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Biomedical subjects

P Stryckmans

Publications and source records attributed to P Stryckmans.

At least 19 recordsLinked to original sources

Screening for psychiatric disorders in a lymphoma out-patient population.

The Hospital Anxiety and Depression Scale (HADS), a four-point, 14-item self-assessment questionnaire, was tested as a screening method for psychiatric disorders in a sample of 117 Hodgkin's lymphoma and non-Hodgkin lymphoma consecutive out-patients. A receiver operating characteristic (ROC) analysis was performed, giving the relationship between the true positive rate (sensitivity) and the false positive rate (1--specificity). This makes it possible to choose an optimal cut-off score that takes into account the costs and benefits of treatment of psychiatric disorders (mainly adjustment, depressive and anxiety disorders) in a lymphoma out-patient population. A cut-off point of 10 gave 84% sensitivity and 66% specificity. HADS appears in this study to be a well accepted, simple, sensitive and specific tool.

Adjustment Disorders

[Current perspectives in bone marrow transplantation].

Peripheral blood and umbilical cord blood are promising sources of hemopoietic stem cells for autologous as well as allogeneic transplantation. The nature of the progenitors responsible for early marrow reconstitution after transplantation on one hand and for permanent reconstitution on the other hand is getting more precise. Features of the cells responsible for GVHD and of those responsible for GVL effect (graft versus leukemia effect) will soon allow a distinct monitoring of these two activities. Molecular biology will soon permit genetic labelling of the graft and thereby bring more precision for its follow-up and modulation in vivo in the post-graft period. Correction of an autologous transplant by introduction of the adequate gene in the hematopoietic stem cells in case of genetic anomaly at this level, should in the future, as suggested by animal studies, allow permanent correction of genetic disorders in patients autografted according to such a procedure. Finally, introduction of procedure like antisense nucleotides against DNA regions responsible for the malignant proliferation of tumoral cell, could extend the therapeutic possibilities of autograft.

Bone Marrow Transplantation

[Bone marrow grafts. Introduction].

Allogeneic bone marrow transplantation (BMT) is a therapeutic procedure which has a powerful antileukemic activity in addition to that of high dose radiochemotherapy. Its indications have progressively extended from leukemia to most malignant hemopathies. It allows in some of these disorders to increase the number of cures above that obtained by conventional chemotherapy and in others to cure diseases never curable by chemotherapy. Allogeneic BMT, in addition, found more recently many promising indications in the field of genetic disorders of the cellular systems derived from the hematopoietic stem cell. Autologous BMT (ABMT) is also efficient in the majority of malignant hemopathies. Its efficacy however is limited mainly to that of high dose(s) of radiochemotherapy. The efficacy of ABMT thus appears lower than that of allo BMT but in terms of survival this disadvantage is more or less compensated by its lower lethal toxicity. Its efficacy in comparison with that of conventional chemotherapy is still under study. The lethality induced by BMT itself, the risk of mortality due to the disease, the age of the patient and the degree of resistance of the disease to conventional therapies are, among others, crucial parameters to take into consideration for each specific case and of which will depend the quality and the duration of the patient's survival.

Bone Marrow Transplantation

[Bone marrow autograft in malignant hemopathies. The Team of the Sterile Unit].

Only in the last decade have autologous grafts begun to be studied extensively. Their most attractive feature is the avoidance of GVHD. However, GVHD has antitumoral effect on residual leukemic cells called "graft versus leukemia" effect and better understanding of this phenomenon explains the higher relapse rate after autologous bone marrow transplantation. New approaches such as cyclosporin--induced GVHD and IL-2 administration after autograft bring great expectations in this field. Colony stimulating factors and harvesting of peripheral stem cells help to reduce the duration of neutropenia. Finally, various techniques for marrow purging and hematopoietic cell isolation should make it possible to eliminate minimal residual disease. Recent results of autologous bone marrow transplantation in various malignancies are discussed.

Bone Marrow Transplantation

Prevention of CMV-induced myelosuppression by anti-CMV antibodies: an in vitro model.

Pathogenesis of cytomegalovirus (CMV)-induced myelosuppression is not clearly understood and could be related to a direct toxic effect on the marrow progenitors and/or an alteration of the marrow environment. Myeloid progenitors (granulocyte-macrophage colony-forming units, CFU-GM) were not affected by incubation with increasing titers of CMV (10-10(5) plaque-forming units [pfu]/ml) during 2-6 h. By contrast, using the blast colony-forming cell (Bl-CFC) assay, we confirmed that CMV induced myelosuppression through an alteration of the marrow-derived stromal layer. Using this experimental model, we compared the capacity of nonspecific human immunoglobulins (IgG), specific polyclonal anti-CMV IgG, and a human monoclonal anti-CMV IgG to prevent the myelosuppressive effect of 10(4) pfu/ml of CMV. Specific anti-CMV IgG (polyclonal or monoclonal) at the concentration of 10 micrograms/ml were able to prevent the CMV-induced myelosuppressive effect, whereas nonspecific human IgG was not effective in this model. Our results suggest that 1) CMV-induced myelosuppression is related to an alteration of the marrow microenvironment, 2) specific monoclonal and polyclonal anti-CMV IgG prevent this myelosuppressive effect in vitro, and 3) human monoclonal anti-CMV IgG could be useful in vivo in the immunoprophylaxis of CMV infections.

Antibodies, Monoclonal

Analysis of interferon-inducible genes in cells of chronic myeloid leukemia patients responsive or resistant to an interferon-alpha treatment.

Recombinant human interferon-alpha (IFN-alpha) can induce a hematologic remission in patients with chronic myeloid leukemia. However, some patients are resistant and others develop late resistance to the IFN-alpha treatment. To understand the molecular mechanism of this resistance, we have analyzed the expression of 10 IFN-inducible genes in the cells of three resistant patients, two responsive patients, and six healthy controls. Northern blot hybridizations showed that all the genes were induced in in vitro IFN-alpha treated peripheral blood cells of the patients and healthy controls. These genes were also inducible in peripheral blood and bone marrow cells of two out of two resistant patients administered an injection of IFN-alpha. We conclude that the resistance to the IFN-alpha treatment of the chronic myeloid leukemia patients we studied is not due to (1) the absence of induction of any of the 10 IFN-inducible genes we studied, including the low-molecular-weight 2'-5'oligoadenylate synthetase; (2) the presence of an antagonist of IFN-alpha in the peripheral blood or bone marrow cells; and (3) the presence of neutralizing anti-IFN-alpha antibodies.

2',5'-Oligoadenylate Synthetase

Pentostatin in refractory chronic lymphocytic leukemia: a phase II trial of the European Organization for Research and Treatment of Cancer.

Pentostatin was used to treat 26 patients with advanced B-cell chronic lymphocytic leukemia resistant to conventional treatment. Twenty patients had progressive disease on previous regimens and six had had partial remission and then relapsed 3-34 months after previous chemotherapy. Eleven patients had previously been treated with three different regimens. 10 had been treated with two regimens, and five had been treated with one regimen. Pentostatin was administered at a dosage of 4 mg/m2 weekly for 3 weeks, then 4 mg/m2 every other week for 6 weeks and once a month for 6 months. Seven of 26 assessable patients (27%) achieved partial remission and five (19%) achieved clinical improvement. The median duration of partial remission until relapse or death was 210 days. Myelosuppression was minor and transient in responsive patients, indicating some degree of selective effect on lymphocytes. Except for one patient who died of cerebral hemorrhage during the first 6 weeks of treatment, no drug-related deaths were registered. Major toxic effects included nausea in 17 patients (mainly grade 1), infections in 15, and liver enzyme elevations in five. Thus, pentostatin is active, even in patients with advanced B-cell chronic lymphocytic leukemia that is refractory to multiple chemotherapy regimens. Response can be achieved with mild myelosuppression.

Adult

Production of human monoclonal IgG antibodies reacting with cytomegalovirus (CMV).

A human monoclonal antibody (MoAb) reacting with cytomegalovirus (CMV) has been produced using somatic cell hybridization between Epstein-Barr virus (EBV) infected B lymphocytes and a human-mouse heteromyeloma cell line (SHM-D33). The hybrids were selected in HAT medium containing 5 x 10(-7) ouabain. The median level of Ig production was 5 (0.1-20) micrograms/10(6) cells/day. One selected hybridoma (IB-8E9H5) has been maintained in continuous culture for more than 30 months with a stable IgG2, lambda production. Molecular hybridization using EBV-specific probes demonstrate that our hybrids have lost the IR-1 EBV sequence during fusion. Unexpectedly, these blotting experiments revealed the presence of multiple EBNA-1 sequences dispersed among the genomic DNA of the SHM-D33 cell line. Screening for anti-CMV specificity was performed by ELISA and confirmed by immunofluorescence staining. Thus far, three CMV reference strains and 14 local strains are stained by the MoAb as early as 3 h after CMV infection of human fibroblasts, apparently through the recognition of a nuclear viral antigen of 67 kDa. In conclusion, this technique permits (a) the removal of the EBV genome contained in the lymphoblastoid parental cell line and (b) the production of human anti-CMV MoAb with potential applications in the prevention of life threatening CMV infections.

Antibodies, Monoclonal

A randomized comparison of intensive maintenance treatment for adult acute myelogenous leukemia using either cyclic alternating drugs or repeated courses of the induction-type chemotherapy: AML-6 trial of the EORTC Leukemia Cooperative Group.

Out of 515 evaluable patients (median age, 47 years) who entered the study from 1983 to 1986, 67.4% achieved complete remission (CR) after one cycle (256) or two cycles (91) of daunorubicin (DNR) (45 mg/m2 days 1-3), cytosine arabinoside (Ara-C) (200 mg/m2 i.v. days 1-7), and vincristine (VCR) (1 mg/m2 day 2). A partial remission was achieved by 3.7% of patients, 15% were resistant, 11.3% died during hypoplasia, and 2.7% died during induction. Patients achieving CR received one consolidation course in which administration of DNR was limited to 1 day. Two hundred and forty-eight patients were randomized for six courses of maintenance every 6 weeks: either DNR + VRC day 1 + Ara-C s.c. days 1-5, or AMSA 150 mg/m2 day 1 alternating with high-dose (HD)-Ara-C 3 g/m2 q12 h day 1 + 2 or 5-azacytidine 150 mg/m2 days 1-3. Two hundred and thirty-three patients were randomized when bone marrow transplantation (BMT) had not been planned or performed and 15 patients were randomized before the BMT. Sixty patients received BMT, 17 autografts, and 43 allografts. Median time from CR to BMT was 15 weeks. Forty-two patients were not randomized mainly because of toxicity or treatment refusal. Median DFS for both chemotherapy groups was 12 months and 23% were alive at 4 years. Median survival from CR was 22 months, and 34% were alive at 4 years. There was no difference in disease-free interval (DFI) and disease-free survival (DFS) between the two chemotherapy arms. Of 60 transplanted patients, 42% were alive at 4 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Inhibitory effects of potent inhibitors of human immunodeficiency virus and cytomegalovirus on the growth of human granulocyte-macrophage progenitor cells in vitro.

Phosphonoformate, ganciclovir, zidovudine and the novel acyclic nucleotide analogues (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA] and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine [(S)-HPMPC] were evaluated for their inhibitory effect on colony forming unit formation by human granulocyte-macrophage progenitor cells (obtained from 11 healthy volunteers) in vitro. The 50% inhibitory dose of zidovudine, (S)-HPMPA, (S)-HPMPC, ganciclovir and phosphonoformate were 10.61, 16.55, 80.88, 41.02 and 668.64 microM, respectively, when the median-effect principle was applied. The bone marrow toxicity of zidovudine used at a low concentration (3.74 microM) was significantly decreased if the drug was combined with (S)-HPMPA, (S)-HPMPC or ganciclovir. If used at higher concentrations (74.90 microM), zidovudine showed increased myelotoxicity in the presence of (S)-HPMPA and ganciclovir, but not (S)-HPMPC.

Adenine

Influence of recombinant alpha and gamma interferons on the in vitro proliferation of myeloid and leukemic progenitors.

We have compared the effect of alpha 2-C and gamma recombinant interferons (rIFNs) on normal myeloid progenitors (N-CFU-GM), chronic myeloid leukemia (CML) progenitors (CML-CFU-GM) and leukemic progenitors (L-CFU) of acute non-lymphoblastic leukemia (ANLL) patients. Within 14 days of continuous exposure in culture, a dose-dependent inhibition of CFU-GM was seen for most normal subjects. Resistance to rIFNs was frequent in leukemic patients and even more in acute leukemia than in CML. Stimulation of clonogenic cell growth was seen for a minority of leukemic patients. When only the sensitive cases were considered, no difference in sensitivity was noticed between normal, CML and ANLL patients. A good correlation was observed between the activity or the lack of activity of alpha and gamma rIFNs.

Bone Marrow

[Adoptive immunotherapy with interleukin 2. Initial results of a pilot study in 6 cancer patients].

Adoptive immunotherapy of cancer consists of using interleukin-2 to induce the formation of lymphokine-activated killer (LAK) cells which are toxic to tumoral cells. Six patients, 3 with hypernephroma and 3 with melanoma, were treated with interleukin-2. Drug toxicity consisted of capillary leakage syndrome in one case and reversible renal impairment in another. One patient showed an objective response; transient subjective improvement was observed in all patients.

Acute Kidney Injury