To examine the efficacy of intensified maintenance chemotherapy, we conducted a prospective multicenter trial in adult patients with newly diagnosed acute promyelocytic leukemia treated with alltrans retinoic acid and chemotherapy. Of the 302 registered, 283 patients were assessable and 267 (94%) achieved complete remission. Predicted 6-year overall survival in all assessable patients and disease-free survival in patients who achieved complete remission were 83.9% and 68.5%, respectively. A total of 175 patients negative for PML-RAR␣ at the end of consolidation were randomly assigned to receive either intensified maintenance chemotherapy (n ؍ 89) or observation (n ؍ 86). Predicted 6-year disease-free survival was 79.8% for the observation group and 63.1% for the chemotherapy group, showing no statistically significant difference between the 2 groups (P ؍ .20). Predicted 6-year survival of patients assigned to the observation was 98.8%, which was significantly higher than 86.2% in those allocated to the intensified maintenance (P ؍ .014). These results indicate that the intensified maintenance chemotherapy did not improve disease-free survival, but rather conferred a significantly poorer chance of survival in acute promyelocytic leukemia patients who have become negative for the PML-RAR␣ fusion transcript after 3 courses of intensive consolidation therapy. (Blood. 2007;110:59-66)
A new megakaryoblastic cell line (CMK), which also exhibits erythroid and myeloid markers, was established from a Down's syndrome patient suffering from acute megakaryoblastic leukaemia. The CMK cells were found to be positive in reactions with anti-platelet antibodies (anti-glycoproteins IIb/IIIa and Ib, and Plt-1). Platelet peroxidase (PPO) reactivity was found to be associated with the nuclear envelope and the endoplasmic reticulum but not with the Golgi apparatus. Some cells possessed cytoplasmic granules with the characteristics of alpha-granules and demarcation membranes. Karyotyping revealed near-tetraploidy (modal chromosome number of 95; ranging 87-98) and a translocation der(17)t(11;17), also found in the original leukaemic cells, confirming that the cells were derived from the patient's malignant blasts. The CMK cells were also found to be positive in reaction with anti-glycophorin A antibody, as well as with anti-myeloid antibodies (MY4, MY7 and MY9). Treatment of CMK cells with phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) greatly enhanced the reactivity with anti-platelet antibodies, increased the number of cells in which cytoplasm was dissociated into numerous segments and suppressed the reactivity with anti-glycophorin A. The proliferation of CMK cells was stimulated by interleukin-3 (IL-3) and granulocyte-macrophage colony stimulation factor (GM-CSF). This cell line should be a useful tool for analysing the basis of the afferent association between megakaryoblastic leukaemia and Down's syndrome, as well as for further study of megakaryocytic differentiation.
These results indicate that fatal hemorrhage represents a major obstacle in curing APL, and that patients with such high-risk features may benefit from more aggressive supportive care.
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