrophils and platelets was observed on days +18 and +41, respectively. Transplant-related side-effects were mild and transient. After a follow-up of 32 months, the patient is alive and enjoys a normal life, off any immunosuppressives. Immunological and hematological reconstitution is complete while other phenotypic characteristics (pancreatic insufficiency, short stature, femur dysostosis) are stable. Although experience in this field is scarce, we speculate that bone marrow failure in Shwachman-Diamond syndrome (even if not linked to the appearance of clonal disorders or leukemic transformation) is an indication for bone marrow transplantation and may be associated with a better outcome. Bone Marrow Transplantation (2001) 27, 97-99. Keywords: Shwachman-Diamond syndrome; myelodysplasia; bone marrow transplantation; pancreatic insufficiency; marrow aplasia Marrow dysfunction including neutropenia, marrow aplasia, myelodysplasia and leukemic transformation are well known features of Shwachman-Diamond syndrome (SDS), a rare recessive autosomal disorder of infancy that is also characterized by pancreatic insufficiency, metaphyseal dysostosis and short stature. 1 Very limited information has been published on the long-term survival range in SDS. A projected median survival time of 35 years has been reported 2 but this figure could be an over-simplification. SDS was first described only 35 years ago and the true long-term survival is unknown. However, the development of pancytopenia and leukemia significantly reduce survival, infections and hemorrhage being the major causes of death. 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. The patient is alive and well after a follow-up of 32 months. We speculate that the reduced incidence of transplant-related mortality, the recent availability of larger panels of volunteer bone marrow donors and a growing cord blood bank could provide a better chance of long-term survival for SDS patients with severe (even if not clonal) hematologic complications. Case reportA diagnosis of SDS was made in a 5-month-old boy with exocrine pancreatic insufficiency and steathorrea, failure to thrive, maln...