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J Reiffers

Publications and source records attributed to J Reiffers.

At least 145 records · Page 8Linked to original sources
PubMed1995

A controlled study of recombinant human granulocyte colony-stimulating factor in elderly patients after treatment for acute myelogenous leukemia. AML Cooperative Study Group.

BACKGROUND: Intensive chemotherapy for acute myelogenous leukemia (AML) continues to yield low rates of complete remission and survival among patients over the age of 65 years. Infection-related mortality is particularly high among these patients during the period of neutropenia that follows chemotherapy. We determined the effect of lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) on mortality at eight weeks (the main end point) and the rate of complete remission among patients with AML who were 65 years old or older. METHODS: After induction chemotherapy with daunorubicin (45 mg per square meter of body-surface area per day for 4 days) and cytarabine arabinoside (200 mg per square meter per day for 7 days), 173 patients with newly diagnosed AML were randomly assigned on day 8 to receive either lenograstim (5 micrograms per kilogram of body weight per day) or placebo, starting on day 9, until there was neutrophil recovery or a treatment failure, or for a maximum of 28 days. Salvage chemotherapy was also followed by lenograstim or placebo. Patients with a complete remission received two consolidation courses of chemotherapy without lenograstim or placebo. RESULTS: The mortality rate at eight weeks was similar in the lenograstim and placebo groups (23 and 27 percent, respectively; P = 0.60), as was the incidence of severe infections. The median duration of neutropenia (absolute neutrophil count < or = 1000 per cubic millimeter) was shorter in the lenograstim group (21 days, as compared with 27 days in the placebo group; P < 0.001). Eight percent of the patients in both groups had regrowth of AML cells. The rate of complete remission was significantly higher in the lenograstim group (70 percent, as compared with 47 percent in the placebo group; P = 0.002). Overall survival, however, was similar in the two groups (P = 0.76). CONCLUSIONS: The administration of lenograstim after chemotherapy for AML did not decrease the mortality rate at eight weeks among patients over the age of 65 years. The patients who received lenograstim had a significantly higher rate of complete remission than those who received placebo. Nevertheless, the overall survival in the two groups did not differ significantly.

Adjuvants, Immunologic↗
PubMed1995

Fractionated or single-dose total body irradiation in 171 acute myeloblastic leukemias in first complete remission: is there a best choice? SFGM. Société Française de Greffe de Moelle.

PURPOSE: To evaluate the importance of fractionating total body irradiation (TBI) in patients receiving an allogenic bone marrow transplant (BMT) for an acute myeloblastic leukemia (AML) in first complete remission (CR1). METHODS AND MATERIALS: Between 1983 and 1990, 171 consecutive patients received either single dose TBI (STBI) (n = 65) or fractionated TBI (FTBI) (n = 106) after being conditioned with cyclophosphamide and before receiving a non-T-depleted Human Leucocyte Antigen (HLA)-identical marrow. Both groups were comparable except for date of BMT and diagnosis-to-BMT interval (D-BMT). RESULTS: After 63 months median follow-up, transplant-related mortality (TRM), probability of relapse, and 5-year disease-free survival (DFS) were 0.38 and 0.27 (p = 0.04), 0.29 and 0.26 (p = 0.22), 0.43 and 0.56 (p = 0.06), respectively, for STBI and FTBI. The supposed influence of the schedule of TBI disappeared in the multivariate analysis: TRM was enhanced by severe acute graft vs. host disease (p = 0.0002), early years of transplant (before January 1, 1987) (p = 0.0003), and longer D-BMT intervals (p = 0.038). Relapse was linked to early years of transplant (p < 0.00001), and the absence of chronic GVHD (p = 0.007). Longer DFSs were observed for later years of transplant (after January 1, 1987 and later) (p = 0.001), milder acute GVHD (p = 0.005), and shorter D-BMT intervals (p = 0.045). Important improvements of the results were made during the 7-year observation period: TRM, probability of relapse, and DFS were, respectively, 0.36, 0.28, and 0.46 for patients transplanted before January 1, 1987 vs. 0.21, 0.15, and 0.67 after that date. CONCLUSION: Our data strongly suggest that allogenic BMT is the best postremission treatment for AML in CR1, and the results are better when BMT shortly follows the achievement of remission. The schedule of TBI was of little importance compared with the improvements made in the management of patients undergoing BMT during the 1980s, and, therefore, reports concerning data prior to 1985 should be interpreted cautiously.

Adult↗
PubMed1995

Autologous bone marrow transplantation for first remission acute myeloblastic leukemia in patients older than 50 years: a retrospective analysis of the European Bone Marrow Transplant Group.

High-dose chemotherapy, with or without radiotherapy, followed by autologous stem-cell rescue is used increasingly for the intensification of first remission in acute myeloblastic leukemia (AML). However, these treatments have been limited to young patients due to the increased risks of regimen-related toxicities and mortality with age. Several investigators have recently published the upper age limit for autologous bone marrow transplant (ABMT) in AML because of encouraging results. The results of ABMT for AML were studied in 111 patients > or = 50 years of age intensified in first remission. Median age at transplant was 53 years (range, 50 to 63 years). Fifty patients were conditioned with total body irradiation and 61 with polychemotherapy: 23 with busulfancyclophosphamide, 11 with the University College Hospital (UCH; London, UK) regimen, 6 with BAVC, and 21 with various other treatments. Marrow was purged in only 11 cases. Results were compared with 786 ABMTs performed for AML in patients between 16 and 49 years of age (median, 35 years). For AML in first remission, the probability of leukemia-free survival (LFS) at 4 years was 34% +/- 5% for patients aged 50 years or more and 43% +/- 2% for patients less than 50 years of age (P = .004), with a survival probability of 35% +/- 6% and 48% +/- 2%, respectively (P = .004). The probability of relapse was not significantly different between the two groups (52% +/- 7% v 50% +/- 2%), but transplant-related mortality was significantly higher in the older age group (28% +/- 5% v 14% +/- 2%; P < .0001) and mainly due to infectious complications. In a multivariate analysis, age less than 50 years was a favorable risk factor for LFS, treatment-related mortality (TRM), and survival but not for relapse incidence. These data suggest that ABMT should be considered in older AML patients.

Acute Disease↗
PubMed1995

Peripheral blood stem cell transplantation in acute myeloid leukemia: the experience of the Bordeaux Group.

Since our initial report of successful peripheral blood stem cell transplantation (PBSCT) in a patient with acute myeloid leukemia (AML), we have performed more than 300 PBSCTs; 49 of them were done for AML patients. PBSC mobilization (and collection) was influenced by the number of previous courses of chemotherapy and significantly increased when G-CSF was combined with chemotherapy for mobilization. Hematopoietic recovery (HR) was complete in every patient. The HR rate was influenced by the number of cells transplanted. Platelet recovery was significantly quicker for patients given G-CSF for mobilization. The outcome of patients transplanted in first or second remission was similar to that usually observed after bone marrow transplantation.

Blood Specimen Collection↗
PubMed1995

Correction of the enzyme defect in cultured congenital erythropoietic porphyria disease cells by retrovirus-mediated gene transfer.

Congenital erythropoietic porphyria (CEP) is a genetic disease characterized by an overproduction and accumulation of porphyrins in bone marrow. The enzyme defect concerns uroporphyrinogen III synthase (UROIIIS), the fourth enzyme of the heme biosynthetic pathway. It is the most severe porphyria and the treatment is largely symptomatic: gene therapy would represent a great therapeutic improvement. As a step toward the development of an effective gene therapy, we have constructed two retroviral vectors, LUSN and pMFG-US (with and without the selectable marker Neo), containing a full-length human cDNA for UROIIIS. Recombinant retroviruses were obtained by transfection of the LUSN or pMFG-US plasmid into the amphotropic packaging cell line psi CRIP. For each construct, three different producing clones were selected for their high titer (LUSN) or for their ability to express the message at a high level (pMFG-US). In vitro amplification of genomic DNA from target tissue demonstrated the presence of vector sequences. Murine fibroblasts infected in vitro expressed the human enzyme efficiently, as indicated by RNA and enzymatic studies. Retroviral-mediated gene transfer was then used to introduce the UROIIIS cDNA into human deficient cells. Enzyme activity was increased from 2% (deficient fibroblasts) to 121-274% of the normal value for the different clones. Transduced cells selected with G418 presented an 18-fold increase in enzyme activity compared to the normal cells. Furthermore, high gene transfer rate into peripheral blood progenitor cells (PBPB) was documented by in vitro amplification (PCR). These results demonstrate the potential usefulness of somatic gene therapy for the treatment of CEP.

3T3 Cells↗
PubMed1995

Development of an efficient serum-free semisolid culture system for the evaluation of hematopoietic progenitors.

Three different combinations of serum-free (SF) media proposed by Drouet et al., Ieki et al., and Wu et al. were tested to assess their ability to replace fetal calf serum (FCS) in a human hematopoietic progenitor semisolid culture system using human bone marrow and peripheral blood stem cells. This study confirmed that two (Drouet and Wu) of the three SF media tested were able to induce progenitor growth in the presence of either 5637-conditioned medium or a defined combination of growth factors: stem cell factor (SCF), interleukin-1 (IL-1), interleukin-3 (IL-3), and erythropoietin (EPO). The best results were obtained using the SF media described by Wu. The number of 5637-stimulated CFU-GM obtained with the Wu SF media was not different from that obtained with FCS-supplemented media when cultures were assessed on day 14 (79 +/- 14 versus 104 +/- 17), day 18 (64 +/- 11 versus 79 +/- 12), or day 21 (58 +/- 13 versus 62 +/- 12). Similar findings were obtained when the previously defined combination of growth factors was used to stimulate progenitor growth. Because the Wu medium was the most efficient SF medium to promote hematopoietic progenitor growth, we attempted to improve its efficacy by modifying the concentrations of the various components. A reduction in the concentration of bovine serum albumin (BSA) dramatically reduced the total number of clonogenic elements. Soybean lectin was not essential for colony proliferation; however, its presence had an favorable effect on the overall appearance of the colonies (greater number of cells per colony).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Evaluation of the leukocyte differential flags on an hematologic analyzer. The Cobas Argos 5 Diff.

To evaluate the leukocyte differential flags of the Cobas Argos 5 Diff., the authors performed a comparative study between their current analyzer, the Technicon H2, and the manual leukocyte differential. Samples (n = 1,600) were collected from the Blood Disease Department of their hospital and were tested on both Cobas Argos 5 Diff. (ABX/Roche Hematology Division, Montpellier, France) and Technicon H2. Abnormalities of the manual leukocyte differential (immature granulocytes, blast cells, atypical lymphocytes, hyperbasophil cells, erythroblasts, and hairy cells) were found in 597 samples. The authors determined the best cut-off of the quantitative flags--atypical lymphocytes (ALYs) and large immature cells (LICs)--using the likelihood ratio method, and the capability of the 5 Diff. qualitative flags to determine abnormal subpopulations by the predictive value of a positive result. The presence of particular combinations of flags was associated with band cells and blast cells of acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML). The sensitivity, specificity, and efficiency of the two analyzers were 92.1, 53.9, and 68.2, respectively, for the Argos 5 Diff., and 93.5, 36.7 and 57.9, respectively, for Technicon H2. In conclusion, the Cobas Argos 5 Diff. is well adapted for detecting leukocyte abnormalities.

Data Interpretation, Statistical↗
PubMed1995

Overview of peripheral blood progenitor cell usage in France.

Peripheral blood progenitor cell (PBPC) transplantation offers a number of advantages over the use of bone marrow (BM) cells. Both the number and percentage of transplants performed with blood cells in France increased dramatically from 1990 to 1992. This report presents an analysis of 573 patients who underwent autologous transplantation of PBPC without BM. Approximately 50% received total body irradiation (TBI) and 12% received busulphan (Bu). The 200 patients receiving haematopoietic growth factors (HGF) for mobilisation showed an increase in the number of CFU-GM and CD34+ cells collected. Multivariate analysis showed that granulocyte recovery was significantly influenced, positively, by the number of CFU-GM cells infused, and by the use of HGF both for PBPC mobilisation and after transplantation; and negatively by the use of Bu. Further studies are still required to establish whether PBPC, in addition to reducing the duration of marrow aplasia, will also lead to decrease in transplant-related mortality or morbidity.

Bone Marrow Transplantation↗
PubMed1995

Cytokine-mediated expansion of 5-FU-resistant peripheral blood stem cells.

We evaluated the expansion capacity of untreated and 5-fluorouracil (5-FU)-resistant peripheral blood stem cells (PBSC) after 7-day incubation with interleukin-1 (IL-1) plus IL-3 plus stem cell factor (SCF) or with medium alone. We found a significant increase in the proportion of CD34+ cells in the PBSC fraction resistant to 25 micrograms/mL 5-FU after 7-day incubation with IL-1 plus IL-3 plus SCF as compared with the untreated fraction (p = 0.011). We also showed that 5-FU-resistant PBSC have a greater capacity for expansion of IL-1/IL-3/SCF-responsive immature progenitors (p = 0.05), amplification of IL-3 plus GM-CSF responsive progenitors (p = 0.01), and production of committed single growth factor-responsive (granulocyte-macrophage colony-stimulating factor [GM-CSF]) precursors (p = 0.01) than the untreated PBSC. The expansion of all types of progenitors and CD34+ cells was only observed after 7-day incubation with IL-1 plus IL-3 plus SCF. These results suggest that PBSC contain a primitive stem cell population with an enhanced expansion capacity that is identified by 5-FU resistance. As these cells can be expanded in vitro, they may then be suitable for a number of clinical applications.

Antigens, CD↗
PubMed1995

Peripheral T-cell lymphoma in a chronically immunosuppressed renal transplant patient.

Non-Hodgkin large cell lymphomas occurs more commonly in organ-transplanted patients than in the general population. They are usually of B-cell origin whereas T-cell lymphomas are rare. We report a new case of peripheral T-cell lymphoma in an immunosuppressed renal transplanted patient. The patient presented a hepatosplenic mass with a widespread extension causing serious pancytopenia. It was classified as a pleomorphic medium and large cell type and corresponded to the "common" alpha beta-TCR type lymphoma. Lymphomatous cells exhibited an incomplete mature T-cell phenotype. T-cell receptor gene clonal rearrangement associated with a germline configuration of the immunoglobulin heavy chain gene confirmed a clonal T-cell genotype. By using both Southern blot analysis and polymerase chain reaction, we failed to demonstrate any association with Epstein-Barr virus or human T-cell lymphotropic virus type I or type II.

Adult↗
PubMed1995

Busulphan and melphalan prior to autologous transplantation for myeloid malignancies.

We report our experience with 67 patients with myeloid malignancies (acute myeloid leukaemia (AML) or chronic myelogenous leukaemia (CML) conditioned with busulphan and melphalan as preparation for autologous haemopoietic cell transplantation. The major non-haematological toxicities were severe mucositis, nausea and vomiting, but the marrow aplasia was delayed and of short duration. The anti-tumor effect was appreciable with subsequent chronic phase (CP) obtained in 30/31 CML in transformation and complete remission (CR) obtained in 2/3 refractory AML. Among 32 patients treated while they had no evidence of active disease, 12 remained in CR or CP with a median follow-up of 54.7 months.

Adolescent↗
PubMed1995

Impact of cytogenetic abnormalities on outcome of bone marrow transplants in acute myelogenous leukemia in first remission.

This study analyzed the impact of cytogenetic abnormalities on outcome of 1516 HLA-identical sibling bone marrow transplants for acute myelogenous leukemia (AML) in first remission reported to the International Bone Marrow Transplant Registry by 188 centers. 708 patients (47%) had cytogenetic studies performed. Transplant outcome in these subjects was similar to the 808 in whom cytogenetic studies were not performed. One or more cytogenetic abnormalities were detected in 284 (40%) of subjects studied. Relapse rates were higher and leukemia-free survival lower in patients with poor prognosis abnormalities vs those with no abnormality or with good or intermediate prognosis abnormalities (relative risk of relapse 2.40, P < 0.01; relative risk of treatment failure 1.68, P < 0.03). We conclude that cytogenetic abnormalities correlated with increased relapse in patients treated with chemotherapy. HLA-identical sibling transplants are similar.

Adolescent↗
PubMed1995

Allogeneic bone marrow transplantation remains an efficient consolidation for adults with acute myeloid leukemia even when performed very soon after diagnosis (< 100 days). The SFGM (Société Française de Greffe de Moelle.

Allogeneic BMT is presently recognized as one of the reference anti-leukemic treatments for AML patients. It could be a very useful therapy in CR1 AML if it is efficient as an early form of consolidation after induction therapy. Later procedures may be of lesser importance since they concern a population which may have already been cured by chemotherapy. Alternatively it is not solved if very early BMT gives patients sufficient therapy and provides lower toxicity. To answer this question we analyzed data from the Société Française de Greffe de Moelle (SFGM) on a sub-group of patients according to the following criteria: (1) Allogeneic BMT carried out on patients with AML in CR1; (2) after January 1985; (3) conditioning with CyTBI; (4) GVHD prophylaxis with MTX-CsA; (5) interval between diagnosis and BMT < 100 days. Forty-two fulfilled all criteria. Age was 31 +/- 8 years and M/F ratio was 19/23. WBC at diagnosis were 36 +/- 49 x 10(9)/l and four patients needed two induction courses to achieve CR1. Median follow-up is now 51 (24-116) months. Twenty-two patients developed a grade > or = 2 acute GVHD. Early transplant mortality at 1 year is no higher than 14%. Two patients died of secondary malignancies at 3.5 and 6.5 years after BMT. Finally 5-year (and 7-year) probabilities for relapse, survival, leukemia and event-free survival are respectively 17% (17%), 71% (62%), and 71% (71%) and 68% (59%). These data indicate the feasibility of such an approach with low mortality and low relapse rates providing a good long-term outcome. This should prompt an invitation to initiate the search for an HLA-identical sibling when AML is diagnosed in a young patient eligible for allo-BMT.

Adult↗
PubMed1995

[Detection of the resistance to Ara-C blast cells in acute myeloid leukemia using flow cytometry].

Ara-C is currently used in the treatment of adult acute myeloid leukemia (AML). The cytotoxicity of Ara-C derives from an inhibition of DNA synthesis which can be determined using flow cytometry from the amount of bromodeoxyuridine (BrdUrd) incorporated into cells after a short exposure to BrdUrd. We developed a computer program to quantify inhibition of the rate of DNA synthesis by analysis of the distribution of BrdUrd/DNA. A resistance index (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 Ara-C sensitive and resistant HL60 cell lines, a linear relationship between RI and log Ara-C concentration was observed. This technique was applied to 96 bone marrow samples from patients with de novo AML treated by a regimen containing Ara-C. A first group of nine patients with high RI values included only drug resistant (DR) patients; a second group of 63 patients with low RI values included 62 patients who achieved a complete remission (CR); a third group of 24 patients with intermediate RI values included 19 CR and five DR patients. In view of these results, we think that it is possible to detect a majority of DR patients treated by Ara-C.

Adolescent↗
PubMed1995

[Hematopoietic growth factors (choice, chronology, combination].

Hematopoietic growth factors (HGF) or blood stem cell (BSC) transplantation can be used to decrease hematological toxicity due to high dose radio-chemotherapy. HGF can also be combined to BSC transplantation in different ways: administered either alone (during the steady state) or combined standard chemotherapy, HGF can increase BSC mobilisation and consequently the yield of BSC collected leading to a decrease of aplasia duration after transplantation; administered to the patient after transplant, they can decrease the period of granulocytopenia; HGF can also be used to expand ex vivo BSC before reinfusion to the patient. In these different situations, the best combination of HGF needs to be clarified.

Combined Modality Therapy↗
PubMed1995

5-Fluorouracil-resistant CD34+ cell population from peripheral blood of CML patients contains BCR-ABL-negative progenitor cells.

Despite the marked expansion of leukemic cells observed in the hematopoietic system of chronic myeloid leukemia (CML) patients, there is clinical and experimental evidence that normal nonclonal cells persist in the bone marrow (BM) and peripheral blood (PB) of patients in the early chronic phase. In this study, we attempt to select the benign progenitor-enriched population from the PB of CML patients. The CD34+ cells isolated from the PB of 12 CML patients in the chronic phase were treated with low doses (5 or 10 micrograms/mL) of 5-fluorouracil (5-FU). We expanded these cells for 7 days in liquid cytokine-mediated cultures. This expansion in the presence of interleukin-1 (IL-1) plus stem cell factor (SCF) plus IL-3 or leukemia inhibitory factor (LIF) plus SCF plus IL-3 seemed at least to preserve the initial clonogenic potential of CD34+ and 5-FU-resistant CD34+ cells. For the presence of BCR-ABL, mRNA from each of the 12 patients was studied by reverse-transcriptase-polymerase chain reaction (RT-PCR) on 10-15 pooled CFU-GM colonies plucked from methylcellulose cultures of starting and expanded populations. Although all PCR results were positive for colonies harvested before liquid culture, we were able to identify BCR-ABL-negative colonies from an expanded CD34+ population cultured in the presence of recombinant cytokines in 11 of 12 patients studied. 5-FU pretreatment of CML CD34+ cells markedly reduced their clonogenic potential and growth factor-mediated cell proliferation but favored higher frequency of BCR-ABL-free colonies. In conclusion, these data show that 5-FU-resistant CD34+ cells from the PB of CML patients contain normal progenitor cells, which can be selected and expanded in short-term cytokine-mediated cultures.

Antigens, CD34↗