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  • 1
    ISSN: 1432-0584
    Keywords: Acute leukemia ; (4; 11) chromosome translocation ; Early B-precursor cell origin ; Mixed lineage leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Clinical and laboratory features of seven patients with acute leukemia associated with the (4; 11) chromosome translocation are presented. Leukemic blasts of these patients showed lymphoid morphology in 6 (although 1 was treated for monoblastic leukemia 3 years earlier) and monocytoid morphology in 1, were positive for TdT and HD 37 (CD 19) in 6 patients, whereas weak expression of CALLA was seen in only 1 patient and T-lineage-associated antigens in none. Leukemic blasts from four patients showed the simultaneous expression of B-lymphoid and myeloid antigens, suggesting leukemogenesis in a very early multipotent progenitor cell. In 2 patients an isochromosome of the long arm of No. 7 chromosome was found in the leukemic karyotypes in addition to t (4; 11) (q21; q23); in one instance present at diagnosis, in the other one occurring at relapse. In one other patient leukemia karyotype also demonstrated trisomy 8. Leukemic cells of three patients were investigated by molecular genetics and demonstrated immunoglobulin gene rearrangements for the Ig heavy chain sequences but not for the light chain constant regions and T cell receptor sequences. All patients were treated by intensive chemotherapy. Four of the 7 patients are in continuous complete remission. The longest event-free survival time (over 2 1/2 years) was seen in one patient who had also DOWN-syndrome. Including these 7 patients a clinical analysis of 71 patients with t (4; 11) acute leukemia was made, emphasizing the following characteristics at diagnosis: female sex (62%), age under 2 years (49%), leukocyte count over 100×109/1 (61%), splenomegaly (80%), CNS-disease (11%). Survival of over 2 years was reported in less than 15% of the patients. It remains to be seen if risk-adapted treatment can alter the course of this early B-precursor acute leukemia with hitherto very bad prognosis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0584
    Keywords: Key words Childhood ALL ; Immunophenotype ; Leukocyte Common Antigen ; CD45
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To evaluate the expression pattern of the leukocyte common antigen CD45 in acute leukemias and to investigate whether the lack of CD45 expression in childhood acute lymphoblastic leukemia (ALL) is associated with other immunophenotypic features and a distinct clinical behavior, we have carried out extensive immunophenotypic analyses of bone marrow and peripheral blood samples from 638 patients with childhood B-cell precursor (n=529) or T-lineage ALL (n=109). All 638 patients were enrolled in the German ALL-BFM 90 and ALL-BFM 95 trials. CD45 was detected on the surface of childhood ALL cells (cut-off ≥20% positive cells) in only 88.7% (n=566) of all cases. Among 529 patients with childhood B-cell precursor ALL, 12.9% (n=68) did not express CD45, compared with only 3.7% (n=4) of patients with childhood T-lineage ALL (p〈0.001). In the B-cell precursor ALL subtypes, the highest frequency of CD45- cases (15.1%) was observed in common ALL (56/372) compared with only 7.2% in pro-B ALL (3/41) and 7.8% in pre-B ALL (9/116). Assessment of clinical parameters (age, organ enlargement, WBC, etc.) and event-free survival did not reveal significant differences between CD45- and CD45+ patients. Myeloid antigen coexpression was not correlated with CD45 expression. The mean percentage of antigen expression for CD34, CD10, TdT, CD22, and CD24 was significantly higher in children with CD45- B-cell precursor ALL than in those with CD45+ B-cell precursor ALL. In 28 patients with B-cell precursor ALL, cell cycle analyses of freshly isolated leukemic cells were performed with propidium iodide (PI) staining and flow-cytometric analysis. The percentage of cells in S-phase was inversely correlated to the percentage of CD45+ cells (r=-0.48, p〈0.05). With two-parameter analysis of CD45-fluorescein isothiocyanate (FITC)- and PI-stained cells in nine patients with a percentage of CD45+ cells between 40 and 60%, two populations were distinguishable in a single patient. It was shown that the CD45- subpopulation had a higher percentage of cells in S-phase than the CD45+ subpopulation (10.7±4.0 vs. 2.7±1.8, p〈0.007). We conclude that the lack of CD45 expression contributes to the identification of a distinct functional and immunological subgroup of B-cell precursor ALL, but that it has no significant impact on clinical behavior or on therapy outcome in childhood ALL.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 151 (1992), S. S50 
    ISSN: 1432-1076
    Keywords: Acute lymphoblastic leukaemia ; Bone marrow transplantation ; Chemotherapy ; Risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Twenty-five years ago over 90% of children with acute lymphoblastic leukaemia (ALL) died of this disease. Dramatic improvement has been achieved since then by employing risk-adapted, aggressive polychemotherapy protocols. More than 90% of children with ALL treated according to, for example BFM-protocols, have nowadays cure rates in the range of 70%–80%. However, 10% of patients do not initially respond adequately to standard induction chemotherapy. They are characterized by distinct chromosomal abnormalities such as translocation (9; 22) or combinations of early treatment failure and other risk factors as cytogenetic abnormalities, lineage-specific surface markers or tumour load at diagnosis. In this group of patients in first complete remission and certainly in the vast majority of relapsed patients, allogeneic bone marrow transplantation (BMT) has evolved as an alternative approach allowing further intensification of myeloablation and the introduction of an additional antileukaemic alloreactivity. Nevertheless, the decision for a marrow transplant in children has to be made very carefully because of a significant increase in treatment related mortality and BMT-specific risks like acute and chronic graft-versus-host disease with a critical iatrogenic chronic morbidity. This is even more evident, if mismatched or unrelated transplants are being considered. The indications for one or the other treatment modality according to the current BFM strategy are discussed.
    Type of Medium: Electronic Resource
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