Myelodysplastic syndromes in children. A critical review of the clinical manifestations and management

Abstract

The FAB group has defined myelodysplasia in adults but direct application of this categorization to children has been controversial. Consequently, to outline the natural history of the disease better we have retrospectively analysed case reports and series published in English between 1982 and 1996. This study also included children with juvenile chronic myelomonocytic leukaemia (JCML) and monosomy 7 (Mo7). 340 patients were described in 27 publications. The mean presentation age was 5.91 (SD 5.04) years, and 34.9% were female. Constitutional alterations were described in 68 (20%) where refractory anemia (RA) and RA with excess of blasts (RAEB) predominated and were associated with a significantly longer survival. Among all patients progression to higher forms of MDS was noted in 61 (18%). Cytogenetic anomalies were detected in 59% of 227 children, and in 67 it was to Mo7. Amid those with Mo7, the clinical and laboratory characteristics as well as survival, closely followed their FAB type. Of the treatment options described, survival was significantly higher in those who underwent bone marrow transplant (BMT) (46.9%; P = 0.00021). Among children with JMML (CMML/JCML) not receiving a BMT, time to death was shortest in those best described as JCML (absence of constitutional and karyotypic derangement, thrombocytopenia and elevated Hb F). We conclude that children with constitutional abnormalities survive longer, Mo7 disorders are clinically and morphologically heterogeneous and should not be grouped into a single entity and that CMML and JCML may have biological differences. Finally, BMT remains the treatment of choice for those with primary MDS, as intensive chemotherapy is no better than supportive measures.

Identification of an immunogenic CD8+ T-cell epitope derived from γ-globin, a putative tumor-associated antigen for juvenile myelomonocytic leukemia

“…[10][11][12][13] Although allogeneic stem cell transplantation can induce long-term remissions, relapse rates remain high and novel modalities are needed. 14,15 Since donor lymphocyte infusion after relapse is TERT (open curve) was analyzed by flow cytometric analysis using the FL1 channel.…”

“…[10][11][12][13] Patients with JMML respond poorly to most standard chemotherapy regimens and, although allogeneic stem cell transplantation can be curative, relapse rates are unacceptably high. 14,15 Since a graft-versus-leukemia effect is demonstrated by the efficacy of donor lymphocyte infusions, it is possible that JMML can be treated with T-cell-mediated immunotherapy.…”

Allogeneic bone marrow transplantation for juvenile myelomonocytic leukemia: a single center experience of 23 patients

“…Although the only curative approach for JMML is to perform an allogeneic BMT, 2,[11][12][13] this procedure is accompanied by a high relapse rate and a high TRM, resulting in an OS of 31-58% as reported in the recent literature. 8,10,11,14,15 In our series, OS is 43.5710% at 5 and 10 years; the probability of relapse-free survival (TRM censured) is 48712%.…”

“…9,10 Allogeneic BMT has been shown to improve outcome: retrospective evaluations of series including 15 patients or more reported an overall survival (OS) of 39-58%. 2,[11][12][13][14][15] Woods 10 found a similar OS at 6 years of 31% for 13 patients treated on a prospective study (CCG protocol 2891). The major causes of failure in all series were a high relapse rate and a high transplant-related mortality (TRM).…”

Myelodysplasia in the Wellington region 2002–2007: disease incidence and treatment patterns

“… A bone marrow biopsy not consistent with myelodysplasia. An alternative diagnosis explaining the dysplasia seen on bone marrow biopsy. Living outside the study area (excluded so as to obtain accurate incidence figures for the Wellington region). A previous diagnosis of MDS before the study period. Less than 20 years of age (excluded because of the different clinical behaviour of childhood MDS) 8 …”