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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute myeloid leukemia preceded by a myelodysplastic syndrome (MDS-AML) is generally regarded as a high-risk type of AML, where remissions are rare and of short duration. Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is suggested to increase the sensitivity of leukemic cells to cycle-specific drugs. In this study 14 MDS-AML patients were given rhGM-CSF together with standard induction chemotherapy (TAD). rhGM-CSF was started 48 h prior to chemotherapy and given for up to 3 weeks. The results showed eight (58%) complete and two (14%) partial remissions, while another two (14%) patients had minor responses. One patient relapsed after 1 year, and then responded a second time. rhGM-CSF had to be stopped owing to local allergic reactions in two patients, both non-responders, but was otherwise well tolerated. Compared with our historical group of controls we found significantly higher remission rates, fewer early deaths, fewer fever days, and fewer days with both neutropenia and thrombocytopenia among the patients treated with rhGM-CSF and TAD. The estimated median over-all survival was 332 days. The severity of initial myelodysplastic changes did not correlate to the outcome of therapy but the degree of peripheral blood dysplasia decreased among responding patients. MDS-AML patients in this pilot study did respond better, and with minimal toxicity, when standard induction chemotherapy was given in combination with rhGM-CSF.
Leukemia 1994 Oct
PMID:Recombinant human granulocyte-macrophage colony-stimulating factor in combination with standard induction chemotherapy in acute myeloid leukemia evolving from myelodysplastic syndromes: a pilot study. 793 58

To assess p53 expression in the hematopoietic cells of the bone marrow in premalignant as well as malignant conditions, we examined immunohistochemically bone marrow biopsies from patients with myelodysplastic syndromes (MDS, n = 51), acute myeloid leukemia (n = 42) and as a nonneoplastic condition, aplastic anemia (n = 20) and samples from individuals who had no hematological disorder (control, n = 12). Nuclear accumulation of p53 protein was found in seven of 51 patients with MDS (14%) and two of 42 acute myeloid leukemia patients (5%), whereas patients with aplastic anemia and control subjects were uniformly negative for p53 protein. In the bone marrow of patient with MDS, p53-positive cells constituted about 5 to 30% of the total bone marrow cells. Two-color immunohistochemical analysis revealed that the p53-positive cells were also positive for the myeloid cell marker. Half of the MDS cases that evolved to overt leukemia (seven of 14) exhibited positive p53 reaction in the bone marrow at the time of initial diagnosis. This frequency (50%) was significantly higher than that in de novo acute myeloid leukemia cases. All of the seven MDS cases that exhibited p53 expression at the time of initial diagnosis developed overt leukemia later, and p53 expression was maintained throughout the progression of MDS. The results suggest that p53 mutations that occur in the myeloid cells in MDS may confer a growth advantage to these cells resulting in the progression to overt leukemia. Thus, immunohistochemical examination for p53 is very useful for predicting the evolution to overt leukemia from MDS.
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PMID:p53 expression in myeloid cells of myelodysplastic syndromes. Association with evolution of overt leukemia. 805 92

We have analysed the mechanism of PMA-induced adhesion of the MDS human leukemia cell line. Affinity to various matrix ligands indicated that PMA induced fibronectin adhesion of MDS cells. This interaction could not be inhibited by RGDS-peptide, therefore it was most probably not mediated by integrins. Rather, both the basal and PMA-induced fibronectin adhesion of MDS cells could be inhibited by heparin and much less efficiently by chondroitin sulphate, suggesting that glycosaminoglycans of proteoglycans may be responsible for the change in adhesive phenotype. PMA stimulation of MDS cells induced a significant increase in proteoglycan biosynthesis. Studies on the glycosaminoglycan pattern of the proteoglycans showed that PMA treatment initiated a shift in glycanation of the MDS-proteoglycans from the predominant chondroitin sulphate-proteoglycans in control cells to a predominant heparan sulphateproteoglycans in adherent cells. These data indicate that protein kinase C, the main target of PMA, may have a profound role in the regulation of glycanation pattern of proteoglycans. Furthermore, such alterations in the cellular proteoglycans may significantly affect the matrix adhesion potential of hematopoietic cells.
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PMID:PMA induces shift from chondroitin to heparan sulphate on proteoglycans correlating with fibronectin adhesion of MDS human leukemia cells. 807 77

Among AML with maturation, acute promyelocytic leukemia (APL) represents a distinct subtype which accounts for 5-10% of all the FAB variants. APL may be recognized by different cytological pictures: (i) Hypergranular APL, the most typical form, showing promyelocytes with cytoplasm packed with purple granules. Most of the primary granules may be incorporated into Auer rods, sometimes stacked in bundles of faggots. (ii) Microgranular APL, characterized by fine dustlike granulation in the cytoplasm; some promyelocytes may even appear agranular by light microscopy. Most of the cells show bilobed or folded nuclei, a picture which may simulate that of acute myelomonocytic leukemia. (iii) Hyperbasophilic form, characterized by cells with high N/C ratio, and strongly basophilic cytoplasm with either sparse or no granules. Conspicuous cytoplasmatic budding is usually present, recalling the feature of micromegakaryocytes. Strong positivity for myeloperoxidase, Sudan black B and chloroacetate esterase represents the typical cytochemical pattern of M3; usually a weaker reactivity may be observed in M3v. However, sometimes a degree of cytochemical heterogeneity of APL cells may be observed, as suggested by cases displaying a strong sodium fluoride-sensitive non-specific esterase reaction. Recently a distinct entity associated with basophilic differentiation has been described. Differential diagnosis of this form with M2-baso subtype and with cases of MDS or AML with basophilia (M2, M4 with t(6;9) translocation) may be obtained by the use of cytochemistry, cytogenetic investigations, and electron microscopy.
Leukemia 1994 Sep
PMID:Acute promyelocytic leukemia: morphological aspects. 809 23

Allogeneic bone marrow transplantation (BMT) is potentially curative therapy for leukemia, lymphoma, and marrow failure. Ninety-two patients have received allogeneic BMT at Oklahoma Memorial Hospital in the past 10 years. Patients with acute myelogenous leukemia (AML; N = 30), chronic myelogenous leukemia (CML; N = 27), acute lymphoblastic leukemia (ALL; N = 12), myelodysplastic syndromes (MDS; N = 8), lymphomas (N = 8), and aplastic anemia (N = 7) were treated with a variety of myeloablative preparative regimens. The major causes of mortality were bacterial, viral, and fungal infections, or disease relapse. Standard and high risk (refractory or multiply-relapsed disease) AML, CML, and ALL patients had median survivals of 14.5 months vs. 3 months, > 18 months vs. 9 months, and 10 months vs. 4.5 months (p = 0.01), respectively. At 7.5 years median follow-up, 71% of the aplastic anemia patients are disease-free. Guidelines for the optimal time for BMT have been developed that encourage transplantation earlier in the course of the disease, thus facilitating better outcomes with these otherwise fatal disorders.
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PMID:Allogeneic bone marrow transplantation: experience with 92 patients. 812 87

Bone marrow monosomy 7 (Mo 7) is associated with childhood preleukemic myeloproliferative and myelodysplastic syndromes (MPS and MDS). We used a series of polymorphic markers to investigate the parental origins of chromosomes lost from the bone marrows of 12 children with MPS/MDS and Mo 7. Eight Mo 7 bone marrows lost a maternal chromosome 7 and four cases lost the paternal homologue. Our data and the results of previous laboratory and clinical observations in the familial and sporadic forms of childhood Mo 7 suggest that chromosome 7 deletions contribute to leukemogenesis by gene dosage.
Leukemia 1994 Mar
PMID:Parental origins of chromosome 7 loss in childhood monosomy 7 syndrome. 812 52

Case 1: A 26-year-old female was admitted because of leukocytosis with 43.6% myeloblasts and 33.6% monocytes, and trilineage myelodysplasia (T-MDS) was detected on bone marrow (BM) smear. She was diagnosed as having acute myeloid leukemia (AML) (M4) with T-MDS and was treated with the Japan Adult Leukemia Study Group (JALSG) AML87 protocol. After completion of chemotherapy, leukemic myeloblasts remained minimally and myelodysplastic changes were still detected on BM smear. She underwent allo-BMT from an HLA-identical sibling. The conditioning regimen consisted of busulfan and cyclophosphamide. Cyclosporine A and short term methotrexate were administered prophylactically for graft-versus-host disease (GVHD). She developed slight veno-occlusive disease and pancytopenia, which improved soon. She is surviving free of disease for 37 months from BMT. Case 2: A 41-year-old male was diagnosed as having T-MDS AML (M2) and achieved complete remission with the AML89 protocol, but relapsed soon. He underwent allo-BMT from an HLA-identical sibling. The conditioning regimen and prophylaxis against GVHD were the same as in case 1. He developed mild acute GVHD, pleural effusion and later mild chronic GVHD. These improved soon. He is surviving free of disease for 21 months from BMT. Some reports suggest that intensive chemotherapy can induce CR in 40%-70% of patients with T-MDS AML, but most of them tend to relapse and rarely survive long. We consider that the best strategy for treatment of T-MDS AML is allo-BMT at present, if suitable donors are available.
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PMID:[Allogeneic bone marrow transplantation for two patients with acute myeloid leukemia with trilineage myelodysplasia (T-MDS)]. 813 16

198 patients with MDS were followed cytogenetically for up to 90 months. There were significant differences in survival between patients with a normal karyotype, single abnormalities (p < 0.05) and multiple abnormalities (p < 0.0001). Survival differences were also seen in each of the FAB sub-types but were only significant in RAEB/RAEB-t and CMML (p = 0.001) where a normal karyotype was associated with prolonged survival. Single and multiple abnormalities of chromosomes 7 and 8 but only multiple abnormalities of chromosome 5 were also associated with reduced survival. 126 patients were successfully investigated on more than one occasion. Karyotype evolution occurred in 15 and was associated with reduced overall survival in those patients who had previously been karyotypically normal (p < 0.05). Median survival following evolution was only 10 months. 29 patients developed leukaemia. The incidence of transformation was significantly higher in patients with multiple abnormalities than in those with a normal karyotype (p < 0.05) or single abnormalities (p < 0.05).
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PMID:Extended cytogenetic follow-up and clinical progress in patients with myelodysplastic syndromes (MDS). 818 Jun 3

Clonality, in MDS, can only be assessed in patients with chromosomal rearrangements or in females heterozygote for X chromosome restricted polymorphisms. "Illegitimate" rearrangements of the immunoglobulin heavy chain (IgH) gene and incomplete rearrangements involving V delta 2 and D delta 3 segments of the T-cell receptor delta (TcR delta) gene are seen in some cases of AML, and AML post-SMD, and can be detected by a sensitive PCR method. In order to analyse clonality in additional cases in MDS, we looked for Ig H and TcR delta gene rearrangement by PCR in 95 cases of MDS. A rearrangement of the Ig H gene was seen in 2 of the 95 patients: in the circulating blood of 2 of the 36 cases of chronic myelomonocytic leukaemia (CMML) and in none of the marrow samples of the other 59 MDS. A rearrangement of the TcR delta gene (involving V delta 2 and D delta 3 segments) was seen in three cases (in the circulating blood of two other CMLL patients, and in the bone marrow of another MDS patient). Twenty-five of the 90 cases of MDS with negative PCR findings, in addition to the five cases with positive PCR findings underwent Southern blot analysis of Ig H and TcR delta genes, and PCR analysis of V delta 1 and J delta 1 segments of the TcR delta gene. Those examinations were normal in all the cases tested. In patients with positive PCR findings for Ig H or V delta 2 D delta 3 rearrangements, the proportion of rearranged cells was evaluated at 1-5% in four cases, and 5-10% in the remaining patient. Because the analysis was performed on total circulating leukocytes or total nucleated marrow cells, the nature of the clonal population in positive cases (lymphoid cells? myeloid cells? blasts?) could not be determined. From a practical point of view, Ig H and TcR delta gene rearrangements seem to very rare in MDS, and cannot be used as clonality markers in most cases.
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PMID:Immunoglobulin and T-cell receptor delta gene rearrangements are rarely found in myelodysplastic syndromes in chronic phase. 818 27

This review deals with the differences between leukemias--induced by alkylating agents as opposed to a "new form" of treatment related leukemia due to prior exposure to epipodophyllotoxins the latter having a short treatment--disease onset interval, absence of a MDS phase, a monocytic component and cytogenetic abnormalities involving the 11q23 band. The link between the existence of oncogenes or tumor suppressor genes located on the involved portion of chromosome 11 and the development of epipodophyllotoxin-related leukemia still needs to be examined. Alkylating agents--induced leukemias have a longer treatment--disease onset interval, have a prior myelodysplastic syndrome, and are most frequent myeloblastic or myelomonocytic in nature. Karyotype analysis reveals partial or complete deletion of chromosomes no. 5 or 7. This form of leukemia is highly resistant to treatment in the majority of cases. Some of the possible molecular mechanisms of leukemogenesis are discussed.
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PMID:A comparative analysis of alkylating agent and epipodophyllotoxin-related leukemias. 822 Jan 58


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