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Biomedical subjects

J Reiffers

Publications and source records attributed to J Reiffers.

At least 217 records · Page 12Linked to original sources
PubMed1992

Incomplete stroma formation after allogeneic marrow or autologous blood stem cell transplantation.

Long term and semi-solid culture techniques were used to evaluate the quality of stroma produced by bone marrow from 33 normal subjects and 57 patients (46 allogeneic bone marrow and 11 autologous blood stem cell transplant recipients). Bone marrow from transplant recipients was capable of sustained CFU-GM and nucleated cell production in long term culture. However, only 13% of the marrow investigated developed a complete, confluent stromal layer. These stromal abnormalities were observed in spite of complete hematopoietic reconstitution after transplantation and rarely improved with time. Our results suggest that the hematopoietic microenvironment is very fragile and susceptible to long term damage as a result of chemotherapy and the conditioning regimes used prior to transplantation.

Adolescent↗
PubMed1992

Comparative cost of allogeneic or autologous bone marrow transplantation and chemotherapy in patients with acute myeloid leukaemia in first remission.

We compared the direct costs of allogeneic bone marrow transplantation (Allo-BMT), autologous bone marrow transplantation (Auto-BMT) and chemotherapy (Chemo) in 40 adult patients under the age of 55 years with acute myeloid leukaemia (AML) in first complete remission (CR). Fourteen patients were treated with Allo-BMT, 11 with Auto-BMT and 15 with Chemo. These patients, who were part of two cooperative consecutive trials enrolling a total of 196 patients (BGM 84 and BGMT 87 studies), were those who were treated in the CHR Bordeaux and achieved CR after induction chemotherapy. Cost accounting extended over a maximum period of 5 years. The average cost of the procedure for a mean follow-up of 2 years and excluding the cost of treatment after relapse which eventually occurred was significantly higher for the Allo-BMT group (FF 392,724) and the Auto-BMT group (FF 393,461) than for the group that received Chemo (FF 128,947) (p < 0.00001). The average cost for the treatment of relapse was estimated at FF 266,436, irrespective of the previous treatment. The total cost, including the estimated cost of relapse according to its probability of occurring calculated from the original population, was significantly higher for the Allo-BMT group (FF 424,696; p < 0.01) and the Auto-BMT group (FF 505,364; p < 0.0001) than for the Chemo group (FF 304,846).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Regimen-related toxicity in patients undergoing BMT with total body irradiation using a sweeping beam technique.

In our institution, total body irradiation (TBI) is performed by means of a sweeping beam technique. Toxicity of the procedure was evaluated according to the only grading system designed for high dose chemoradiotherapy. One hundred patients undergoing TBI and conditioned with a standard cyclophosphamide regimen before BMT were evaluated. Regimen-related toxicity was graded according to the Seattle transplantation toxicity system, from 0 to IV (fatal toxicity), in eight organs on days 0, 7, 14, 28 and 100 for lungs. Eighteen patients did not develop any toxicity. Grades III, IV toxicities were uncommon (9%) and were not influenced by dose of TBI, GVHD prophylaxis, disease status and allogenicity although no grade IV toxicity was observed among autologous marrow recipients. However, grade II toxicity was more common in patients receiving allogeneic vs autologous grafts (p < 0.01) because of increased mucosal (p = 0.002) and liver (p = 0.12) toxicities. Renal toxicity was unevaluable. When cumulative toxicity was equal or higher than 4, day 100 survival was worse (p = 0.05). These data confirm the safety of our TBI procedure and the validity of the grading system except for renal toxicity. We suggest that a more aggressive conditioning regimen may be tolerated by patients receiving autologous grafts.

Adolescent↗
PubMed1992

Serial cytogenetic studies in allografted patients with chronic myeloid leukemia.

Serial marrow karyotyping was performed in 31 chronic myeloid leukemia (CML) patients treated with allogeneic bone marrow transplantation (BMT). Of 11 hematological relapses, seven were heralded for up to 20 months by a cytogenetic relapse (characterized by increasing percentages of Philadelphia (Ph)-positive metaphases, seen on serial karyotypes). Chromosomal abnormalities additional to the Ph, seen before BMT, were not found again at relapse. Relapses were characterized by clonal evolutions of the Ph-positive cells, likely corresponding to cytogenetic patterns of treatment-induced leukemia [del(5q), del(7q), complex karyotypes] and were different from those generally found in CML evolution. Involvement of chromosome 1 was also frequent. Sporadic Ph-positive metaphases (not seen in repeated karyotypes) were seen only during the first 8 months after BMT.

Adolescent↗
PubMed1992

Complete cytogenetic conversion in chronic myelocytic leukemia patients undergoing interferon alpha therapy: follow-up with reverse polymerase chain reaction.

Fifteen chronic myelocytic leukemia patients in durable complete cytogenetic conversion (CCC) under interferon therapy, were monitored every three to six months by bone marrow (BM) karyotypes and/or reverse-transcription polymerase chain reaction (RT-PCR) on peripheral blood (PB) leukocytes (by a nested primer approach using two rounds of amplification, 30 cycles each). Special care was taken to minimize the risk of contamination. The median time of follow-up after first CCC was 12 months (range, 6-30). Thirty five BM karyotypes were performed. Only three patients demonstrated the transient reappearance of a few Philadelphia-positive metaphases, while other patients remained in CCC. Forty five PB samples were studied by RT-PCR. In two patients, no BCR/ABL transcript could be detected in three consecutive samples. In the 13 other cases, RT-PCR was intermittently negative, indicating a level of residual leukemic cells close to the threshold of sensitivity of the technique.

Adult↗
PubMed1991

High-dose recombinant interleukin-2 and acute myeloid leukemias in relapse.

Interleukin-2 (IL-2) is able to induce the regression of metastatic cancers when administered in vivo. IL-2-activated natural killer cells and lymphocytes show, in vitro, activities against leukemic cells. To assess if in vitro observations could have significant clinical relevance, we evaluated the in vivo activity of high-dose recombinant IL-2 (6 to 8 x 10(6) IU/m2/8H intravenous bolus for 5 days) in 10 patients with acute myeloid leukemias (AML) in relapse after chemotherapy (n = 7) or autologous bone marrow transplantation (n = 3). Two patients achieved a complete remission and one had a minimal improvement in his marrow blast cells. Response was observed after one cycle of IL-2 in the two patients achieving a complete remission. These two patients relapsed at 3 and 4 months. These results showing clinical activity of high-dose recombinant IL-2 in AML invite further evaluation of this new form of immunotherapy in other clinical situations, like an adjuvant setting for selected groups of high-risk patients.

Adolescent↗
PubMed1991

Modalities of synthesis of Ki67 antigen during the stimulation of lymphocytes.

The antibody Ki67 is currently used to evaluate the proliferative fraction of solid tumors and some hematological malignancies. We have used phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes as a model to study the entry of quiescent cells into cell cycle and to follow their progress to the next cycle. Flow cytometric analysis of lymphocyte samples stained with the antibody Ki67 and a DNA marker has allowed us to follow the expression of Ki67 antigen (Ki67 Ag) as a function of the position of the cells in the cell cycle. The use of drugs blocking the stimulated lymphocytes in different phases of the cell cycle permitted us to demonstrate that Ki67 Ag expression started from the beginning of the first S phase. The level of Ki67 Ag increased during S phase until mitosis, when its expression was maximal. After division, the cells in G1 phase showed a decrease in Ki67 Ag expression (possibly corresponding to degradation) until they reentered S phase, when the level of Ki67 Ag increased again. The results confirm that the expression of Ki67 Ag is related to the proliferative state of the cells and suggest that it may be used to determine the proliferative cell fraction in hematopoietic tissues.

Antigens, Surface↗
PubMed1991

Anti-LFA1 monoclonal antibody (25.3) for treatment of steroid-resistant grade III-IV acute graft-versus-host disease.

The in vivo efficacy of 25.3 monoclonal antibody (mAb) directed against human LFA1 molecule was assessed in ten patients with steroid-resistant grade III-IV acute graft-versus-host disease (AGVHD). These patients received non-T-cell-depleted allogeneic bone marrow transplantation for aplastic anemia in two cases and hematologic malignancies in eight cases. Five grafts were fully matched, three were one antigen-mismatched, and two were two antigen-mismatched. Despite GVHD prophylaxis with cyclosporin A and short-term methotrexate, AGVHD occurred after a median of 24 days and clearly progressed under prednisone (median 2 mg/kg), given for a median of 12 days. 25.3 mAb was given at a dosage of 0.1 mg/kg in a 4-h perfusion for five daily doses without any clinical or biological side effects. Thirty percent of the patients experienced a reduction in the overall grading with two complete responses. Partial response in at least one involved organ (mostly skin) occurred in 80% of the patients. However, seven out of the eight responding patients experienced a new episode of AGVHD. This observation, which confirms that inhibiting a functional molecule is as efficient as a cytolytic therapy, offers an alternative strategy to antithymocyte globulin (ATG) and cytotoxic mAb in controlling steroid-resistant GVHD.

Acute Disease↗
PubMed1991

Hydroxyurea versus interferon alfa-2b in chronic myelogenous leukaemia: preliminary results of an open French multicentre randomized study.

In order to compare the effects of interferon versus hydroxyurea for the treatment of chronic myelogenous leukaemia (CML), 58 CML patients, having received no previous treatment, were randomized into two treatment groups (hydroxyurea or interferon) for an open multicentre study from 1 May 1987 until 1 July 1990. Fifty patients were evaluable: 24 in the interferon group and 26 in the hydroxyurea group. Haematological response was obtained in 16/24 interferon-treated patients and 23/26 hydroxyurea patients. Failure to obtain haematological remissions occurred in eight of 24 interferon-treated patients and in three of 26 hydroxyurea patients. Four interferon-treated patient failures and one hydroxyurea-treated failure were due to drug intolerance. Progression occurred in one interferon-treated patient and in three patients given hydroxyurea. Fourteen of 16 patients in the interferon group and 17/23 in the hydroxyurea group continue on study and show no progression.

Adult↗
PubMed1991

Influence of the fractionation of total body irradiation on complications and relapse rate for chronic myelogenous leukemia. The Groupe d'Etude des greffes de moelle osseuse (GEGMO).

One hundred eighty patients with chronic myelogenous leukemia, who received an unmanipulated marrow graft from an Human Leucocyte Antigen identical sibling donor, were reported to our group (G.E.G.M.O.) by 21 transplant teams. All were grafted after a total body irradiation-cytoxan conditioning regimen. Of these 180 patients, 126 were non-randomly assigned to single dose total body irradiation (STBI group) and, 54 to fractionated total body irradiation (FTBI group). With a median follow-up of 40 months, there is no statistically significant difference in the 5-year survival rate between the two groups (51% for the whole population). In a first step we demonstrate by multivariate analysis that total body irradiation fractionation can dramatically decrease the incidence of interstitial pneumonitis. However, a multivariate analysis of potent risk factors for relapse post-transplant strongly suggests that TBI fractionation is also linked to an increased relapse rate. So, a sparing effect of fractionation for lung tissue could be offset by a less effective leukemic stem cell kill. Those results from a retrospective, non-randomized, multi-institutional study clearly need additional clinical data, ideally from a randomized study.

Bone Marrow Transplantation↗
PubMed1991

Autologous blood stem cell transplantation for chronic granulocytic leukaemia in transformation: a report of 47 cases.

Forty-seven patients with chromosome Philadelphia-positive (Ph1) chronic granulocytic leukaemia (CGL) in transformation underwent autologous transplantation of peripheral blood stem cells (ABSCT) collected at the original diagnosis before any treatment. They were treated with three consecutive strategies: single transplant (group I = 17 patients), double transplant (group II = 13 patients), double transplant followed by recombinant alpha interferon (group III = 17 patients). Forty-three patients were restored to a second chronic phase with a cytogenetic conversion (more than 10% Ph1-negative marrow metaphases) occurring in 14 of the 29 evaluable patients. Most patients had a recurrent transformation occurring 2-43 months after ABSCT and finally eight patients are still alive in second chronic phase 4-49 months after ABSCT (median = 24 months). The actuarial median duration of second chronic phase was 3 months, 10 months and 18 months for group I, group II and group III patients (P less than 0.0001). The encouraging results observed for group III patients prompt us to propose ABSCT for patients in chronic phase with initial prognostic factors, suggesting that recombinant alpha interferon will not be effective if administered as front-line therapy.

Adult↗