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Biomedical subjects

A Delmer

Publications and source records attributed to A Delmer.

At least 91 records · Page 5Linked to original sources
PubMed1993

Resistance to all-trans retinoic acid (ATRA) therapy in relapsing acute promyelocytic leukemia: study of in vitro ATRA sensitivity and cellular retinoic acid binding protein levels in leukemic cells.

All-trans retinoic acid (ATRA) induces leukemic cell differentiation and complete remission (CR) in a high proportion of patients with acute promyelocytic leukemia (AML3 subtype). However, relapses occur when ATRA is prescribed as maintenance therapy, and resistance to a second ATRA-induction therapy is frequently observed. An induced hypercatabolism of ATRA has been suggested as a possible mechanism leading to reduced ATRA sensitivity and resistance. CRABPII, an RA cytoplasmic binding protein linked to RA's metabolization pathway, is induced by ATRA in different cell systems. To investigate whether specific features of the AML3 cells at relapse could explain the in vivo resistance observed, we studied the CRABP levels and in vitro sensitivity to ATRA of AML3 cells before and at relapse from ATRA. Relapse-AML3 cells (n = 12) showed reduced differentiation induction when compared with "virgin"-AML3 cells (n = 31; P < .05). Dose-response studies were performed in 2 cases at relapse and showed decreased sensitivity to low ATRA concentrations. CRABPII levels and in vitro differentiation characteristics of AML3 cells before and at relapse from ATRA therapy were studied concomittantly in 4 patients. High levels of CRABPII (median, 20 fmol/mg of protein) were detected in the cells of the 4 patients at relapse but were not detected before ATRA therapy. Three of these patients showed a decrease in differentiation induction of their leukemic cells, and a failure to achieve CR with a second induction therapy of ATRA 45 mg/m2/day was noted in all patients treated (n = 3). Results from this study provide evidence to support the hypothesis of induced-ATRA metabolism as one of the major mechanisms responsible for ATRA resistance. Monitoring CRABPII levels after ATRA withdrawal may help to determine when to administer ATRA in the maintenance or relapse therapy of AML3 patients.

Adult↗
PubMed1993

Primary digestive tract lymphoma: a prospective multicentric study of 91 patients. Groupe d'Etude des Lymphomes Digestifs.

BACKGROUND: The optimal management of primary gastrointestinal lymphoma including the use of surgery remains unsettled. This prospective study aimed to determine the prognostic factors of primary gastrointestinal lymphoma and to evaluate a therapeutic strategy based on surgical tumor reduction, followed by chemotherapy adapted to the histological type of tumor and tumor removal or nonremoval. METHODS: Ninety-one patients were included (mean age, 50.4 years) with mainly gastric (61%) or several digestive tract organ (18%) involved sites in clinical stages IE (43%), IIE (27%), and IV (30%). Three therapeutic groups were defined: group I, patients with low-grade lymphoma (n = 28); group II, patients with high-grade lymphoma who had complete tumor removal (n = 24); and group III, patients with high-grade lymphoma who had only partial or no tumor removal (n = 39). Each group underwent adapted chemotherapy. RESULTS: The respective overall 5-year survival rates for groups I, II, and III were 81% +/- 6%, 100%, and 56% +/- 8%, respectively (P < 0.0001). By Cox multivariate analysis, the prognostic factors of survival were age under 65 (P < 0.05), gastric localization (P < 0.05), stage IE (P < 0.001), and radical or incomplete surgery (P < 0.01). CONCLUSIONS: Combined radical surgery and chemotherapy according to histological grading is associated with prolonged remission in patients with primary digestive tract lymphoma. Moreover, compared with chemotherapy alone, incomplete resection of tumor is associated with increased survival of high-grade lymphomas.

Adolescent↗
PubMed1993

Acute myelomonocytic leukemia in a XYY man.

A case of acute myeloid leukemia (M4) in a 29-year-old male with a 47,XYY karyotype is reported. This aneuploidy was found in both bone marrow cells and mitogen-stimulated lymphocytes. Monosomy 7 correlated with myelodysplastic features. The possible role of XYY in increasing the risk of leukemia is discussed.

Adult↗
PubMed1993

In vitro effect of rGM-CSF on proliferation and maturation of leukemic cells from patients with acute myelogenous leukemia.

We investigated the effect of rGM-CSF on the proliferation/differentiation balance of the leukemic cells maintained in liquid cultures during 7 days, from 16 patients with acute myelogenous leukemia (AML). Cell proliferation was measured by tritiated thymidine (3HT) incorporation, and by the plating efficiency (PE) observed after 7 days of culture. Differentiation was measured by the ability of cells to reduce nitroblue tetrazolium (NBT) and by the percentage of immature myeloid cells. After 7 days of culture without rGM-CSF, an increase of 3HT incorporation (p = 0.01 compared to control) was observed in 8 cases. In these patients, an absence of PE was noted in only one case. Among the 8 patients with decreased 3HT incorporation (p = 0.01 compared to control), 6 exhibited functional maturation (increase of % of NBT + cells, p = 0.01), and 4 showed no PE. Seven days exposure to 50 ng/ml rGM-CSF increased the leukemic cell proliferation in 9 cases, induced complete functional differentiation in 4, and enhanced the CFU-L recovery in 6 cases. These effects were mainly observed in the "proliferative" group, where 7 of the cases had an increase of 3H-T. However, two of the "non proliferative" cases were also stimulated by GM-CSF. An absence of proliferation was generally accompanied by functional maturation.

Cell Division↗
PubMed1993

Treatment of chronic myelogenous leukemia in blast crisis and in accelerated phase with high- or intermediate-dose cytosine arabinoside and amsacrine.

Twenty-two patients (mean age 41 years) in blast crisis or accelerated phase (AP) of chronic myelogenous leukemia (CML) were treated with cytosine arabinoside (Ara-C) 500 mg/m2 [intermediate dose] or 1000 mg/m2 [high dose] twice a day for 6 days and amsacrine (AMSA) 120 mg/m2 for 3 days. Twenty-one cases were of myeloid type and one was a lymphoid BC. The mean duration of aplasia (neutrophils < 0.5 x 10(9)/l) was 21.5 days. Four patients (18%) died of infection during aplasia and minor toxicities were noted for the remainders. Nine patients (41%) achieved a complete remission (CR) and 4 (18%) a partial response. Various additional therapies were proposed after induction treatment including allogeneic bone marrow transplantation (2 patients), Ara-C and AMSA maintenance or other regimens with or without alpha-interferon (9 patients). Median survival for the entire cohort was 20 weeks (wks), significantly superior for complete responders (37 wks) than for others (7 wks) (p = 0.008). In this study, age, sex, initial platelet or basophil counts, interval between diagnosis of CML and blast crisis were not predictive of response. Although inducing a high CR rate and associated with acceptable toxicity, this regimen did not improve the survival of patients with BC or CML, strengthening the need for alternate approaches to be defined.

Adult↗
PubMed1993

Treatment of relapsing and refractory adult acute myeloid leukemia according to in vitro clonogenic leukemic cell drug sensitivity.

In an attempt to improve the results of treatment in patients with relapsing or refractory acute myeloid leukemia (AML), we conducted a pilot study using a two-drug salvage regimen according to the in vitro clonogenic leukemic cell (CFU-L) drug sensitivity. Fourteen patients were included in the study, 10 with relapsing and 4 with refractory AML. Drug exposure was assessed for daunorubicin, cytosine arabinoside, etoposide, mitoxantrone and amsacrine. The two drugs with the best inhibitory effect on CFU-L were selected for the treatment. A complete remission was achieved in only 4 patients and a partial remission in 3 patients. Although the number of patients is too small for appropriate statistical analysis and for a definite conclusion to be drawn, the observed response rate with directed therapy did not appear better than that expected from empiric salvage regimen.

Adult↗
PubMed1993

[Treatment of high malignancy lymphoma with intensive short-term chemotherapy using the MACOP-B regimen].

We present our results of a MACOP-B regimen in a series of 46 patients with high-grade NHL. The complete remission rate was 74% for patients with advanced stage disease. The excellent tolerance allowed this regimen to be given on an outpatient basis in the majority of cases. The median follow-up for the living patients is 28 months. Although some patients received additional treatment that could influence the results, the predicted DFS (disease-free survival) at 45 months of 57% compares favorably with the best results published so far with more toxic regimens.

Adult↗
PubMed1993

[Prognostic factors in multiple myeloma. Review of the literature].

Apparition of new tools in the therapy of multiple (MM) strengthens the need for valuable prognostic categorization of each patient in order to propose the most adequate treatment. Prognostic factors in MM can be divided in four groups. The first, including beta 2 microglobulin (beta 2m), hemopoiesis impairment, osteolytic lesions, calcemia and albuminemia, reflects the tumor mass. The second: type of monoclonal component, labeling index (LI), C-reactive protein (CRP), cytologic, histologic and immunophenotypic aspects of plasmocytes, renal biology, ADN and ARN, contents of malignant cells, LDH levels, activation of ras oncogene represents the intrinsic malignancy of the clone. The third illustrates the type of response to chemotherapy. Finally, the last group characterizes the host and his reactivity against the disease. Thus, the referential prognostic classification of Durie and Salmon representing only the tumor burden, seems to be now insufficient. New classifications including CRP, beta 2m and LI as more discriminant parameters are currently proposed.

Dose-Response Relationship, Drug↗
PubMed1993

Cyclosporin A as a modifier agent in the salvage treatment of acute leukemia (AL).

Sixteen adult patients with relapsed (7 patients) or refractory (9 patients) acute leukemia received mitoxantrone (10 mg/m2 per day for 3 days) and etoposide (200 mg/m2 per day for 3 days) with escalating dose of cyclosporin A (CsA) from a loading dose of 2 mg to 6.5 mg/kg per 2 h followed by 3 days continuous infusion of 5-15 mg/kg per day. The major toxicities were stomatitis and prolonged aplasia, occurring for 15 mg/kg per day of CsA. Transient conjugated hyperbilirubinemia occurred in all patients, and was CsA dose-dependent (r = 0.7). Adequate serum levels of CsA (> 1 microgram/ml) were obtained in 3/6 patients treated with 10 mg/kg per day and 4/4 patients with 15 mg/kg per day. The pharmacokinetic of mitoxantrone showed an unusual increase of carboxylic metabolites, parallel to CsA levels. We observed six responses (two complete and four partial remissions), and eight resistances. Two patients died at days 3 and 8 from sepsis. Before treatment, 7/16 patients tested for P-gp with C219 were positive (> 10% positive cells). 3/6 responders were P-gp-positive. At time of leukemic regrowth, cells expressing P-gp before therapy reverted to P-gp-negative cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Acquired von Willebrand disease: correction of hemostatic defect by high-dose intravenous immunoglobulins.

High-dose intravenous immunoglobulins (ivIG) were used in a 57-year-old patient with acquired von Willebrand disease in order to correct a hemostatic defect before pneumonectomy for lung carcinoma. IvIG induced a rapid and complete correction of factor VIII (F VIII) and von Willebrand factor (vWF) and allowed surgery without additional factor coverage. F VIII and vWF returned to baseline values within 10 days after ivIG.

Dose-Response Relationship, Drug↗
PubMed1992

Treatment of myelodysplastic syndromes (MDS) and high leukaemic risk with low-dose cytosine arabinoside (LD-AraC) plus granulocyte-macrophage colony-stimulating factor (rh GM-CSF). The EORTC Leukaemia Group.

Symptomatic patients with myelodysplastic syndromes (MDS) and 10-30% blasts in the bone marrow were treated with low-dose AraC (2 x 10 mg/m2 subcutaneously (sc) days 1-14) and GM-CSF (fully glycosylated, Sandoz/Schering-Plough, 2 x 150 micrograms protein/day sc) given either subsequently (days 15-21) or simultaneously (days 8-14 and one week rest). Evaluations were carried out after three courses (nine weeks); responding patients could be continued for two further cycles. Eighty-two patients with refractory anaemia and excess of blasts (RAEB), with (RAEBt) or without transformation, were evaluable: 45 RAEB and 37 RAEBt, mean age 64 years (range 17-80 years). A complete remission was achieved in 14 cases (17%), 11 had a good response (13%), and 12 a partial response (15%). Stable disease was found in 21 cases (26%). There were 12 cases of toxic death (15%), progression was noted in eight patients (10%), and death due to disease in three (4%). No difference existed between the two treatment arms with respect to response. Major adverse events during treatment were haemorrhage (25%), infections (23%), and fever with GM-CSF (21%). GM-CSF did not induce leukaemia nor contribute to haemorrhage induced by AraC, but gave rise to an overall response rate of 46% which is high and relatively durable as compared to other treatments in this disease.

Acute Disease↗
PubMed1992

[Intra-alveolar hemorrhage during treatments of acute leukemia].

Intra-alveolar haemorrhages represent frequent and severe complications in acute leukaemia treated with chemotherapy. Thrombocytopenia with or without associated haemostasis disorder in association with infectious or toxic lesions of the alveolar membrane (related to radio- or chemotherapy) represent the major promoting factors. Presence of intra-alveolar haemorrhage is mainly suspected on X-ray chest roentgenogram and can be confirmed by bronchoalveolar fluid examination demonstrating an excess of siderophages. Prevention of this complication is based upon reduction of risk factors. Platelet transfusions and careful introduction of steroids are proposed in certain cases.

Acute Disease↗
PubMed1992

In vitro effect of P-glycoprotein (P-gp) modulators on drug sensitivity of leukemic progenitors (CFU-L) in acute myelogenous leukemia (AML).

Cyclosporine A (CyA), a potent reversant of multidrug resistance (mdr), was studied for its effects on the sensitivity of leukemic progenitors (leukemia colony-forming units, CFU-L) to daunorubicin (DNR) and mitoxantrone. CyA was first compared to verapamil and cefoperazone for reversion of mdr in the mdr1+ cell line K562/DOX. A dramatic increase of sensitivity to 10(-6) M DNR was noted with CyA (0.5 and 1 microgram/ml) and verapamil (1 and 5 micrograms/ml), but not for cefoperazone (0.3 and 0.6 mg/ml). The sensitivity of K562/DOX to 10(-6) M mitoxantrone was also slightly enhanced by CyA. The change in CFU-L drug sensitivity in the presence of CyA was then tested in 12 relapsing/resisting patients and in 3 untreated patients with acute myelogenous leukemia (AML). No change in CFU-L sensitivity to DNR was noted, despite the presence of a subset of P-glycoprotein positive (P-gp+) cells in three out of the ten evaluable cases. Among the six evaluable cases tested with mitoxantrone and CyA, an increase of 50% in CFU-L sensitivity to mitoxantrone was noted in one (of three) P-gp+ patient. These data suggest that the CFU-L in AML rarely expressed the P-gp and that other mechanisms of drug resistance could be involved in AML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

[Use of hematopoietic growth factors in oncology].

Myelosuppression is the main limiting factor in cancer chemotherapy. The development of recombinant hematopoietic growth factors which stimulate myeloid progenitors and mainly neutrophil precursor cells leads to the evaluation of their potential activity in numerous fields of oncology. The available clinical trials have demonstrated the ability of G-CSF (granulocyte colony-stimulating factor) and GM-CSF (granulocyte-macrophage colony-stimulating factor) to accelerate neutrophil recovery following cytotoxic chemotherapy, and therefore to reduce the incidence of neutropenic febrile episodes and thereby improve the quality of life of patients receiving chemotherapy. The main goals of the future studies will be to determine to what extent the increase of dose intensity may lead to higher response rates and survival at least in patients with chemosensitive tumors.

Animals↗