[Somatic gene transfer and gene therapy in hematology].
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Biomedical subjects
Publications and source records attributed to M Boiron.
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Despite combination of chemotherapy and radiotherapy, some patients with refractory or relapsed Hodgkin's disease (HD) have a bad prognosis. We performed high dose chemotherapy (HDCT) (BCV regimen) with autologous bone marrow transplantation (ABMT) in 26 patients with advanced HD. 11 patients were considered refractory after at least two non cross-resistant chemotherapy regimens and radiotherapy in 8 cases. 15 patients had a poor prognosis relapse (in visceral or irradiated site) after complete remission and they received chemotherapy before ABMT. At the time of transplantation 4 patients had progressive disease with B symptoms and did not respond to HDCT; they all died 3 to 12 months post-transplantation from persistent HD. For the remaining 22 patients, 3 months after HDCT 19 patients (73%) were in complete remission, 2 (8%) in partial remission and one patient died from toxicity. After complete remission 4 patients relapsed at 12 to 18 months and 15 patients are in persistent remission 24 to 46 months after transplantation. These results are encouraging in patients with bad prognostic factors but able to respond to chemotherapy.
Gastric peristalsis has not been studied extensively in patients with dyspepsia. The aim of our study was to further characterize gastric peristalsis in such patients using a newly described fluorographic method. Thirty-two patients with dyspepsia and 18 healthy volunteers were included in our study. Four hours after a standard solid-liquid meal, the subject swallowed 250 ml of a baryum sulfate solution and (100 mm x 100 mm) fluoroscopy of the stomach was performed every 2 s during 30 s. Spot films were analyzed using a graphic table and a amateur microcomputer program. For each subject, the instant velocity, vi, and mean velocity, V, of gastric peristalsis were calculated and used to generate a time-space diagram of contractions, a velocity histogram and an index of propagation, Ip. These parameters were compared to normal values (V = 2.2 +/- 0.2 mm/s; Ip = 2.2 +/- 0.4). When compared with normal values, 3 different motility patterns appeared in dyspeptic patients with a high correlation between V and Ip (P less than 0.01): normoperistalsis (n = 8; 1.8 less than V less than 2.6 mm/s); 1.4 less than Ip less than 30); hypoperistalsis (n = 7; V less than 1.8 mm/s; Ip greater than 3.0) and hyperperistalsis (n = 7; V greater than 2.6 mm/s; Ip less than 1.4). In a 4th group (n = 5), a retroperistalsis was effect observed with Ip less than 0. For 5 other patients, Ip or V was abnormal with atypical motor activity detected on the time-space diagram.(ABSTRACT TRUNCATED AT 250 WORDS)
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We report 2 cases of acute non-lymphocytic leukemia with distinct clinical and karyotypic features shared by therapy-related acute non-lymphocytic leukemia occurring after adjuvant chemotherapy including 5-fluorouracil, doxorubicin and mitomycin C. Our observation suggests a causal relationship between exposure to mitomycin C and the occurrence of acute non-lymphocytic leukemia.
The outcome of advanced Hodgkin's disease has improved since the use of MOPP and ABVD. However 50% of these patients will relapse. Conventional salvage therapy can yield a complete response rate of 50%. However, only 5 to 30 percent can expect to be cured. Autologous bone marrow (ABMT) in reported publications can reach 50 to 80% remission rate in refractory patients with a disease free survival of 40 to 80%. Adverse prognostic factors are: tumor burden, number of prior chemotherapies, response to latest therapy and performance status. At the present time, ABMT is discussed in relapse of poor prognosis with initially stage I to IIIA. Twenty-six patients underwent ABMT at Saint-Louis Hospital. Fifteen were sensitive relapses of poor prognosis, 11 initially refractory disease. After ABMT, 19 were in complete remission including 14 relapses. Disease free survival was 80% for relapsing patients, again 50% for refractory patients (P = 0.001). ABMT should be a tool for refractory patients and relapses of poor prognosis.
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Review on general problems raised by the role of some viruses: parvoviruses, herpes viruses, retroviruses, in the physiopathology of human malignant blood diseases.
Aggressive non Hodgkin lymphoma (NHL) occurs frequently in the elderly and because of drug related toxicity treatment remains controversial. Seventy-two patients over 65 years (68-83 y, median 73 y) with intermediate and high grade NHL were retrospectively studied. We found 22 cases of high grade NHL and diffuse large cell the most frequent type encountered (54%). Seven patients had stage I, 8 stage II, 14 stage III, and 43 stage IV disease. Treatment for localized disease was radiotherapy or chlorambucil, and disseminated stage patients were treated by three different chemotherapy regimens, group I: classic dose chemotherapy without Adriamycin (15 pts), group II: same type of regimen with Adriamycin (45 mg/m2) (42 pts), group III: high dose chemotherapy with Adriamycin (75 mg/m2) (8 pts). Overall complete response (CR) rate was 53% without significant differences between treatment groups. Median duration of survival was 38 months and estimated 5 year survival at 40%. Following complete remission, 15 patients (40%) relapsed. Thirty-seven patients have died, 6 from toxic deaths (5 toxic deaths in group II and III), 28 from NHL, and 3 from other diseases. Toxicity was greater among patients treated with Adriamycin. In a multivariate analysis, the attainment of complete remission was the only factor influencing survival. Our data shows that classical dose chemotherapy leads to the same CR rate and survival as more intensive regimens.
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The cell surface expression of alpha:beta heterodimer was studied using WT31 monoclonal antibody, in peripheral blood lymphocytes (PBL) from a patient who developed a prolonged immunodeficiency after allogeneic bone marrow transplantation. This patient, grafted for chronic myelogenous leukemia, received T cell depleted bone marrow from her HLA, A, B, D matched sibling. The late occurrence of opportunistic infection, led us to analyze the phenotype of patient PBL. 70% of PBL were CD3+ and 29% WT31+, indicating that the majority of CD3+ PBL did not express the alpha:beta heterodimer. Transcription of the genes encoding the alpha, beta, and gamma chains was assessed in cell lines derived from PBL, by Northern blot analysis. We showed that the CD3+ WT31- subset expressed a truncated, beta mRNA (1.0 kb) and also truncated alpha transcript (1.4 kb). To determine the CD3-associated structure on CD3+ WT31- cell line, immunoprecipitation assays were performed using monoclonal anti-CD3 and an hetero antiserum against gamma peptides. These CD3+ WT31- cells expressed a disulfide linked dimer, composed of products of gamma gene (37 kD, 40 kD) and of undefined delta chain (45 kD). Functional analyses were performed in PBL before and after sorting with WT31 and anti-CD3 antibody. These circulating CD3+ WT31- cells were unable to proliferate when triggered with anti-T3 beads and they seemed to mediate a suppressor activity on CD3+ WT31+ cells.
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Thirty-nine patients with acute myeloblastic or lymphoblastic leukaemia had peripheral blood mononuclear cells collected by 3 continuous-flow leukapheresis as they entered first remission after induction chemotherapy. CFU-GM were assayed as a measure of the number of haemopoietic stem cells in each collection. Numbers of CFU-GM harvested varied among the patients (for example 0.27 to 155.10(4)/kg for ANLL patients). Nineteen patients underwent peripheral blood stem cells autografts after a conditioning regimen with high dose cyclophosphamide and TBI. The patients were transfused with a median of 2.2.10(4)/kg CFU-GM cells (0.28 to 100.10(4) CFU-GM/kg). Only 1 patient had a graft failure. The rate of haemopoietic recovery was studied for our patients and those reported in the literature. A strong correlation exists between the numbers of CFU-GM transfused and the rate of granulocytes and platelets recovery. Very rapid recovery are regularly obtained when the number of CFU-GM transfused is superior to 5.10(4)/kg.
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In a consecutive series of 65 patients treated by allogeneic bone marrow transplantation, we have compared the efficacy on prevention of bacterial infection of total gut decontamination with oral non absorbable antibiotics or with oral absorbable broad spectrum antibiotics. On day-8, all patients were randomly allocated to one group: Group I received orally pefloxacin 400 mg/day and penicillin 3 M UI/day. Group II received capsules containing cephalothin 250 mg, gentamicin 20 mg and bacitracin 150 UI. Each patient received 9 to 12 capsules per day according to body weight. Patients less than 5 years old or with severe hepatic abnormalities were excluded from the study. All patients were treated in LAF room with usual precautions of asepsis. They received sterile food. In addition, they were on ketoconazole for prophylaxis of fungal infections and acyclovir for prevention of herpes infections. Antibiotics were started on day-8 before bone marrow transplantation and stopped 15 days after discharge from the hospital. 32 patients were allocated to Group I and 33 in Group II. There was no difference between both groups according to age, sex, diagnosis. After transplant, the one year survival and the complications were similar in both groups. The median time of decontamination was 65 days, the mean number of days of agranulocytosis was 20 days, the mean number of days of fever was 7 days in both groups. The compliance was better in Group I but the treatment had to be modified in 9 patients of Group I because of liver abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
Following allogeneic bone marrow transplantation, prominent expansion of peripheral T cells (40%) bearing gamma T cell receptor was observed in some patients. Biochemical, functional and molecular analyses were performed to characterize this T cell receptor and to understand its role in the immunodeficient state after transplantation.