Biomedical subjects
Publications and source records attributed to F Dreyfus.
Clostridium perfringens (CP) is an infrequent cause of septicemia in neutropenic patients. We report the case of a 17 year old man treated for acute lymphoblastic leukaemia in whom a strain of CP was isolated from blood cultures. The clinical spectrum and evolution of CP septicemia in neutropenic patients are discussed.
Peripheral blood stem cells (PBSC) were collected from 29 patients with high risk Hodgkin's disease (n = 3) or non-Hodgkin's lymphoma (n = 26) in partial remission or first sensitive relapse. Patients had either bone marrow involvement or hypoplastic bone marrow. The conditioning regimen prior PBSC collection included amsacrine and cytosine arabinoside (Ara-C) or Ara-C alone. PBSC collection was performed after leukocyte counts reached 1 x 10(9)/1. A good yield was obtained in 23 patients, whereas sufficient numbers of CFU-GM were not obtained in six cases. Twenty-one patients have been transplanted. All patients except one achieved bone marrow engraftment. Eight patients are in complete remission (mean duration 15 months). The estimated 2 years survival rate is 46.4% (CI 25-68%). This procedure would seems a good alternative in poor prognosis lymphomas.
The Evi-1 zinc-finger protein gene is normally not expressed in hematopoietic cells. However, high Evi-1 mRNA expression has been reported in mouse myeloblastic leukemias, due to transcriptional activation by proviral integration in either the Fim-3 or Evi-1 loci. The human Evi-1 gene is located on chromosome 3q24-q28. In this paper three examples are presented of human acute myelogenous leukemias presenting common characteristics: (i) high Evi-1 mRNA expression; (ii) chromosomal abnormalities t(3;3)(q21;q26) or inv(3;3)(q21-22;q26); and (iii) high platelet counts and dystrophic megakaryocytes. Thirty-four other patients with hematological malignancies, among which 11 had chromosomal rearrangements in the 3q24-q28 region did not exhibit such abnormalities. Of the 13 permanent hemopoietic cell lines tested, Evi-1 RNA expression was found in HEL and K-562 cell lines. Weak Evi-1 expression was also seen in fibroblasts and lung cells. This expression was affected neither in skin cells from a patient with a 3q27 constitutional translocation nor in a lung epithelioma cell line containing an excess of chromosome 3 long arm. Ectopic strong expression of Evi-1 in human leukemias could define an uncommon subclass of acute myelogenous leukemias with translocations involving the 3q25-28 chromosomal domain and abnormal megakaryopoiesis.
Intensive sequential chemotherapy with mitoxantrone, 12 mg/m2/d on days 1 through 3, etoposide, 200 mg/m2/d as a continuous infusion on days 8 through 10, and cytarabine, 500 mg/m2/d as a continuous infusion on days 1 through 3 and 8 through 10 was administered to 72 patients aged less than 60 years with previously treated acute myelogenous leukemia (AML). Forty patients had refractory AML (nonresponse to prior therapy, early first relapse, or multiple relapse) and 32 had late first relapse. Sixty-one percent of patients, with a 95% confidence interval (CI) ranging from 49% to 72%, achieved complete remission (CR), including 45% (CI: 30% to 62%) of refractory patients and 81% (CI: 64% to 93%) of late first relapse patients. Twenty-nine percent of patients (CI: 19% to 41%) did not respond to therapy and 10% (CI: 4% to 19%) died from therapy-related toxicity. Median duration of aplasia was 30 days. Nonhematologic WHO grade 3 or more toxicity included sepsis (57% of patients), vomiting (10%), mucositis (35%), diarrhea (7%), skin rash (6%), and hyperbilirubinemia (11%). Postinduction therapy was attempted in 36 of 44 CR patients: 16 of them received a second course of the same regimen, 7 received maintenance chemotherapy, 4 underwent autologous bone marrow transplantation (BMT), and 9 allogeneic BMT. At a median follow-up of 20 months, 23 of the 44 complete remitters have relapsed, 1 to 14 months after achievement of CR, including 19 of 31 patients not undergoing BMT. Median survival is 7 months with 16% (CI: 4% to 28%) projected survival at 47 months. Median disease-free survival is 6 months with 21% (CI: 3% to 39%) of CR patients projected to remain disease-free at 46 months. Twenty-six percent (CI: 13% to 43%) of the evaluable patients who did not receive transplantation had inversion of CR duration. Among patients younger than 50 years, there was no significant difference in disease-free survival between patients receiving postinduction chemotherapy and those receiving BMT. We conclude that this chemotherapy regimen is highly efficient and could be used as first-line therapy in young patients with AML.
In order to identify the target epitopes recognized by specific CTL in the NEF protein of HIV-1, 33 peptides derived from the HIV-BRU sequence were tested with NEF-specific CTL generated from HIV-seropositive donors. Six different epitopes were identified and several points were remarkable: 1) They were all located in two regions of the central part of the NEF protein corresponding to residues 73 to 94 and 113 to 147, respectively. 2) The CTL issued from a single donor could recognize several peptides of the NEF protein. 3) Some of these peptides could be recognized in association with at least two or three different HLA class I molecules. 4) Two different overlapping epitopes were present in a relatively short sequence of 15 amino acids. These results suggest that multiple epitopes corresponding to different HLA restrictions could coexist in a relatively small region of the NEF protein. The implications of these results in vaccine strategies using synthetic peptides bearing CTL epitopes are discussed.
OBJECTIVE: To assess the prognosis of patients with hematologic malignancies in acute renal failure who require hemodialysis. DESIGN: Retrospective study. SETTING: ICU. PATIENTS: Forty-three consecutive patients. METHODS: Prognostic analysis using both univariate and multivariate (stepwise regression) methods. RESULTS: Fifteen (35%) patients recovered from acute renal failure and 12 (28%) were discharged from the ICU. The prognosis of patients with acute renal failure linked to sepsis is poorer than the prognosis of the patients with acute renal failure from other etiologies. Only one patient survived in the former group (n = 26) and 11 in the latter group (n = 17); p less than .0001 in multivariate analysis. When accompanied by associated respiratory failure, mortality rate was higher (93% vs. 33%; p less than .0001). The Simplified Acute Physiology Score (SAPS) calculated within the first 24 hr of admission was significantly (p less than .001) related to mortality when the SAPS was greater than or equal to 13. The presence of neutropenia and the type of hematologic malignancy were not related to a worse prognosis. Tolerance to hemodialysis appeared good, and complications were rare.
Cutaneous lymphomas other than mycosis fungoides (MF) represent a rare and heterogeneous group of lymphomas. Their clinical behavior remains largely unknown. In this study, the clinical and immunohistologic characteristics and follow-up data of 52 well-documented cases of cutaneous lymphomas other than MF, presenting with initial cutaneous lesions, were reviewed. Twenty-seven patients presented with skin disease alone (stage IE), and 25 patients had concurrent cutaneous and extracutaneous disease (stage IV). The tumors were grouped into high-grade lymphomas (HGLs; 21%), intermediate-grade lymphomas (IGLs; 58%), and low-grade lymphomas (LGLs; 21%). A B-cell phenotype was most often expressed by cutaneous lymphomas (73%), particularly by stage IE lymphomas (85%). Among 13 cases of T-cell lymphomas, loss of one of the pan-T-cell antigens was detected in all cases but one. The clinical course of cutaneous lymphoma was closely dependent on stage and histologic subtype but not on T-cell or B-cell phenotype. Of 20 patients with stage IV HGL or IGL, 13 were treated by polychemotherapy with curative potential. Their median survival was 37 months. Fourteen patients with stage IE HGL or IGL were treated by radiotherapy alone. Nine patients (69%) relapsed within 2 years posttreatment. Seven of them relapsed in the skin outside the initial site involved, suggesting that radiotherapy alone is not an adequate treatment for these patients. Preliminary results concerning seven other patients with stage IE IGL or HGL treated by an initial third-generation polychemotherapy regimen are presented.
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The authors observed a pleiomorphic lymphoma mimicking Hodgkin's lymphoma in a French Guyana black woman lacking antibodies for human T-cell lymphoma/leukemia virus type I (HTLV I). After two courses of chemotherapy with either mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or doxorubicin, bleomycin, vincaleukoblastine, and dacarbazine (ABVD), a typical acute T-cell leukemia/lymphoma developed with HTLV I seroconversion. Specific HTLV I DNA sequences were detected using the polymerase chain reaction (PCR) on a lymph node biopsy obtained before chemotherapy. The mechanisms of the seroconversion are discussed.
The course of 260 adults with haematological malignancies admitted to a medical intensive care unit was studied to evaluate the value of life support techniques and to research predictive factors. The overall in the medical intensive care unit (MICU) and hospital mortality rates were respectively 43% (113 patients) and 57% (148 patients). Among survivors, 64% (49 patients) were still alive after 6 months and 44% (35 patients) after 1 year. Among 34 haemodialysed patients, the MICU mortality was 67% (23 patients) and among 111 mechanically ventilated patients 85% (94 patients). Prolonged mechanical ventilation, more than seven days, was performed in 11 of the 17 survivors and did not influence long term survival. No individual predictor of mortality was found comparing survivors and non-survivors. However, SAPS, intractable sepsis and failure of more than one organ system were significantly different in non-survivors (p less than 0.001). Among the 20 patients requiring both mechanical ventilation and haemodialysis, only two left the MICU and both died soon thereafter. We conclude that life support therapy should be initiated in patients with haematological disorders and that prolonged mechanical ventilation is compatible with long term survival. However, the combination of mechanical ventilation and haemodialysis is always associated with a poor prognosis and therefore the use of both techniques simultaneously for one patient is questionable.
A report is given on two neutropenic patients with staphylococcal septicemia caused by Staphylococcus haemolyticus and Staphylococcus aureus (both strains methicillin-resistant) who failed to respond to therapy with teicoplanin. Both strains were resistant to teicoplanin (MIC 16 and 8 mg/l respectively), but remained sensitive to vancomycin (MIC 2 and 4 mg/l respectively). Replacement of teicoplanin with vancomycin led to full recovery of both patients and their discharge from hospital. These two cases emphasize the importance of clinical and microbiological monitoring of patients with staphylococcal septicemia, even when glycopeptides are used for treatment.
The Friend helper leukemia virus (F-MuLV) induces in mice leukemias of the erythroid, lymphoid, and myeloblastic lineages. Erythroleukemic cell DNAs were examined for genetic alterations at loci described as common proviral integration regions in MuLV-induced myeloid or lymphoid leukemias or in Friend complex-induced erythroleukemias. No alteration of the Fim-1, Fim-2, Fim-3, pvt-1, and Spi-1 loci were detected in 17 erythroleukemias, p53 gene rearrangement was observed in 6 (30%) erythroleukemias and was always associated with a loss of the germ line allele. Interestingly, genetic alterations were also detected at two loci, c-myc and Pim-1, previously described as common provirus integration regions in T lymphoid leukemias. Rearrangements of these two genes were often associated with p53 gene alteration within the same tumor.
By using target cells that expressed only the regulatory NEF protein of the human immunodeficiency virus (HIV), we were able to identify specific cytolytic T cells (CTL) from most of the seropositive patients tested. This NEF-specific cytolytic activity was mediated by CD8+ lymphocytes. In two different donors, we identified a unique peptide in the NEF protein that could be recognized in association with two different HLA class I molecules. The definition of such a peptide should prove useful in evaluating vaccine strategies.
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We tested the efficiency of a nasal spray of Amphotericin B (AmB) in leukemic patients, in an attempt to prevent pulmonary Aspergillosis. From January to July, 8 cases of invasive Aspergillosis (IA) in 19 new leukemic patients were identified. Between July and September 15 patients were treated by prophylactic nasal spray of AmB (daily dose 5 mg). Compliance was excellent, but nevertheless typical IA developed in 5 patients. We conclude that at the dosage used prophylactic administration of nasal spray of (AmB) does not prevent IA.
c-ets-1 and c-ets-2 are 2 proto-oncogenes known to be possibly involved in some human myelomonocytic leukemias. However, very few studies concern c-ets-1 and c-ets-2 RNA expression in human hematologic malignancies. We have studied 18 leukemic patients, and 10 cell lines for their ets RNA contents. c-ets-1 was strongly expressed in 5 and c-ets-2 in 8 of the 18 patients. All the cell lines expressed both c-ets-1 and c-ets-2 RNAs. This expression was highly variable from one patient to another, and from one cell line to another, regardless of the cellular leukemia subtype. The variability of this expression in patients may reflect differences in the proliferative potential of leukemic cells.