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Myelodysplastic and myeloproliferative disorders of childhood: a study of 167 patients
S Luna-Fineman1, K M Shannon, S K Atwater
1University of California, San Francisco, San Francisco, CA 94143, USA.
Abstract:
Myelodysplastic syndromes (MDS) and myeloproliferative syndromes (MPS) of childhood are a heterogeneous group of clonal disorders of hematopoiesis with overlapping clinical features and inconsistent nomenclature. Although a number of genetic conditions have been associated with MDS and MPS, the overall contribution of inherited predispositions is uncertain. We report a retrospective study examining clinical features, genetic associations, and outcomes in 167 children with MDS and MPS. Of these patients, 48 had an associated constitutional disorder. One hundred one patients had adult-type myelodysplastic syndrome (A-MDS), 60 had juvenile myelomonocytic leukemia (JMML), and 6 infants with Down syndrome had a transient myeloproliferative syndrome (TMS). JMML was characterized by young age at onset and prominent hepatosplenomegaly, whereas patients with A-MDS were older and had little or no organomegaly. The most common cytogenetic abnormalities were monosomy 7 or del(7q) (53 cases); this was common both in patients with JMML and those with A-MDS. Leukemic transformation was observed in 32% of patients, usually within 2 years of diagnosis. Survival was 25% at 16 years. Favorable prognostic features at diagnosis included age less than 2 years and a hemoglobin F level of less than 10%. Older patients tended to present with an adult-type MDS that is accommodated within the French-American-British system. In contrast, infants and young children typically developed unique disorders with overlapping features of MDS and MPS. Although the type and intensity of therapy varied markedly in this study, the overall outcome was poor except in patients with TMS.
Insights
Childhood myelodysplastic syndromes (MDS) and myeloproliferative syndromes (MPS) are clonal hematopoiesis disorders with uncertain inherited links. Outcomes are poor, with a 25% survival rate at 16 years, except for transient myeloproliferative syndrome in infants with Down syndrome.
Area of Science:
- Pediatric Hematology Oncology
- Clonal Hematopoiesis Disorders
- Genetic Predispositions in Cancer
Background:
- Childhood myelodysplastic syndromes (MDS) and myeloproliferative syndromes (MPS) are heterogeneous clonal hematopoietic disorders.
- Inconsistent nomenclature and overlapping clinical features complicate diagnosis and classification.
- The role of inherited predispositions in these pediatric disorders remains uncertain.
Purpose of the Study:
- To retrospectively analyze clinical features, genetic associations, and outcomes in children with MDS and MPS.
- To differentiate between adult-type MDS (A-MDS), juvenile myelomonocytic leukemia (JMML), and transient myeloproliferative syndrome (TMS) in children.
- To identify prognostic factors influencing survival in pediatric MDS/MPS.
Main Methods:
- Retrospective study of 167 children diagnosed with MDS and MPS.
- Analysis included clinical presentation, cytogenetics, associated constitutional disorders, and treatment outcomes.
- Classification into A-MDS, JMML, and TMS based on age, clinical features, and specific conditions (e.g., Down syndrome).
Main Results:
- 48 out of 167 patients had an associated constitutional disorder.
- JMML (60 patients) presented with younger age and hepatosplenomegaly; A-MDS (101 patients) with older age and no organomegaly.
- Monosomy 7 or del(7q) was the most common cytogenetic abnormality (53 cases). Leukemic transformation occurred in 32% of patients.
- Overall survival was 25% at 16 years; favorable prognostic factors included age < 2 years and low Hemoglobin F (<10%).
- TMS in infants with Down syndrome had a better outcome compared to A-MDS and JMML.
Conclusions:
- Pediatric MDS/MPS encompass distinct entities like A-MDS, JMML, and TMS, with differing clinical characteristics and outcomes.
- Monosomy 7/del(7q) is a frequent cytogenetic abnormality across pediatric MDS/MPS subtypes.
- Prognosis is generally poor, highlighting the need for further research into therapeutic strategies and understanding inherited predispositions.