[Long-term remissions in postmyelodysplasia acute myeloblastic leukemia].
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Biomedical subjects
Publications and source records attributed to E Prieto.
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Intradermally injected tumor necrosis factor alpha (TNF-alpha) mimics the effects of UV B light (UVB) radiation and neutralizing anti-TNF-alpha antibodies abolish the deleterious effects of UVB on induction of contact hypersensitivity suggesting that TNF-alpha is the major mediator of UVB effects on cutaneous immunity. In the present study we have shown that in lipopolysaccharide-sensitive inbred strains of mice, the ability of acute, low-dose UVB radiation to impair the induction of contact hypersensitivity to dinitrofluorobenzene is genetically determined by polymorphic alleles at the Tnf alpha locus. We have analyzed by the sequence analysis and restriction fragment length polymorphism the Tnf alpha alleles of numerous inbred strains expressing UVB susceptibility (UVB-S) and UVB-resistance (UVB-R). The Tnf alpha alleles of all UVB-R, but not UVB-S, strains contain a BamHI site in the first intron. Moreover, the 5' regulatory region of the Tnf alpha allele of UVB-R mice possesses a (CA)14 minirepeat that is located immediately 5' of the cytokine response element nearest the tumor-associated transplantation antigen box. By contrast, the Tnf alpha alleles of UVB-S mice display repeats of < > 14 at this site. It is proposed that the unique microsatellite of UVB-R mice impairs transcriptional efficiency at Tnf alpha compared to UVB-S mice and that the quantitative difference in Tnf alpha produced intracutaneously in response to UVB radiation accounts for the phenotypic traits of UVB-R and UVB-S.
Auto-immune haemolytic anaemia (AIHA) has been found in a case of alpha-interferon treatment. Serum antibody and eluate were positive in the absence of the drug. Although the patient recovered after the treatment was stopped, DAGT remained positive for at least 8 months. The mechanism proposed to explain why this drug induced AIHA is similar to that proposed for alpha-methyl-dopa. Drugs could alter the red cell membrane and impair the immune system. Such changes have been observed with alpha-interferon and were related with increased autoimmunity.
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Myelodysplastic syndromes represent an entire group of clonal panmyelopathies with very distinct evolutionary pathways. Their common denominator, however, is a self-maintained functional failure of the myeloid hemopoiesis which tends to evolve into severe non-lymphoid leukemia (SNLL) in 20-30% of the cases. First, the prognostic value of each the following is reviewed: the morphological classification F.A.B., the stratification system for "Bournemouth group", the abnormal placement of immature myeloid precursors (ALIP) in bone marrow, and cytogenetic changes. Second, the therapeutic potential for each of the following is assessed: vitamin and support treatments; suprarenal steroids; conventional androgens and danazol; agents of cellular differentiation (cytosine arabinoside in low doses, retinoid acids, vitamin D3, etc.). Finally, the role of aggressive chemotherapies (in succession or unrelated to marrow transplant) in the eradication of myelodysplastic clone or post-myelodysplasia SNLL is examined.
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PURPOSE: To retrospectively analyse all the patients diagnosed and treated in the same hospital for acute lymphoblastic leukaemia (ALL) in whom therapy was suppressed after sustained complete remission (CR) for a variable period. PATIENTS AND METHODS: Eighty cases of ALL treated at the Jiménez Díaz Foundation between 1968 and 1991 were revised. Treatment had been suppressed after 60 months of maintained CR (1968-1974) or after 28 months (1986-1991), with a median follow-up after suppression of 6 years. All the patients had been treated with several protocols (FJD-68, FJD/BFM, APO, BFM-83, BFM-86 and BFM-90). Maintained CR, relapses and course after therapy cessation were analysed. Actuarial curves of RC duration and survival were drawn according to the Cutler and Ederer life tables. RESULTS: The age at diagnosis ranged from 1.5 to 68 years. Childhood (< 15 years) ALL presented in 49 cases; 25 were young adults (15-30 years), and 6 others were over 30 years of age. Two of the 80 patients (2.5%) died in CR (astrocytoma and demyelinating leukoencephalopathy). Fifty-eight patients (72.5%) are living in maintained CR; 20 others relapsed (25%), 14 of them (70%) attaining a second CR. Allogenic BMT was carried out in 4 such cases. Four patients are out of any treatment after the second CR. The actuarial curves of CR duration after suppression of therapy gave a stable plateau at 73% for children, at 75% for young adults and at 22% for patients over 30 years. The survival after suppression of therapy showed a plateau at 75% for children and at 86% for young adults. CONCLUSIONS: 1) Relapse was seen in 25% of the patients after cessation of therapy. 2) Relapse occurred in the first two years after therapy cessation in 75% of the instances. 3) At this writing, 78.7% of the patients keep up the CR. 4) Adults over 30 years of age comprise the poorest prognosis. 5) The course of young adults in this series after cessation of therapy is as good as that of children.
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Forty-four cases of essential thrombocytosis (ET) were diagnosed in the last 20 years, 19 males and 24 females (M/F: 0.76), aged between 3 and 86 years (median, 62 years), and 9 of them being under 40 years of age. The M/F ratio for patients under 60 years was 0.5, whereas it was 1.09 for patients over 60. The clinical forms at onset were: asymptomatic, 36.5%; as a bleeding disorder (BD), 20.4%; as thrombotic disease (TD) 22.7%; BD/TD, 13.6%, and others, 6.8%. The most important biological features included platelet count over 1.000 x 10(9)/L (59.1%), abnormal platelet aggregation, chiefly with ADR (56.5), mild reticulin myelofibrosis (55%), abnormal karyotype (2.6%), moderately high LDH levels (56.8%) and pseudo-hyperkalaemia (40%). The initial therapeutic approach was: observation (12 cases), antiaggregating agents (6 cases), and chemotherapy (BSF, HU, etc.) in the remainders. One patient evolved quickly into acute myelogenous leukaemia and two others suffered a late transformation into polycythaemia vera (PV) and myeloid metaplasia, respectively. The median survival was over 11 years, this being longer in patients under 60 years of age, in those with platelet count at diagnosis between 600 and 1000 x 10(9)/L and in those without initial symptoms of thrombosis. The advent of electronic blood-cell counters has made ET no longer a rare chronic myeloproliferative disease, its incidence coming now closer to that of PV; thus, in the last four quinquennial periods the incidence of ET/PV has evolved as following: 1/19, 4/16, 13/18 and 26/29.
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An 80 year-old woman presented subleukaemic acute monoblastic leukaemia (AML-M5a). Her bone marrow showed invasion by highly dysplastic histio-monocytic cells of great size and wide cytoplasm, with intense phagocytic activity (erythrophagocytosis was frequently seen), and with abnormal karyotype (50XX, +8, +8, +16, +21). The different malignant and reactive features of the mononuclear phagocytic system are commented, along with the haemophagocytic activity of the histio-monocytic cells in different states. The cytogenetic anomalies more frequently found in AML-M5 are also dealt with as compared to this patient's. The case reported here seems to correspond to subleukaemic acute "monophagocytic" leukaemia, with a biologic phenotype close to that of malignant histiocytosis.
A defect of haemoglobin synthesis is the classically recognized mechanism affecting the erythron functionalism in chronic iron deficiency. The poor erythroblastic bone-marrow response, plus a number of dyserythropoietic nuclear features, have led to think of an impairment of the cell cycle of erythroblasts in iron-lack anaemia. The aim of the present work was to study such hypothesis, not proven so far. Ten subjects with normal haemopoiesis and 39 patients with iron-lack anaemia of different aetiologies (namely, 19 with digestive tract bleeding, 16 with gynaecological bleeding, and 4 with haemorrhages on other locations) were included in a previously reported protocol. The scheme of such protocol consisted of: 1) bone-marrow erythroblast quantification; 2) analysis of their maturation gradient; 3) erythroblast mitotic index; 4) measure of the mitotic time in bone-marrow culture; 5) tritiated-thymidine incorporation to short-term bone-marrow culture and quantification of the erythroblastic labelling index. To these were added the degree of nuclear dyserythropoiesis according to Hill and Lewis, and the reticulocyte production index. The following mean values were found in the control group: erythroblasts, 25.5 (+/- 3.63) %; E1-E4, 47.66 (+/- 3.09) %; IDN, 0.67 (+/- 0.27); MI, 2.82 (+/- 0.66) %; MT, 1.05 (+/- 0.15 hr); LI, 34.88 (+/- 5.82) %. The mean values found in iron-lack anaemias were as follows: erythroblasts 39.42 (+/- 9.1) %; E1-E4, 42.25 (+/- 4.11) %; IDN, 7.77 (+/- 4.69); MT, 1.81 (+/- 0.95) hr; LI, 13.08 (+/- 6.51) %. The statistical analysis (Student's t) showed highly significant differences (p less than 0.001) in the increased IDN and decreased MI and LI in iron deficiency patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Thirty-four new cases of acute promyelocytic leukaemia (M3) were diagnosed at the authors' Centre between 1970 and 1988 (19 males and 15 females) with ages between 5 and 73 years (median age, 32 years). Three cases were of the hypogranular variant or M3-v (8.8%). The clinical picture included: haemorrhagic diathesis (85%), pallor/malaise (82%), fever/infection (41%), hepatomegaly (26%), splenomegaly (12%). Leucopenia of less than 5 x 10(9)/L was present in 23/34 cases, laboratory signs of DIC in 26/31, increased LDH, over 400 U/mL, in 6/31, and abnormal karyotype in 7/15. One of the patients rejected any treatment; two others died of brain haemorrhage before therapy was started, and seven died in the first two weeks of treatment. Of the 31 patients treated, complete remission (CR) was achieved in 21 cases (67.7%). Allogeneic BMT was carried out in two of them, with further relapse and death. Post-remission treatment was given to the remaining 19 patients, and there were 13 relapses. Six patients have been in CR, 5 of them after cessation of therapy, for the last 1.5-11.5 years. Age under 50 years and leucocyte count below 5 x 10(9)/L at diagnosis were favourable prognostic factors according to the univariate statistical analysis performed. The survival plateau of the actuarial curve was reached beyond 2.75 years by 15% of all the patients treated (33 cases), 23% of the patients who achieved CR (21 cases), 31% of the patients under 50 years of age and 5 x 10(9)/L leucocyte count at diagnosis (15 cases) and 36% of these last achieving CR (13 cases).
One hundred and thirty-three cases of myelodysplastic syndromes studied during the last ten years were revised. Of them, 79 were males and 54 females, and their ages ranged between 15 and 91 years (median, 69 years). Five patients (3.7%) had secondary myelodysplasias. The haematological phenotype (FAB) of the cases was: RA, 41.3%; SRA, 24%; RAEB, 18%; RAEBT, 3.7%; CMML, 8.3%. Leucopenia/thrombocytopenia without initial anaemia was present in 4.5% of the cases. Abnormal karyotype was found in 54 patients (40.6%), MIKA in 41 cases and MAKA in 13 cases. The cytogenetic anomalies most commonly found were +8, 5q-, -7, 11q- and 13q-. Cytogenetic abnormalities were commonest amongst the RAEB (50%), and least frequent in CMML (18.2%). Thirty-one patients evolved into acute leukaemia (29 ANLL and 2 ALL). Such blastic changes were more frequent in RAEB (62.5%) and rarest in SRA (9.4%), and they appeared mostly in patients with complex karyotype (MAKA) (53.8%) as compared with those who had normal karyotype (17.7%). Short-lasting complete remission was achieved by 40% of the patients treated with conventional chemotherapy. The survival of the group as a whole (median 30 months) varied in accordance with the haematological phenotype: SRA, 81 months; RA, 65 months; CMML, 13 months; RAEB +/- T, 8 months. The finding of a MAKA karyotype significantly shortened the survival (4 months) with regard to MIKA (44 months) or normal karyotype (39 months). The following median survivals were attained after patients' staging (Bournemouth's criteria): stage A, 84 months; stage B, 22 months, and stage C, 5 months.(ABSTRACT TRUNCATED AT 250 WORDS)
Between 1969 and 1983, 51 (35 men and 16 women) new cases of acute lymphoblastic leukemia (ALL) were diagnosed in patients aged 15 to 85 years (mean 21 yrs.). All patients received a "total therapy" which included: 1st induction (PRD, VCR, DBR, and/or L-ASN); 2nd, Central Nervous System profilaxis (craneal TCT and/or intrathecal MTx); 3rd, maintenance (6MP and MTx) and 4th, reinductions every 3 months (PRD, VCR, and DRB). This treatment lasted for at least 3 years. Complete Remission (CR) was achieved in 45 patients (88.2%): 3 of these patients were referred to other centers to continue treatment, 1 patient developed an early "metamorphosis" to hemophagocytic hystiocytosis and another patient developed a late chronic granulocytic leukemia (Ph +) dying a few months later after an acute myeloblastic worsening. During treatment 16 patients relapsed (9 in bone marrow and 7 in Central Nervous System). Treatment was discontinued in 24 patients with complete remission of which 5 relapsed in bone marrow 17 to 61 months after treatment). In one of the latter (ALL Ph +) an allogenic bone marrow transplant was performed and CR was achieved and maintained 46 months later. The post diagnosis acutarial curve of the 51 patients gave a mean survival of 6 years with a plateau at 43% of the patients after 11 years. The duration of the first uninterrupted CR was of 6.5 years and a plateau was reached at 46% of the patients after 10.5 years. At the present time, 20 patients are in CR (46 to 129 months) without treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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