[Efficacy of pipobroman in the treatment of essential thrombocythemia].
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Biomedical subjects
Publications and source records attributed to F Bauters.
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Twenty-nine adult patients with primary myelodysplastic syndromes (MDS) and an excess of marrow blasts were treated by aggressive chemotherapy while still in MDS phase (20 cases) or after progression to ANLL (9 cases). Median age was 47.5 (range 18-68). Twenty-eight patients received a combination of Rubidazone and Ara C and 1 received High dose Ara C. Fourteen patients (48%) achieved complete remission (CR), 5 (17%) were treatment failures (F) and 10 (35%) died during therapy induced aplasia (DA). Median disease free survival was 8.5 months. Median survival of the whole population was 6 months from the onset of treatment, and 17 months in patients achieving CR. These results were significantly less favorable than those obtained at our institution in de novo ANLL with the same chemotherapy regimens. No statistically significant prognostic factors of treatment outcome emerged but patients with normal cytogenetic findings seemed to have both a higher CR rate and longer remissions than patients with abnormal karyotypes. Patients under 50 did not have higher CR rates than older patients, although they had longer remissions (with 3 out of 6 CRs exceeding 2 years). Finally, treatment outcome and survival were identical in patients treated in the MDS phase and in those treated after progression to ANLL. Combination chemotherapy is a highly toxic approach in MDS and essentially seems to benefit younger patients with a normal karyotype, in whom some long remissions can be obtained.
Between 1980 and 1986, we diagnosed refractory anaemia (RA), according to the FAB classification, in 69 patients, who constituted 22% of the 312 cases of myelodysplastic syndromes (MDS) seen over that period. The haematological features were variable, with pancytopenia in 14 cases (20%), bicytopenia in 24 (36%) and mono-cytopenia in the remaining patients, including 21 (30%) cases of anemia alone, 8 (12%) cases of refractory neutropenia and 2 (3%) cases of refractory thrombocytopenia. Myelodysplastic features were also quite variable, involving one, two or all three lineages. In patients with a single cytopenia or only one dysplastic lineage, FAB criteria appeared insufficient for adequate inclusion among RA and we suggest more precise diagnostic criteria, resulting from the utilization of cytogenetics, ferrokinetics, progenitor cultures and perhaps molecular biology, in such cases. Median survival was 42 months. 12 patients (17%) progressed to RAEB (of whom 7 finally developed ANLL) and 4 patients (6%) to CMML. In spite of the heterogeneity of haematological features, only two factors were associated with poor prognosis, namely age greater than 70 yr at diagnosis and haemoglobin less than 10 g/dl, whereas, to a lesser extent, neutropenia was associated with progression to RAEB.
Adult chronic myelomonocytic leukemia (CMML), as defined by the French-American-British (FAB) group, is associated with a variable survival, ranging from a few weeks to several years. From 1971 to 1986, we made the diagnosis of CMML in 107 cases, according to FAB criteria (except for patients with 20% to 30% bone marrow [BM] blasts who were also included). Median survival was 30 months (range 1 to 81 months) and life expectancy did not seem to be influenced by treatment modalities other than supportive care. Eighteen patients (17%) progressed to acute nonlymphoblastic leukemia (ANLL). In a Cox regression model, main factors associated with short survival were: an excess of marrow blasts (P = 10(-6], anemia (P = .17 x 10(-5], high peripheral blood (PB) monocytosis (P = .26 x 10(-5], presence of PB blasts (P = .49 x 10(-4], and to a lesser extent hyperleukocytosis (P = .001), presence of PB immature granulocytes, thrombopenia, and splenomegaly. Survival (less than 1 year v greater than 1 year) could be predicted at diagnosis in a multivariate stepwise discriminant analysis using two parameters only (percentage of BM blasts and hemoglobin level), with 82% accuracy. Among patients surviving greater than 1 year, initial PB leukocyte count was higher in patients with intermediate survival (12 to 42 months) than in long survivors (greater than 42 months) and was the only discriminating factor between these two subgroups in multivariate analysis. Abnormal cytogenetic findings and increased lysozymuria were also poor prognostic factors, but could not be analyzed in the multivariate models, as they were determined in a minority of patients. Parameters associated with subsequent progression to ANLL included younger age at diagnosis, thrombopenia, increased BM blasts, and splenomegaly. Our study allows for the identification of subgroups with different prognoses in CMML, on the basis of a small number of hematologic parameters, particularly initial percentage of BM blasts, hemoglobin level, and leukocytosis. These subgroups probably require different therapeutic approaches.
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Cytogenetic analysis was performed in 47 newly diagnosed patients with agnogenic myeloid metaplasia (AMM); 32 had a normal karyotype (68%, group I), whereas 15 had clonal abnormalities (32%, group II). The most frequent abnormal findings were a 20q- deletion in six cases (either alone or within complex anomalies), interstitial 13q- deletion in three cases (and monosomy 13 in one case), and acquired trisomy 21 or 21p+ in three cases. Four cases exhibited complex aberrations involving several chromosomes, sometimes with a mosaicism. In two patients with an initial abnormal karyotype, further cytogenetic analysis during the disease course showed the appearance of additional clonal anomalies, and particularly of a probable Philadelphia (Ph1) variant in one case. Treatment was essentially supportive. Survival was significantly shorter in group II (median, 30 months) compared with group I (median, not reached at 6 years; P = .015). In univariate analysis, other parameters significantly associated with a poor prognosis (P less than .05) were higher age, anemia, and increased percentage of circulating blasts. However, in a multivariate analysis, only cytogenetic abnormalities and age retained their independent prognostic value.
A case of secondary chronic myelomonocytic leukemia with t(1;7)(p11;p11) is reported. This patient had been treated without interruption with chlorambucil for multiple sclerosis since 1970. The t(1;7), to our knowledge, is the first described in secondary chronic myelomonocytic leukemia.
A case of chronic myelogenous leukemia in an elderly man with a new translocation, t(8;11)(q24;q13), associated with a Philadelphia t(9;22) translocation is described. The clinical and hematologic aspects of the disease did not seem to differ from those of the usual cases of chronic myelogenous leukemia except for a basophilic blast crisis.
We report a promyelocytic blast crisis in a case of Ph-positive thrombocythemia with both t(9;22) and t(15;17). Our patient confirms the specificity of t(15;17) in malignant proliferation of promyelocytes and suggests its appearance as a second genetic event in the genesis of blast crisis occurring in a Ph-positive clone.
In three cases of acute nonlymphocytic leukemia we observed a translocation (8;16)(p11;p13); in one case it was the sole karyotypic change and in the other two cases it was associated with other structural anomalies. All three cases were nonhyperleukocytic myelomonocytic leukemias with erythrophagocytosis by some blast cells and cytochemistry results consistent with leukemic proliferation of a common monocytic-granulocytic precursor. The importance of this translocation is discussed, and the implication of band 16p13 in myelomonocytic leukemia is stressed.
We report 60 cases of chronic and subacute myelomonocytic leukaemias (CMML and SMML) in the adult, using the FAB group criteria. The M/F sex ratio was 3.3 and the mean age 67.5 years. Splenomegaly was found in 32% of cases, hyperleucocytosis in 52% of cases and mean blood monocytosis was 4.3 X 10(9)/l. Marrow smears showed an excess of blasts in 57% of patients, a moderate increase in monocytes in most cases and frequent myelodysplastic features. An increase in serum lysozyme and polyclonal hypergammaglobulinaemia were usual and clonal cytogenetic anomalies found in about half of the patients tested. Treatment was usually palliative and the median survival was 28 months, a blastic transformation being responsible for a third of the deaths. Prognostic factors at diagnosis were analysed retrospectively in the 46 patients who had sufficient follow up. Percentage of marrow blasts haemoglobin level and blood monocytosis at diagnosis, were subject to multivariate analysis, resulting in a discriminant 'score'. This allowed assignment of each patient into one of two prognostic subgroups (10.9% probability of error): a poor prognosis one, with a life expectancy of less than 1 year and a high risk of acute transformation (subgroup termed SMML) and a better prognosis subgroup (termed CMML), with some CMML patients surviving over 5 years.
16 adult idiopathic thrombocytopenic purpura (ITP) patients, with mean age 51 years, were treated by 5 weekly slow intravenous infusions of vinblastine (0.1 mg/kg). When a complete or partial response (CR or PR) was obtained, slow infusions were repeated at 2-weekly then monthly intervals, as maintenance therapy. In 4 cases with ITP of recent onset, but presenting contraindication or failure to prednisone and high dose intravenous immunoglobulins, CR was obtained in all patients after 4 to 15 days (mean 9.5). Only one of these patients relapsed. In 12 cases of refractory chronic ITP (of whom 10 had been splenectomized), there were 2 CR, 6 PR and 4 failures. The 8 responding patients had a mean interval to response of 20 days. The 6 PR were short and did not exceed 15 days. Our results do not support a superiority of this treatment compared to other modes of administration of vinca alkaloids in ITP (intravenous bolus, vinca loaded platelets).
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We report on a 74-year-old male patient who presented with jaundice, highly increased unconjugated bilirubin and slight nonregenerative anemia. Ferrokinetic studies demonstrated ineffective erythropoiesis and red cell survival, studied by 51 Cr, showed moderately increased hemolysis. Other findings showed no evidence of an underlying myelodysplastic syndrome but strongly favored the autoimmune origin of the disorder, with immunologic destruction of erythroblasts (and to a far lesser extent erythrocytes) by autoantibodies.
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In a cytogenetic study of 54 patients with acute monoblastic leukaemias (AML5) two had a (9;11) (p21;q23) translocation. In addition to the clone, with t(9;11), both patients had a second clone with t(9;11) and trisomy 8. These two patients were aged 23 and 35 years at diagnosis and were classified as M5a in the FAB formulation. A complete remission was achieved in each case, persisting after 19 and 18 months respectively (autograft for one patient). Whereas chromosome 11 anomalies are involved in 13% of all AML5 cases, t(9;11) is less frequently encountered (3.7% in our experience).
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