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Biomedical subjects

I Aurer

Publications and source records attributed to I Aurer.

At least 19 recordsLinked to original sources

Long-term results of conventional-dose salvage chemotherapy in patients with refractory and relapsed Hodgkin's disease (Croatian experience).

BACKGROUND: The aim of this study was to analyze outcome of patients with Hodgkin's disease (HD) in whom first-line chemotherapy with mustine/vincristine/procarbazine/prednisone (MOPP) had failed. PATIENTS AND METHODS: From January 1982 to December 1989 among 210 patients treated with MOPP and radiotherapy to initial bulky sites, 65 patients were primary refractory to or relapsed after initial treatment. RESULTS: Twenty-nine of 65 patients (44%) were primary refractory to initial chemotherapy, 20 relapsed within 12 months after complete remission (CR) and 16 relapsed after CR that lasted more than 12 months. Patients with primary refractory HD and early relapse (<12 months after CR) were treated with doxorubicin/bleomycin/vinblastine/darcarbazine. In patients with late relapse (>12 months after CR) MOPP was repeated. The median follow-up for all patients was 115 months. The overall response rate was 63%. Thirty-three patients (51%) achieved a second CR and eight patients (12%) partial response. Remission rate was greatest in patients with late relapse (CR >12 months) (75 versus 55% for early relapse versus 35% for primary refractory HD) (P <0.01). At 10 years, overall and failure-free survival rates were 21 and 16%, respectively. Patients who were in first remission longer than 12 months had a superior overall survival (37 versus 18% for early relapse) and failure-free survival (24 versus 10% for early relapse). No patient with primary refractory HD was alive beyond 52 months after initial treatment failure (P <0.01). Main prognostic factors were duration of the first remission and tumor bulk at relapse. CONCLUSIONS: Our results confirm previous observations that a significant proportion of patients with HD who experience induction treatment failure cannot be cured with conventional treatment and probably need more aggressive therapy.

Adolescent↗

Bone marrow immunoscintigraphy in haematological patients with pancytopenia: preliminary results.

The aim of this study was to assess the clinical value of bone marrow immunoscintigraphy using the (99m)Tc labelled anti-NCA-95 antigranulocyte antibodies (AGAb) and of AGAb bone marrow uptake ratio (UR) in the initial diagnostic work-up of diseases with depression of the bone marrow. Twenty-four whole-body bone marrow scans were performed in 23 patients (11 women, 12 men; median age 46 years, range 17-74 years) 5 h after i.v. injection of 370 MBq of AGAb. The UR was calculated from the posterior view drawing an irregular region of interest around the sacroiliac and a background areas. The mean UR in pancytopenic patients was 2.3+/-1.5 (range 0.3-5.8), thus being significantly lower (P=0.45 x 10(-6)) than the mean UR in a control group of 50 patients (mean UR 7.3+/-2.3; range 4.4-12.6) obtained previously. Considering patient age, there was no overlap between UR of pancytopenic patients and the respective normal ranges. The bone marrow appearance on scans seemed to be characteristic for the different haematological diseases investigated. In six patients with myelofibrosis, bone marrow scans demonstrated diffusely decreased bone marrow activity and prominent splenic uptake, possibly related to extramedullary haematopoiesis. In aplastic anaemia, highly reduced and patchy marrow uptake was observed in four patients (five scans), in one of them persisting even after blood cell counts had recovered to the near-normal range. In another two patients with aplastic anaemia, diffusely decreased bone marrow uptake was obtained. In patients with myeloid leukaemia, bone marrow patterns were almost normal probably because the target antigen is often expressed on neoplastic myeloid cells, too. Bone marrow extension was a common finding in these patients. There is an obvious differentiation between haematological patients with pancytopenia and normal subjects by means of AGAb bone marrow uptake ratio. The distinct patterns of AGAb distribution may be indicative for particular haematological diseases.

Adolescent↗

Effects of a membrane-metallopeptidase blocking agent thiorphan in long-term cultures of human bone marrow.

Thiorphan [(DL-3-mercapto-2-benzylpropanoyl)-glycine], a drug blocking the activity of membrane metalloendopeptidase EC 3.4.24.11 (CD10, CALLA), was added to long-term cultures of human bone marrow. Progression of the cultures was assessed by cell counts, cytology and clonogenic (GM-CFU) ability of the non-adherent cells in the supernatant and by morphology of the adherent stromal layer. A stimulatory effect on hematopoiesis was noted.

Bone Marrow Cells↗

Analysis of clonality in T-lymphoproliferative diseases by multiplex PCR.

Distinction between benign and malignant T-cell lymphoproliferative diseases can be difficult using morphological criteria. Using multiplex polymerase chain reaction system we have tested a series of patients with various lymphoproliferative disorders to detect clonal T-lymphocyte populations. Results show that clonal amplification products were obtained from all 10 patients with T-cell lymphoproliferative disorders while the amplification of DNA samples from B-cell neoplasms and normal individuals revealed polyclonal amplification products. By splitting the multiplex primer mix, the patient specific T-cell receptor gamma rearrangement was determined: five out of ten patients showed the exclusive presence of a single T-cell receptor gamma gene rearrangement. Three patients exhibited two rearranged T-cell receptor gamma genes, while in two patients positive reactions were obtained with three pairs of primers for variable and joining segments. Molecular analysis of rearranged T-cell receptor genes by multiplex polymerase chain reaction represents a useful and rapid tool for confirming diagnosis, to determine the extent of disease and to monitor the response to therapy.

Gene Rearrangement, T-Lymphocyte↗

Treatment of chronic myeloid leukemia in relapse after umbilical cord blood transplantation.

Umbilical cord blood (UCB) is increasingly used as a source of hematopoietic progenitor cells for allotransplantation. Donor-derived buffy coat cells are considered optimal treatment for leukemia relapses after transplantation of allogeneic bone marrow. Experience with relapses after UCB transplants are sparse. Here we report a girl who received an UCB transplant for chronic myeloid leukemia, relapsed after three years, failed to respond to donor buffy coat cells, but achieved a complete hematologic, cytogenetic, and molecular remission on interferon-alpha.

Child, Preschool↗

High incidence of conservative RAS mutations in acute myeloid leukemia.

RAS mutations are found in about 25% of acute myeloid leukemia (AML) cases. The importance of these changes is unknown. If RAS mutations confer growth advantage to leukemia subclones in which they emerge, substantially more nonconservative than conservative mutations should be found. The incidence of conservative mutations was not reported previously. We sequenced N-RAS and K-RAS codons 12 and 13 and N-RAS codon 61 in 20 subjects with newly diagnosed AML. Four nonconservative N-RAS mutations and 4 conservative K-RAS mutations were found. There were no differences between subjects with AML and nonconservative RAS mutations and those with conservative or without RAS mutations. Additional studies are needed to examine the incidence of conservative RAS mutations in subjects with AML.

Acute Disease↗

Ph1-chromosome positive acute lymphoblastic leukemia: is t(9;22) the initial abnormality?

We report a case of pre-B-cell acute lymphoblastic leukemia (ALL) with the Ph1-chromosome, t(9;22) translocation and P190 associated BCR/ABL rearrangement. One cell with the Ph1-chromosome and t(9;22) also had del(5q). Interestingly, another diploid cell with iso(17q) lacked the Ph1-chromosome and t(9;22). This finding, similar to one reported in chronic myelogenous leukemia, is consistent with the possibility that abnormality manifest as chromosome instability antedates the Ph1-chromosome and t(9;22) in some cases of Ph1-chromosome positive acute leukemia.

Chromosome Aberrations↗

Analysis of BCR/ABL abnormalities in mRNA from 20-year-old paraffin-embedded tissue for BCR/ABL rearrangement by polymerase chain reaction.

We studied whether it is possible to obtain sufficient mRNA from old paraffin-embedded samples of spleen and bone marrow for reverse transcription and polymerase chain reaction analysis. Spleen tissue from 6 subjects with chronic myelogenous leukemia was studied for rearrangement of BCR and ABL genes. Analysis was successful in 4 cases. These data indicate the feasibility of retrospective analysis of tissue samples of special interest by molecular techniques.

Adult↗

Prostaglandin E2 for prophylaxis of oral mucositis following BMT.

Between October 1988 and December 1990, 60 patients with leukaemia (25 with AML, 19 ALL and 16 CML) undergoing BMT were randomised in a double-blind clinical trial to receive prostaglandin E2 (PGE) (Prostin E2, 0.5 mg per tablet) or placebo for prophylaxis of oral mucositis. Patients had to dissolve tablets in the mouth three times daily starting 7 days before BMT and continuing until 21 days after BMT. The incidence of severe oral mucositis was similar for both groups, 55% in patients receiving PGE and 52% in patients receiving placebo. The duration of severe mucositis did not differ between PGE and placebo groups (chi-square 0.95, p = NS). The incidence of HSV infection was significantly higher in patients receiving PGE. Patients with HSV infection receiving PGE also had a higher incidence of severe oral mucositis. The results presented indicate that PGE is not effective for prophylaxis of oral mucositis in BMT recipients.

Adolescent↗

BCR-ABL rearrangements in children with Philadelphia chromosome-positive chronic myelogenous leukemia.

Leukemia cells from adults with Philadelphia (Ph1)-chromosome positive chronic myelogenous leukemia (CML) have a characteristic molecular rearrangement between the BCR and ABL genes whereby major breakpoint cluster region (Mbcr) exons 2 or 3 are joined to ABL exon II. Ph1-chromosome positive CML is uncommon in children and it is unknown whether these children have similar rearrangements. We studied 17 children with Ph1-chromosome positive CML. Five were studied for Mbcr rearrangement using Southern blotting, nine for the presence of chimeric BCR-ABL mRNA using reverse transcription and polymerase chain reaction, and three for both. All eight children studied by Southern blotting had BCR rearrangement. Of 12 children in whom BCR-ABL mRNA was studied, 10 had Mbcr exon 2 joined to ABL exon II, one had Mbcr exon 3 joined to ABL II, and one had both Mbcr-ABL junctions. These data indicate a similarity to adult CML. However, mRNA processing in children may preferentially splice Mbcr exon 2 to ABL exon II. No child had BCR exon 1 joined to ABL exon II, the rearrangement typical of childhood Ph1-chromosome positive acute lymphoblastic leukemia.

Adolescent↗

Are new conditioning regimens for transplants in acute myelogenous leukemia better?

Pretransplant conditioning regimens designed to decrease leukemia relapse and increase leukemia-free survival in allotransplants in acute myelogenous leukemia (AML) were developed recently. We review studies of new regimens containing drugs like busulfan, cytarabine, melphalan or etoposide as well as novel radiation schemes. Results are compared to those achieved with cyclophosphamide and total body radiation. Some new regimens seem inferior. Others seem to decrease relapse but do not improve leukemia-free survival because of increased deaths from causes other than leukemia. In a third group of new regimens reporting improved antileukemia efficacy and increased leukemia-free survival, results are not convincingly superior to cyclophosphamide and total body radiation. This failure to detect major improvements with new conditioning regimens may indicate the relative insensitivity of current clinical trial designs to detect improvement or the absence of an effective dose-response relationship in AML.

Adult↗

What is the role of recombinant colony stimulating factors in bone marrow transplantation?

Colony stimulating factors (CSFs) regulate production of myeloid cells. Use of CSFs post bone marrow transplant accelerates granulocyte recovery by shortening the interval of relative but not absolute granulocytopenia. Data from non-randomized trials suggest that CSFs decrease documented infections by about one-third; there is no apparent increase in survival. Adverse effects of CSFs are modest; there are no indications of increased graft failure, graft-versus-host disease or cancer recurrence after their use. Future studies of CSFs should be in the context of randomized trials where their therapeutic efficacy is best evaluated. CSFs may also be useful in other transplant settings such as treating graft failure or increasing the efficiency of harvesting myeloid progenitor cells from the blood for subsequent transplantation. Controlled trials are needed to evaluate these uses. Future directions will probably include combinations of CSFs and, possibly, in vitro treatment of the graft.

Animals↗