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Biomedical subjects

M Monconduit

Publications and source records attributed to M Monconduit.

At least 55 records · Page 3Linked to original sources

Rearrangements of immunoglobulin light and heavy chain genes and correlation with phenotypic markers in B-cell chronic lymphocytic leukemia.

Twenty-five patients with B-cell chronic lymphocytic leukemia (B-CLL) were investigated to correlate the immunological phenotype with the description of the Ig gene rearrangements of the B-cell clone. All patients were positive for the CD19 antigen and one pan B-antigen, markers of late cells (CD20, CD37 or Y2955). Twenty-four of the 25 patients tested expressed monoclonal cell surface immunoglobulin (SIg). The CD5 antigen was present in 21 of the 25 tested patients. Immunoglobulin gene rearrangements were detected by hybridization of the BamHI, EcoRI, BgIII, and HindIII digested genomic DNAs to the IGHJ, IGKC, IGLC, and IGLJ2 probes. Twenty-four of 25 patients had two rearranged IGH loci. The IGKC rearrangements were observed in 20 patients. In four patients, the IGK loci were deleted on both chromosomes. One patient without SIg displayed a germline pattern. All six patients with lambda producing B-CLL showed a lambda gene rearranged band, although the use of IGL polymorphism to investigate IGL rearrangements must be noted. These clonal rearrangements of IGL genes, together with the detection of either the kappa or lambda light chain of SIg, confirm that patients with B-CLL meet the developmental scheme of ordered light chain gene rearrangements.

B-Lymphocytes↗

Causes of death after therapy for early stage Hodgkin's disease entered on EORTC protocols. EORTC Lymphoma Cooperative Group.

The risk of dying from different causes after Hodgkin's disease (HD) therapy has been quantified from a series of 1,449 patients with early stages included in four successive clinical trials conducted by the European Organization for Research and Treatment of Cancer (EORTC) Lymphoma Cooperative Group since 1963. Overall, 240 patients died and the 15-year survival rate was 69% whereas the expected rate was 95%. The standardized mortality ratio (SMR) technique was used to quantify excess deaths as a function of time since first therapy. At each interval, SMR was significantly increased, giving: 0-3 year, 8.86 (p less than 0.001); 4-6 year, 9.25 (p less than 0.001); 7-9 year, 7.08 (p less than 0.001); 10-12 year, 9.53 (p less than 0.001); 13-15 year, 4.37 (p less than 0.01); and 16+ years, 3.80 (p less than 0.05). While the proportion of deaths as a consequence of HD progression, treatment side-effect, and intercurrent disease decreased with time, that of second cancer and cardiac failure peaked during the 10-12 year post-treatment interval. After 15 years of follow-up, the risk of dying from causes other than HD continued to increase. These findings indicate that although probably cured from HD, patients are at higher risk for death than expected, a risk that might be a consequence of therapy.

Adult↗

Protein C: Rouen, a new hereditary protein C abnormality with low anticoagulant but normal amidolytic activities.

A family is described in which venous thrombo-embolic disease is associated with reduced plasma protein C anticoagulant activity but normal levels of protein C amidolytic activity and antigen. The partial characterization of the heterozygous defect is described using crossed immunoelectrophoresis (CIE) with or without calcium and seven functional assays which differ by activators (thrombin-thrombomodulin complex, bovine thrombin and Protac snake venom) and by an eventual preliminary adsorption on insoluble salts. PC activity was thereafter determined either by chronometric or amidolytic assays. The results indicate that this abnormal protein C (PC) is normally activated and at least partially carboxylated. Three hypothesis are proposed to explain the discrepancy between normal amidolytic and low anticoagulant activities.

Adult↗

Peripheral blood stem cells collected before and after leukapheresis in the very early remission phase of hematopoietic malignancies.

Human peripheral blood obtained after chemotherapy-induced remission in hemopoietic malignancies has been suggested to be a potential substitute for autologous bone marrow as regards autologous hematopoietic reconstitution. The schedule and consequences of early leukapheresis are, however, still imprecise. We report a study performed in two series of, respectively, 10 and 14 patients where sequential leukapheresis (total number = 84) was evaluated with regard to colony-forming unit (CFU) potency. Our data demonstrate that adequate numbers of progenitor cells can be collected by leukapheresis and that, even when this is performed at an early stage after remission, subsequent hematopoietic reconstitution is not impaired.

Adult↗

[Splenectomy in chronic idiopathic thrombopenic purpura in adults. Apropos of 49 cases].

The authors reviewed the case files of 49 adult patients undergoing splenectomy for chronic idiopathic thrombocytopenic purpura at the Centre Henri Becquerel between 1970 and 1987. Although the postoperative course was straightforward in 83.7% of cases, one reoperation for subphrenic abscess was necessary and there was one postoperative death. Remission from thrombocytopenia was obtained in 87.5% of the patients, but only transiently in 8.5% of them. No preoperative predictive factors could be demonstrated. An early postoperative rise in the platelet count to more than 500 G/litre appears to ensure a good subsequent result. Secondary infectious complications are not exceptional and can be fatal (one death in our series); they require prophylaxis by anti-pneumococcal vaccination. The place of prophylactic antibiotic therapy has yet to be defined.

Adolescent↗

Del(14)(q22) in diffuse B-cell lymphocytic lymphoma.

Some recurrent chromosomal abnormalities have recently been found to be associated with distinctive histologic subtypes of non-Hodgkin's lymphoma (NHL). In a study of 62 patients with NHL whose karyotypes was determined at diagnosis, 3 patients were found to have a deletion of the long arm of chromosomes 14 at band 22 (del[14][q22]). All had a diffuse lymphoma with generalized lymphadenopathy and bone marrow involvement. All three lymphomas were of B-cell origin, as shown by the presence of surface immunoglobulin and monoclonal antibody phenotyping. For each patient, a trisomy 12 was associated with del(14)(q22) in a clone. These data suggest that del(14)(q22), perhaps in association with trisomy 12, could identify a subtype of NHL and that band 22 of chromosome 14 may be implicated in the B-cell ontogeny.

Antigens, Differentiation↗

Clinical stages I and II Hodgkin's disease: a specifically tailored therapy according to prognostic factors.

The H5 program in clinical stage (CS) I to II supradiaphragmatic Hodgkin's disease (HD) was tailored to prognostic factors identified in former European Organization for the Research and Treatment of Cancer (EORTC) studies. Among the 494 adult patients included in the study, the 237 patients belonging to the favorable group (H5F) underwent a staging laparotomy (Sx) in order to select the patients who could be treated with limited radiotherapy (RT) only. Thus, 198 patients (84%) with negative laparotomy were treated with RT alone and randomized to either mantle irradiation (M) or extended field mantle plus para-aortic (M + PA) irradiation. Complete remission (CR) was achieved in 99% of the patients. There was no difference in the 6-year relapse-free survival (RFS) rate (74% and 72%, respectively) or survival rate (96% and 89%). Therefore, Sx helped to define those patients who could be treated with M alone in contrast to those who required more aggressive therapy. The 39 patients with positive laparotomy were treated as the unfavorable group (H5U) from onset and randomized to either total/subtotal nodal irradiation (TNI/STNI) or a sandwiched mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) X 3, M irradiation, MOPP X 3 protocol (3M). Although the RFS rate was higher in the 3M arm (100% v 53%; P = .002), the 6-year survival was not significantly different between the two arms (overall, 92%). In the 257 patients with initial unfavorable disease, the Sx was avoided. They were randomized to either TNI/STNI or 3M. In complete responders (96%), the 6-year RFS was 91% in the 3M arm and 77% in the TNI/STNI arm (P = .02). The pattern of failure differed in the two arms: the inverted Y and spleen irradiation controlled occult infradiaphragmatic disease better than MOPP; conversely, less patients begun on MOPP recurred in the involved mantle areas. The difference in 6-year actuarial total survival (TS) (89% and 82%; P = .05 in favor of the 3M arm) was not retrieved after exclusion of the unrelated deaths from the analysis. The two arms produced similar TS in patients under 40 years of age. TNI retains interest, especially in young men wishing to preserve fertility. The overall result shows that when treatment is tailored to initial prognostic factors, excellent results can be obtained in all patient subgroups at minimal morbidity and toxic cost.

Antineoplastic Combined Chemotherapy Protocols↗

Comparison of total nodal irradiation versus combined sequence of mantle irradiation with mechlorethamine, vincristine, procarbazine, and prednisone in clinical stages I and II Hodgkin's disease: experience of the European Organization for Research and Treatment of Cancer.

The H5 study of supradiaphragmatic Hodgkin's disease in clinical stages I-II consisted of two controlled trials adapted to patients considered to have either favorable or unfavorable characteristics, based on prognostic factors identified in two former studies by the European Organization for Research and Treatment of Cancer. Of 494 patients, 257 who were classified as having unfavorable prognosis qualified for the more intensive treatment and consequently were spared a staging laparotomy. They were randomized either to total nodal irradiation (TNI) (132 patients) or to treatment with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alternated with mantle irradiation (MOPP X 3-mantle irradiation-MOPP X 3; 3M) (125 patients). In complete responders (96%), the 6-year relapse-free survival was 77% in the TNI arm and 91% in the 3M arm (P = .02). Relapses in the initially involved and irradiated mantle area were less frequent in patients started on MOPP. The 6-year actuarial total survival (TS) (TNI, 82%, and 3M, 89%; P = .05) appeared to favor the 3M arm, but this difference disappeared when patients dying from causes unrelated to cancer were excluded from analysis. In men less than or equal to 40 years old, there was no difference in relapse-free survival, freedom from disease progression, or TS between the groups receiving TNI and 3M. Thus, TNI is a short and appealing treatment, especially because it preserves fertility. The same observation was true in women less than or equal to 40 years old. In addition, even irradiation less than TNI, which is meant to spare the ovaries, provided a TS similar to that for 3M.

Adult↗

Prognostic value of response after three MOPP cycles in Hodgkin's disease--stage III and IV.

Sixty-eight patients with Hodgkin's disease stage III and IV were evaluated after three out of six MOPP cycles. At that time, 46 (68%) were classified as early responders and 22 as slow responders. The criteria of response were: disappearance of B symptoms, decrease in the size of the largest lymph nodes (by more than 50%) and significant reduction (more than 20%) of mediastinal enlargement. Out of 43 early responders, 38 were in complete remission after six MOPP cycles and only five out of 22 slow responders. Such an early response is only related to the absence of B symptoms at the time of diagnosis (p less than 0.05). The survival curves of early responders and slow responders were significantly different (p less than 0.02). A rapid erythrocyte sedimentation rate (ESR) (greater than 50 mm) was the most frequently abnormal sign found in the group not responding after three MOPP cycles (p less than 0.0001). Such a significant prognostic value of early response is observed for stage III but not for stage IV patients. We conclude that early clinical response after three MOPP cycles is a good prognostic factor which must be kept in mind in the formulation of the therapeutic regimen for Hodgkin's disease stage III and IV.

Antineoplastic Combined Chemotherapy Protocols↗

[Bone lymphomas].

Non-hodgkin's lymphomas have benefitted from recent progresses in pathology and from new classifications having a prognostic value. In reference to a case of primary osseous lymphoma, we mention their definition and main characteristics. We stress the good sensitivity of the osseous scintigraphy to detect the osseous localizations of lymphomas. These secondary osseous lymphomas have a poor prognosis. The difficulties of the pathological diagnosis are frequent, but should decrease with the wider use of immunohistochemical marking of the bone or node biopsies.

Adult↗

A randomized comparison of maintenance treatment with androgens, immunotherapy, and chemotherapy in adult acute myelogenous leukemia. A Leukemia-Lymphoma Group Trial of the EORTC.

Twenty-three European centers participated in a randomized clinical trial (AML-5) to study the effect of androgens and immunotherapy during maintenance in adult acute myelogenous leukemia. Induction treatment consisted of Adriamycin (doxorubicin) 50 mg/m2 day 1, vincristine VCR 1 mg/m2 day 2, and cytosine arabinoside 80 mg/m2 every 12 hours by push injection days 3-9. Patients in complete remission were randomized into four groups: (1) 6-mercaptopurine 70 mg/m2 days 1-14, methotrexate 15 mg/m2 twice weekly days 15-28, and reinduction with daunorubicin 35 mg/m2 and vincristine 1 mg/m2 day 29; (2) chemotherapy as in group 1 plus stanozolol 0.15 mg/kg/day; (3) 6-thioguanine 70 mg/m2 orally on 4 consecutive days and cytosine arabinoside 80 mg/m2 subcutaneously day 5 every week; and (4) chemotherapy as in Group 3 plus irradiated blast cells treated with neuraminidase. Three hundred forty-eight patients were eligible and 295 were evaluable. The median age was 45 yrs. A complete remission was achieved in 64% of the patients, with 158 complete remissions randomized. Patients not randomized and patients receiving bone marrow transplantation (BMT) were analyzed separately. There was no difference in disease-free survival (DFS) or survival in the four maintenance arms. For patients reaching complete remission, the median DFS was 40 weeks, and median survival was 22 months with 30% surviving at 4 years. The overall survival was 18% at 4 years. There was no beneficial effect for DFS or survival by adding either immunotherapy or androgens to chemotherapy during maintenance. However, patients receiving immunotherapy seemed to have a higher rate of responses to reinduction after relapse than those in the other treatment arms.

Adolescent↗