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Biomedical subjects

J Reiffers

Publications and source records attributed to J Reiffers.

At least 181 records · Page 10Linked to original sources
PubMed1994

Allogeneic bone marrow transplantation for children with acute myeloblastic leukemia in first complete remission: impact of conditioning regimen without total-body irradiation--a report from the Société Française de Greffe de Moelle.

PURPOSE: To analyze the French experience of chemotherapeutic preparation before human leukocyte antigen (HLA)-identical bone marrow transplantation (BMT) in children with acute myeloblastic leukemia (AML) in first complete remission (CR). PATIENTS AND METHODS: The data base used for this study was a French BMT registry for childhood AML. Twenty-three children were conditioned with busulfan and 120 mg/kg cyclophosphamide (Bu-Cy 120 group). Nineteen received busulfan and 200 mg/kg cyclophosphamide (Bu-Cy200 group). During the same time period, 32 patients were prepared with total-body irradiation (TBI group) most often in combination with 120 mg/kg of cyclophosphamide. RESULTS: The probability of relapse was 54%, 13%, and 10% for the Bu-Cy120, Bu-Cy200, and TBI groups, respectively (P < .05 in the univariate analysis, log-rank test, 2 df). In the multivariate analysis, a conditioning regimen with Bu-Cy120 was significantly associated with a higher risk of relapse (P = .02; relative risk, 3.62). The probability of transplant-related mortality (TRM) was 0% for Bu-Cy120, 5% for Bu-Cy200, and 10% for TBI. Kaplan-Meier estimations of event-free survival (EFS) were 46% +/- 24%, 82% +/- 18%, and 80% +/- 14%, respectively, for the three groups, with median follow-up durations of 28 months (range, 3 to 78), 31 months (4 to 68), and 48 months (2 to 73). In the multivariate analysis, two factors adversely affected EFS: a conditioning regimen with Bu-Cy120 (P = .07) and a long interval from diagnosis to BMT (> or = 120 days, P = .08). CONCLUSION: Bu-Cy120 is a well-tolerated preparation, but results in a high risk of relapse for children with AML in first CR. This high risk of relapse is not observed when the dose of cyclophosphamide is increased to 200 mg/kg.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Autologous transplantation in chronic myelogenous leukemia: European results: Chronic Leukemia Working Party of the EBMT.

Autologous stem cell transplantation (ASCT) was performed in 95 patients with chronic myelogenous leukemia (CML) in chronic phase and their data were reported to the European Bone Marrow Transplant Registry. Most patients presented bad prognostic factors. The results were analysed by September 1, 1993. The actuarial proportion of patients who achieved a complete hematological response at one year was 87.3+/-7.5% (95% CI). The 3-year percentage of major cytogenetic response was 38.6+/--13% (95% CI). The actuarial risk of transformation for the evaluable patients was 31.5+/-14% (95% CI) and the actuarial survival at four years was 83.3+/-10% (95% CI). These encouraging results suggest that ASCT by itself could play a role to prolong survival in CML patients.

Adolescent↗
PubMed1994

Peripheral neuropathy after autologous blood stem cell transplantation for multiple myeloma.

We report a case of peripheral neuropathy occurring after autologous blood stem cell transplantation (ABSCT) for multiple myeloma. The patient, free of neurological symptoms, was transplanted in partial remission, and achieved a complete remission after transplantation. A severe peripheral, symmetric, distal sensori-motor polyneuropathy appeared at day 25 and worsened progressively until commencement of corticosteroid therapy. A peripheral nerve biopsy showed endoneurial cellular infiltrates which were predominantly composed of T cells identified by immunocytochemistry. Ultrastructural examination showed acute axonal damage. Electrophysiologic studies performed before and during the treatment were consistent with a severe axonal degeneration and showed a marked improvement, concomitant with the favorable clinical outcome. This is the first report of peripheral neuropathy after ABSCT.

Axons↗
PubMed1994

Quality and functional capacity of the bone marrow microenvironment of autologous blood stem cell transplantation (ABSCT) recipients.

We have previously reported that the rate of haematopoietic recovery following Autologous Blood Stem Cell Transplantation (ABSCT) could be influenced by the type of conditioning regimen or by the underlying disease. Furthermore, Peripheral Blood Stem Cell (PBSC) growth was found to be sensitive to stimulation by irradiated allogeneic stromal layers. In the present study, we used the long term culture system (LTC) to investigate the quality of the bone marrow (BM) microenvironment from patients who had undergone ABSCT for either Malignant Lymphoma (ML, 13 patients) or Multiple Myeloma (MM, 8 patients) after conditioning regimens comporting myeloablative chemotherapy (CT) or Total Body Irradiation (TBI). Among the 13 ML patients, 10 received CT conditioning and 9 of the 10 BM samples developed a complete confluent stromal layer. The remaining 3 ML patients received TBI prior to ABSCT and 2 of the 3 samples developed confluent stroma. In contrast, when LTC were established with BM from the 8 MM patients, all of whom were treated with TBI prior to ABSCT, only 3 of the 8 marrow samples developed a complete confluent stromal layer. Thus BM from patients who had received CT conditioning therapy tended to form confluent stroma more often than BM from those who had received TBI (p = 0.08). CFU-GM production was also evaluated for the stromal layers derived from all transplanted patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow↗
PubMed1994

What's new in blood progenitor cell autotransplants?

Autotransplants of blood progenitor cells are increasingly used in persons with cancer, sometimes added to bone marrow cells but increasingly in their stead. Clearly, transplants of blood progenitor cells accelerate hematopoietic recovery after high-dose therapy. However, because some residual recipient-derived hematopoiesis typically persist even after the most intensive therapy, it is not certain that long-term hematopoiesis is from the blood progenitor cell autograft. However, this issue may be unimportant since the immediate goal is short-term recovery of bone marrow function regardless of which cells are responsible for long-term recovery. This issue is, however, of considerable import were more intensive treatment to be used or where blood progenitor cells were to be used for allografts. There are some reasons to think that transplants of blood-derived cells might have a lower likelihood of returning cancer cells to the recipient, at least in some lymphomas and solid tumors, than an autotransplant of bone marrow cells. This notion is as yet unproven and may be important only when and if more effective anti-cancer pretransplant regimens are developed. The potential role of transplants of blood progenitor cells depends on how useful autotransplants prove. Whether use of blood progenitor cells rather than bone marrow cells offers any advantage requires considerable additional data and controlled trials.

Animals↗
PubMed1994

Autologous stem cell transplantation in chronic myelogenous leukemia: a retrospective analysis of the European Group for Bone Marrow Transplantation. Chronic Leukemia Working Party of the EBMT.

Over a 3 year period (1989-1991), 49 patients who underwent autologous stem cell transplantation (ASCT) for chronic myelogenous leukemia (CML) in chronic phase were reported to the European Bone Marrow Transplant Registry. Most patients had bad prognostic factors. The results were analyzed by 1 September 1993. Hematological recovery was observed in 45 cases and was significantly quicker after blood stem cell transplantation (n = 30) than after BMT (n = 19). Five patients died early and five other patients did not achieve a complete hematological response (CHR) following ASCT. Of the 39 patients who achieved CHR, 34 are still alive 17 to 52 months after ABSCT. Fifteen of the 34 patients who had cytogenetic evaluation exhibited a major response (> or = 65%, Ph-negative metaphases). The actuarial risk of transformation for the 44 evaluable patients was 28.1 +/- 15% (95% CI) and the actuarial survival at three years was 81.5 +/- 15% (95% CI). No factors were found to significantly influence the response rate or the patients' survival. These encouraging results suggest that ASCT by itself could play a role in prolonging survival in CML patients.

Adolescent↗
PubMed1994

Colony-stimulating factors and cell cycle in the chemotherapy of acute myelogenous leukemia.

Over the past decade, Hematopoietic Growth Factors (HGFs) have been shown to improve the treatment of malignant blood diseases. They reduce the duration of leucopenia after chemotherapy and the associated infectious morbidity, without affecting remission duration, or percentage of patients resistant to chemotherapy. Moreover, HGFs are able to increase the percentage of leukemic cells in the S phase. In consequence, HGFs have been used in acute myeloblastic leukemia (AML) to recruit quiescent clonogenic blasts to improve the cytotoxic effects of cell cycle specific drugs. The clinical results are divergent and do not allow definite conclusions. However, in vitro, the efficacy of HGFs to enhance cytosine arabinoside (ara-C)-mediated cytotoxicity has been reported. Whether the HGFs-mediated increase in the antileukemic activity of ara-C is caused by changes in the cell cycle status of AML blasts or by other mechanism(s) is currently debated.

Acute Disease↗
PubMed1993

Flow cytometric estimation of poly(A)+ RNA by fluorescent in situ hybridization.

A method for the detection of poly(A)+ RNA in cell suspensions by in situ hybridization and flow cytometry is described. The hybridizing properties of oligothymidylate o(dT) was well preserved after coupling to fluorescein. This fluorescent oligonucleotide was used as a probe to determine the poly(A)+ RNA content of fixed HL60 leukemic cells by flow cytometry. Labeling was considerably reduced by treating the cells with RNAse, and by competitive hybridization with either poly(U) or free poly(A). Labeling was also decreased in a time-dependent fashion by incubating the cells with actinomycin D prior to fixation. This method represents an improvement on the methods measuring total RNA and could be of value in investigations on the effect of drugs on RNA metabolism.

Dactinomycin↗
PubMed1993

5-fluorouracil permits access to a primitive subpopulation of peripheral blood stem cells.

Peripheral blood stem cells (PBSC) contain a mixture of mature and immature hematopoietic progenitors. Resistance to 5-Fluorouracil (5-FU) has been used to identify and characterize primitive quiescent stem cells among bone marrow (BM) cells. To see if the same technique could be used to isolate a similar population of cells among PBSC, low-density peripheral blood mononuclear cells (PBMNC) were collected by cytapheresis in the regenerative phase after high-dose chemotherapy from patients with hematological malignancies. These PBMNC were incubated with increasing concentrations of 5-FU for 24 h. The viable 5-FU resistant cells were then cultured in semi-solid media in the presence of either single cytokines: TCM 5637, Granulocyte Macrophage Colony Stimulating Factor (GM-CSF), or a combination of cytokines: interleukin 1 (IL-1) IL-1 + IL-3 + 5637, IL-1 + IL-3 + Stem Cell Factor (SCF). Low concentrations (5-10 micrograms/ml 5-FU) eliminated mature day 7 Colony Forming Units-Granulocyte Macrophage (CFU-GM) and spared day 7 clusters while enriching for day 14 CFU-GM, irrespective of the growth factors used. Higher concentrations of 5-FU (15, 20, 25 micrograms/ml) selected for later forming clonogenic elements. A combination of synergistic growth factors was required for the development of morphologically identifiable clonogenic elements resistant to 25 micrograms/ml 5-FU at day 21 of culture. Further experimentation demonstrated that SCF could effectively replace TCM 5637 in the cytokine combination for the detection of primitive late forming clonogenic elements. The presence of SCF potentiated colony formation by 5-FU resistant PBMNC. It was confirmed that GM-CSF alone was unable to support colony formation by PBMNC resistant to 25 micrograms/ml. These observations demonstrate that PBSC contain a heterogenous mixture of hematopoietic progenitors and that incubation with 25 micrograms/ml 5-FU permits access to a quiescent primitive stem cell population that requires a combination of synergistic growth factors for the development of morphologically identifiable clonogenic elements at day 21. Taken together, these results suggest that PBSC have similar characteristics to BM derived stem cells.

Antineoplastic Agents↗
PubMed1993

Autologous blood stem cell transplantation followed by recombinant alpha interferon as treatment for patients with high-risk chronic myelogenous leukemia. A report of 32 cases.

Autologous blood stem cell transplantation (ASCT) was performed in 32 patients with high risk chronic myelogenous leukemia (CML). Prior to ASCT, the patients were given Busulfan and high-dose Melphalan. Peripheral blood stem cells collected at diagnosis were used to rescue hematopoiesis. Recombinant Interferon was administered after ASCT. In 24 patients transplanted in transformation, 23 achieved a complete hematological response and nine are still alive 9 to 73 months after ASCT. Eight other patients were transplanted in chronic phase for either the presence of bad prognostic factors (Sokal's classification) or no response to IFN. Seven are alive without transformation 16 to 48 months after ASCT. Although few patients presented a cytogenetical response (10/28), the survival observed in this series of patients compares favorably with that of patients treated conventionally. Thus, the place of ASCT in CML could now be tested prospectively.

Adult↗