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Biomedical subjects

L Volin

Publications and source records attributed to L Volin.

At least 55 records · Page 3Linked to original sources

A randomized comparison between early and late vaccination with tetanus toxoid vaccine after allogeneic BMT.

Forty-five adult HLA-matched sibling BMT recipients were randomized to receive tetanus toxoid (TT) vaccine at 6, 8 and 14 months (early group, n = 23) or at 18, 20 and 26 months after BMT (late group, n = 22). At 6 months after BMT, prior to the first vaccination, 90% of the early group patients had a protective tetanus antibody concentration of > or = 0.1 HU/ml (passive haemagglutination test) but only 70% of the late group patients did so at 18 months after BMT. The antibody responses 1 month after each of the three TT vaccine doses were similar in the two vaccination groups, except that after the first dose, four-fold responses occurred more frequently in the late group. All vaccinated patients achieved the protective antibody concentration of > or = 0.1 HU/ml. In the late group the recipient antibody responses after the first and second vaccine doses correlated with the donor anti-TT level. A tetanus vaccination schedule consisting of three vaccine doses is equally immunogenic when started at 6 or 18 months after BMT. Donor immunity against tetanus may influence recipient responses to TT vaccination.

Adolescent↗

Randomized comparison of early and late vaccination with inactivated poliovirus vaccine after allogeneic BMT.

Forty-five adult HLA-matched sibling BMT recipients were randomized to receive inactivated poliovirus vaccine (IPV) at 6, 8 and 14 months (early group, n = 23) or at 18, 20 and 26 months after BMT (late group, n = 22). Ninety-five percent of the early group patients had protective antibody titres of > or = 4 to poliovirus type 1 (PV1), poliovirus type 2 (PV2) and poliovirus type 3 (PV3) by a microneutralization assay prior to the first vaccination, at 6 months after BMT. The corresponding proportion for the late group patients was only 67% at 18 months. The antibody responses 1 month after each of the three IPV doses were similar in the two vaccination groups, except that four-fold responses occurred more frequently after the first dose to PV2 and PV3 in the late group. All patients had a protective antibody titre to all poliovirus serotypes 1 and 22 months after the third vaccine dose, except one patient in the early group who lacked antibodies to PV3 at 22 months. Acute GVHD accelerated the decrease of poliovirus antibody titres prior to vaccination but had no influence on vaccination response. Chronic GVHD neither influenced the patient's ability to retain poliovirus antibodies prior to vaccination nor impaired responses to vaccinations. A vaccination schedule consisting of three IPV doses was equally immunogenic when started at 6 or 18 months after allogeneic BMT.

Adult↗

Follow-up of residual disease using metaphase-FISH in patients with acute lymphoblastic leukemia in remission.

Metaphase-FISH (fluorescence in situ hybridization) was used to detect cells with a chromosomal trisomy and/or translocation in 25 patients with acute lymphoblastic leukemia (ALL) in remission. Twelve patients were treated with chemotherapy alone and 13 patients received bone marrow transplantation after initial chemotherapy. Patients were followed up for 8-56 months (median 18 months). In this study, a total of 82 bone marrow samples were analyzed. Metaphase-FISH identified chromosome morphology, even banding, in cells from which FISH signals were studied. Thus, it is as reliable as standard karyotype analysis and does not cause false positive results. Furthermore, more than 1000 cells can be analyzed in 3-6 h which equals the time it takes to analyze 20 metaphases by standard karyotype. The time span before the first positive sample seems to be insignificant with regard to the outcome of relapse. All six patients, who had more than 1% of abnormal cells detected at any sampling or whose consecutive follow-up samples showed an increasing frequency (up to 1%) of abnormal cells, relapsed. Absence or occurrence of low numbers of abnormal cells at a frequency of 0.05-0.8% followed by their disappearance was in agreement with continuing complete clinical and hematologic remission (CR) in 16 (84%) of 19 patients. Our results indicate that metaphase-FISH is a reliable technique for quantifying residual leukemic cells. The technique is available in standard cytogenetic laboratories and can be applied to routine follow-up of ALL patients who have a suitable chromosomal aberration.

Adolescent↗

Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: a retrospective case-matched study from the European Group for Blood and Marrow Transplantation.

A retrospective case-matched analysis was performed comparing 189 myeloma patients treated with allogeneic bone marrow transplantation (allo-BMT) with an equal number of patients who received autologous stem cell transplantation (ASCT). Matching was performed with respect to gender and number of treatment lines before transplantation. The groups were comparable with the exception of median age (43 years for allo-BMT v 49 years for ASCT, P = .0001) and median posttransplant follow-up (46 months for allo-BMT v 30 months for ASCT, P = .0003). The overall survival was significantly better for ASCT than for allo-BMT, with a median survival of 34 months and 18 months, respectively (P = .001). However, this survival advantage was only observed in men, but not in women. The statistically significant survival advantage for ASCT was seen in most subgroups, ie, chemotherapy-responsive patients, patients who had received two or more treatment lines before transplantation, patients in partial remission, patients with an IgG-subtype, patients older than 46 years of age, patients with stage II disease, and patients with a low or high serum-beta-2-microglobulin at diagnosis. The main reason for the poorer survival in allo-BMT patients was higher transplant-related mortality (41% v 13% for ASCT, P = .0001), which was not compensated for by a lower rate of relapse and progression. However, in patients alive at 1 year posttransplant, there was a trend for better long-term survival (P = .09) and significantly better progression-free survival (P = .02) for allo-BMT as compared with ASCT. We conclude that the median survival is superior for ASCT. However, allo-BMT has a lower relapse rate, which results in a similar long-term outcome for both approaches, but a longer follow-up is needed to assess the final outcome.

Acute Disease↗

Overgrowth of Enterococcus faecium in the feces of patients with hematologic malignancies.

The objective of this study was to characterize the overgrowth and susceptibility of Enterococcus faecium, compared with that of other enterococci, in the feces of patients with hematologic malignancy. During a 52-week period, surveillance samples of feces were cultured weekly. Three hundred thirty-three samples were obtained from 92 patients. E. faecium outnumbered other enterococci in 170 (44%) of the samples, while the opposite was true in 119 (31%) of the samples. Fecal overgrowth of E. faecium (> or = 9.0 log10 cfu/g) was found in 62 samples (16%), while overgrowth of other enterococci was documented in 20 samples (5%) (P < .001). Treatment with third-generation cephalosporins preceded the overgrowth of E. faecium in 93% of the patients. Resistance of E. faecium isolates to ampicillin, high-level gentamicin, and vancomycin was detected in 41%, 4%, and 2% of the patients, respectively. There were 6 patients with enterococcal bacteremia (due to E. faecium in 5 and Enterococcus faecalis in 1) during the study period. The high prevalence of resistance to ampicillin and imipenem rendered few (if any) intravenous antibiotics able to prevent fecal overgrowth of E. faecium.

Aminoglycosides↗

Loss of protective immunity to polio, diphtheria and Haemophilus influenzae type b after allogeneic bone marrow transplantation.

Immunity to poliovirus, diphtheria and Haemophilus influenzae type b (Hib) was studied in 16 adult recipients of a bone marrow transplant from an HLA-identical sibling donor in order to evaluate the need for revaccinations. T-cell depletion was not done in any case. The donors and patients were studied before bone marrow transplantation (BMT) and the patients 1, 3, 6, and 12 months later. Prior to the BMT 10 of 11 patients were immune (titre > or = 4) to all vaccine poliovirus types by a standard microneutralization assay. At 12 months after BMT only two of seven patients were immune to all vaccine types, and none had immunity against an antigenically altered poliovirus type 3 strain Finland. The geometric means of antibody titres against poliovirus types 1, 2, and 3 strain Saukett and strain Finland declined gradually after 1 month postgrafting, being 4.4, 5.4, 3.3, and 1.3 respectively at 12 months after BMT. At 1 year 6 of 11 patients had immunity against diphtheria by a toxin neutralization method, but the antitoxin geometric mean level had decreased to a barely protective level, 0.01 IU/ml. The geometric mean Hib antibody concentration decreased during the first 6 months after BMT and thereafter increased slightly. A significant proportion of BMT recipients lose their protection against polio, diphtheria and Hib, and revaccinations are necessary.

Adult↗

Acute iritis induced by granulocyte colony-stimulating factor used for mobilization in a volunteer unrelated peripheral blood progenitor cell donor.

We describe a volunteer unrelated peripheral blood progenitor cell donor with previously diagnosed dermatitis herpetiformis in whom the administration of G-CSF for the mobilization of precursor cells induced acute iritis. G-CSF has been administered to healthy people with minimal side-effects but when used in patients with autoimmune disorders worsening of symptoms or new manifestations may be a potential concern.

Acute Disease↗

Feasibility and toxicity of interferon maintenance therapy after allogeneic BMT for multiple myeloma: a pilot study of the EBMT.

A pilot study was undertaken in order to determine the feasibility and toxicity of rh-alpha-2b-interferon as maintenance therapy after allogeneic BMT for multiple myeloma. The study incorporated planned dose escalation of interferon in successive patient cohorts from an initial dose of 1 MU three times weekly to a target dose of 3 MU three times weekly. No clinical complications were observed in five patients receiving a dose of 1 Mu three times weekly. At a dose of 2 MU three times weekly, one of seven patients developed acute GVHD, which was fatal. At a dose of 3 MU three times weekly, four of five patients developed acute or chronic GVHD, and the study was therefore terminated at this point. We conclude that the use of interferon in myeloma patients early after allogeneic BMT is associated with a significant risk of GVHD, which is dose-related, and that the maximum tolerated dose in the early post-transplant period is 1-2 MU three times weekly.

Adult↗

Late onset Pneumocystis carinii pneumonia following allogeneic bone marrow transplantation.

We retrospectively reviewed all positive Pneumocystis carinii findings among adult patients who had received an allogeneic BM transplant at the Helsinki University Central Hospital between July 1990 and December 1993. The aim was to define the incidence of late onset Pneumocystis carinii pneumonia (PCP) in BMT patients who had routinely received PCP prophylaxis for 6 months post-BMT. In 110 BMT patients, 16 episodes of PCP were documented. Only one patient had been receiving PCP prophylaxis at the onset of PCP. Fourteen of the episodes occurred more than 6 months post-BMT. (median 10.5, range 4-42 months); three of them beyond 1 year. All three had extensive chronic GVHD. Of the 11 patients with an onset between 7-12 months post-BMT, all but one were on methylpredisolone because of chronic GVHD (n = 7) or cytopenia (n = 2) and five of them were in relapse of their hematological malignancy. No mortality from PCP was detected. The risk of developing PCP between 7-12 months post-BMT among patients at risk was 13.4%. We conclude that PCP prophylaxis should be continued until 1 year post-BMT in patients receiving corticosteroid treatment as well as in those with a hematological relapse. Long-term prophylaxis beyond 1 year should be considered in cases with extensive chronic GVHD.

Adolescent↗

Invasive cutaneous mucormycosis caused by Absidia corymbifera after allogeneic bone marrow transplantation.

Mucormycotic infections caused by fungi of the families Rhizopus, Mucor or Absidia are rare and usually associated with diabetes or immunosuppression. We describe a patient with invasive necrotizing cutaneous mucormycosis caused by Absidia corymbifera shortly after allogeneic BMT. The infection was successfully treated with surgical debridement and liposomal amphotericin B for 6 weeks. Recognition of these rare infections requires a high index of suspicion. These patients should be evaluated with tissue biopsy and cultures and treated without delay.

Adult↗

A comparison of early and late vaccination with Haemophilus influenzae type b conjugate and pneumococcal polysaccharide vaccines after allogeneic BMT.

Forty-five adult allogeneic BMT recipients were randomized to receive Haemophilus influenzae type b (Hib)-diphtheria toxoid conjugate vaccine (PRP-D) at 6 and pneumococcal polysaccharide vaccine (Pnc PS) at 8 months (early group; n = 23) or at 18 and 20 months (late group; n = 22) after BMT, respectively. Serum antibody concentrations against Hib and Pnc PS types with varying immunogenicity (serotypes 3, 6B, and 19F) were measured by ELISA. The responses at 1 month after vaccination with PRP-D and Pnc PS were poor and similar in the two vaccination groups, except that two-fold responses in the concentration of antibodies to the most immunogenic Pnc serotype 3 occurred more frequently in the late group. In the late group recipients, the antibody responses elicited by Pnc serotypes 3 and 19F correlated with the concentrations of the corresponding antibodies in the donor. This study on allogeneic BMT recipients shows that vaccination at 6-8 months after BMT with one dose of PRP-D and Pnc PS vaccine is as immunogenic as vaccination at 18-20 months after BMT, and suggests that donor immunity to Pnc PS affects recipient responses to Pnc PS vaccination. Consequently, as among allogeneic BMT recipients the greatest risk for infections by encapsulated bacteria occurs during the first 1-2 years after BMT, Hib and Pnc vaccines should not be given later than 6-8 months post-BMT.

Adolescent↗

A randomized trial comparing busulfan with total body irradiation as conditioning in allogeneic marrow transplant recipients with leukemia: a report from the Nordic Bone Marrow Transplantation Group.

Between October 1988 and December 1992, 167 patients with leukemia receiving marrow transplants from HLA-identical donors and conditioned with cyclophosphamide (120 mg/kg) were randomized to additional treatment with either busulfan (16 mg/kg, n = 88) or total body irradiation (TBI; n = 79). The busulfan-treated patients had an increased cumulative incidence of veno-occlusive disease of the liver, ie, 12% compared with 1% in the TBI group (P = .009). Furthermore, hemorrhagic cystitis occurred in 24% of the busulfan patients versus 8% in the TBI patients (P = .003). In patients with advanced disease beyond first remission or first chronic phase, transplantation-related mortality was 62% among the busulfan-treated patients compared with 12% among the TBI recipients (P = .002). These differences between the two groups were statistically significant in multivariate analysis. Seizures were seen in 6% of the busulfan-treated patients and were absent in the TBI group (P = .03). Grade II-IV of acute graft-versus-host disease (GVHD) was similar in the two groups, but grade III-IV and chronic disease was more common in the busulfan-treated group (P = .04). Death associated with GVHD occurred in 17% of the busulfan-treated group and 2% of the TBI group (P = .003). Patients treated with busulfan had a 3-year actuarial survival of 62%, which was worse than the 76% among those treated with TBI (P < .03). In multivariate analysis, poor survival was associated with advanced disease (P < .0001), no posttransplant septicemia (P = .0006), grade II-IV GVHD (P = .006), and busulfan treatment (P < .02). The incidence of relapse did not differ between the two groups. Relapse-free survival was also similar in the two treatment groups on analysis of data from all patients, children, patients with early disease, and those with acute myeloid leukemia, acute lymphoblastic leukemia, and chronic myeloid leukemia. However, in adults (P = .05) and patients with advanced disease (P = .005), leukemia-free survival was significantly better in those treated with TBI. We conclude that patients treated with busulfan have more early toxicity and an increased transplant-related mortality in patients with advanced disease. TBI is therefore the treatment of choice, especially in adults and patients with advanced disease. However, busulfan is an acceptable alternative for patients with early disease and for those in whom TBI is not feasible.

Adolescent↗

Adverse reactions to platelet transfusions are reduced by use of platelet concentrates derived from buffy coat.

We closely observed 86 transfusions to multitransfused hematologic patients with leukocyte-depleted platelet concentrates (PCs) prepared from buffy coats (BC PCs), filtered either prior to storage (BC1) or after 3-4 days' storage (BC3). The patients were first given, randomly, either BC1 or BC3, and were thereafter used as their own controls by giving them the two BC types alternately. The results were compared with an earlier study on standard platelet-rich plasma (PRP) PCs (46 transfusions to 23 patients) and leukocyte-depleted PRP PCs (23 transfusions to 12 patients). There was no difference in adverse reactions between BC1 and BC3 PCs, but BC PCs caused significantly fewer and milder adverse reactions than PRP PCs. Febrile reactions (FTR) occurred in 4.6%, urticarial skin reactions in 21%, and pulmonary reactions in 0% of BC PC transfusions (17, 29 and 0% of patients). The mean corrected increments (CI) at 16-18 h were higher after BC1 PCs than BC3 PCs (10.3 vs. 8.0, p = 0.046). We conclude that adverse reactions are reduced by use of BC PCs. Prestorage leukocyte depletion may improve platelet increments.

Adolescent↗

Detection of residual host cells after bone marrow transplantation using non-isotopic in situ hybridization and karyotype analysis.

Karyotype analysis and interphase cytogenetics by means of non-radioactive in situ hybridization (NISH) with Y and X-specific probes were used to detect residual host cells in BM of 18 male patients who had received a BMT from their sisters. All patients but one had a malignant blood disease; 17 patients were clinically in continuous remission at the time of the investigations and throughout the follow-up period. No host cells were detected by karyotype analysis in patients who were in clinical remission. NISH with a biotinylated Y-specific probe showed residual host cells in 16 of the 17 patients in clinical remission. In samples from three patients the existence of host cells was further confirmed by revealing the XY-containing cells with two-color fluorescence in situ hybridization (FISH) using X- and Y-specific probes on direct BM smears showed > 3% residual host cells in 50% of the samples studied at or later than 2 months post-BMT. On conventional cytogenetic preparations < 1% Y-specific cells were detected in all but two samples at > or = 2 months post-BMT. There was no difference in the proportion of host cells between patients conditioned with total body irradiation and CY and those who received busulphan and CY. The recipient's stromal or epithelial cells in the aspirates probably account for most of the host cells detected. In conclusion, small numbers of residual host cells detected by interphase cytogenetics with a Y-specific probe do not indicate an imminent relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Immunohistology of skin and rectum biopsies in bone marrow transplant recipients.

We have studied histological and immunohistological specimens of 39 skin biopsies from 21, and 30 rectal biopsies from 17 bone marrow transplant recipients. The biopsies were taken before transplantation, during acute and chronic graft-versus-host disease (GVHD), and at times with no GVHD. In biopsies taken during cutaneous aGVHD grade I to III, epithelial changes were seen in 16/23 biopsies. The cutaneous infiltrates during aGVHD consisted of CD2-, CD4-, CD8- and FMC-33-positive cells both in the epithelium and in the dermis. CD57-positive NK cells were also detected in most biopsies. During chronic GVHD the cutaneous cellular infiltrates were similar to those seen in moderate aGVHD, i.e. both CD4- and CD8-positive lymphoid cells were present. When the biopsy was taken after the beginning of corticosteroid treatment for aGVHD, or at times when the patient did not have GVHD symptoms, the cellular infiltrates were considerably smaller in the dermis. During clinical intestinal aGVHD mucosal epithelial changes were relatively uncommon; instead, increased numbers of both CD4- and CD8-positive lymphocytes in the lamina propria (LP) were seen in 11/13 samples. During chronic GVHD the number of CD4-positive cells exceeded that of CD8-positive cells in the LP, and the large lymphoid infiltrates also reached the muscularis mucosae. In rectal biopsies the differences were not so prominent because most of the pretransplant biopsies showed CD2-, CD4-, CD8- and CD57-positive lymphocytes both in the lamina propria and epithelium.

Acute Disease↗

Serum amyloid A levels in acute graft-versus-host disease in bone marrow transplant recipients.

We studied serum amyloid A levels of 31 bone marrow transplant recipients with and without acute graft-versus-host disease. Before transplantation the mean SAA concentration was 5.1 +/- 0.8 mg/l (mean +/- SEM). It remained low in patients with no signs of aGVHD but increased significantly during aGVHD to 54.0 +/- 8.2 mg/l (p less than 0.001 compared to pre-BMT value). Severe infections also induced high SAA levels.

Adrenal Cortex Hormones↗