Objectives. Shwachman-Diamond syndrome (SDS) is characterized by varying degrees of marrow failure. Retrospective studies suggested a high propensity for malignant myeloid transformation into myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). The study's aims were to determine the cellular and molecular characteristics as well as the clinical course of malignant myeloid transformation and clonal marrow disease in patients with SDS. Methods. This is a longitudinal prospective study of 14 patients recruited for annual hematological evaluations. Results of baseline and serial hematological assessments for up to 5 years are reported. Results. Clonal marrow cytogenetic abnormalities (CMCA) were detected in 4 patients (29%) on first testing or at follow-up. The abnormalities were del(20q) in two patients, i(7q) in one, and combined del(20q) and i(7q) in one. The following tests did not distinguish patients with CMCA from other SDS patients: severity of peripheral cytopenia, fetal hemoglobin levels, percentage of marrow CD34+cells, colony growth from marrow CD34+cells, cluster-to-colony ratio, marrow stromal function, percentage of marrow apoptosis cells, and granulocyte colony-stimulating factor receptor expression. RAS and p53 mutation analysis and AML blast colony assays were uniformly negative. No patients showed progression into more advanced stages of MDS or into AML. In one patient, the abnormal clone became undetectable after 2 years of follow-up. Conclusions. We conclude that although CMCA in SDS is high, progression into advanced stages of MDS or to overt AML may be slow and difficult to predict. Treatment should be cautious since some abnormal clones can regress. © 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc.
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