True histiocytic lymphoma of the facial sinuses associated with acute myeloblastic leukemia (FAB-M2)
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Biomedical subjects
Publications and source records attributed to F Bauduer.
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We aimed to perform a prospective analysis of the main characteristics of deaths occurring in the oncohaematology department of a general hospital. From November 1995 to February 1997, a total of 81 patients died in our unit, 50 of whom (61.7%) were male. Their mean age was 67.8 (range 19-96) years. Underlying diseases were: multiple myeloma (9 cases), acute myeloid leukaemia (22), lymphoma (14), chronic lymphocytic leukaemia (6), acute lymphoblastic leukaemia (4), myelodysplastic syndromes (3), solid tumours (11), and other (12). The previous disease duration ranged from 5 days to 276 months (mean 31.9 months). The duration of the last hospital stay varied between 0 (death on arrival or on way to hospital) and 40 days (mean 9.3 days). Two patients died in the emergency unit just before entering our department (1 suicide). Only 15 patients had been admitted for the first time. In 70% of these cases death appeared predictable, as the consequence of refractory or end-stage disease. In these cases, all the "do not resuscitate" orders were in place at least 48 h before death. About half the patients died without any relative present. The frequencies of the clinical complaints evaluated were the following: pain necessitating opiates 27%; infection- or disease-related fever 40%; dyspnoea 44%; haemorrhage 20%; CNS disturbances 25%. The percentages of use of therapy tools chosen as indicators were: benzodiazepines 80%; chemotherapy 46%; anti-infectious agents 47%; transfusions 42%; major analgesics 27%; and steroids 40%. The circumstances and quality of patient deaths must be regularly evaluated so that palliative care in the final stages of life can be improved.
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PURPOSE: To determine whether the use of a recombinant human granulocyte colony-stimulating factor ([G-CSF] lenogastrim) can increase the chemotherapy dose-intensity (CDI) delivered during consolidation chemotherapy of childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Sixty-seven children with very high-risk ALL were randomized (slow early response to therapy, 55 patients; translocation t(9;22) or t(4;11), 12 patients). Consolidation consisted of six courses of chemotherapy; the first, third, and fifth courses were a combination of high-dose cytarabine, etoposide, and dexamethasone (R3), whereas the second, fourth, and sixth courses included vincristine, prednisone, cyclophosphamide, doxorubicin, and methotrexate (COPADM). G-CSF was given after each course, and the next scheduled course was started as soon as neutrophil count was > 1 x 10(9)/L and platelet count was > 100 x 10(9)/L. CDI was calculated using the interval from day 1 of the first course to hematologic recovery after the fifth course (100% CDI = 105-day interval). RESULTS: CDI was significantly increased in the G-CSF group compared with the non-G-CSF group (mean +/- 95% confidence interval, 105 +/- 5% v 91 +/- 4%; P <.001). This higher intensity was a result of shorter post-R3 intervals in the G-CSF group, whereas the post-COPADM intervals were not statistically reduced. After the R3 courses, the number of days with fever and intravenous antibiotics and duration of hospitalization were significantly decreased by G-CSF, whereas reductions observed after COPADM were not statistically significant. Duration of granulocytopenia was reduced in the G-CSF group, but thrombocytopenia was prolonged, and the number of platelet transfusions was increased. Finally, the 3-year probability of event-free survival was not different between the two groups. CONCLUSION: G-CSF can increase CDI in high-risk childhood ALL. Its effects depend on the chemotherapy regimen given before G-CSF administration. In our study, a higher CDI did not improve disease control.
From January 1995 to June 1998, 136 new cases of non-Hodgkin lymphomas (NHLs) were seen in our center which serves all the French Basque Country (300000 inhabitants). The crude and standardized incidence rates were respectively 13.2 and 7.6 cases/100000/year. The distribution of histologic subtypes according to the REAL classification showed a good correlation with the previous published data. Eleven patients (8%) were HIV-positive and two (1.4%) were HCV carriers. Hence, in our region, contrary to Italy, there is no evidence of relationship between HCV and NHLs.
We have conducted a phase II outpatient trial testing weekly oral administration of idarubicin (ZAVEDOS-ZVD) alone to determine the rate of objective response and toxicity in poor risk acute myeloid leukemia (AML) patients over 60 years of age. The treatment consisted of three phases: induction, with 20 mg/m2 of ZVD on days 1, 8, 15 and 22; consolidation with 20 mg/m2 of ZVD for 4 weeks; and maintenance with six cycles lasting 3 months and consisting of oral 6 mercapto-purine 2 mg/kg/day, 4 days a week for 2 months; subcutaneous cytarabine 1 mg/kg, once a week for 2 months; and oral ZVD 20 mg/m2 on day 1 and day 8 of the third month. In case of failure after induction course, patients received salvage treatment with 4 weekly oral doses of 40 mg/m2 ZVD. Fifty-one patients with a median age of 76 years were enrolled and could receive induction course. Of these 51 patients, 37 could receive subsequent courses, which consisted either of consolidation, or salvage. Only 11 patients underwent maintenance treatment. Sixty-three percent of patients had to be hospitalized during induction, for a median duration of 14.5 days, and 87% required hospitalization during salvage for a median duration of 17.5 days. Only five patients (38%) required hospitalization during consolidation. There were three toxic deaths (6%), two from hemorrhage and one from pulmonary embolism. The overall response rate was 29%, with 12 patients in complete response (25%) and two in partial response (4%). The median overall survival rate is 4 months for the whole population, and the median DFS is 9.6 months among the 14 responding patients. The results of this trial show that this new weekly schedule of oral ZVD chemotherapy is feasible and effective in poor risk elderly patients with AML. This regimen may be helpful for patients unable to tolerate intensive intravenous regimens, and is a real alternative to palliative treatments.
Thirty-nine patients with factor XI deficiency were diagnosed in our general hospital, which serves all the French Basque Country (about 290 000 inhabitants), between 1985 and 1995. Biological and clinical data of these cases are reported herein. Factor XI deficiency seems significantly more frequent in Basques than in the other non-Ashkenazi populations. Molecular studies should be performed for typing these cases in the view of population genetics.
Anxiety can increase the risk of chemotherapy related emesis. We have studied the role of a benzodiazepine (alprazolam: A) in addition to granisetron for controlling emesis in patients treated with moderately emetogenic chemotherapy for malignant lymphomas according to an anxiety scale (Covi score). Two hundred twenty-five patients receiving at least 3 cycles of chemotherapy including adriamycin and/or cyclophosphamide and/or epirubicin and/or dacarbazine were randomized. Patients in arm G (n = 111) received 3 mg i.v. granisetron 10 min before chemotherapy at cycles (C) 1, 2 and 3 while in arm G+A (n = 114), alprazolam (A) was added per os 1 mg 1 hour before chemotherapy (H-1) and 0.5 mg at H+6 for C1. At C2 and C3, A was given 0.75 or 1.5 mg at H-48, H-24, H-1 and 0.5 mg at H+6. Patients characteristics were comparable between the 2 arms. Complete response rates (i.e. no emesis or at least slight nausea) were similar in both arms: G: 83, 94 and 93% versus G+A: 89, 93 and 97% in C1, C2 and C3 respectively. Nevertheless, the Covi score of the population was low rendering difficult the study of the factor "anxiety". Somnolence was significantly more frequent in the G+A arm (p < 0.0001).
Fifty-six patients older than 65 (median age: 77, range: 65-91) were treated in our general hospital, between January 1991 and November 1995 with the diagnosis of AML. Twenty-five were de novo AML (45%). The other cases which were considered as secondary AML (sAML) occurred after: myelodysplastic syndromes (19 cases: 34%), myeloproliferative disorders (7: 13%) or therapy of malignancies (5: 9%). Distribution of FAB subtypes was: M0: 4, M1: 8, M2: 14, M4: 10, M4eo: 1, M5: 10, M6: 1, unclassified: 8. Twenty-seven patients (48%) (de novo: 18, sAML: 9) received conventional "3 + 5" or "3 +7" induction chemotherapy +/- consolidation and maintenance (group 1). Low-dose Ara-C was given in eighteen cases (32%) (group 2), miscellaneous single agents were prescribed in seven cases and two patients received only supportive care. Sixteen early deaths (ED) (<1 month) occurred (29%). Distribution of age, WHO-PS, hyperleukocytosis, ED and median survival (MS) (3 months) was equivalent in de novo and sAML. Fifteen CR were achieved including twelve patients from group 1 (no difference between age <75 versus >75 years) and three from group 2. The MS of CR patients was 13 months. Eleven patients survived more than one year (de novo: 8). M5 subtype, fever >38 degrees C, high LDH level, WHO-PS>2, CR non achievement were predictive of reduced survival. Besides conventional induction, investigational therapies currently remain the best antileukemic modalities. Age per se should not be an exclusion criteria for treatment. Our data underline the high frequency of sAML in the community. Of note, this common type AML is largely excluded from many trials.
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We report on 3 female patients with immunologic thrombocytopenic purpura (ITP) for whom diagnostic procedures evidenced a chronic Hepatitis C virus (HCV) infection. In 2 cases, a transfusion performed more than 10 years ago represented the probable way of contamination. One patient received a course of steroids, which normalized the platelet counts. Another one has been treated with repeated IV immunoglobulins, which induced partial responses of variable duration. HCV is responsible for many autoimmune manifestations and a search for this virus seems warranted for exploring patients with ITP.
Epidemiologic studies concerning myelodysplastic syndromes (MDS) are rare. The estimated incidence varies between 1 and 12.6/100,000/year. The aim of this work was to compare our own experience with these data. Our general hospital represents a structure with 1197 beds which serves a population of 290,000 individuals (French Basques). Most of the inhabitants live in a rural environnement. Twenty percent of the population are aged over 65. During a 4-year period (1993-1996), 90 new cases of MDS were diagnosed on bone marrow studies in our laboratory. Among FAB subtypes refractory anemia (RA) represented 27 cases (31%), RA with ring sideroblasts (RARS): 21 (23%), RA with excess of blasts (RAEB) and in transformation (RAEB-t): 22 (24%), chronic myelomonocytic leukemia (CMML): 10 (11%). Ten cases were unclassifiable (11%). Therapy-related MDS were seen in 8 patients. The sex ratio was 1 and the mean age of the patients was 74.3 (range: 23-96), 37% of them being 80 years or older. The calculated incidence was 7.7/100,000/year for the entire cohort and 31.4/100,000/year for people over 65.
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Clinical, morphological, cytogenetic and molecular (fluorescence in situ hybridization and RT-PCR) data were analyzed in twelve Philadelphia negative chronic myeloid leukemias (Ph-negative CMLs). Four patients were classified as BCR-positive. A standard b2a2 or b3a2 transcript was found, and the BCR-ABL hybrid gene was located on the 22q11 band in three cases and on the 1p35 band in one case with a t(1;9)(p35;q34). All were classified as typical chronic granulocytic leukemia (CGL) according to the French-American-British (FAB) morphological guidelines. Responses to therapy were evaluated by FISH in the four patients, and proved to be poorer than in Ph-positive CMLs. Eight BCR-negative patients were identified. They could be characterized by an older age, a less proliferative form of disease than the BCR-positive patients, and a frequent (six out of eight) abnormal karyotype. The FAB classification identified four CGLs and four atypical CMLs (aCML). A normal karyotype was more frequent in the patients classified as CGL whereas all the aCMLs had a chromosomal abnormality. Three patients had chromatin clumping and this morphologic feature was associated with trisomy 8 in two. No correlation between the cytogenetic, morphologic and the clinical data were found. Five patients had poor tolerance to therapy with a frequent occurrence of bone marrow failure and hemorragic syndrome, whereas three patients responded to a standard treatment of CML. Our study reinforces previous data on Ph-negative BCR-positive CMLs and emphasizes the difficulty in correlating clinical, morphologic, cytogenetic data in Ph-negative BCR-negative CMLs. However, our data also argue in favor of the existence of true Ph-negative BCR-negative CMLs and suggest that some of them can respond to a standard treatment of CML.
Autoimmune neutropenia (AIN) is a rare hematological disorder for which no standard treatment has been established so far. A brief review of the literature is presented herein concerning the use of G-CSF in this indication. The good results in terms of neutrophils increment and infection prophylaxis render G-CSF attractive for treating AIN. Hypotheses explaining its mechanisms of action are also discussed.
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