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Biomedical subjects

F Maloisel

Publications and source records attributed to F Maloisel.

At least 73 records · Page 4Linked to original sources

Interferon alfa-2b combined with cytarabine versus interferon alone in chronic myelogenous leukemia. French Chronic Myeloid Leukemia Study Group.

BACKGROUND: Treatment with interferon prolongs survival in chronic myelogenous leukemia. We conducted a clinical trial to assess the efficacy of treatment with a combination of interferon and cytarabine. METHODS: Previously untreated patients with chronic myelogenous leukemia were randomly assigned to receive either hydroxyurea (50 mg per kilogram of body weight per day) and interferon alfa-2b (5 million units per square meter of body-surface area per day), or hydroxyurea and interferon in the same dosages plus monthly courses of cytarabine (20 mg per square meter per day, for 10 days). The end points were overall survival, complete hematologic remission at 6 months, and major cytogenetic response (less than 35 percent Philadelphia chromosome-positive cells in the bone marrow) at 12 months. RESULTS: The trial was stopped when a sequential analysis showed a benefit of interferon and cytarabine. A significant improvement in survival was observed in the interferon-cytarabine group (360 patients) as compared with the interferon group (361 patients) (P=0.02; relative risk of death, 0.64; 95 percent confidence interval, 0.44 to 0.93). After three years, the survival rate was 85.7 percent with interferon and cytarabine and 79.1 percent with interferon alone. The rate of hematologic response was higher in the interferon-cytarabine group than in the interferon group (P=0.003). Major cytogenetic responses were observed 12 months after randomization in 126 of 311 patients treated with interferon and cytarabine (41 percent) and in 75 of 314 patients treated with interferon only (24 percent, P<0.001). CONCLUSIONS: The combination of interferon and cytarabine, as compared with interferon alone, increases the rate of major cytogenetic response and prolongs survival in patients with the chronic phase of chronic myelogenous leukemia.

Adolescent↗

Lymphomas in patients with Sjogren's syndrome are marginal zone B-cell neoplasms, arise in diverse extranodal and nodal sites, and are not associated with viruses.

The occurrence of non-Hodgkin's lymphoma (NHL) is the most serious complication of Sjogren's syndrome (SS). We performed a study of 16 NHLs occurring in patients with an underlying SS. These lymphomas arose not only in salivary glands (7 cases) but also in other mucosal extranodal sites (the stomach [4 cases], the lung [3 cases], the skin [3 cases], the buccal mucosa [1 case], the thymus [1 case]) and in nodal sites (8 cases). Low-grade marginal zone lymphomas (MZL) were diagnosed in 12 of the 16 patients, 9 of mucosa-associated lymphoid tissues (MALT) type in mucosal sites and 3 exclusively nodal. The 4 other patients presented with a high-grade B-cell lymphoma that was probably a histological transformation of an underlying low-grade MZL at least in 3 of the cases involving skin, stomach, and parotid, respectively. A t(14;18) translocation was detected in 1 of 8 lymphomas tested. We detected serum anti-p53 antibodies in 2 of the 14 studied patients. p53 protein was detected in 1 of 11 lymphomas tested. LMP protein and Eber RNAs of Epstein-Barr virus (EBV) were not detected in the 16 NHL biopsies. Using polymerase chain reaction, EBV was never detected except in 1 of 4 parotid lymphomas. No human T-lymphotropic virus 1 or human herpes virus 8 DNAs were detected in NHL biopsies. None of the patients had hepatitis C virus infection found using serological methods. Chemotherapy was usually efficient. In conclusion, lymphomas occurring in patients with an underlying SS are in most cases MZL. These lymphomas are not associated with viruses known to be present in other types of lymphomas. Some of the translocations or mutations of oncogenes or antioncogenes described in other lymphomas are detected in SS-associated lymphomas.

Adolescent↗

[Macrophage activation syndrome disclosing leukemic transformation of mycosis fungoides].

BACKGROUND: Mycosis fungoides can mimic pigmented purpuric dermatitis. We report such a case which progressed to peripheral T-cell lymphoma; progression was revealed by reactive hemophagocytic syndrome (RHS). CASE REPORT: A 65-year old male patient was hospitalized for a pigmented and purpuric eruption. The skin lesions appeared 2 years earlier and at that time biopsy had shown pigmented and purpuric dermatitis. One month before hospitalization, general signs appeared. On admission, he had papular and purpuric rash, mainly on the trunk, hepatosplenomegaly, enlarged axillar and inguinal lymph nodes, and fever at 38.2 degrees. A skin biopsy showed histologic changes typical of mycosis fungoides. He also had bicytopenia, hepatitis, and increased triglyceride and ferritin levels suggesting RHS which was proved by means of bone marrow biopsy. These tests also evidenced peripheral T-cell lymphoma. The patient was treated with two courses of chemotherapy (CHOP) but the disease progressed and he deceased. DISCUSSION: Mycosis fungoides can occasionally begin with an eruption very closely resembling pigmented purpuric dermatitis. Therefore, repeated biopsies should be done in case of widespread permanent pigmented purpuric dermatitis of no apparent origin. RHS is a life-threatening disease. The diagnosis should be suspected in any cytopenic patient with fever, increased triglyceride levels and abnormal liver tests. A search for an etiology must then be undertaken a prompt treatment is needed.

Aged↗

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↗

[POEMS syndrome: role and value of interleukin-6].

POEMS syndrome is a systemic disorder with peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes. The association of POEMS syndrome with lympho-proliferative disorder is very commun. The pathogenesis remains poorly understood but implication of cytokines (interleukins 1 and 6) is suspected. We report a case of a classic POEMS syndrome (with polyneuropathy, hepatomegaly, diabetes melitus, hyperpigmentation, monoclonal IgG lambda, anasarca and solitary plasmocytoma), associated with high serum levels of interleukin 6.

Humans↗

Intraperitoneal recombinant interferon gamma in ovarian cancer patients with residual disease at second-look laparotomy.

PURPOSE: The purpose of this study was to evaluate the efficacy and tolerance of recombinant human interferon gamma (rIFN-gamma) as second-line treatment in patients with persistent disease at second-look laparotomy. PATIENTS AND METHODS: One hundred eight patients with residual disease at second-look laparotomy were treated with rIFN-gamma (20 x 10(6) IU/m2) administered intraperitoneally (IP) twice a week for 3 to 4 months. In the absence of clinically assessable disease, response to rIFN-gamma was assessed with a third-look laparotomy. RESULTS: Of 98 assessable patients, 31 (32%) achieved a surgically documented response, including 23 patients (23%) with a complete response (CR). The age and size of residual tumor were significant prognostic factors for the response to rIFN-gamma. A 41% CR rate was observed in 41 patients younger than 60 years and with residual tumor less than 2 cm. The probability of response was independent of previous response to first-line chemotherapy. The median duration of response was 20 months and the 3-year survival rate in responders was 62%. Response to rIFN-gamma was the most significant prognostic factor for survival of patients with residual disease. Adverse events included fever, flu-like syndrome, neutropenia, and liver enzyme disturbances. No significant peritoneal fibrosis was noted. CONCLUSION: These results support the potential interest of IP rIFN-gamma as adjuvant treatment in ovarian cancer. Controlled prospective trials are required to determine its place in the therapeutic strategy of this malignancy.

Adult↗

Idarubicin and high dose cytarabine: a new salvage treatment for refractory or relapsing non-Hodgkin's lymphoma.

Twenty three patients with relapsing (n = 11) or refractory (n = 12) non-Hodgkin's lymphoma (NHL) to one or two prior anthracycline based combination chemotherapy regimens were treated as second or third line regimen with 3 induction cycles of Idarubicin (IDA) (7 mg/m2/d i.v. d1-d3) and high dose cytarabine (HD Ara-C) (1 g/m2/12 h i.v. d1-d3), each cycle was repeated every 3 weeks. Responding patients received a maintenance therapy with monthly cycles of IDA: 15 mg/m2 d1-d3, Etoposide 100 mg/m2 d1-d3, both by oral route. Twenty two patients are evaluable and we observed 13 CR and 1 PR with an overall response rate of 61% (14/23: 95% Cl = 38.5% 80.3%). The median time to progression was 32 months (6.5 - 63 + m.). The response rate to IDA-HD Ara C was not different for patients with (n = 14) or without (n = 9) objective response to the last prior therapy. The main toxicity was hematological: all patients experienced grade 4 neutropenia and 22 patients had grade 4 thrombopenia, but there were no toxic deaths. IDA and HD-Ara-C combination is highly effective in refractory or relapsed. NHL. As hematological toxicity was the limiting factor for further escalation of dose-intensity, further studies might include hematopoietic growth factors support in the therapeutic scheme.

Adult↗

[Fetal and neonatal immune thrombocytopenias].

Fetal and neonatal immune thrombocytopenias with platelet count less than 150.10(9)/l, result from transplacental passage of maternal platelet-specific antibodies. The main risk of these diseases is severe brain damage or death due to intracranial hemorrhage. Prevention and screening are difficult because of the lack of predicting factors. Only some women are at high risk of fetal thrombocytopenia (HLA DRW 52a HPA-la negative women or women with a previous history of immune thrombocytopenic purpura and having platelet-specific autoantibodies). Antenatal diagnosis and therapy have altered the natural course of fetal alloimmune thrombocytopenia. No prenatal treatment has proved to be effective in autoimmune thrombocytopenia and prenatal diagnosis by fetal blood sampling is controversial. A better knowledge of the pathogenesis of gestational incidental thrombocytopenia in otherwise healthy pregnancies, could define a group at high risk of fetal thrombocytopenia.

Algorithms↗

[Carboplatin and cyclophosphamide in stage Ic-IV ovarian carcinoma: retrospective study of 101 cases].

We report our experience of CBDCA-CPM combination chemotherapy as first line therapy in 101 ovarian cancers. The therapeutic scheme was: initial cytoreductive surgery followed by six chemotherapy cycles (CBDCA 400 mg/m2/d IV dl, CPM 600 mg/m2/d IV dl, dl = d21) and second-look laparotomy. The initial stages were four Ic, three IIa, four IIb, four IIc, 15 IIIa, 28 IIIb, 23 IIIc and 20 IV. After initial surgery, there were 39 macroscopic residual diseases superior to 2 cm, 26 macroscopic residual diseases inferior or equal to 2 cm, four microscopic diseases and no residual disease in 30 cases (unknown in two cases). The overall response rate to chemotherapy was 83% with 56% histologic complete response rate. The main toxicity was haematological with 60% of leucopenia grade III-IV, 52% of thrombopenia grade III-IV. Age at diagnosis, residual disease after first look surgery and length of CA 125 normalization were significant prognostic factors for survival in this series.

Adolescent↗

[Management of hematologic malignancies during pregnancy].

Hodgkin's disease, non-Hodgkin lymphoma or leukemia occurring in a pregnant patient is a rare event. Diagnosis of hematologic malignancies in a pregnant woman usually poses a quandrum of psychological, ethical and medical considerations. All of these situations require a multidisciplinary team. Adequate staging and treatment of hematologic malignancies are complicated by the pregnancy. In the first trimester, termination of the pregnancy should be considered in order to provide the best outcome for the woman and fetus. In this review we have focused on the use of chemotherapy for the pregnant patient. This review reveals that the use of chemotherapy resulted in both objective disease remissions and the subsequent delivery of normal infant.

Antineoplastic Combined Chemotherapy Protocols↗