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Biomedical subjects

A M Stoppa

Publications and source records attributed to A M Stoppa.

At least 73 records · Page 4Linked to original sources
PubMed1994

Phase I study of in vivo lenograstim (rHuG-CSF) for stem cell collection demonstrates improved neutrophil recovery after autologous bone marrow transplantation.

Colony stimulating factors and especially rHuG-GSF, the first available neutrophil growth factor, have led to considerable interest in the field of stem cell transplantation because of their ability to induce stem cell peripheralization either alone or in association with high-dose chemotherapy. Few data exist, however, on the impact of rHuG-CSF on large scale bone marrow collection and autologous bone marrow transplantation (ABMT). This phase I, non-randomized, dose escalation study of rHu-G-CSF (lenograstim) administered to 30 patients at doses ranging from 1 to 40 micrograms/kg/day for 5 days before bone marrow harvesting showed that priming with rHu-G-CSF in vivo increased the number of bone marrow cells and D14 myeloid restricted progenitors (CFU-GM) and led to a better neutrophil recovery after ABMT compared with a contemporary unprimed control population. Otherwise, this study established that 5 days of rHuG-CSF therapy, as a sole stimulus, induced a tenfold increase in the circulating CFU-GM amongst which immature progenitors, estimated by the Delta assay (secondary CFU-GM grown after 7 days of liquid culture/primary CFU-GM), are detected. These conclusions were valid for doses as low as 2 micrograms/kg/day which induced only mild neutrophilia up to the highest dose (40 micrograms/kg/day) and suggest that a short course of rHuG-CSF is beneficial in increasing the stem cell collection.

Adolescent↗
PubMed1994

Enrichment of peripheral blood stem cells in a primate model following administration of a single dose of rh-IL-1 beta.

In a pre-clinical primate model, the effect of a single intravenous injection of rh-GM-CSF (50 micrograms/kg), rh-IL3 (20 micrograms/kg), rh-IL-1 beta (1 micrograms/kg), rh-G-CSF (50 micrograms/kg) and rh-pIXY 321 (50 micrograms/kg) on peripheral blood mononuclear cell and hematopoietic stem cell concentration was determined. The results indicated that administration of a single dose of rh-IL-1 beta increased the concentrations of hematopoietic stem cells, including CFU-GM progenitors and precursors to CFU-GM. No toxicity was noted with this procedure. None of the remaining cytokines tested caused a significant increase in the peripheral blood hematopoietic stem cell concentration when administered in this manner and only G-CSF caused an increase in peripheral blood mononuclear cell concentrations. Autologous transplantation with limiting numbers of peripheral blood mononuclear cells (1 x 10(7) cells/kg) collected either 24 or 72 h following injection of 1 microgram/kg rh-IL-1 beta conferred a survival advantage to recipients compared with controls. These results imply that a single intravenous administration of rh-IL-1 beta may increase the concentration of peripheral blood stem cells to levels sufficient for transplantation.

Animals↗
PubMed1994

Delayed administration of granulocyte colony-stimulating factor after autologous bone marrow transplantation: effect on granulocyte recovery.

Recombinant granulocyte colony-stimulating factor (rhG-CSF) has been shown to hasten granulocyte recovery after autologous BMT. In current protocols, rhG-CSF treatment starts 1 day after BM reinfusion. Our study retrospectively examined the effects on haematological recovery of a day 6 delayed administration. Seventy-eight patients receiving autologous BMT for malignant lymphoma (21 non-Hodgkin's lymphoma and 9 Hodgkin's disease) or solid tumors (33 breast carcinoma and 5 ovarian carcinoma) were split up into three study groups. Two groups receiving a 5 micrograms/kg/day of rhG-CSF starting either 1 day (day +1 group, n = 25 patients) or 6 days (day +6 group, n = 24 patients) after BM reinfusion were compared with 29 historical control patients. Granulocyte recovery to 0.5 x 10(9)/l was 12 days in day +6 and day +1 groups versus 16 days in control group (p < 0.005) without any difference in other hematological parameters, infectious complications or length of hospitalisation between the three groups. The day +6 administration allows elimination of a median of 7 days rhG-CSF. It has been concluded that the day +6 administration gives the same clinical benefit as day +1 administration with consequent cost reductions.

Adult↗
PubMed1994

Bone marrow transplantation in 63 adult patients with acute lymphoblastic leukemia in first complete remission.

Over a 10 year period, we transplanted 63 patients with acute lymphoblastic leukaemia (ALL) who had achieved first complete remission (CR). All were > 15 years old and 45 (71%) had at least one poor prognostic factor. Twenty-nine patients with a suitable sibling underwent autologous bone marrow transplantation (BMT). Beginning in 1984, patients without a donor received an allogeneic BMT (34 patients). Preparation consisted of cyclophosphamide (CY)/TBI (78%) or melphalan (Mel)/TBI (22%); marrow was treated in vitro in 31 patients (allogeneic: 7; autologous: 24). Kaplan-Meier estimates of the probability at 6 years of relapse, survival and DFS were 41% (allogeneic: 10%, autologous: 65%, p < 0.05), 44% (allogeneic: 62%, autologous: 26%, p = NS) and 42% (allogeneic: 62%, autologous: 27%, p < 0.06), respectively. This report confirms that allogeneic BMT permits long-term remissions giving high levels of survival when performed shortly after entering first CR while autologous BMT, when performed in the same setting, is less successful at preventing relapse. This study also confirms the high sensitivity of ALL to the graft-versus-leukemia effect provided by allogeneic BMT. Chemoradiotherapy dose intensification delivered at autologous BMT is not sufficient to prevent relapses. Autologous BMT must therefore be augmented by other approaches of which immunotherapy may be one.

Adolescent↗
PubMed1994

Modifications of leukemic blast cells induced by in vivo high-dose recombinant interleukin-2.

High-dose recombinant human Interleukin-2 was given to 21 patients with acute myeloid (n = 11) or lymphoid (n = 10) leukemia in relapse. A rapid decrease in the peripheral leukemic blasts numbers was observed in six patients. We were unable to demonstrate at the bone marrow level a diminution in the percentage of leukemic blasts. However an increase in the expression of the adhesion molecule CD54/ICAM-1(LFA-1 ligand) affected the leukemic bone marrow blasts of these six patients. This increase in CD54 was found in eight of the 11 (73%) AML and four out of the ten (40%) ALL blasts and CD58/LFA-3 (CD2 ligand) to a lesser extent. This increased expression was not associated with modifications in the expression of MHC class II molecules. In vivo IL-2 also dramatically modified the bone marrow T-cell subsets via the increase of CD3+ cells expressing the CD45RO 'memory' marker (six out of the eight tested patients) or CD54 (seven out of the eight tested patients). Altogether these results demonstrate that leukemic blasts can be affected by in vivo IL-2 via mechanisms that could involve T cells.

Acute Disease↗
PubMed1993

[Hematopoietic growth factors].

Haematopoietic growth factors are a family of genetically determined low molecular weight glycoproteins which regulate the proliferation and differentiation of haemopoietic cells through specific membrane receptors. GCSF and GMCSF reduce the morbidity from infections associated with the neutropenia induced by chemotherapy of onco-haematological neoplasia; EPQ totally corrects not only the anaemia of patients with chronic renal failure, but also 50 percent of anaemias related to chemotherapy; finally, the activity of IL 3 on platelet production seems to control the thrombocytopenia which restricts the use of therapeutics.

Erythropoietin↗
PubMed1993

[Cytokines and malignant hemopathies: leukemias and bone marrow graft].

Cytokines are now part of the modern armentarium utilized against malignant blood diseases. The essentially lymphocytic haematopoietic growth factors (G-CSF, GM-CSF, IL-3) reduce the infectious morbidity associated with the deep and prolonged neuropoenia induced by the myelo-ablative conditioning for autologous or allogeneic bone marrow transplantations, and widening their indications is tempting. The reluctance expressed about their use in chemotherapy of acute myeloid leukaemia is abating now that controlled studies have shown that they preserve the complete response rate and shorten the duration of leucopoenia. Moreover, they modify the leukaemia biological response, which makes it possible to increase the cytotoxicity of certain drugs and constitutes a new approach to drug-resistant leukaemias. Immuno-modulating cytokines (interferon alpha, interferon gamma, interleukin-2) act through mechanisms that are still ill-defined: antitumoral activity, modification of biological responses, immunoactivation. Nevertheless, interferon alpha has revolutionized the treatment of hairy cell leukaemia and myeloid leukaemia, with a 70% remission rate. The scarcity of complete responses (10% of hairy cell leukaemias) or cytogenetic responses (20% of chronic myeloid leukaemias) justifies a combined treatment (chemotherapy+immunotherapy?) to improve these patients' cure rate. The anti-leukaemic activity of interleukin-2, observed in patients with refractory relapses, produces 33% of responses, including 10% of complete responses, and it is tempting to test the impact of this immunotherapy on the control of residual leukaemia as adjuvant of complete remission using randomized trials.

Antineoplastic Agents↗
PubMed1993

Autoimmune polyendocrine failure--type 1 (insulin-dependent) diabetes mellitus and hypothyroidism--after allogeneic bone marrow transplantation in a patient with lymphoblastic leukaemia.

In this report we describe a patient who, after allogeneic bone marrow transplantation from her HLA-identical sister, developed polyendocrine failure in the form of Type 1 (insulin-dependent) diabetes mellitus and hypothyroidism. This was the result of the transfer of donor lymphoid cells which were activated by allogeneic bone marrow transplantation. The full chimerism of the recipient was demonstrated by restriction fragment length polymorphism analysis from nucleated blood cells and fibroblast DNA. During the 9-year follow-up, the donor developed hypothyroidism and signs of pre-Type 1 diabetes. This clinical observation resembles the adoptive transfer of diabetes observed in non-obese-diabetic mice and BB rats and confirms the role of immune processes in the pathogenesis of this disease.

Adolescent↗
PubMed1993

A tumour-associated antigen expression in human haematological malignancies.

Objective responses obtained with high-dose in vivo recombinant interleukin 2 (r-IL2) in some leukaemic patients suggest among other hypotheses that blasts might express tumour rejection antigens potentially recognized by cytolytic T lymphocytes. Such antigens have been described in human melanomas and the MAGE-1 gene, coding for a tumour rejection antigen was recently identified. This gene is expressed in various solid tumours, but not in normal cells. We have screened a panel of haematological malignancies by reverse transcription and PCR and we report that MAGE-1 is not expressed in the blasts from 48 patients whereas three cell lines derived from leukaemias express this gene.

Antigens, Neoplasm↗
PubMed1993

In vitro inhibition of interleukin-2-induced defective polymorphonuclear chemotaxis by TNF inhibitor.

Patients undergoing immunotherapy with interleukin-2 experience multiple side effects and are highly susceptible to bacteremia. In a previous study, we confirmed that a profound deficiency of neutrophil chemotaxis is induced by interleukin-2 therapy. Migration in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP), being normal before therapy, was markedly impaired after the first cycle and further decreased after the third cycle of treatment. A direct effect of interleukin-2 on neutrophil chemotaxis is controversial. However, peripheral blood cells exposed to interleukin-2 secrete secondary cytokines. In particular, the release of tumor necrosis factor after interleukin-2 injection has been proposed as an important regulatory mechanisms. When testing random migration and chemotaxis of neutrophils from normal subjects after incubation with the serum from treated patients, we found that this serum induced a defective chemotaxis similar to that of neutrophils from interleukin-2-treated patients. In order to assess the influence of tumor necrosis factor, we tested the effect of anti-tumor necrosis factor-alpha antibody on the chemotactic response of cells after incubation with the serum, and we observed a dose-dependent reduction of neutrophil chemotaxis deficiency. These data suggest that TNF is counteracting the neutrophil chemotactic deficiency observed during IL-2 treatment.

Adult↗
PubMed1993

Therapy-related acute myeloid leukemia with t(8;21), inv(16), and t(8;16): a report on 25 cases and review of the literature.

PURPOSE: To analyze therapy-related acute myeloid leukemias (tAMLs) with t(8;21), inv(16), or t(8;16). PATIENTS AND METHODS: Twenty-five patients with tAML and t(8;21)(q22;q22), inv(16)(p13;q22), or t(8;16)(p11;p13) from seven centers, along with 23 previously published cases, were studied. RESULTS: Twenty-six, 16, and six patients, respectively, had t(8;21), inv(16), and t(8;16). Prior cancer was a solid tumor in 27 cases, and a hematologic malignancy in all other patients. Five patients had received prior radiotherapy (RT) alone, and 43 had received prior chemotherapy with or without RT. Prior chemotherapy included a drug that directly reacts with DNA (alkylating agent or cisplatin) and/or an agent that targets topoisomerase II (ATTop, an anthracycline or derivative or, less often, epipodophyllotoxin) in most patients. The interval between prior tumor and diagnosis of tAML was less than 3 years in most cases, and only seven patients had a preleukemic phase of disease. Morphology was M2 AML for t(8;21), M4eo for inv(16), and M4 or M5 for t(8;16). Sixteen of 21 (76%), 12 of 14 (86%), and zero of four patients with t(8;21), inv(16), and t(8;16), respectively, achieved complete remission (CR) with intensive chemotherapy. The actuarial disease-free survival rate at 24 months was 47% and 54% in patients with t(8;21) and inv(16), respectively. CONCLUSION: Like other tAMLs with a karyotype specific of de novo AML [balanced 11q23 rearrangement or t(15;17)], tAMLs with t(8;21), inv(16), or t(8;16) are usually characterized by a short latent period, previous treatment often combining a drug that directly reacts with DNA and an ATTop, and absence of preleukemic phase. Hematologic characteristics and response to treatment are also identical to those of de novo AML with the same karyotypes.

Actuarial Analysis↗
PubMed1993

Incidence rate and risk factors for thyroid dysfunction during recombinant interleukin-2 therapy in advanced malignancies.

Immunotherapy using recombinant interleukin 2 (rIL-2) has been shown to induce thyroid dysfunction in some cancer patients. The purpose of the present study was to evaluate the incidence and risk factors of this adverse autoimmune response. Triiodothyronine, thyroxine and thyrotropin levels were measured serially in 146 consecutive patients treated with rIL-2 for refractory solid tumor (77 patients) or malign hemopathy (69 patients); rIL-2 was administered intravenously in 5-day cycles (18 x 10(6)-24 x 10(6) IU.m-2.day-1) either alone in 79 cases or in combination with autologous bone marrow transplantation in 26 cases, with interferon-gamma in 37 cases, with tumor necrosis factor-alpha in 13 and with cyclophosphamide in five cases. Some patients underwent more than one therapeutic protocol. Peripheral hypothyroidism was present upon entry in nine (6.2%) patients. Thyroid dysfunction appeared or worsened during rIL-2 therapy in 24 (16.4%) patients. Sixteen (10.9%) patients exhibited peripheral hypothyroidism, out of which four exhibited biphasic thyroiditis. Another five (3.4%) patients developed transient hyperthyroidism. Anomaly could not be classified in three patients. Thyroid dysfunction appeared early after one or two cycles. All surviving patients recovered. Only gender and presence of antithyroid antibody were correlated significantly with rIL-2-induced thyroid abnormalities. No correlation was found with any of the other risk factors studied, i.e. type of malignancy, rIL-2 treatment procedure, clinical efficacy, evolution of circulating lymphocyte subsets or other autoimmune antibodies. Antithyroid antibodies were detected in 60.9% of patients with this complication. Thyroid-stimulating antibodies were never detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
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↗