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Biomedical subjects

N Ifrah

Publications and source records attributed to N Ifrah.

At least 19 recordsLinked to original sources
PubMed1998

Graft-versus-leukemia effects in T lineage and B lineage acute lymphoblastic leukemia.

T and B lineage ALL cells express different levels of HLA-class II antigens, which may serve as targets for graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL). The object of this study was to determine whether GVL effects after HLA-identical sibling bone marrow transplantation differed in T and B lineage ALL. We studied 1132 patients with ALL of T lineage (n = 416) or of B lineage (cALLa+) (n = 716) transplanted in first (n = 605) or second (n = 527) remission with bone marrow from an HLA-identical sibling donor, between 1982 and 1992, and reported to the IBMTR by 165 teams. Cox proportional hazards regression models were used to determine the relative risk (RR) of relapse in patients with acute (grades II-IV) or chronic GVHD vs patients without GVHD. Acute and chronic GVHD were considered as time-dependent covariates. Patients transplanted in first and second remission were analyzed separately. GVHD decreased relapse risks to a similar extent in T and B lineage ALL. For first remission transplants, relative risks of relapse for patients with vs those without GVHD was 0.34 for T lineage ALL and 0.44 for B lineage ALL. Corresponding relative risks in second remission transplants were 0.54 and 0.61. This study confirms earlier findings of an antileukemia effect of GVHD in ALL. This effect was similar in T lineage and B lineage ALL, despite probable differences in HLA-class II antigen expression.

Adolescent↗
PubMed1997

Human cytomegalovirus DNA kinetics using a novel HCMV DNA quantitative assay in white blood cells of immunocompromised patients under Ganciclovir therapy.

The clearance of human cytomegalovirus (HCMV) was evaluated in infected patients under Ganciclovir (GCV) treatment, using a novel HCMV DNA quantitation assay (HCMV DNA hybrid capture system, Murex Diagnostics). Peripheral white blood cells (WBC) from whole blood specimens of seven AIDS patients, three kidney and two allogeneic bone marrow transplant (BMT) recipients suffering from HCMV disease, were assessed by this method. HCMV DNA 50 and 90% mean clearances were observed at 2.11 +/- 1.97 and 6.22 +/- 4.31 days, respectively, after initial GCV treatment. The viral DNA kinetics were correlated with positive and negative pp65 antigenaemia and viral blood culture. Two-fold higher clearances and initial DNA levels were observed in the AIDS group compared to the transplant group. Neither clinical nor virological relapses were observed under GCV treatment. HCMV DNA quantitation in WBC appears well adapted for a therapeutic follow up of patients with HCMV disease.

Antigens, Viral↗
PubMed1997

Early allogeneic transplantation favorably influences the outcome of adult patients suffering from acute myeloid leukemia. Société Française de Greffe de Moelle (SFGM).

Allogeneic BMT for patients with acute myeloid leukemia (AML) is presently a reference therapy. The indications for this therapy mainly rely upon prognostic factors, and their importance is constantly reassessed. To examine the impact of time from diagnosis to transplant on survival and leukemia-free survival (LFS), we analyzed 109 patients from the database of the SFGM comprising patients who had all received an HLA-identical allogeneic BMT for a diagnosis of AML in first complete remission (CR1) between January 1987 and December 1992. All patients were conditioned with cyclophosphamide (CY) and total body irradiation (TBI) (CYTBI), and methotrexate (MTX) + cyclosporin A (CsA) were used as graft-versus-host disease (GVHD) prophylaxis. Patient characteristics were: age = 33 +/- 9, M/F = 64/45, white blood cell count (WBC) at diagnosis = 27 +/- 42 x 10(9)/l, FAB distribution: M1 and M2 = 55; M3 = 15, M4 and M5 = 33, M0, M6 and M7 = 6. Karyotyping was carried out for 64 patients: 32 had a normal karyotype, 16 had good prognosis abnormalities (t(8;21), t(15;17), inv 16) and 16 patients had other abnormalities. Eleven patients needed two courses of induction to achieve CR. Time between diagnosis and BMT was 120 (64-287) days. Forty-nine patients developed grade > or = 2 acute GVHD (actuarial probability = 46%). With a median follow-up of 50 months (27-100), the 5-year probabilities for transplant-related mortality (TRM), relapse, overall survival and LFS are respectively 25%, 26%, 59% and 55%. A multivariate analysis showed that survival is adversely influenced by three independent factors: time to transplant (> 120 days vs < or = 120 days), acute GVHD (grade 2-4 vs grade 0-1) and age (> 33 vs < or = 33). LFS is only influenced by the first two of these factors. The favorable impact of a shorter time from diagnosis to transplant should lead to performing the transplant as early as possible. Practically speaking, this means that when such therapy is chosen for a patient with CR1 AML, the search for an allogeneic donor should begin immediately and transplant be performed as soon as possible.

Acute Disease↗
PubMed1997

Avascular necrosis of bone after allogeneic bone marrow transplantation: analysis of risk factors for 4388 patients by the Société Française de Greffe de Moëlle (SFGM).

Increasing numbers of patients are surviving after allogeneic bone marrow transplantation and are therefore at risk for developing late complications. Among these complications, avascular necrosis of bone has been reported, but only two single-centre studies included sufficient patients to enable analysis of the risk factors for developing avascular necrosis. In this multicentre retrospective study the aim was to assess risk factors for this complication in a large number of patients. The population consisted of 4388 patients, recorded in the Societe Francaise de Greffe de Moelle (SFGM) data base, who had undergone a single allogeneic bone marrow transplant between January 1974 and December 1993. 77 patients developed avascular necrosis leading to a 4.3% projected incidence at 5 years. Symptoms developed 2-132 months after transplantation. In these 77 patients a mean of 1.87 joints per patient were affected (range 1-7). The hip joint was the most often affected (88% of patients) and 48% of the patients required joint replacement. All but two patients received steroids for acute and/or chronic graft-versus-host disease (GvHD) over a mean period of 15 months. In univariate analysis, among eight factors tested as risk factors for developing avascular necrosis, six were shown to be linked to an increased risk: older age, diagnosis of aplastic anaemia or acute leukaemia, an irradiation-based conditioning regimen, type of GvHD prophylaxis regimens, acute and chronic GvHD. In multivariate logistic regression analysis, five factors remained significantly associated with an increased risk for developing avascular necrosis: chronic GvHD (odds ratio (OR) 3.52), acute GvHD (OR 3.73), age > 16 years (OR 5.81), aplastic anaemia (OR 3.90), and acute leukaemia (OR 1.72). Avascular necrosis is not a rare late complication of allogeneic bone marrow transplantation causing significant morbidity. In this study, older age, initial diagnosis, and GvHD and/or its treatment with steroids emerged as significant risk factors.

Acute Disease↗
PubMed1997

Successive transformation of chronic myelomonocytic leukaemia into acute myeloblastic then lymphoblastic leukaemia, both with minor-bcr rearrangement.

We report a case of chronic myelomonocytic leukaemia (CMML), which transformed first into acute myeloblastic leukaemia (AML) and then into acute lymphoblastic leukaemia (ALL). In the AML and ALL phases, chromosome analysis showed a classic Philadelphia chromosome (Ph) t(9:22)(q34:q11). Molecular studies showed breakpoint cluster region rearrangement between exons e1 and a2 compatible with a p190(bcr/abl) breakpoint as observed in Ph-positive lymphoblastic acute leukaemia. The minor (m-bcr) rearrangement was also detected during complete remission. This observation supports a multistep pathogenesis of leukaemias, and that the p190(bcr/abl) breakpoint may influence the course of the disease.

Aged↗
PubMed1997

Allogeneic bone marrow transplantation for agnogenic myeloid metaplasia. French Society of Bone Marrow Transplantation.

Agnogenic myeloid metaplasia is a rare indication for allogeneic bone marrow transplantation (BMT). We have retrospectively studied 12 patients allografted for this disease within the French BMT group. Prior to BMT, the mean age was 40 years (range 14-49). Diagnosis was based on the Polycythaemia Vera Study Group criteria. Before BMT, 10 patients had been splenectomized, eight required transfusions, and four had received at least two lines of chemotherapy. Cyclophosphamide and total body irradiation was the main conditioning regimen used (n=8). The donor was an HLA-identical sibling except in one case where there was one HLA-DR mismatch. Acute graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate and cyclosporine A. 11 patients engrafted with median times to achieve absolute neutrophil count > 0.5 x 10(9)/l and platelet count > 50 x 10(9)/l of 17 (range 12-44) and 29 (range 12-196) days respectively. One primary graft failure occurred. 10 patients developed grade II-IV acute GVHD, four developed extensive chronic GVHD. One patient relapsed 16 months post-BMT and was untreated and well 14 months later. Three patients died from the BMT procedure. In May 1996 the median follow-up was 25 months and the 4-year overall and event-free survivals were 71% and 59%, respectively. Thus, we conclude that extensive myelofibrosis is not associated with delayed engraftment, and that HLA-identical sibling allogeneic BMT can be considered in a small proportion of patients with agnogenic myeloid metaplasia.

Adolescent↗
PubMed1997

[Hematologic manifestations related to hepatitis A virus. 3 cases].

We report 3 cases of acute hepatitis A infection with haematological manifestations. In the first case, severe aplastic anemia occurred in a 6 year-old child, who underwent 3 bone marrow grafts before responding favourably. In the second and third cases, severe anemia and thrombocytopenia occurred in a 42 year-old man with cholestatic hepatitis, and in a 66 year-old man with fulminant hepatitis; there was a favourable outcome in both cases. These cases demonstrate that haematological manifestations in hepatitis A can be severe, independent of the severity of liver disease. Although these manifestations seem to be rare, we suggest performing systematic haematological evaluations in cases of viral hepatitis A with unusual outcomes.

Adult↗
PubMed1996

Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study.

A phase III prospective randomized multicenter study was performed to determine whether quinine could improve the response rate of poor-risk acute leukemias (ALs) to standard chemotherapy including a multidrug resistance (MDR)-related cytotoxic agent. The rationale of the study was based on the negative prognostic value of MDR phenotype in ALs and the ability of quinine to reverse this phenotype both in vitro and ex vivo. Three hundred fifteen patients (median age, 49 years; range, 16 to 65) with relapsed (n = 108) or refractory (n = 32) acute myeloblastic leukemia (AML), relapsed (n = 27) or refractory (n = 9) acute lymphoblastic leukemia (ALL), secondary AL (n = 22) or blastic transformation of myelodysplastic syndrome ([MDS] n = 74) or myeloproliferative syndrome ([MPS] n = 43) were randomly assigned to receive mitoxantrone ([MXN] 12 mg/m2/d, days 2 to 5) and cytarabine ([Ara-C] 1 g/m2/12 h, days 1 to 5) alone or in combination with quinine (30 mg/kg/d, days 1 to 5; continuous intravenous infusion beginning 24 hours before MXN infusion). Side effects of quinine were observed in 56 of 161 quinine-treated patients and disappeared in all but four cases after one or two 20% dose decreases. Sera from quinine-treated patients showed increased MXN uptake in an MDR-positive cell line compared with matched sera obtained before quinine infusion. Quinine induced a significant increase in the incidence of nausea, vomiting, mucositis, and cardiac toxicity. A complete response (CR) was observed in 85 of 161 patients (52.8%) from the quinine-treated group versus 70 of 154 patients (45.5%) in the control group (P = .19). The most important differences between quinine and control group CR rates were observed in patients with refractory AMLs and blastic transformation of MDS and MPS. The CR rate was higher in P-glycoprotein-positive cases, although the difference was not significant. Failure of the regimen due to blastic persistence or blast number increase was higher in the control group (61 of 154 patients) than in the quinine group (45 of 161, P = .04). Early death was observed in eight cases (four in each arm) and death in aplasia in 27 cases (20 in quinine group v seven in control group, P = .01). The significant increase of toxicity in the quinine arm could have masked the clinical benefit of MDR reversion in poor-risk ALs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome.

BACKGROUND: The median survival of patients with myeloma after conventional chemotherapy is three years or less. Promising results have been reported with high-dose therapy supported by autologous bone marrow transplantation. We conducted a randomized study comparing conventional chemotherapy and high-dose therapy. METHODS: Two hundred previously untreated patients under the age of 65 years who had myeloma were randomly assigned at the time of diagnosis to receive either conventional chemotherapy or high-dose therapy and autologous bone marrow transplantation. RESULTS: The response rate among the patients who received high-dose therapy was 81 percent (including complete responses in 22 percent and very good partial responses in 16 percent), whereas it was 57 percent (complete responses in 5 percent and very good partial responses in 9 percent) in the group treated with conventional chemotherapy (P < 0.001). The probability of event-free survival for five years was 28 percent in the high-dose group and 10 percent in the conventional-dose group (P = 0.01); the overall estimated rate of survival for five years was 52 percent in the high-dose group and 12 percent in the conventional-dose group (P = 0.03). Treatment-related mortality was similar in the two groups. CONCLUSIONS: High-dose therapy combined with transplantation improves the response rate, eventfree survival, and overall survival in patients with myeloma.

Adult↗
PubMed1996

Factors influencing outcome in de novo myelodysplastic syndromes treated by allogeneic bone marrow transplantation: a long-term study of 71 patients Société Française de Greffe de Moelle.

We report on 71 consecutive patients with de novo myelodysplastic syndromes referred to physicians belonging to the Société française de greffe de moelle from 1982 through 1991 and transplanted with marrow from HLA-identical siblings. There were 16 cases of refractory anemia, 27 of refractory anemia with excess of blast cells, and 28 of refractory anemia with excess of blast cells in transformation. Seventeen patients had received cytoreductive chemotherapy before the graft. The disease progressed in 17 patients between diagnosis and grafting. Twenty-three patients are alive with a median follow-up of 6 years, whereas 24 died from relapse and 24 from transplant-related complications. Kaplan-Meier estimates of event-free survival, relapse and transplant-related mortality at 7 years were 32%, 48%, and 39%, respectively. The log-rank test and Cox's model revealed better outcome among young patients, patients in an early stage of the French-American-British (FAB) classification or with a low percentage of marrow blasts before transplantation, patients who did not undergo cytoreductive chemotherapy before transplantation, and patients conditioned with total body irradiation and cyclophosphamide. The high rate of relapse in advanced FAB stages has led us to graft patients earlier in the course of the disease, and we are currently conducting a multicenter, randomized study to determine the value of intensive chemotherapy before grafting in patients with an excess of marrow blasts.

Adult↗
PubMed1996

Histopathology of bone marrow after allogeneic bone marrow transplantation for chronic myeloid leukaemia.

The histopathology of bone marrow after allogeneic bone marrow transplantation for chronic myeloid leukaemia (CML) was studied in 20 bone marrow biopsy specimens from 14 patients. Biopsies were performed at day 30 post-transplantion (5 biopsies), between day 90 and day 100 (14 biopsies), and one year post-transplantation (1 biopsy). Eight biopsies taken at day 30 post-transplantation for lymphoproliferative disorder were studied as controls. Granulopoiesis was predominant in all day 30 bone marrows in patients treated for CML. In 2 cases, rejection was suspected because of marrow hypoplasia at day 30: one case developed acute leukaemia soon after persistant hypoplasia at day 90 while the evolution of the other case was good. Two day 30 biopsies showed granulocytic hyperplasia but follow-up proved complete remission of CML. Thus, in our series, early biopsies at day 30 did not have any prognostic value. Twelve cases at day 90-100 showed little modifications, such as minor dyserythropoiesis and dysmegakaryopoiesis. One case showed granulocytic hyperplasia at day 100 but bone marrow was normal one year later and the patient in complete remission. The haematopoietic reconstitution after allogeneic bone marrow transplantation may present a transient granulocytic hyperplasia that must not be diagnosed as a persistence of CML.

Adult↗
PubMed1996

Myelodysplastic syndrome with t(5;12)(q31;p12-p13) and eosinophilia: a pediatric case with review of literature.

PURPOSE: Myelodysplastic syndrome with chromosomal translocation t(5;12)(q31-33;p12-13) and eosinophilia is a new entity recently described. Nine cases have been described in adults. We report the first pediatric case with a long follow-up (7 years). PATIENTS AND METHODS: An 8-year-old girl presented with hyperleukocytosis, eosinophilia, and no clinical symptoms. Bone marrow investigations revealed myeloid hyperplasia and clonal chromosomal translocation t(5;12)(q31;p12-13). No treatment was prescribed, but 4 years later the white blood cell count reached 144 X 10(9)/L with immature myeloid cells and splenic enlargement. Hydroxyurea chemotherapy led to a hematopoietic remission. The patient is now 16 years old and well, >7 years after the initial diagnosis. RESULTS: The association: myelodysplastic syndrome, eosinophilia and translocation t(5;12)(q31-33;p12-13), seems to be a specific hematologic disorder. Study of cases previously reported in the literature shows the most important characteristics of this disease. However, there are still a number of questions about the disease itself (especially its treatment) and the significance of the chromosomal abnormalities. CONCLUSION: This case seems to be the first report of the disease in a child and has had the longest follow-up. Other data should be collected to improve our knowledge of this hematopoietic disorder.

Adult↗
PubMed1996

Infradiaphragmatic Hodgkin's disease: long term results of combined modality therapy.

Hodgkin's disease (HD) confined below the diaphragm accounts for less than 5% of all patients with HD. Although the major characteristics of this presentation appear established, optimal modalities of treatment still remain difficult to define. From April 1972 to October 1988, 28 patients with newly diagnosed infra-diaphragmatic HD, clinical stages I or II have been treated with 3 successive prospective protocols combining initial chemotherapy and radiotherapy (40 gy). This series of patients accounted for 4,3% of patients with HD limited to clinical stages (CS) I and II. Overall survival and freedom from relapse at 15 years were 74,4% and 73% respectively, without significant differences between clinical stages I and II, presence or absence of B symptoms or histologic subtype. There is only a trend (p < 0,10) in favour of patients younger than 40 years. In all 7 clinically staged IA patients no relapses were seen and combined treatment does not appear to be better than inverted Y irradiation alone. On the other hand initial chemotherapy seems necessary in patients with CS II A and B since 15 of our 21 patients are alive in first CR whereas the crude rate of transdiaphragmatic nodal relapses may reach up to 53% following radiotherapy alone.

Adolescent↗
PubMed1996

Pulmonary toxoplasmosis after allogeneic bone marrow transplantation: case report and review.

We report an isolated case of toxoplasma pneumonitis in a 27-year-old man. This acute infection occurred after induction chemotherapy for AMLo relapsing 3 years post-allogeneic BMT. The detection of Toxoplasma gondii in the bronchoalvolar lavage (BAL), by culture in fibroblast cell line MRC5 enabled us to make the diagnosis. Pyrimethamine and sulfadiazine were effective.

Acute Disease↗
PubMed1995

Allogeneic bone marrow transplantation for chronic myeloid leukemia in first chronic phase: a randomized trial of busulfan-cytoxan versus cytoxan-total body irradiation as preparative regimen: a report from the French Society of Bone Marrow Graft (SFGM).

From March 1988 to March 1991, 19 French bone marrow transplant (BMT) centers participated in a prospective randomized trial comparing two conditioning regimens for patients with chronic myeloid leukemia transplanted in first chronic phase with an HLA identical sibling donor. A total of 120 consecutive patients were randomized to receive either 120 mg/kg of cyclophosphamide followed by total body irradiation (CY-TBI; n = 55) or 16 mg/kg of busulfan followed by 120 mg/kg of CY (BU-CY; n = 65). Two different TBI regimens were used. Thirteen patients received a 10-Gy single-dose TBI (SDTBI), and 42 received a fractionated TBI (FTBI). Median time between diagnosis and BMT was 315 days. Overall 5-year actuarial survival was 62.9% (65.8% +/- 12.5% for CY-TBI and 60.6 +/- 11.7% for BU-CY; P = .5), and overall disease-free survival was 55% (51% +/- 14% for CY-TBI and 59.1% +/- 11.8% for BU-CY; P = .75). All patients conditioned with CY-TBI experienced sustained engraftment; in contrast, 4 of 65 patients conditioned with BU-CY rejected the graft (P = .18). There was no significant statistical difference between the two groups regarding transplant-related mortality (29% for CY-TBI and 38% for BU-CY; P = .44). So far, with a median follow up of 42 months, 11 patients have relapsed; 9 relapses occurred after CY-TBI, mostly after FTBI (8 of 9) and 2 after BU-CY (P = .02). The actuarial risk of relapse was 4.4% +/- 6.7% after BU-CY, 11.1% +/- 20.8% after SDTBI, and 31.3% +/- 18.1% after FTBI (P = .039). In addition, independently of the conditioning regimen, the increase of posttransplant immunosuppression in 16 patients with an anti-interleukin-2 receptor monoclonal antibody (MoAb) in addition to a short course of methotrexate and cyclosporine was shown to increase the actuarial risk of relapse (57% +/- 30% with MoAb v 9% +/- 7.3% without MoAb; P = .001). We conclude that BU is an acceptable alternative to TBI for patients with chronic myeloid leukemia in first chronic phase receiving BMT from HLA identical sibling donors. Both BU-CY and CY-TBI regimens gave similar transplant-related mortality, and the antileukemic efficiency of BU-CY regimen was either similar or even higher than that of CY-TBI.

Adolescent↗
PubMed1995

Peripheral primitive neuroectodermal tumour after allogeneic bone marrow transplantation.

We report a case of peripheral primitive neuroectodermal tumour (PNET) in a 36-year-old man who 10 years earlier received an allogeneic bone marrow transplantation (BMT) for a non-Hodgkin's lymphoma. Immunohistochemistry proved definitive elimination of a relapse of the original disease and confirmed the diagnosis of PNET. The role of total body irradiation pre-BMT in the genesis of this secondary tumour is discussed. The importance of registering secondary malignant solid tumours after BMT is emphasized. To our knowledge, an Ewing family tumour following BMT has not previously been reported.

Adult↗
PubMed1995

[Immunohistochemical characterization of acute leukemia. Study of 31 bone marrow biopsies].

An immunohistochemical study by avidin-biotin-peroxidase was performed on paraffin-embedded and decalcified bone marrow biopsies in 31 acute leukemias (19 myeloid and 12 lymphoblastic). The Ulex Europaeus lectin and 14 antibodies (anti-CD45, -CD34, -myeloperoxidase, -lysozyme, -CD15, -CD68, -carcinoembryonic antigen, -factor VIII-related antigen, BNH9, anti-CD45RO, -CD3, -CD20, DBB42 and DBA44) were tested. All acute myeloid leukemias from M0 to M5 type were stained by either the anti-myeloperoxidase or anti-lysozyme antibodies. CD68, CD15 and the carcinoembryonic antigen were respectively expressed in 80%, 40% and 20% of myeloid leukemias from M1 to M5 type. The Ulex Europaeus lectin and the anti-factor VIII-related antigen antibody stained only the M7 leukemia and the anti-CD3 antibody stained only the T acute lymphoblastic leukemia. DBB42 was expressed by 63% of B-lineage lymphoblastic leukemias and CD20 by 36%. No leukemia was stained by DBA44. Immunohistochemistry on bone marrow biopsy can assess the lineage of most acute leukemias with the use of a panel of antibodies such as the anti-myeloperoxidase, -lysozyme, -CD68, -CD20, DBB42, -CD3, BNH9, anti-factor VIII-related antigen antibodies and the Ulex Europaeus lectin.

Acute Disease↗