[Bone marrow autotransplantation in patients with acute myeloblastic leukemia in primary remission]. / Autotrasplante de medula ósea en pacientes con leucemia mieloblástica aguda en primera remisión.

Fifteen bone marrow autotransplants (BMAT) in patients with acute myeloblastic leukemia (AML) were performed after the first remission. The mean age was 37 years (range 12 to 60 years). According to the morphological classification FAB, 8 patients had monocytic leukemia (M4, M5) and 7 myeloid leukemia (M1, M2, M3). The mean interval elapsed between the date of complete remission and the BMAT was 3.9 months (range 1 to 5-9 months). In 8 patients this interval was longer than 6 months and in 7 cases it was shorter than 6 months. After achievement of the complete remission all patients underwent certain cycles of intensification before the BMAT. Eight patients received only a cycle whereas 7 patients received more than one cycle (between 2 and 4). The conditioning protocol consisted of cyclophosphamide (CP) (60 mg/kg x 2) and total body radiotherapy (TBR) (10 Gy) in 9 patients; CP and busulfan in five; and CP, cytarabine at high doses and melphalan in one case. Marrow extraction was performed after completion of chemotherapy of intensification. In 5 cases the bone marrow was depleted of leukemic cells by previous in vitro treatment with ASTA-Z. There are at present 8 alive patients. The survival free of illness was 51.8%. Seven patients died: 3 cases because relapse of the leukemia, 3 due to attachment failure of the transplantation, and one patient suffered a viral myocarditis. The survival free of illness was significantly longer in those patients transplanted after 6 months of the complete remission.

[Infectious complications in bone marrow transplantation]. / Complicaciones infecciosas en el trasplante de medula ósea.

BACKGROUND: Initially, the aim of the present study was to evaluate the incidence and implicated organisms in the infections in patients receiving a bone marrow transplants (BMT). METHODS: 194 febrile episodes (FE) were evaluated in 115 patients having received a BMT between 1980 and 1987. The analysis was carried out at three different moments: during the period of most marked neutropenia (period I) to the 100th day after BMT (period II) and beyond the 100th day (period III). RESULTS: The unequivocal confirmation that FE was infective was found in 62% of cases (confirmation was microbiological in 46% and clinical in 16%), while 31% of FE were considered as possible infections and the remaining 7% as doubtful infections. The causative organisms were bacteria (73%), viruses (10%), fungi (8%), and combinations of them (polymicrobial infections) (9%). Gram negative and Gram positive organisms were more common, respectively, in period I and in periods II and III (p = 0.02). Bacteremia was the commonest cause of confirmed infection. The overall mortality rate due to infection was 18%. There was a remarkably high mortality from pneumonia (54%) and a low mortality in patients with sepsis (6%) (p less than 0.0001). The number of FE was lower in patients with autografts than those with allografts (p = 0.08). 33% of the FE in patients with allografts were coincident with acute or chronic graft-versus-host disease, and in two thirds of them infections was confirmed. CONCLUSIONS: Infection represents a major complication of BMT. The different antimicrobial treatments used in association with bone marrow grafting allowed us to control most FEs. Pneumonia was the most severe infective localization and the leading cause of death. Mortality rate due to sepsis was small.

Refractory anemia with ringed sideroblasts associated with thrombocytosis: comparative analysis of marked with non-marked thrombocytosis, and relationship with JAK2 V617F mutational status.

The World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues (2001) defined a provisional entity named refractory anemia with ringed sideroblasts associated to marked thrombocytosis (RARS-MT). Diagnosis of RARS-MT requires more than 15% of ringed sideroblasts in bone marrow aspirate and the existence of a thrombocytosis in blood, with a platelet count above 600 x 10(9)/L. Nevertheless, controversy exists regarding this platelet count "cut-off" value and, when RARS-MT was defined, the JAK2 mutation and its importance in the study of myeloproliferative disorders was unknown. We present the results of a Spanish retrospective multicentric study, which includes 76 cases of RARS with associated thrombocytosis (platelet count above 400 x 10(9)/L) at diagnosis (RARS-T), 36 of them with a platelet count above 600 x 10(9)/L. Our aim was to analyze their clinical, analytical and morphological characteristics, and to establish correlations with the JAK2 mutational status.

[Iron deficiency in female blood donors. Results obtained by applying a prevention protocol]. / Ferropenia en mujeres donantes de sangre. Resultados obtenidos aplicando un protocolo de prevención.

Iron deficiency, often associated to anaemia, is the main cause of deferring women from blood donation: an incidence of 9.5% over a series of 1,437 women was found in our region. The strategy designed to face this problem was based upon precise diagnosis (erythrocyte protoporphyrin values) dietetic counselling, occasional iron therapy, and reduction of the frequency of blood donations. The results attained were encouraging, as the incidence of deferments was 13%; however, the percentage of women who quit blood donation was 86% of the first-time female donors.

Miconazole oral gel enhances acenocoumarol anticoagulant activity: a report of three cases.

OBJECTIVE: To describe three cases of interaction between miconazole oral gel and acenocoumarol, manifested as an increase in the international normalized ratio (INR). CASE SUMMARIES: Three patients (62-year-old woman, 89-year-old woman, 43-year-old man) following oral antithrombotic treatment with acenocoumarol for different pathologies were diagnosed with oral candidiasis and started miconazole oral gel. In all cases, the previous INR values were repeatedly within the therapeutic range. The following routine monitoring of the antithrombotic therapy showed a marked increase in anticoagulant activity in all cases, which returned to the therapeutic range after miconazole was withdrawn. None of the patients needed substantial changes in their habitual dosages of acenocoumarol in subsequent measurements of the INR to stay within the therapeutic range. DISCUSSION: We report three cases in which a possible interaction between miconazole oral gel and acenocoumarol is suggested by the chronological relationship between the introduction of miconazole and an increase in the INR. Miconazole exerts its fungistatic action by inhibiting some isoenzymes of the fungal cytochrome P450 system. Oral mucosa inflammation (as in oral candidiasis) may enhance its transmucosal absorption. In this setting, cytochrome P450 isoenzymes belonging to the host may be inhibited too. This mechanism provides an explanation for different interactions observed with miconazole oral gel. CONCLUSIONS: Miconazole oral gel enhances acenocoumarol anticoagulant activity. Although we did not observe major bleeding complications, we suggest the use of other families of antifungal drugs, such as nystatin, to treat oral candidiasis in patients taking acenocoumarol.

[Prognostic value of the changes in the DNA of blast cells from patients with acute lymphoblastic leukemia]. / Importancia pronóstica de las alteraciones en el ADN de las células blásticas en pacientes con leucemia aguda linfoblástica.

The cytogenetic characteristics of 37 patients diagnosed of acute lymphoblastic leukaemia are presented. The studies were performed by cytofluorometry (CFM) after DNA staining with propidium iodide (34 cases) and/or chromosome identification with trypsin G bands (13 patients). Hyperdiploid DNA index was present in 15% of the patients, whereas none of them had hypodiploid DNA index. Abnormal karyotype was found in 69% of the evaluated cases. Good correlation was observed between the ploidy attained by CFM and by karyotyping cells. The highest percentage of aneuploidy corresponded to the L2 morphological subtype (55%), followed by L1 (36%). Structural alterations were the commonest in L2 variant, while numerical ones were commonest in the L1 variant. The 4 L1 patients with aneuploidy had the common immunophenotype, whereas the 6 aneuploidic patients of the L2 variant had common, early pre-B and undifferentiated immunophenotype. The actuarial survival of patients with diploid DNA index was 48.5% (IC 95%, 25-73%), whereas pseudodiploid patients have relapsed and died before 16 months from diagnosis (p less than 0.005). None of the patients with hyperdiploid DNA index and lacking structural alterations has relapsed. Patients with structural abnormalities have the poorest prognosis, while patients with hyperdiploid DNA index showed several favourable risk factors and are in the first complete remission.

[Empirical treatment of febrile episodes in patients with neutropenia in bone marrow transplantation]. / Estudio del tratamiento empírico de los episodios febriles en pacientes con neutropenia en el trasplante de medula ósea.

The results of therapy of febrile episodes during the pregraft phase in bone marrow transplant was retrospectively evaluated in 84 granulocytopenic patients. Most patients received co-trimoxazole and i.v. ticarcillin as antibacterial prophylaxis. 47 episodes were treated with a third generation cephalosporin plus an aminoglycoside, with a 55% favorable response rate. 37 episodes were treated with a wide spectrum penicillin plus an aminoglycoside, with a 41% response rate (p greater than 0.05). Among the 23 infections caused by gram-negative bacilli the response rate was 89% (8 of 9) with the first regimen, and 21% (3 of 14) with the second one (p = 0.003). The investigation of in vitro sensitivity suggested that prophylactic ticarcillin favors the infections due to bacilli with cross-resistance to wide spectrum penicillins. The antibiotic regimen did not influence the final resolution or the mortality rate of the febrile episode.