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.
Subject(s)
Myelodysplastic Syndromes , Myeloproliferative Disorders , Child , Child, Preschool , Chromosome Aberrations , Chromosomes, Human, Pair 7 , Female , Fetal Hemoglobin/metabolism , Gene Deletion , Humans , Infant , Infant, Newborn , Leukemia/etiology , Male , Monosomy , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/therapy , Myeloproliferative Disorders/diagnosis , Myeloproliferative Disorders/genetics , Myeloproliferative Disorders/therapy , Prognosis , Retrospective Studies , Survival RateSubject(s)
Biopsy, Needle/methods , Histiocytosis, Langerhans-Cell/diagnosis , Orbital Diseases/diagnosis , Antigens, CD1/metabolism , Child, Preschool , Histiocytes/metabolism , Histiocytosis, Langerhans-Cell/metabolism , Humans , Immunoenzyme Techniques , Magnetic Resonance Imaging , Male , Orbit/diagnostic imaging , Orbit/pathology , Orbital Diseases/metabolism , S100 Proteins/metabolism , Tomography, X-Ray ComputedSubject(s)
Chromosome Aberrations/genetics , Chromosome Deletion , Chromosomes, Human, Pair 7 , Leukemia, Myeloid/genetics , Monosomy , Myelodysplastic Syndromes/genetics , Adolescent , Adult , Child , Child, Preschool , Chromosome Aberrations/epidemiology , Chromosome Disorders , Female , Genes, Neurofibromatosis 1 , Genes, ras , Genetic Diseases, Inborn/genetics , Genetic Predisposition to Disease , Hematopoietic Stem Cells/pathology , Humans , Incidence , Infant , Infant, Newborn , Leukemia, Myeloid/classification , Leukemia, Myeloid/epidemiology , Leukemia, Myeloid/pathology , Leukemia, Radiation-Induced/genetics , Male , Myelodysplastic Syndromes/classification , Myelodysplastic Syndromes/epidemiology , Myelodysplastic Syndromes/pathology , Neoplasms, Second Primary/chemically induced , Neoplasms, Second Primary/etiology , Neoplasms, Second Primary/genetics , RiskABSTRACT
BACKGROUND: Previously, autologous Burkitt lymphoma-specific cytotoxic T-lymphocytes (CTL) were found to express the gamma and delta T-cell receptor and recognize tumor idiotype in a major histocompatibility complex (MHC) unrestricted fashion. METHODS: In this study, the authors established autologous CTL lines and clones specific for a B-cell follicular lymphoma. RESULTS: These CTL are tumor specific and inhibited by antiimmunoglobulin monoclonal antibodies, but unlike the Burkitt lymphoma-specific CTL, they are MHC restricted and express the alpha and beta T-cell receptor. CONCLUSIONS: These studies suggest that different B-cell lymphomas can induce CTL of different phenotypes and MHC restriction.
Subject(s)
Lymphoma, B-Cell/immunology , Lymphoma, Follicular/immunology , Major Histocompatibility Complex/immunology , T-Lymphocytes, Cytotoxic/immunology , Adult , Antibodies, Monoclonal/immunology , CD3 Complex/analysis , CD8 Antigens/analysis , Cell Communication , Cytotoxicity Tests, Immunologic , Female , Humans , Immunotherapy , Lymphoma, B-Cell/therapy , Lymphoma, Follicular/therapy , Receptors, Antigen, T-Cell, alpha-beta/analysis , Remission Induction , T-Lymphocytes, Cytotoxic/chemistry , Tumor Cells, CulturedABSTRACT
More than one-half of adults with non-Hodgkin's B cell lymphomas present with low-grade follicular lymphomas. These tumor cells are found in close association with follicular T lymphocytes and dendritic cells, suggesting that the surrounding cells may play a role in the support of follicular tumors. Supernatants from activated human peripheral blood lymphocytes were found to promote the in vitro proliferation of follicular tumor cells. This effect was entirely due to interleukin 3 (IL-3), a factor generally thought to cause the growth and differentiation of immature hematopoietic cells. IL-3 receptors were detected on fresh isolates of all primary follicular cell tumors examined. These findings suggest that follicular cell tumors may be dependent in vivo on IL-3 and that therapies directed against IL-3, its receptor, or the T cells that produce it may be effective treatment for follicular lymphoma.
