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Biomedical subjects

N Ifrah

Publications and source records attributed to N Ifrah.

At least 73 records · Page 4Linked to original sources
PubMed1992

High-dose salvage chemotherapy without bone marrow transplantation for adult patients with refractory Hodgkin's disease.

PURPOSE: For patients with Hodgkin's disease (HD) who do not achieve complete response (CR), who experience a relapse within the first year of CR, and for those who have two or more relapses, the outcome is poor. Salvage chemotherapy regimens at conventional doses produce a CR rate that ranges from 10% to 50% and a 5-year disease-free survival (DFS) between 10% and 25%. On the other hand, high-dose chemotherapy regimens given in combination with bone marrow transplantation (BMT) produce a CR rate that ranges from 40% to 80% and a 3-year DFS of approximately 40%. We report the 5-year results of a prospective study in patients with refractory HD who were treated with three courses of intensive chemotherapy without BMT. PATIENTS AND METHODS: Thirty-nine adult patients with refractory HD were treated with three courses of intensive chemotherapy. Each cycle of chemotherapy comprised vindesine 1 mg/m2/d in continuous intravenous (IV) infusion from day 1 to day 5; Adriamycin (doxorubicin; Roger Bellon Laboratories, Neuilly, France) 40 mg/m2/d in continuous IV infusion from day 1 to day 3; carmustine 140 mg/m2/d at day 3; etoposide 200 mg/m2/d from day 3 to day 5; and methylprednisolone 120 mg/m2/d from day 1 to day 5. After the third cycle of chemotherapy, irradiation (20 Gy) was performed whenever possible and depended on previous irradiation. RESULTS: At the end of the treatment, 31 patients (79%) were in CR. Among these patients, 10 relapsed after a median time of 3 months. The overall 5-year survival rate was 46%. The freedom from progression (FFP) and the freedom from treatment failure (FFTF) rates were 48% and 43%, respectively. The main toxicities were hematologic (neutropenia and thrombocytopenia) and digestive. Four patients died due to treatment-related complications (two from septic shocks, one from respiratory insufficiency, and one from posttransfusional AIDS). CONCLUSION: The results of this study seem to be comparable to those results obtained with high-dose chemotherapies with autologous BMT.

Adolescent↗
PubMed1992

Autologous bone marrow transplantation vs intensive chemotherapy in first complete remission: interim results of GOELAM study in AML.

In November 1987, the French group GOELAM initiated a randomized study comparing allogeneic bone marrow transplantation (BMT), autologous bone marrow transplantation (ABMT) and intensive consolidation chemotherapy (ICC). The induction treatment was randomized between Idarubicin plus Cytarabine and Zorubicine plus Cytarabine: 223 patients with de novo AML and aged 15-50 years are currently evaluable and 178 of them (80%) have achieved complete remission (CR) with no significant difference between both arms. Forty four patients under 40 years of age and having a HLA identical sibling were assigned to BMT and 38 were actually transplanted. Thirty of the 134 other patients did not receive the planned first course of ICC, 4 patients died during this course, and 21 were excluded before randomisation. Thus, only 64 patients have currently been randomized between the 2nd course of ICC (34 patients) and ABMT (30 patients). ABMT was prepared by the Baltimore regimen and the marrow was unpurged. With a median follow-up time of 29 months, the actuarial risk of relapse at 3 years is 29% for BMT, 38% for ABMT and 53% for ICC. The 3 year disease free survival (DFS) is 51% for BMT, 62% for ABMT and 47% for ICC. These differences are not statistically significant. When intention to treat is considered, there is no difference in the actuarial DFS between the BMT and the non BMT groups. Longer follow-up time and larger number of patients are warranted to demonstrate any significant advantage of one of these approaches.

Acute Disease↗
PubMed1992

[Coexistence of monoclonal IgM and ankylosing spondylitis. Apropos of 2 cases].

Two cases of the association of monoclonal IgM and ankylosing spondylitis are reported. Their presentations are in accordance with local epidemiological data (monoclonal IgM, both kappa, one of them malignant, discovered in 71 and 79 year-old men). Ankylosing spondylitis does not appear as either favouring the incidence of monoclonal immunoglobulins or, in our opinion, having a major influence on their isotype. Conversely, while each member of this association could have its own story, the possible role of the coexistence of HLA B27 together with ankylosing spondylitis should be considered.

Aged↗
PubMed1991

Double intensive consolidation chemotherapy in adult acute myeloid leukemia.

Of 115 adult patients with de novo acute myeloid leukemia (AML), 87 (75.5%) achieved complete remission (CR) after induction treatment with zorubicin and conventional doses of cytarabine (Ara-C). Patients under age 45 years with histocompatibility locus antigen-identical sibling underwent bone marrow transplantation (BMT). The others were treated with two courses of intensive consolidation chemotherapy (ICC): course 1 with 4 days of high-dose Ara-C and 3 days of amsacrine (m-AMSA); course 2 with carmustine (BCNU), Ara-C, cyclophosphamide, and etoposide. Forty-two patients received both planned courses, 15 received only the first, and 13 patients could only support conventional maintenance therapy. Four patients died during consolidation. With a median follow-up of 60 months, the disease-free survival (DFS) after ICC at 5 years is 40.3% (+/- 6.5%), with no statistically significant difference between patients receiving one or two courses. The DFS for the 17 transplanted patients is comparable (P = .72) and is lower for the 13 excluded patients (23% +/- 11.5%, P = .046). Age did not influence the probability of remaining in CR. In univariate analysis, three parameters had a negative impact on the 5-year DFS: a high initial WBC count (52% for patients with less than 30 x 10(9) WBC/L v 12% for patients with greater than 30 x 10(9) WBC/L, P = .01), a long delay between induction treatment and course 1 (+/- 60 days; 63% v 29%, P = .01), and a long delay between course 1 and course 2 (+/- 60 days, 61.5% v 28.5%, P = .05). In multivariate analysis (Cox model), only the WBC count remained significant. This study confirms the value of intensive postremission chemotherapy, which can be compared in AML with allogeneic or autologous BMT. It also demonstrates the prognostic value of the initial WBC count. The optimal modalities of ICC remain to be defined by further studies.

Acute Disease↗
PubMed1990

The position of the M-BCR breakpoint does not predict the duration of chronic phase or survival in chronic myeloid leukemia.

It has been reported that patients with chronic myeloid leukemia (CML) with 5' breakpoints within the major breakpoint cluster region (M-BCR) of the BCR gene have somewhat better prognoses than those with 3' breakpoints. We studied the position of the breakpoint in 67 patients with CML in chronic phase using conventional Southern blotting. Using restriction enzymes BglII, BamHI and HindIII and two genomic probes, a 0.6 kb (3' M-BCR) probe hybridizing to a part of the intron between exons b3 and b4 and a 2.0 kb (5' M-BCR) probe hybridizing to sequences including exon b1, we localized the breakpoint in M-BCR as occurring 5' (n = 38) or 3' (n = 28) of the HindIII restriction site located just downstream of exon b3. We failed to localize the breakpoint in one patient. The median durations of chronic phase (37 versus 44 months respectively) and of survival (50 versus 51 months respectively) for patients with 5' and 3' breakpoints were not significantly different. When we analysed only patients whose DNA was collected within 4 weeks of diagnosis (5' breakpoints, n = 30; 3' breakpoints, n = 19), there was again no significant difference in duration of chronic phase or survival. The median survivals of patients divided into good, intermediate and poor prognosis categories in accordance with the prognostic index developed by Sokal and colleagues were 54, 50 and 26 months respectively. This study confirms the value of the Sokal prognostic index but provides no support for the notion that the precise genomic position of the breakpoint in M-BCR correlates with prognosis.

Adolescent↗
PubMed1990

Increased risk of secondary acute nonlymphocytic leukemia after extended-field radiation therapy combined with MOPP chemotherapy for Hodgkin's disease.

The purpose of this study was to evaluate the influence of the number of mechlorethamine, vincristine, procarbazine, and prednisolone (MOPP) cycles and the extent of irradiation on the risk of secondary acute nonlymphocytic leukemia (SANLL) after a single combined treatment for Hodgkin's disease (HD). Between April 1972 and May 1980, 462 patients with HD clinical stage (CS) I, II, and III were prospectively treated with three or six cycles of MOPP and supra- and/or infradiaphragmatic irradiation (40 Gy). Four hundred forty-one patients achieved complete remission (CR). By January 1988, 237 patients had been followed-up in first CR for at least 10 years. Ten patients developed SANLL between the 34th and 123rd month of CR. The 15-year SANLL risk is 3.5% +/- 2.7%. Cox's stepwise regression analysis performed with all initial and treatment covariates (sex, age, histology, splenectomy, MOPP chemotherapy, and irradiation extent) showed that the only significant explanatory variable of SANLL risk was the irradiation extent (P less than .002). Using the log-rank test, SANLL risk ranged from 2.2% for supradiaphragmatic irradiation alone to 9.1% for subtotal (STNI) or total nodal irradiation (TNI) (P less than .001). These results strongly suggest that extended high-dose irradiation and MOPP chemotherapy should not be combined for the treatment of HD.

Adolescent↗
PubMed1990

Transient acanthosis nigricans following bone marrow transplantation for lymphoid malignancy.

Transient acanthosis nigricans (AN) was observed 3 months after bone marrow transplantation (BMT) for lymphoblastic lymphoma. The patient had no endocrine abnormality and had not received any drug known to induce AN. Forty-eight months post-BMT no malignancy recurred or appeared. Although usual hyperkeratosis, papillomatosis and acanthosis were present on skin biopsy, these were associated with the finding of keratinocyte necrosis and CD8+ lymphocytic infiltrate. It is suggested that graft-versus-host disease may be one of the triggers for AN.

Acanthosis Nigricans↗
PubMed1990

Association between acute lymphoblastic leukemia and partial IgA deficiency in a young man--a family study.

We report on an unusual association between partial IgA deficiency and acute lymphoblastic leukemia in a young man. We also report results of the family study of immunoglobulin levels, sIgA B cells, in vitro IgA synthesis and molecular analysis of the structural C alpha genes. The IgA deficiency was present at diagnosis of leukemia prior to any therapy. The indirect arguments for a preexisting IgA deficiency are the absence of improvement of the IgA level during complete remission and especially the finding of a similar partial IgA deficiency in a sister who shared the same HLA haplotype, had a low percentage of sIgA B cells and decreased in vitro IgA production. The mother, who had a normal IgA serum level also had decreased in vitro IgA synthesis. No major structural C alpha gene defect was found. The relationship between acute lymphoblastic leukemia and IgA deficiency remains to be elucidated.

Adolescent↗
PubMed1989

[Treatment of localized forms of Hodgkin's disease with 3 courses of chemotherapy (ABVD-MP) in combination with wide focal and prophylactic lumbo-splenic radiotherapy. The POF 81/12 protocol].

Between October 10, 1981 and December 31, 1987, we used the Hodgkin POF 81/12 protocol to treat 235 patients aged from 5 to 65 years (mean 30 years) with localized Hodgkin's disease clinically classified as stage IA (n = 6), stage IIA (n = 128) and stage IIB (n = 53). A contiguous lesion was present in 22 cases and a mediastinal lesion in 170 cases. The patients received 3 monthly courses of ABVD-MP (doxorubicin 25, bleomycin 10, vinblastine 6, dacarbazine 375 and methylprednisolone 120 mg per sq.m intravenously on days 1 and 15), except for stage IA non-mediastinal patients who received only one course. Thereafter, in the absence of failure (lack of changes or progression under chemotherapy), a 40 Gy wide focal irradiation and a 30 Gy prophylactic lumbo-splenic irradiation were performed. Complete remission (CR) was obtained in 229 patients, and the 6 failures (4 after ABVD-MP, 2 after radiotherapy) were treated with specific programmes. On December 1, 1988 (median survival 42 months, range 12-86 months) we had recorded 9 relapses (after 9 to 51 months) and 7 deaths (2 failures, 2 relapses and 3 patients in CR: ovarian carcinoma, road accident, exploratory pleural puncture). The current actuarial relapse and survival rates at 7 years are 5 and 94 respectively. Two unfavourable forms of the disease were identified: infra-diaphragmatic with massive lumbo-aortic lesions (5 cases: 1 failure, 1 relapse) and supra-diaphragmatic with a mediastinum/chest ratio of 0,45 or more (30 cases: 5 failures, 5 relapses). In the 200 patients devoid of these 2 risk factors the results obtained were: CR 100 percent, only 2 relapses and survival at 7 years 98 percent.

Adolescent↗
PubMed1989

Four brothers with Waldenstrom's macroglobulinemia.

An exceptional family including four brothers with Waldenstrom's macroglobulinemia was studied. The four patients had different light chain IgM monoclonal components: two of the kappa type and two of the lambda type. Anti-idiotypic rabbit antisera, prepared for each monoclonal component, revealed no cross-reactivity. The four brothers did not share a common HLA A B DR haplotype and a genetic linkage to the HLA complex cannot be ascertained. Five of the 12 relatives had high serum immunoglobulin concentration (four IgG, three IgA, and two IgM) without monoclonal components. Two relatives showed auto-antibodies at low titer. Some of the youngest relatives exhibited immunological abnormalities and they may be high-risk subjects with regard to Waldenstrom's macroglobulinemia.

Aged↗
PubMed1989

Bone marrow transplantation for adult poor prognosis lymphoblastic lymphoma in first complete remission.

Twenty-five adult patients, 19 males, six females, age 16-43 years (median 23), with lymphoblastic lymphoma received allogeneic or autologous bone marrow transplantation in first complete remission. Twelve patients were Murphy stage IV with bone marrow and/or CNS involvement and 13 were stage III of whom nine had thoracic involvement. Complete remission was achieved with an intensive anthracycline containing multiagent chemotherapy protocol. Twelve patients with an HLA identical sibling received an allogeneic marrow and 13 without a donor received their own marrow harvested a median of 2 months (0-4 months) after complete remission and purged in vitro with either mafosfamide (eight patients) or anti T-cell monoclonal antibodies and complement (three patients). Bone marrow transplantation was performed 1-7 months (median 3 months) after achieving first complete remission. The conditioning regimen consisted of cyclophosphamide or high dose melphalan and total body irradiation. The actuarial 4-year disease-free survival is 68% (+/- 9% SE). The actuarial probability of relapse was 26% (+/- 3% SE) with a median follow up to 22 months. There was no difference between allogeneic and autologous transplantation with eight out of 12 allo patients in first continuous complete remission 26-45 months after transplant and nine out of 13 auto in continuous complete remission 15-75 months after transplant. These results compare favourably with those achieved with the best chemotherapeutic regimen used for such patients.

Adolescent↗