Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Survival, causes of death and hospitalization have been studied in 99 patients with the myelodysplastic syndrome. The median survival of the patients was 702 days, and the 10 year actuarial survival only 10 per cent, which is not significantly better than the corresponding figures in the remission stage of AML. Although MDS-patients who developed acute leukemia had significantly (p less than 0.05) more platelets, they also had significantly (p less than 0.05) more major bleeding as a contributory cause of death than patients who did not develop leukemia. Bleeding seems to be diagnosed only in 12 per cent in vivo, whereas major bleeding is found at autopsy in 38 per cent of the patients. The patients who did not develop leukemia died significantly (p = 0.018) more often of cardiovascular causes. MDS patients spend one sixth of their remaining life in hospital, on an average. This is true both for those who develop leukemia and for those who do not. The terminal hospital stay lasts an average of 24 days, which is comparable to the figure for myeloma.
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PMID:Survival, hospitalization and cause of death in 99 patients with the myelodysplastic syndrome. 281 15

We have examined the efficacy of various drugs in 44 patients with MDS and found the different effectiveness which depends on the type of MDS. Namely, RA appears to respond to steroid hormone, androgen, and/or vitamin D3, regardless of single or combined use. In particular, it is obvious in androgen, and as our previous reports, high content of acidic ferritin in RBC with RA have changed to more basic ones by treatment with androgen. On the contrary, these drugs were not effective on RAEB, RAEB-T, and CMML. A long-term observation is needed to determine whether the prolonged or decreased occurrence of leukemia could be obtained in the effective cases with RA. Most of the cases who did not develop overt leukemia during this study died of bleeding or infections due to thrombocytopenia or leukocytopenia, thus indicating that supportive therapies are important in patients with MDS. Since it has recently been reported that recombinant G-CSF or GM-CSF is helpful to increase the number of leucocyte and to enhance their functional recovery in MDS, these factors may be powerful agents against infections when they are carefully used with regard to the activation of leukemic clones.
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PMID:[Therapy of the preleukemic state: effect of androgens on refractory anemia]. 283 1

This thesis is a survey of nine previously published articles on MPO deficient PMN. The incidences in leukaemia and allied disorders of the presence of this abnormal subpopulation of mature neutrophils and the relationship to clinical course in AML, susceptibility to infections in AML, FAB classification in AML and MDS, cytogenetically defined aberrations in MDS and morphometrical characteristics were investigated. The aims of the studies were to examine the diagnostic as well as the prognostic value of the parameter, to examine the usefulness of the parameter as an predictive indicator of CR and relapse in AML and to examine the concept that MPO deficient PMN may originate from leukaemic precursors. MPO deficient PMN were found to occur in a minor number (less than 4% of the total number of PMN) in normal humans and the incidences of an abnormal number (greater than 4%) were found to be about 40% in AML (I, II, III, IV, VIII), 60% in CML (I, VII), 30% in MPD other than CML (VII) and 30% in MDS (V). The highest incidences in AML were found in the FAB subtypes possessing the most myeloid differentiation potential i.e. FAB M2 and FAB M4 (IV). In ALL, CLL, HCL, Hodgkin's disease, anaemia not related to leukaemia and leukaemoid reactions the incidences all were 0% (I, unpublished data). The abnormal MPO deficient PMN subpopulation, if present, disappeared when CR was achieved and reappeared when relapse eventually was developed (II, VIII). In both situations serial determinations showed that the change occurred before the usual routine blood examinations predicted CR and relapse; several days and several months prior, respectively (VIII). The probability of obtaining CR was lower in the AML patients with the abnormal subpopulation and the risk of developing relapse higher than in AML patients without the anomaly (II, VIII). These differences were not statistically significant, however. AML patients, showing an increased number of MPO deficient PMN, revealed a statistically significant increased susceptibility to infections (P less than 0.01) during the preremission phase accounting for 18% to 67% of the total number of infections in this period (III). This increase was positively correlated to the extent of the anomaly (P less than 0.002). The spontaneous occurrence of a subpopulation of MPO deficient PMN in MDS went together with a simultaneous progression in cytogenetically determined clonal chromosomal aberrations and were related to progression in FAB subtype as well (VI). Morphometrically MPO deficient PMN were characterized by a decreased total cell size and an increased nucleus size of the projected images (IX).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Myeloperoxidase deficient polymorphonuclear leucocytes in leukaemia and allied disorders. 285 15

We treated 11 patients who had Philadelphia-chromosome-positive chronic myelogenous leukemia with natural interferon alpha (human lymphoblastoid interferon; HLBI). HLBI was given at 6-12 X 10(6) u/day i.m. or i.s.c. during induction therapy. Nine patients responded to the treatment, of whom 7 had hematologic remission and 2 had partial remission. Six patients with MDS or hypoplastic leukemia, and 3 patients with overt leukemia from MDS were treated with recombinant interferon gamma (GI-3). GI-3 was given at 0.4 X 10(6) u/m2 of body-surface area per day i.s.c. or i.v. for 4-6 weeks. In 2 patients with RAEB and hypoplastic leukemia, the blast cell count in bone marrow decreased from 8-16% to 2-3% after 4 weeks of administration. In another patient with hypoplastic leukemia, blast cells in the marrow did not decrease, but anemia was improved without transfusion, increasing the bone marrow NCC and erythroblast count. In patients with overt leukemia and CMML, no clinical effect was obtained. Interferons can therefore be offered to patients in a preleukemic state.
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PMID:[Clinical investigation of interferons in the preleukemic state (CML and MDS)]. 313 93

A low-dose Ara C (LDAC) regimen (0.2 mg/kg/d) was tried in two groups of eleven patients with MDS and in ten with hypoplastic leukemia (HL) proven by biopsy. In HL, seven patients achieved complete remission (CR), but CR duration was rather short (4-9 months). Some cases showing relapse could be induced back into CR by the LDAC regimen. All patients showed marked bone marrow aplasia before reaching CR. Therefore, the main effect of LDAC was considered to be cytotoxic activity. In one HL patient, the karyotype of 47, XX, +8 at diagnosis was converted to normal, 46, XX after CR. In MDS, there were no CR cases but five patients partially responded to the LDAC regimen. One patient died of cerebral hemorrhage soon after LDAC treatment. Three patients developed overt leukemia and in one of them the disease was well controlled by LDAC over thirty months. One patient with typical refractory anemia with excess blasts (RAEB) suffered severe bone marrow aplasia after 12 mg/d for 10 days of LDAC, but one month later his hematopoiesis gradually recovered and reached a normal hemoglobin level (12 g/dl). However, all of his karotypes showed 45, XY, -7 at that time. LDAC regimen is effective, especially for HL, but may have a limited effect on MDS.
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PMID:[Effect of low-dose Ara-C regimen on myelodysplastic syndrome (MDS)]. 316 77

The available data fail to support a standard therapy for MDS. Any therapy should therefore, include participation in a well designed clinical trial. The MDS include patients with a variety of prognoses. Since most studies show that death from infection and bleeding are more likely than progression to frank leukaemia, attention to supportive care is crucial for all patients with MDS. Some patients with MDS may be successfully supported with transfusions and observation for prolonged periods. Patients with significant comorbid disease or patients without increased marrow myeloblasts are good candidates for this conservative approach. Conversely, young patients have a better likelihood of benefit from aggressive therapy, and intensive chemotherapy or allogenic bone marrow transplantation should be considered. Patients with preleukaemia related to prior cytotoxic therapy are another poor prognosis group for whom aggressive therapy may be the best alternative. Therapy with low-dose ara-C or other differentiating agents should be considered investigational and unproven until comparative trials can demonstrate a definitive survival advantage. In addition to comparative trials, innovative clinical studies are needed to address differentiation as an in vivo mechanism of action and its importance in MDS therapy.
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PMID:The treatment of myelodysplastic syndromes. 355 48

A deletion of the long arm of chromosome #5 (5q-) occurs nonrandomly in human malignancies. As a rule, the deletion is interstitial; the distal breakpoint by conventional techniques is usually in band q32, the proximal breakpoints in q12 or q14. Variant breakpoints occur in less than 10% of all cases. As the sole anomaly, 5q- is characteristically found in refractory anemia with or without excess of blasts. It can occur as the sole anomaly in de novo or secondary acute nonlymphocytic leukemia, but is usually accompanied in those disorders by other chromosome changes that are also nonrandomly distributed. In addition, it can be found in lymphoproliferative disorders, and occasionally, also in solid tumors. The 5q- myelodysplastic syndrome typically occurs in older age groups, particularly in females. Characteristic features are macrocytic anemia, normal or elevated platelets in the presence of megakaryocytic anomalies, and a mild clinical course. In cases with 5q- only, transformation into ANLL occurs rarely. Additional chromosome anomalies and male sex are prognostically unfavorable signs. Sex ratio is also at the disadvantage of females in de novo 5q- ANLL, and the latter disorder can occur without being preceded by a myelodysplastic phase. A myelodysplastic phase usually precedes 5q- secondary leukemia, in males as well as in females, and additional chromosome anomalies, especially of chromosome #7, are almost invariably present in those cases. We conclude that 5q- is the most frequently occurring single chromosome anomaly in secondary leukemia. Furthermore, the resemblance between de novo and secondary 5q- MDS and ANLL is striking; clinically, as well as cytogenetically, they are indistinguishable, suggesting that all de novo cases may be due to environmental (chemical) carcinogens. Response to treatment and prognosis are very poor with current therapeutic regimens in de novo as well as in secondary 5q- ANLL. Morphologically, these ANLLs fall into all FAB categories. There is considerable evidence to show that the 5q- anomaly occurs in a myeloid precursor stem cell. The occasional occurrence in lymphoid malignancies, of B cell as well as T cell type, suggests that, as in Ph-positive disorders, a common progenitor stem cell may be affected in 5q- also. The 5q- lymphoid malignancies, however, are much more rare; it is not clear at the present time whether or not a 5q- counterpart of Ph-positive ALL exists, and mixed lymphoid-myeloid 5q- disorders have not yet been documented.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The 5q-anomaly. 389 Oct 74

Serial haematopathological and cytogenetic studies disclosed three distinct clinical phase in a case of refractory anaemia (RA), a subtype of myelodysplastic syndrome (MDS; FAB group, 1982): first, chronic MDS phase (1 year 10 months) with karyotypic abnormality (45, XY, --7) (Clone I); second, hypo-aplastic phase concurrent with first clonal evolution (45, XY, --7, 12p--) (Clone II); third, acute myelomonocytic leukaemia phase (6 months) with second clonal evolution (45, XY, --7,t (1q --; Bq+), Bq --, 12p --) (Clone III). In the second phase the bone marrow became almost aplastic as Clone II expanded progressively, indicating simultaneous occurrence in Clone II stem cells of growth advantage for self-renewal function over Clone I and normal stem cells, and arrest of differentiation. These observations support the hypothesis that leukaemic change in MDS, at least in RA, occurs by stepwise clonal evolution(s), not by progressive arrest of differentiation in original MDS clone.
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PMID:Sequential karyotypic evolutions and bone marrow aplasia preceding acute myelomonocytic transformation from myelodysplastic syndrome. 659 91

Bone marrow smears of 263 protocol patients with acute nonlymphoblastic leukemia (ANLL) and related disorders treated between 1970 and 1978 at MSKCC were reviewed blindly by two pairs of hematomorphologists and classified according to the FAB system. It was found necessary to add one category (MO) for acute undifferentiated leukemia and to define more precise quantitative criteria for the categories M1-M6 based on bone marrow differential counts. Using this modified FAB classification, agreement between the two observer groups based on morphology alone was 69%. Cytochemical stains were essential in establishing the diagnosis in 9%, led to a change of diagnosis by one observer team in 14%, and helped to confirm the diagnosis in 32% of cases. Complete remission rates, remission duration, and survival were not significantly different among diagnostic categories. Myelodysplastic syndromes (MDS: M6, RAEB, CMML; CR rate 48%) and ANLL without differentiation (M0, M1, M5a; CR rate 50%) appeared to do less well than ANLL with partial differentiation (M2, M3, M4, M5b; CR rate 59%) on all three protocols studied. Auer rods were present in 53% of all cases with 63% in the myeloid categories (M1-M4). Auer rods were found to be the single most important prognostic parameter in this study, with a complete remission (CR) rate of 68% in the Auer-rod-positive and of 40% in the Auer-rod-negative group (p < 0.0001). Survival was significantly longer for patients exhibiting Auer rods (p < 0.0002). Median survival for the total group was 13.5 mo and median remission duration for responders was 11.5 mo in the Auer-rod-positive group compared to 6.2 mo median survival and 9.2 mo median remission duration for the Auer-rod-negative group.
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PMID:Morphological classification, response to therapy, and survival in 263 adult patients with acute nonlymphoblastic leukemia. 693 77

We conducted a prospective, multicenter pilot study of remission induction therapy in patients with poor prognosis MDS and AML evolving from a preceding phase of MDS. Fifty evaluable patients from 15 institutions were treated with one or two remission-induction courses consisting of i.v. idarubicin 12 mg/m2/day on days 1, 2, and 3 combined with a continuous i.v. infusion of cytarabine of 200 mg/m2/day on days 1 to 7. Of the 27 complete remitters (54%), 23 received a consolidation course which was identical to the remission-induction course except for the idarubicin 12 mg/m2 which was given on day 1 only. Fifteen patients received maintenance therapy consisting of six courses of cytarabine 10 mg/m2, s.c. twice daily, for 14 days. Two complete remitters were allografted and five patients received an ABMT. The median survival of all 50 treated patients was 14 months. The median duration of disease-free survival was 11 months with two patients in CR more than 2 years after entering CR. Twenty-four of the 27 remitters have relapsed. Four patients died during remission-induction therapy, but no patient died as a result of persisting hypoplasia. No fatal complications occurred during the consolidation and maintenance courses. Age and stage of disease had no significant impact on CR rate nor on remission duration. The CR rate was significantly (P = 0.03) higher in patients with only normal metaphases compared to patients with cytogenetic abnormalities. The DFS at 2 years was 33 vs 8%, respectively, for patients without or with cytogenetic abnormalities (P = 0.02). This study shows that patients below the age of 60 years with poor risk features are candidates for treatment with combination chemotherapy. A complete remission rate of more than 50% may be expected. Maintaining remission after remission-induction chemotherapy is a difficult issue. Patients not eligible for allogeneic BMT may be treated with intensive post-remission chemotherapy or autologous BMT.
Leukemia 1995 Nov
PMID:Intensive chemotherapy for poor prognosis myelodysplasia (MDS) and secondary acute myeloid leukemia (sAML) following MDS of more than 6 months duration. A pilot study by the Leukemia Cooperative Group of the European Organisation for Research and Treatment in Cancer (EORTC-LCG). 747 66


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