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81.
Wolff SN; Marion J; Stein RS; Flexner JM; Lazarus HM; Spitzer TR; Phillips GL; Herzig RH; Herzig GP 《Blood》1985,65(6):1407-1411
High-dose (HD) cytosine arabinoside (ARA-C) is more effective treatment than conventional-dose ARA-C regimens for patients with relapsed acute nonlymphocytic leukemia (ANLL). We report here that HD ARA-C given during the first remission of ANLL has resulted in long remission durations and a high proportion of patients who survive more than three years free of disease. From August 1979 to September 1983, 36 adult patients with ANLL in first remission received one to three courses of HD ARA-C (3 g/m2 by one-hour infusion every 12 hours for 12 doses on days 1 through 6) alone or with daunorubicin (30 mg/m2 for two or three doses on days 7 through 9). Three patients died of sepsis or hemorrhage during consolidation, and 14 patients have relapsed from five to 48 months after diagnosis. The remaining 19 patients are in continued complete remission (CCR) from 11 to 62 months. Denoting all deaths in remission as relapse, the actuarial probability of CCR is 42% at 62 months, with an apparent plateau in the survival curve. Of the first 22 patients treated, ten remain in CCR from 37 to 62 months with no therapy for at least three years. Due to its heightened anti-leukemic activity, HD ARA-C allows brief but effective consolidation of ANLL in first remission, with long-term disease-free survival comparable to other approaches. 相似文献
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83.
Ways DK; Qin W; Riddle RS; Garris TD; Bennett TE; Steelman LS; McCubrey JA 《Blood》1991,78(10):2633-2641
FD/PMA is a subclone of the interleukin-3 (IL-3)-dependent, FDC-P1 cell line, which proliferates in response to either 12-O- tetradecanoylphorbol-13 acetate (PMA) or IL-3. While several endogenous substrates were phosphorylated in response to protein kinase C (PKC) activation in FDC-P1, phospholipid-dependent phosphorylation in the FD/PMA grown in PMA was not observed. Basal, phosphatidylserine- independent, and diolein-independent phosphorylation of cytosolic substrates with molecular weights of 17, 52, 57, and 105 Kd were enhanced in FD/PMA cells grown in PMA as compared with FDC-P1 cells cultured in IL-3. Phosphorylation of a 105-Kd substrate was enhanced in the particulate fraction of FD/PMA cells maintained in PMA. The 17-Kd substrate in FD/PMA cells comigrated with a substrate phosphorylated in a PKC-dependent manner in FDC-P1 cells. Phosphorylation of the 52- and 57-Kd substrates, but not of the 17-Kd substrate, was inhibited by H-7 and staurosporine. A portion of the PMA-induced cytosolic kinase activity coeluted with PKC on diethyl aminoethyl chromatography. While FD/PMA cells cultured in PMA contained negligible PKC-dependent phosphorylation of endogenous substrates or histone, alpha and epsilon PKC isoforms were detected by Western blot analysis. PKC phosphotransferase activity was observed in FD/PMA cells grown in PMA when peptides corresponding to residues 720 to 737 of PKC-epsilon or residues 4 to 14 of myelin basic protein were used as substrates. These data indicate that maintenance of FD/PMA cells in PMA stimulates proliferation and markedly alters PKC substrate specificity. Generation of at least two phospholipid-independent kinases occurs in PMA-treated cells. 相似文献
84.
Somatic cell hybrid analyses of hematopoietic differentiation 总被引:1,自引:0,他引:1
A differentiated cell expresses an entire set of specialized features. Somatic cell hybridization provides a method to examine control of gene regulation. We studied the expression of tissue-specific features in hybrids between human promyelocytes (HL-60) and human Burkitt's lymphoma cells (P3HR-1). Two hybrid lines, HP-1 and HP-2, and 18 hybrid clones were established and confirmed by karyotype, isozyme, and surface antigen analyses. The hybrids extinguished the 10 myeloid (HL- 60) features that we examined including myeloid morphology, histochemistry, and functions that included response to colony- stimulating factor and ability to differentiate to granulocytes or macrophages. In contrast, the hybrids synthesized immunoglobulin and expressed Epstein-Barr nuclear, early, and viral capsid antigens similar to the P3HR-1 lymphoid parental line. Results are contrasted to the findings when P3HR-1 lymphocytes are fused to human erythroid- myeloid cells (K562). Taken together, our results suggest that phenotypic differences between human myeloid and lymphoid cells in the hematopoietic lineage involve mutually exclusive programs and may possibly be mediated by the activity of diffusible, transacting molecules. 相似文献
85.
Chronic myelocytic leukemia (CML) may display a lymphoproliferative phase (lymphoid blast crisis) that is generally of B cell phenotype. Since lymphoproliferative disorders may occur following bone marrow transplantation (BMT), it may be difficult to distinguish posttransplant relapse of CML lymphoid blast crisis from de novo lymphoproliferation. Lymphoid blast crisis cells from a patient with CML displayed immunoglobulin heavy chain gene (C mu) rearrangement before BMT. Following BMT the patient developed a lymphoproliferative disorder involving multiple organs. Clonal rearrangement of C mu was demonstrated in several involved tissues. The rearranged C mu restriction fragment was distinct from that displayed before BMT. Additionally, rearrangement of the breakpoint cluster region (bcr) was demonstrated in the pretransplant blast crisis sample, but not in the posttransplant lymphoproliferation samples, thus confirming that these lymphoproliferative disorders were distinct. Molecular genetic techniques offer powerful diagnostic tools for monitoring the course of patients with CML undergoing BMT. 相似文献
86.
The management of stage I--II Hodgkin's disease with irradiation alone or combined modality therapy: the Stanford experience 总被引:1,自引:0,他引:1
At Stanford University, between 1968 and 1978, 230 patients with pathologic stage I--II Hodgkin's disease were treated on prospective clinical trials with either irradiation alone or irradiation followed by 6 cycles of adjuvant combination chemotherapy. The actuarial survival at 10 yr was 84% for patients in either treatment group. Freedom from relapse at 10 yr was 77% among patients treated with irradiation alone and 84% after treatment with combined modality therapy [p(Gehan) = 0.09]. Freedom from second relapse at 10 yr was 89% and 94%, respectively [p(Gehan) = 0.56]. Several prognostic factors were evaluated in order to identify patients at high risk for relapse or with poor ultimate survival after initial treatment with irradiation alone. Systemic symptoms, histologic subtype, age, and limited extranodal involvement (E-lesions) did not affect the prognosis of patients and failed to identify patients whose survival could be improved by the routine use of combined modality therapy. Patients with large mediastinal masses (mediastinal mass ratio greater than or equal to 1/3) had a significantly poorer freedom from relapse when treated with irradiation alone than when treated initially with combined modality therapy [45% versus 81% at 10 yr, p(Gehan) = 0.03). The 10-yr survival of these patients, however, was not significantly different (84% versus 74%). The implications of these observations on the management of patient with early stage Hodgkin's disease are discussed. 相似文献
87.
Snyder DS; Negrin RS; O'Donnell MR; Chao NJ; Amylon MD; Long GD; Nademanee AP; Stein AS; Parker PM; Smith EP 《Blood》1994,84(5):1672-1679
Ninety-four consecutive patients with chronic myelogenous leukemia in first clinical chronic phase, median age of 34.0 years (range, 6.8 to 52.4 years), with a histocompatible sibling donor, were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation (BMT). The median time from diagnosis to BMT was 7.0 months (range, 2.3 to 72.0 months). Sixty patients were treated before BMT with hydroxyurea alone, four patients with busulfan alone, one patient with interferon alone, and the other 29 patients were treated with various combinations of these drugs. Cumulative probabilities of overall survival, event- free survival, and relapse at 5 years were 73%, 64%, and 14%, respectively. The median follow-up time for surviving patients was 38 months, ranging from 12 to 88 months. By stepwise Cox regression analysis, significant prognostic variables were age at transplant, acute graft-versus-host disease > or = grade II, cytomegalovirus- associated interstitial pneumonitis, and years from diagnosis to BMT. 相似文献
88.
Chronic myelocytic leukemia (CML) is a clonal disorder involving neutrophil, monocyte, erythrocyte, and platelet precursors. In order to determine if the eosinophils are also involved in the leukemic clone, we purified the eosinophils from a woman heterozygous for the common electrophoretic variants of the G6PD gene. Only type B enzyme was demonstrable in the eosinophils, neutrophils, and red cells, but both A and B enzymes were found in the fibroblasts. The data provide evidence that the eosinophil is involved in the malignant clone. 相似文献
89.
90.