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Biomedical subjects

J Reiffers

Publications and source records attributed to J Reiffers.

At least 199 records · Page 11Linked to original sources
PubMed1993

Treatment of relapsed acute myeloid leukemia using GM-CSF before intensive chemotherapy.

Ten patients with acute myeloblastic leukemia (AML) in first relapse were treated with high-dose cytosine-arabinoside (ara-C, 3 g/m2/12 hours x 4) and amsacrine (150 mg/m2/day x 5). In order to prime the cells, the patients were given rh-GM-CSF (3 micrograms/kg/d) for four days, the first infusion starting 48 hours before chemotherapy. Two patients died during the aplastic phase, seven patients achieved a second complete remission (CR2) and one patient remained leukemic. The median duration of aplasia was 17 days (14-21). These results were comparable to those obtained in our previous series of 27 patients treated for AML in first relapse with the same chemotherapy but without GM-CSF (66% CR2). After 48 hours of GM-CSF infusion, (before chemotherapy was started), seven patients had an increase in the white blood cell count with an increase in the absolute number of blast cells in five of these cases. Marrow blast cells percentages increased in 3 of the 8 patients analysed. Six of seven patients tested showed an increase in the percentage of cells in S-phase (studied by flow cytometry using the bromodeoxyuridine (BrdU/DNA) labelling technique and BrdU incorporation). GM-CSF used to prime leukemic cells may be safely administered but its clinical usefulness needs to be further evaluated.

Adolescent↗
PubMed1993

Isolated peripheral nerve relapse masquerading as Guillain-Barré syndrome in a patient with acute lymphoblastic leukemia.

We report a 30 year old patient with acute lymphoblastic leukemia (ALL) whose leukemic relapse presented as an isolated symmetrical peripheral neuropathy with facial diplegia. Initially, this was consistent with a Guillain-Barré syndrome but the peripheral nerve biopsy revealed leukaemic infiltration. This was followed by a systemic relapse. Reports of peripheral nerve infiltration are scarce and to the best of our knowledge this is the first documented case of peripheral polyneuropathy as a presenting manifestation of ALL relapse.

Adult↗
PubMed1993

Autologous stem cell transplantation versus chemotherapy for adult patients with acute myeloid leukemia in first remission: the BGMT Group experience.

The BGMT 87 study was designed to compare prospectively Allogeneic Bone Marrow Transplantation (AlloBMT), Autologous Stem Cell Transplantation (ASCT) and Chemotherapy (CT). Of the patients who could not undergo AlloBMT and were still in remission after two cycles of intensive CT were randomized for ASCT (n = 39) or CT (n = 38). The actuarial risk of relapse was 48.7 +/- 8.8% (95% ci) in the ASCT group and 61.1 +/- 8.4% (95% ci) in the CT group (p = NS). The estimated chance of surviving without disease at three years was similar in both groups (48.3 +/- 8.5% versus 38.9 +/- 8.4; p = NS).

Actuarial Analysis↗
PubMed1993

Collection of peripheral blood stem cells in multiple myeloma following single high-dose cyclophosphamide with and without recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF).

High-dose cyclophosphamide (HD-CY; 7 g/m2) was administered to patients suffering from high risk multiple myeloma (MM). The safety of this procedure, the recirculation and collection of peripheral blood stem cells (PBSC) and the effect of rhGM-CSF and HD-CY were studied. Group I patients (n = 21) were treated with HD-CY alone. Group II patients (n = 10) received 5 micrograms/kg/day rhGM-CSF iv after HD-CY. Neutropenia was shorter in group II (p = 0.01). In group II, the number of circulating colony forming units (CFU-GM) after 14 days was correlated with the number of circulating CFU-GM after 7 days (r = 0.85, p < 0.0001) and with the number of CD34+ cells (r = 0.839, p = 0.01). The total number of mononuclear cells (MNC) and CFU-GM collected per patient was two and seven-fold higher, respectively, in group II (p = 0.01 and p = 0.03). Recovered MNC and CFU-GM were 1.7 and 7-fold higher, respectively, in group II (p = 0.01 and p = 0.004). Our data show that HD-CY is an efficient means of collecting functional PBSC in MM. We suggest that rhGM-CSF is able to further enhance this yield in MM.

Adult↗
PubMed1993

Interferon gamma is effective for BM purging in a patient with CML.

We report a case of Ph-positive CML where the BM was incubated for 24 h with 10(3) IU/ml IFN gamma and then cultured in liquid media for 4 weeks. After 24 h incubation, there was no differential sensitivity of CML CFU-GM to IFN gamma compared with untreated BM. Subsequent long-term culture (LTC) of the IFN gamma treated CML BM, however, demonstrated a 75% inhibition of production of CFU-GM from the second week onwards. Using PCR, we were able to demonstrate two types of BCR-ABL transcript in the diagnostic BM. After 4 weeks of LTC, the J(bcr b3/ABL II) RNA transcript persisted in the untreated BM, whereas neither BCR/ABL RNA transcripts were detected in the culture established with IFN gamma-treated CML BM. This study has two points of interest with the demonstration of (1) a possible antileukaemic effect of IFN gamma on the progenitors generated in the LTC system, and (2) the use of highly sensitive PCR technology to evaluate the effectiveness of IFN gamma to purge CML BM of Ph-positive cells.

Bone Marrow↗
PubMed1993

Granulocyte-macrophage colony-stimulating factor in association to timed-sequential chemotherapy with mitoxantrone, etoposide, and cytarabine for refractory acute myelogenous leukemia.

Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), given intravenously 5 micrograms/kg per day, was administered on days 4-8 of timed-sequential chemotherapy (TSC) with mitoxantrone, 12 mg/m2 per day on days 1-3, etoposide, 200 mg/m2 per day on days 8-10 and cytarabine, 500 mg/m2 per day on days 1-3 and 8-10, in 22 patients aged < 60 years with refractory acute myelogenous leukemia in an attempt to increase recruitment of leukemic cells in S phase before the second sequence of TSC. Thirty-eight patients treated with TSC without GM-CSF in a previous trial served as historical controls. In GM-CSF-treated patients, median duration of neutropenia < 0.5 x 10(9)/1 was 33 days and of platelet transfusion requirement 30 days, without any increase by comparison with controls. WHO grade 3 or more extra-hematologic toxicity included sepsis in 60% of patients, vomiting in 30%, diarrhea in 15%, hyper-bilirubinemia in 15%, and mucositis in 10%, without any difference with controls. Among 20 evaluable patients six individuals (30%), with a 95% confidence interval (CI) ranging from 12-54% achieved complete remission, 11 (55%, CI 31-77%) did not respond to therapy and three (15%, CI 3-38%) died from infection. There was no demonstrable in vivo proliferation of leukemic cells during the 5 days of administration of GM-CSF. The average percentage of bone marrow cells in S phase in five patients was 4.0 +/- 2.8 on day 4 and 7.0 +/- 7.2 on day 8 (p = NS). In this cohort of patients refractory to cytarabine, addition of GM-CSF did not increase efficacy of TSC by comparison with historical controls.

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

Multicenter randomized study comparing cyclosporine-A alone and antithymocyte globulin with prednisone for treatment of severe aplastic anemia.

We report the results of a randomized multicenter study comparing the efficacy of antithymocyte globulin (ATG) with that of cyclosporin A (CsA) as first-line therapy for severe aplastic anemia (SAA). Patients were randomized to receive ATG and prednisone (PDN) or CsA; hematologic response and toxicity were compared. At 3-month evaluation, patients who had no or minimal response received the alternative therapy to assess the value of a sequential immunosuppressive therapy for treatment of severe aplastic anemia. One hundred nineteen patients were randomized; 25 were excluded, of whom 3 were misdiagnosed and 22 did not follow the cross-over protocol. Ninety-four patients were analyzed; 46 received CsA, and 48 received ATG-PDN. The actuarial survival was 66.7%, with a median follow-up time of 19 months. There was no significant difference in survival between the groups with, at 3 months, an actuarial survival of 88% in the CsA group and 75% in the ATG group (NS); at 12 months, it was 70% in the CsA group and 64% in the ATG group (NS). The percentage of complete and partial response was 11.6% and 16%, respectively, at 3 months, and 31.6% and 30%, respectively, at 12 months (NS). The main prognostic factor was the absolute neutrophil count (ANC) at entry: Patients with ANC less than 0.2 x 10(9)/L had a significantly lower survival as compared with patients with more than 0.2 x 10(9)/L ANC (P = .0001). At 12 months, 62 evaluable patients were alive, with a complete or partial response in 36 patients. Patients who had responded to the first treatment had a better recovery of bone marrow failure than those who had sequential immunosuppression. The main complication was infection, which was more often observed and more often lethal during ATG and PDN therapy. In this study, initial treatment of SAA with either CsA or ATG-PDN followed by cross-over therapy for nonresponders produced comparable response and survival rates.

Adolescent↗
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

Quantitation of resistance of leukemic cells to cytosine arabinoside from BrdUrd/DNA bivariate histograms.

The cytotoxicity of ara-C derives from an inhibition of DNA synthesis after incorporation of ara-CTP into DNA. The rate of DNA synthesis can be determined from the amount of bromodeoxy-uridine (BrdUrd) incorporated into cells after a short exposure to BrdUrd. We developed a computer program to quantify the inhibition of the rate of DNA synthesis by analysis of the distribution of BrdUrd/DNA. Inhibition was evaluated in ara-C-sensitive and resistant cells after incubation with different doses of ara-C. An index of resistance to ara-C (RI) was expressed as the ratio of the amount of BrdUrd incorporated into S phase cells incubated with ara-C to that incorporated in the absence of ara-C. In the ara-C-sensitive and resistant HL60 cells, a linear relationship between RI and log ara-C concentration was observed. Small numbers of slightly resistant cells in mixtures of ara-C-sensitive and resistant cells could be determined using this method, making it suitable for clinical use to test the resistance of leukemic cells to ara-C.

Bromodeoxyuridine↗
PubMed1992

A multicenter randomized study comparing cyclosporin-A alone and antithymocyte globulin with prednisone for treatment of severe aplastic anemia. The cooperative group on the treatment of aplastic anemia.

This article reports the results of a randomized multicentric study comparing the efficacy of antithymocyte globulin (ATG) with cyclosporin-A (CsA) as first line therapy for severe aplastic anemia (SAA). Patients were randomized to receive ATG and prednisone (PDN) or CsA; hematological response and toxicity were compared. At 3 months, patients who had no or minimal response received the alternative therapy in order to assess the value of a sequential immunosuppressive therapy for treatment of severe aplastic anemia. One hundred and sixteen patients were analysed, 60 received CsA and 56 received ATG/PDN. The actuarial survival was 55% with a median follow-up time of 19 months. There was no significant difference in survival between the two groups. The main prognostic factor was the absolute neutrophil count (ANC) at entry: patients with ANC less than 0.2 x 10(9)/L had a significantly lower survival when compared with patients with an ANC greater than 0.2 x 10(9)/L (P = 0.0001). At 3 months, 16% of patients had a complete or partial response and a cross-over treatment was given to 68 patients. At 12 months, 77 patients were alive, with a complete or partial response in 47 patients. Patients who had responded to the first treatment had a better recovery of bone marrow failure than those who had a sequential immunosuppression. The main complication was infection which was more often observed and was more often lethal during ATG and PDN. This study demonstrates that CsA is comparable to ATG for primary treatment of SAA, but it is less toxic with fewer infectious deaths.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Aplastic↗
PubMed1992

Mobilized blood stem cells: immunophenotyping and functional characteristics.

High levels of peripheral blood stem cells (PBSC) can be collected from patients with hematopoietic malignancies or solid tumors after high-dose chemotherapy and/or growth factors. Rapid, complete, and durable hematopoietic reconstitution has been observed in patients who have been transplanted with PBSC after conditioning with supralethal myeloablative therapy. We will review the recent data concerning the immunophenotype and functional capacities of mobilized blood stem cells. PBSC seem to be comprised of a mixture of primitive and committed hematopoietic progenitors and are not that different from bone marrow-derived stem cells.

Cells, Cultured↗