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Biomedical subjects

N Milpied

Publications and source records attributed to N Milpied.

At least 145 records · Page 8Linked to original sources
PubMed1993

Localized invasive pulmonary aspergillosis in patients with neutropenia. Effectiveness of surgical resection.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in patients with neutropenia. Two severe complications with poor outcome can be observed after apparently successful IPA medical treatment: severe hemoptysis and IPA relapse during subsequent cytotoxic treatments. Early surgical therapy has not been considered routinely in the management of localized IPA. METHODS: Six consecutive patients (four women, two men; median age, 52 years) with localized cavitating IPA diagnosed during chemotherapy-induced aplasia were treated with early surgical resection after hematologic recovery. RESULTS: All patients received a lobectomy. Surgery was uneventful. This procedures allows patients to proceed with further intensive chemotherapy and/or bone marrow transplantation without IPA reactivation. CONCLUSIONS: For selected patients, surgical resection of localized IPA with unique cavitating lesion, which prevents hemoptysis and IPA recurrence and allows for subsequent cytotoxic treatment, may be recommended.

Adult↗
PubMed1993

Hb Saint Nazaire (beta 103[G5]Phe-->Ile): a new example of polycythemia due to a hemoglobin variant with increased oxygen affinity.

Hb Saint Nazaire [beta 103 (G5) Phe-->Ile] was found in four apparently unrelated French families. The five patients carrying this hemoglobin have been detected because of a moderate erythrocytosis. The structural abnormality of Hb Saint Nazaire concerns the same residue as in Hb Heathrow [beta 103 (G5) Phe-->Leu). A comparative functional study between these two variants showed that the increase in oxygen affinity is much lower in Hb Saint Nazaire than in Hb Heathrow. The replacement of phenylalanine G5, which is localized within the heme pocket, by a leucine abolishes several contacts between the heme and the globin and leads to an environment of the heme having some similarities with that observed in myoglobin. In contrast, the replacement of G5 by an isoleucine is likely to introduce less structural modifications.

Adolescent↗
PubMed1993

Specificity of T cells invading the skin during acute graft-vs.-host disease after semiallogeneic bone marrow transplantation.

The mechanisms responsible for skin lesions during acute graft-vs.-host disease (aGVHD) after allogeneic bone marrow transplantation (BMT) are poorly understood. The exact role of various effector cell populations and "major" (particularly HLA-DP) or "minor" antigens as target molecules is not known. To investigate the nature of cells responsible for tissue injury, we cultured T cells from skin biopsy first with interleukin 2 (IL-2) alone and then in polyclonal activation conditions to avoid in vitro antigenic sensitization before specificity testing. We applied this method to two biopsies performed during aGVHD after semiallogeneic BMT and obtained cytotoxic T cells against four graft mismatches: CD8+ T cells against HLA-A2.2 and HLA-B27 and CD4+ T cells against HLA-DP101 and HLA-DP401. This demonstrates that T cells with documented specificity can be obtained from an aGVHD lesion without antigenic selection. Moreover, these data directly implicate DP as a potential target antigen for aGVHD.

Adult↗
PubMed1993

Early intensive therapy with autotransplantation for high-risk Hodgkin's disease.

The purpose of this trial was to evaluate the efficacy and the tolerance of high-dose therapy with autologous stem cell transplantation as part of front-line therapy in Hodgkin's disease for patients with both adverse prognostic factors: high tumor burden at presentation and slow response to initial chemotherapy. In a prospective one-center study, 20 consecutive patients with slow response (tumor reduction < 75%) (16 pts) or refractory (4 pts) to 3-4 courses of conventional HD chemotherapy received high-dose therapy followed with autologous bone marrow (14 pts) or peripheral blood stem cell (6 pts) transplantation. They were 13 males, 7 females, median age 26 years (8-45). At the time of initial diagnosis, all but one of the patients had B symptoms, all had high-risk HD defined as Ann Arbor stage IV (7 pts) or large mediastinal involvement (LMI = tumor/thorax > 0.45 at T5-T6) (6 pts) or both stage IV+LMI (7 pts). Median time between diagnosis and autotransplantation was 5 months. Intensive therapy consisted of either CBV (cyclophosphamide 1.5 g/m2 x 4, BCNU 300 mg/m2, etoposide 200 mg/m2 x 3) (12 pts) or cyclophosphamide 120 mg/kg + 12 Gy total body irradiation for 8 patients with diffuse bone or lung involvement. For pts treated with CBV, 40 Gy involved field radio-therapy was performed after hematological recovery. Median duration of neutropenia was 16 days (9-21). Neither veno-occlusive disease, nor interstitial pneumonitis nor toxic death were observed. Seventeen pts are alive with no progression of the disease (16/16 in partial response after initial chemotherapy, 1/4 with refractory disease).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Use of an anti-interleukin-2 receptor monoclonal antibody for GVHD prophylaxis in unrelated donor BMT.

Severe acute GVHD remains the main complication in unrelated donor BMT (UD-BMT). The previous encouraging reports on the use of anti-IL-2 receptor monoclonal Ab (33B31) for GVHD prophylaxis in genoidentical BMT led us to add this Ab to the standard GVHD prophylaxis regimen (MTX plus CsA). Sixty-four consecutive patients received 33B31, 20 mg on days 1 and 2, then 10 mg per day from day 3 to day 28 in association with CsA and MTX. They were compared with a historical control group of 89 patients who received conventional GVHD prophylaxis. The 33B31 was well tolerated. We did not find any statistical difference in terms of incidence and time of onset of severe GVHD, occurrence of chronic GVHD, engraftment, relapse or survival among the two groups. Immunization occurred but did not influence serum levels of 33B31. No correlation was found between the severity of GVHD and serum Ab levels. We conclude that other approaches for reducing acute GVHD should be developed to improve UD-BMT results.

Actuarial Analysis↗
PubMed1992

Double-intensive therapy in high-risk multiple myeloma.

A high remission rate is achieved with high-dose melphalan (HDM) in multiple myeloma (MM), and autologous transplantation of hematopoietic stem cells allows a prompt hematologic recovery after high-dose therapy. We treated 97 patients with high-risk MM (group 1:44 advanced MM including 14 primary resistances and 30 relapses; group 2: 53 newly diagnosed MM) with a first course of HDM. For responding patients a second course of high-dose therapy with hematopoietic stem cell support was proposed. After the first HDM, the overall response and complete remission rates were 71% and 25% with no significant difference between the two groups. The median durations of neutropenia and thrombocytopenia were significantly longer in group 1 (29.5 days and 32 days, respectively) than in group 2 (23 days and 17 days, respectively). This severe myelosuppression led to eight toxic deaths and the fact that only 38 of the 69 responders could proceed to the second course (three allogenic and 35 autologous transplantations). Among the 35 patients undergoing autologous transplantation (10 in group 1, 25 in group 2), 31 received their marrow unpurged collected after the first HDM, and four received peripheral blood stem cells. The median durations of neutropenia and thrombocytopenia after autologous transplantation were 24 days and 49 days, respectively. Two toxic deaths and nine prolonged thrombocytopenias were observed. The median survival for the 97 patients was 24 months (17 months in group 1, 37 months in group 2) and the median duration of response was 20 months. The only parameters that have a significant impact on the survival are the age (+/- 50 years) and the response to HDM. The median survival of the 35 patients undergoing autologous transplantation is 41 months, but the median duration of remission is 28 months with no plateau of the remission duration curve. Patients responding to HDM may have prolonged survival, but even a second course of high-dose therapy probably cannot eradicate the malignant clone.

Adult↗
PubMed1992

Allogeneic bone marrow transplantation for acute myeloid leukemia in first remission: a randomized trial of a busulfan-Cytoxan versus Cytoxan-total body irradiation as preparative regimen: a report from the Group d'Etudes de la Greffe de Moelle Osseuse.

From October 1987 to December 1990, 101 patients with acute myeloid leukemia (AML) were randomized to be transplanted in first complete remission (CR1). Preparative regimen including Cytoxan (120 mg/kg) with total body irradiation (CYTBI) (N = 50) or busulfan (16 mg/kg) (BUSCY) (N = 51) was followed by allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling. Mean time between diagnosis and BMT was 119 days. The outcome for CYTBI at 2 years is better for probability of disease-free survival (DFS) (72% v 47%) (P less than .01), survival (75% v 51%) (P less than .02), relapse (14% v 34%) (P less than .04), and transplant mortality (8% v 27%) (P less than .06). In multivariable analysis, higher relapse and decreased survival and DFS were associated with BUSCY regimen, while chronic graft-versus-host disease also influenced independently the probability of relapse. This demonstrates the present limitation of busulfan use in this setting, possibly due to probable individual variations in biodisponibility. Furthermore, besides the anti-leukemic effect of preparative regimens, this trial points out the progress accomplished in BMT management (transplant mortality = 8% in CYTBI) over the last 20 years as well as the effectiveness of transplant in early first CR after CYTBI (DFS = 72% at 2 years).

Actuarial Analysis↗
PubMed1992

Crucial role of the third and fourth hypervariable regions of HLA-DPB1 allelic sequences in the mixed lymphocyte reaction.

Since HLA-DP mismatches are known to induce proliferative response in MLR I, we investigated the real impact of the different DP alleles and the possible role of one or several hypervariable regions of the DPB allelic sequences. Accordingly, we performed MLR I between HLA-A, B, DR, DQ, and Dw identical individuals DP oligotyped after DNA amplification. A total of 23 one-DP-mismatched healthy stimulator and responder cells displaying nine different DP specificities were thus evaluated in 52 MLRs I. This allowed us to analyze the impact of amino acid composition of each of the six hypervariable regions independently of the amino acid matching or mismatching in the five others. We show here that DP combinations sharing the same amino acid sequence in the third (C) and fourth (D) hypervariable regions are associated with a low proliferative response in vitro (p less than 0.01). These data imply that a perfect HLA-DP matching may not be requisite in selecting bone marrow donors. Indeed, the choice of donors may rely on determination of these particular mismatched HVRs between the DP alleles involved especially in GvHD direction. This policy including prospective DP oligotyping should be of great interest, especially when MLRs I are false negative or nonevaluable. It will enable a better definition of which DP mismatches are acceptable in BMT.

Alleles↗
PubMed1992

Reduced renal toxicity and improved clinical tolerance of amphotericin B mixed with intralipid compared with conventional amphotericin B in neutropenic patients.

The clinical use of amphotericin B is sometimes limited by nephrotoxicity. In a randomized prospective study, 32 patients treated for haematological malignancies received either amphotericin B in 5% dextrose (group A, 16 patients, 0.7-1 mg/kg/day), or amphotericin B mixed with Intralipid (group B, 16 patients, 0.7-1 mg/kg/day) during prolonged neutropenia. Renal dysfunction occurred in 9/16 patients in group A and 2/16 patients in group B (P < 0.05). Clinical tolerance was improved with a reduction of fever with chills in 12/16 patients in group A compared with 5/16 in group B (P < 0.05). Preparation of amphotericin B with Intralipid reduces nephrotoxicity, improves clinical tolerance, may allow an increase in the daily dose of amphotericin B, and be an alternative to liposomal-amphotericin B infusion.

Adult↗
PubMed1992

Improvement in outcome for children receiving allogeneic bone marrow transplantation in first remission of acute myeloid leukemia: a report from the Groupe d'Etude des Greffes de Moelle Osseuse.

PURPOSE: We retrospectively analyzed the outcome of children with acute myeloid leukemia (AML) in first complete remission (CR) who received HLA-identical bone marrow transplantation (BMT) in 13 French transplant centers. PATIENTS AND METHODS: Seventy-four children were treated from June 1979 through December 1990. The conditioning regimen included total-body irradiation (TBI) in 54 cases and busulfan in 20. Prophylaxis of graft-versus-host disease (GVHD) consisted of cyclosporine (CycloA) plus methotrexate (MTX) for 38 patients, MTX for 17, CycloA for 18, and T depletion without other prophylaxis for one. The mean value of the interval from diagnosis to transplantation was 167 days. RESULTS: Sixteen patients died of transplant-related complications, 12 relapsed, and 46 are alive in continuous remission with a median follow-up of 46 months. We examined results obtained over three successive periods: 1979 to 1982 (n = 14 children), 1983 to 1986 (n = 29), and 1987 to 1990 (n = 31). Probabilities of event-free survival (EFS) were 43%, 48%, and 82% for the three successive periods, respectively (P < .02). This improvement in EFS was linked to a decreased risk of transplant-related mortality: 36%, 36%, and 3%, respectively (P < .01). Other factors associated with a better EFS in the univariate analysis were a short time interval from diagnosis to transplant (< 120 days), the absence of significant (grade > or = 2) acute GVHD, and the absence of chronic GVHD. In the multivariate analysis, two factors had a favorable impact on long-term survival: the year of transplantation (years 1987 to 1990 v others) and the absence of acute GVHD. CONCLUSION: The outcome for children receiving allogeneic BMT in first CR of AML has improved in France during recent years.

Acute Disease↗
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↗
PubMed1991

Anti-LFA1 monoclonal antibody (25.3) for treatment of steroid-resistant grade III-IV acute graft-versus-host disease.

The in vivo efficacy of 25.3 monoclonal antibody (mAb) directed against human LFA1 molecule was assessed in ten patients with steroid-resistant grade III-IV acute graft-versus-host disease (AGVHD). These patients received non-T-cell-depleted allogeneic bone marrow transplantation for aplastic anemia in two cases and hematologic malignancies in eight cases. Five grafts were fully matched, three were one antigen-mismatched, and two were two antigen-mismatched. Despite GVHD prophylaxis with cyclosporin A and short-term methotrexate, AGVHD occurred after a median of 24 days and clearly progressed under prednisone (median 2 mg/kg), given for a median of 12 days. 25.3 mAb was given at a dosage of 0.1 mg/kg in a 4-h perfusion for five daily doses without any clinical or biological side effects. Thirty percent of the patients experienced a reduction in the overall grading with two complete responses. Partial response in at least one involved organ (mostly skin) occurred in 80% of the patients. However, seven out of the eight responding patients experienced a new episode of AGVHD. This observation, which confirms that inhibiting a functional molecule is as efficient as a cytolytic therapy, offers an alternative strategy to antithymocyte globulin (ATG) and cytotoxic mAb in controlling steroid-resistant GVHD.

Acute Disease↗
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↗