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M Macro

Publications and source records attributed to M Macro.

At least 19 recordsLinked to original sources

Prognostic factors in patients with aggressive non-Hodgkin's lymphoma treated by front-line autotransplantation after complete remission: a cohort study by the Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: Improved survival has been observed in aggressive non-Hodgkin's lymphoma (NHL) patients with adverse prognostic factors when autotransplantation (ASCT) was performed after complete remission. However, there is no agreement on the prognostic factors for patients treated with ASCT. We aimed to estimate the prognostic effect of clinical and biologic variables on relapse and survival rates by pooling the data from two trials. PATIENTS AND METHODS: Of the patients treated in the LNH87 and LNH93 trials, 330 under age 60 years achieved complete remission after high-dose cyclophosphamide, doxorubicin, vincristine, and prednisone, and received consolidative ASCT; 16% of patients had T-cell NHL. The International Prognostic Index (IPI) score was 0 for 11%, 1 for 23%, 2 for 51%, and 3 for 15%. Univariate and Cox multivariate survival analyses were retrospectively performed on this population. RESULTS: Overall survival was 75 +/- 5% at 5 years and disease-free survival (DFS) 67 +/- 5%. For T-cell NHL, these scores were 54% and 44%, respectively. The IPI score had no prognostic value and only the following parameters adversely affected overall survival and DFS (P <.05): marrow involvement; more than one extranodal site; histology (nonanaplastic T-cell v others); and type of anthracycline (mitoxantrone v doxorubicin, for DFS only). CONCLUSION: These results suggest that ASCT can prevent relapse in patients with adverse IPI factors. However, patients presenting with a nonanaplastic T-cell phenotype, more than one extranodal site, or marrow involvement still have a higher risk of relapse. These factors should be taken into account when designing post-ASCT maintenance studies.

Adolescent↗

[Polycythemia vera and pregnancy].

Polycythemia vera is a rare chronic myeloproliferative disease. Its exceptional association with pregnancy can lead to severe complications. Antithrombotic treatment could prevent such adverse outcome. A patient with two previous pregnancies complicated by preeclampsia, was treated by hydroxyurea for polycythemia vera. She started a new unexpected gestation without this myelosuppressive treatment and the pregnancy was conducted uneventfully with low molecular weight heparin and low dose aspirin. Thrombotic complications required the reintroduction of hydroxyurea. Diagnosis of polycythemia vera during pregnancy is a very difficult task due to physiologic changes occurring during gestation. Adverse outcome including severe vascular complications can be a preclinical phase of the disease. An adequate therapy could prevent these complications.

Adult↗

Incidence and risk factors for central nervous system occurrence in elderly patients with diffuse large-B-cell lymphoma: influence of rituximab.

BACKGROUND: The incidence of secondary central nervous system (CNS) occurrences in diffuse large-B-cell lymphoma is not sufficiently high to warrant the use of CNS prophylaxis in all patients. The addition of rituximab increases the complete response rate and prolongs event-free and overall survival in elderly patients with such lymphoma. PATIENTS AND METHODS: We analyzed a cohort of 399 elderly patients with lymphoma prospectively treated with eight cycles of CHOP with or without rituximab in order to assess if rituximab decreases the risk of CNS localization. Prophylaxis of CNS disease was not part of the treatment protocol. RESULTS: We observed 20 CNS occurrences: 12 on therapy, four after partial remission and four following complete remission. In three patients, the CNS was the only site of relapse. In a multivariate analysis, increased age-adjusted International Prognostic Index (IPI) was the only independent predictive factor of CNS recurrence. Only three of 20 patients are alive with a follow-up of 24 months. CONCLUSIONS: Rituximab did not influence the risk of CNS occurrence, possibly because of low rituximab diffusion. Direct intrathecal administration of rituximab could overcome this problem. We also confirmed that CNS occurrence is related to IPI as well as very poor prognosis of relapses occurring on therapy.

Aged↗

All aggressive lymphoma subtypes do not share similar outcome after front-line autotransplantation: a matched-control analysis by the Groupe d'Etude des Lymphomes de l'Adulte (GELA).

BACKGROUND: Data are still conflicting on the indication of front-line autologous stem-cell transplantation (ASCT) as consolidation for aggressive lymphoma. To assess the therapeutic effect of ASCT among different aggressive lymphoma subtypes, we conducted a matched-control analysis by pooling the data from two Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials. PATIENTS AND METHODS: Between October 1987 and September 1998, 330 patients received ASCT after achieving complete remission with the ACBVP induction regimen. The histological slides showed: B aggressive non-Hodgkin's lymphoma (B-NHL) in 249 patients (75%), T-NHL in 52 patients (15%) (including 23 T anaplastic) and non-classified NHL in 29 patients. The age-adjusted International Prognostic Index (aaIPI) was 2 or 3 in 66%. Patients were matched with controls from the same GELA database but treated with chemotherapy only. RESULTS: ASCT did not benefit non-anaplastic T-NHL patients [5-year overall survival (OS) 44% (chemotherapy) versus 49% (ASCT), P=0.87; disease-free survival (DFS) 38% versus 45%, P=0.89] in comparison with B-NHL [5-year OS 77% (chemotherapy) versus 79% (ASCT), P=0.64; DFS 67% versus 72%, P=0.13]. However, for B-NHL patients with aaIPI score 2 or 3, the benefit of ASCT was significant. CONCLUSIONS: This cohort study confirms the high efficacy of front-line ASCT in responding aggressive B-NHL patients with adverse prognostic factors.

Adolescent↗

[Concomitant pulmonary nocardiosis and Hodgkin's disease: importance of long-term treatment].

A 32-year-old patient taking corticosteroid therapy for 10 months for autoimmune hemolytic anemia developed Hodgkin's disease and concomitant acute pulmonary nocardiosis. After treatment with imipenen and amikacin for 15 days, which was adapted to susceptibility tests, multiple-drug chemotherapy using the ABVD protocol (doxorubicin, bléomycin, vinblastine, dacarbazine) was given without recurrence of the pulmonary infection. Antibiotic prophylaxis using a minocycine-erythromycin combination was continued for 8 months. We discuss the importance of long-term treatment based on data in the literature.

Adult↗

Clinical relevance of gallium-67 scintigraphy in lymphoma before and after therapy.

The clinical impact of gallium-67 scintigraphy before and after therapy for lymphoma remains controversial. The aims of this study were: (1) to compare the staging of lymphoma by 67Ga scintigraphy only with staging by clinical examination and conventional imaging (CI), and (2) to analyse the clinical relevance of both 67Ga imaging and CI after treatment. From March 1995 to November 1998, 86 67Ga scintigraphy studies were performed in 62 patients with Hodgkin's disease (n=52) or non-Hodgkin's lymphoma (n=10). 67Ga scintigraphy was performed at diagnosis (n=44) or after therapy (n=42) using 185-220 MBq 67Ga citrate and planar and single-photon emission tomography (SPET) studies. Treatment comprised radiotherapy, chemotherapy or combined modalities. CI included plain chest radiography, computed tomography (CT) of the chest and abdomen/pelvis, ultrasound of the abdomen, lymphography, bone marrow biopsy and, when necessary, magnetic resonance imaging (MRI) and bone scintigraphy. For individual suspected sites of disease before treatment, complete agreement between clinical examination and CI on the one hand and 67Ga scintigraphy on the other hand was observed in 25/44 patients (57%; 95% confidence interval 41%-72%). Clinical examination and CI showed more sites than did 67Ga scintigraphy in 12/44 patients (27%) and 67Ga imaging demonstrated more sites than CI in 6/44 patients (11%). The clinical stage of the disease as assessed using 67Ga scintigraphy only was in agreement with that using all diagnostic procedures in 34/44 patients (77%; 95% confidence interval 62%-89%). Compared with CI staging, 67Ga scintigraphy downstaged seven patients (16%) and upstaged three (7%). 67Ga scintigraphy downstaged mainly because of the limited value of the technique below the diaphragm and upstaged owing to the good sensitivity in the lung. After therapy, both CI and 67Ga scintigraphy were normal in 11 patients. All but one of these patients were in complete remission after a median follow-up of 31 months. In contrast, radiological residual mass was observed in 31/42 patients. 67Ga imaging was normal in 22/31 (71%); 17 of these 22 patients, including nine with a large residual mass (> or =2 cm), were in complete remission after a median follow-up of 32 months, while four suffered relapses 8-45 months later. The cause of death remained unknown in one patient. 67Ga scintigraphy showed abnormal uptake in 9 of the 31 patients with a large residual mass. Active disease was demonstrated in eight patients and one patient was in complete remission 30 months thereafter. Our data show that 67Ga imaging cannot replace CI in initial staging but can demonstrate additional individual sites of disease in more than 10% of patients and can lead to clinical upstaging with potential prognostic and therapeutic consequences. After therapy, 67Ga scintigraphy has a clinical impact when radiological abnormalities persist because it can either avoid unnecessary complementary treatment or confirm the need to change treatment modalities.

Citric Acid↗

Cyclin D1 expression in patients with multiple myeloma.

INTRODUCTION: Chromosomal abnormalities are detected in 50 to 70% of patients with multiple myeloma (MM). By conventional cytogenetic analysis, a t(11;14)(q13;q32) is observed at a frequency of 3 to 14%. MATERIALS AND METHODS: To demonstrate a cyclin D1 expression in MM patients or MM cell lines, 14 patients with multiple myeloma (MM) and nine human multiple myeloma cell lines (HMCL) were screened by a competitive RT-PCR and/or Northern blot analysis for cyclin D1 expression. Furthermore, we screened 10 MM patients with FISH to demonstrate a relationship between the cyclin D1 expression and the presence of the t(11;14). RESULTS: Five HMCL had a cyclin D1 overexpression: three of them had a t(11;14)(q13;q32) and two had extra copies of chromosome 11. A cyclin D1 expression was found at diagnosis in seven out of 14 untreated MM patients (50%). Out of 14 MM patients, FISH studies were performed in 10 patients. A t(11;14) was detected in three out of 10 patients and extra copies of chromosome 11 were found in two additional patients. CONCLUSION: Cyclin D1 expression is a common event in MM patients (50%) and is associated either with a t(11;14)(q13;q32) or extra copies of chromosome 11. The prognostic role of the cyclin D1 expression and the level of this expression, as compared to other B-cell chronic lymphoproliferative disorders such as mantle cell lymphoma or hairy cell leukemia, remains to be determined in the pathogenesis of multiple myeloma.

Bone Marrow↗

IgE multiple myeloma.

IgE multiple myeloma is a rare disease characterized by a high frequency of Bence-Jones proteinuria and plasma cell leukaemia when compared to other isotypes of monoclonal proteins. Only 35 cases have been reported. We describe a 70-year-old woman with a stage III IgE kappa multiple myeloma presenting with a sacral plasmacytoma. Immunological and biochemical studies showed IgE kappa producing tumoral plasma cells. Serum total IgE was high without clinical symptoms suggesting an hyperIgE syndrome or mast cell activation. The patient underwent surgical removal of the sacral tumor and monthly melphalan-prednisone treatment together with intravenous pamidronate infusions. Magnetic Resonance Imaging (MRI) of the dorsolumbar spine revealed an epidural process leading to T6-T9 radiotherapy. Bone densitometry showed a decreased bone mineral content supporting the management of myeloma-related osteoporosis with bisphosphonate infusions. A good partial response with plateau-phase and increase of bone mineral content was achieved after 1 year of treatment and still persists after a 28 months follow-up.

Aged↗

High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial.

Results to date indicate that high-dose therapy (HDT) with autologous stem cell support improves survival of patients with symptomatic multiple myeloma (MM). We performed a multicenter, sequential, randomized trial designed to assess the optimal timing of HDT and autotransplantation. Among 202 enrolled patients who were up to 56 years old, 185 were randomly assigned to receive HDT and peripheral blood stem cell (PBSC) autotransplantation (early HDT group, n = 91) or a conventional-dose chemotherapy (CCT) regimen (late HDT group, n = 94). In the late HDT group, HDT and transplantation were performed as rescue treament, in case of primary resistance to CCT or at relapse in responders. PBSC were collected before randomization, after mobilization by chemotherapy, and, in the two groups, HDT was preceded by three or four treatments with vincristine, doxorubicin, and methylprednisolone. Data were analyzed on an intent-to-treat basis using a sequential design. Within a median follow-up of 58 months, estimated median overall survival (OS) was 64.6 months in the early HDT group and 64 months in the late group. Survival curves were not different (P = .92, log-rank test). Median event-free survival (EFS) was 39 months in the early HDT group whereas median time between randomization and CCT failure was 13 months in the late group. Average time without symptoms, treatment, and treatment toxicity (TWiSTT) were 27.8 months (95% confidence interval [CI]; range, 23.8 to 31.8) and 22.3 months (range, 16.0 to 28.6) in the two groups, respectively. HDT with PBSC transplantation obtained a median OS exceeding 5 years in young patients with symptomatic MM, whether performed early, as first-line therapy, or late, as rescue treatment. Early HDT may be preferred because it is associated with a shorter period of chemotherapy.

Adult↗

A randomized, double blind, placebo controlled multicenter trial of murine anti-CD4 monoclonal antibody therapy in rheumatoid arthritis.

OBJECTIVE: To assess safety and efficacy of a murine anti-CD4 monoclonal antibody (Mab) in a population of patients with rheumatoid arthritis (RA) compared to treatment with placebo. METHODS: Fifty-eight patients with defined RA were included in this placebo controlled, randomized, double blind, multicenter study. Of the 48 women and 10 men (mean age 54.5 years), 25 were functional class II and 31 were class III, with 9 years' disease duration; the mean of previous disease modifying antirheumatic drugs was 4; 49 were taking steroids (mean dosage 11 mg/day of prednisone). Eighty percent were rheumatoid factor positive. All were in an active state of the disease with: pain > 4 (mean at inclusion 6.6), tender joints > 4 (mean 12), swollen joint count > 3 (mean 9), morning stiffness > 45 min (mean 185), erythrocyte sedimentation rate > 30 mm (mean 59) or C-reactive protein (CRP) > 30 mg/l (mean 63). Treatment was randomized between murine anti-CD4 Mab (B-F5, Diaclone, 20 mg/day) or placebo intravenously for 10 consecutive days. Efficacy was assessed with a composite index (Paulus), with evaluation of number of patients with 20 or 50% improvement in each group. Changes in measures of single clinical or biological variables were also evaluated. RESULTS: The 2 groups were comparable at inclusion. Treatment was well tolerated. Mild side effects (chills, fever, rash) were seen in both groups. Percentage of patients with global 20 or 50% response did not differ between placebo and Mab groups at Day 10 or at Day 30. Evaluation of single variables showed reduced CRP, swollen joint count, and Ritchie index in some B-F5 patients at Day 10, although in the B-F5 group as a whole only CRP was significant. CONCLUSION: No significant improvement in RA after murine anti-CD4 Mab was observed.

Adult↗

[Autoimmune thrombopenic purpura. Therapeutic modalities].

TOP PRIORITY: Preventing hemorrhage is the number one priority in the treatment of idiopathic thrombocytopenic purpura. There are three main treatments: corticosteroids, intravenous immunoglobulins and splenectomy. CORTICOSTEROIDS: The main effects of corticosteroids are to reduce platelet phagocytosis, counteract mechanisms leading to inhibited thrombopoiesis, limit vascular fenestration and endothelial fragility, and immuno-depression. Corticosteroids are usually started at 1 to 2 mg/kg/day for 2 or 3 weeks before rapidly tapering off to final withdrawal after 3 or 4 weeks. IV IMMUNOGLOBULINS: Administered by intravenous injections, immunoglobulins saturate the Fc fragment of the IgGs on the surface of the macrophages, neutralize antiplatelet antibodies, and inhibits synthesis of antiplatelet autoantibodies. Treatment cost is high as is the risk of adverse effects. SPLENECTOMY: The most effective long-term treatment, splenectomy is particularly useful when platelet sequestration, as identified by radiolabeling occurs mainly in the spleen. OTHER THERAPIES: Anti-D immunoglobulins (limited availability), danazol or immuno-suppressors have a beneficial effect which disappears after withdrawal. INDICATIONS: Essential elements are the risk of hemorrhage (low or nil above 30000 platelets/mm3), its severity, patients status (childhood cases usually resolve spontaneously) and prognosis factors (idiopathic thrombocytopenic purpura is a benign disorder).

Adult↗

Septic arthritis of lumbar facet joints. A review of six cases.

Hematogenous infection of the facet joints by pyogenic organisms is exceedingly rare. We report six cases of lumbar facet joint septic arthritis due to hematogenous spread of a pyogenic organism. A review of the literature identified ten anecdotal reports of similar cases. An analysis of these 16 cases showed that the diagnosis was based mainly on imaging study findings and that clinical data failed to discriminate between facet joint septic arthritis and infectious discitis. Increased uptake on the radionuclide bone scan was an early finding and the pattern of uptake was different from that seen in discitis. Computed tomography was the investigation that best delineated the facet joint lesions. Magnetic resonance imaging of the lumbar spine was superior over computed tomography in demonstrating spread of the infection to the epidural space and/or soft tissues and in some instances demonstrated enhancement of the infected facet joint on T1 images after gadolinium injection. Aspiration of the facet joint under fluoroscopic guidance was required only when blood cultures were negative or when the diagnosis of the septic nature of the arthritis was in doubt. Blood cultures yielded a Staphylococcus aureus in the six cases in our series. Appropriate antimicrobial therapy was successful in most cases. In our series, four of the six patients had posterior epiduritis, pyomyositis, or an abscess in the paraspinal muscles or psoas muscle, suggesting that some epidural infections or psoas muscle abscesses believed heretofore to be primary may in fact be complications of facet joint septic arthritis. Facet joint septic arthritis is a new aspect of pyogenic spinal infections that deserves to be considered in patients with febrile spinal syndromes not explained by discitis.

Abscess↗

[Comparison of chemiluminescence and polynuclear neutrophil count after aplasia in hematologic malignancies].

Polymorphonuclear neutrophils (PNN) chemiluminescence results from the luminescence emission in oxidative reactions during phagocytosis. This activity is easily detectable and measurable using a luminometer. PNN luminescence allows precociously the evaluation of the end of the aplasia. We have analysed PNN luminescence emission stimulated by latex beads in 69 patients with hemopathies after 72 aplasias following autologous bone marrow transplantation (9 pts), allogeneic bone marrow transplantation (26 pts) and acute myeloblastic leukemia (AML) induction chemotherapies (37 pts). Luminescence emission was measured in whole blood using a luminometer before, during and after aplasia and was compared to PNN manual count. Chemiluminescence measurement is a simple and reproductable method. Its allows more earlier than the PNN blood count the detection of PNN recovery: chemiluminescence nadir is reached on average on the fourth day of aplasia and correspond to the value procured by sample tubes without PNN. The onset of the chemiluminescence increasing is definite by the doubling of the nadir value. It is reached on average on the fourteenth day of aplasia. It precedes 3.5 days and 10.5 days a total PNN count > or = 0.1 x 10 9/1 and > or = 0.5 x 10 9/1 respectively, in the 72 aplasias. In autologous and allogeneic bone marrow transplantation, chemiluminescence increasing precedes at least PNN > or = 0.1 x 10 9/1 of 4.6 days whereas in AML induction chemotherapies, the advantage is only 1.5 day (p = 0.0078). The chemiluminescence could be considered as an additional tool in daily management of sustained aplasia.

Adolescent↗