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G Oberg

Publications and source records attributed to G Oberg.

At least 37 records · Page 2Linked to original sources
PubMed1996

Intensive treatment in order to minimize the Ph-positive clone in CML. Danish-Swedish CML Group.

With the rationale that a significant reduction of the malignant clone in CML might prolong time to metamorphosis, intensive treatment was given to patients < or = 55 years. Six months of hydroxyurea and high dose interferon-alpha (IFN-alpha) was followed by one to three courses of intensive chemotherapy. Patients who had a donor were allotransplanted and patients who became Ph-negative in bone marrow were autotransplanted. On 1 May 1995, 160 patients were registered in the study. Fifty-one percent of the patients who received six months IFN-alpha and hydroxyurea had a significant Ph-reduction and 5% became Ph-negative. The corresponding figures after two intensive chemotherapy courses were 47 and 28%, respectively. Twenty-seven of 30 autotransplanted patients have been analysed for Ph. Seventeen have relapsed cytogenetically, while ten are Ph-negative 1-64 + months after ABMT. BMT was performed in 59 patients. The actuarial 6-year survival from diagnosis of all 160 registered patients is 68%, which seems to be better than for age-matched historical controls.

Adolescent↗
PubMed1996

Foscarnet for pre-emptive therapy of CMV infection detected by a leukocyte-based nested PCR in allogeneic bone marrow transplant patients.

Fifteen allogeneic BMT patients in a phase II study were given foscarnet 60 mg/kg twice daily for 14 days as pre-emptive therapy against CMV disease. CMV infection was diagnosed by a leukocyte-based nested PCR. All 15 patients were evaluable for toxicity. One patient did not fulfill the inclusion criteria of two consecutively positive CMV PCR tests and therefore was not evaluable for efficacy. Thus, 14 of 15 patients were evaluable for development of CMV disease. None of the patients developed CMV disease and all 14 assessable patients had a negative CMV isolation at the end of therapy. None of the 15 patients had to discontinue therapy due to toxicity. Six patients reported mild gastrointestinal disturbances, three patients headaches, and three patients mild urethritis or hemorrhagic cystitis. Serum-electrolyte disturbances were common including abnormal magnesium, potassium and calcium levels. Two patients developed mild serum-creatinine increases requiring adjustment of the foscarnet dosage according to protocol. We conclude that a dosage of foscarnet of 60 mg/kg given twice daily seems to be safe and effective in preventing CMV disease in allogeneic BMT recipients. A study comparing foscarnet and ganciclovir is indicated.

Adolescent↗
PubMed1995

Busulfan concentration in relation to permanent alopecia in recipients of bone marrow transplants.

Alopecia is an important long-term complication after bone marrow transplantation (BMT). The aim of this study was to analyze the influence of busulfan concentration on the development of permanent alopecia. Sixty five patients who survived for at least 6 months after BMT were studied. The median follow-up was 2.1 years (range 0.5-5.7 years). Thirty one patients (47%) had some degree of alopecia and 19 of these patients had extensive alopecia. The mean minimum busulfan concentration was 656 +/- 222 ng/ml in patients who developed alopecia compared with 507 +/- 224 ng/ml in those who did not (P = 0.005). Patients with more extensive alopecia had higher busulfan concentrations than patients with less significant abnormalities. In multivariate analysis, alopecia was associated with busulfan concentrations higher than the median (OR 3.43; 95% CI 3.04-3.88), allogeneic transplantation (OR 2.56; 95% CI 2.28-2.88) and female sex (OR 1.96; 95% CI 1.73-2.88). There was no association between alopecia and chronic graft-versus-host disease. High busulfan concentrations may contribute to the development of permanent alopecia and the risk for alopecia should be considered when choosing the conditioning regimen before BMT.

Adolescent↗
PubMed1995

Specific T and B cell immunity to measles after allogeneic and autologous bone marrow transplantation.

Lymphocyte stimulation with measles virus antigen (MLY) and ELISA for measles IgG antibodies were performed on 60 patients after allogeneic bone marrow transplantation (BMT), and on 59 patients after autologous bone marrow transplantation (ABMT). The T cell response was significantly higher in the 75 measles seropositive patients than in the 29 seronegative patients (P < 0.001), but not significantly different from the MLY in the 15 patients with uncertain serologic reactivity. When the patient group was divided according to type of transplant, the T cell response to measles was also significantly higher in seropositive patients than in seronegative patients after both ABMT (P < 0.001) and after BMT (P < 0.05). Twenty-three seronegative children who were measles vaccinated after BMT had a significantly higher T cell response to measles (7100 c.p.m.) than 17 seronegative non-vaccinated children (100 c.p.m.; P < 0.01). No significant difference was seen in the T cell response in 12 seronegative children vaccinated after ABMT (2500 c.p.m.) compared to seven children not vaccinated (2800 c.p.m.; NS). Seroconversion after vaccination was more frequent in children after BMT (20/23; 87%) compared to ABMT (5/12; 42%; P < 0.05) but no significant difference was found in the T cell response. Therefore, most patients who lost IgG antibodies to measles after bone marrow transplantation also lost their T cell response to measles. A T cell response to measles developed in most patients who seroconverted after vaccination. Failure to develop antibodies to measles in ABMT patients after revaccination may depend on a persisting T cell immunity.

Adult↗
PubMed1994

Activity of cyclosporins as resistance modifiers in primary cultures of human haematological and solid tumours.

The semiautomated fluorimetric microculture cytotoxicity assay (FMCA) was used for evaluation of the ability of cyclosporin A (CsA) and its novel non-immunosuppressive derivative SDZ PSC 833 (PSC) to modify the response to doxorubicin or vincristine in vitro in different haematological and solid human tumour types. Primary cultures of 322 tumour samples were analysed. Both cyclosporins showed resistance-modifying activity in all haematological tumours tested, and in solid tumours activity was observed in ovarian carcinoma and childhood tumours. Little or no effect was found in the remaining tumour types, including breast, renal and adrenal cortical carcinomas and adult sarcomas. In most of the responsive cases the interaction between the modifier and the cytotoxic drug was synergistic. There was a tendency to higher activity in samples from previously treated patients, and an inverse relationship between degree of cytotoxic drug resistance and resistance-modifying activity was noted. No difference in potency between CsA and PSC could be discerned. The results indicate differential in vitro resistance-modifying activity of the cyclosporins depending on tumour type. The results also suggest that treatment with resistance modifiers should be considered also for primary therapy of drug-sensitive tumours. Drug resistance assays such as the FMCA may become useful in preclinical evaluation of resistance modifiers.

Antineoplastic Agents↗
PubMed1994

Immunity to poliovirus and immunization with inactivated poliovirus vaccine after autologous bone marrow transplantation.

Titers of antibody to poliovirus in 102 patients were determined with a sensitive neutralization assay before and 1 year after autologous bone marrow transplantation. At 1 year 14 patients (14%) had lost antibodies to poliovirus type 1 (P < .001), 10 (10%) to poliovirus type 2 (P < .05), and 13 (13%) to poliovirus type 3 (P < .01). Twenty-two patients had lost antibodies to at least one type of poliovirus. Follow-up of unimmunized patients 2 years (n = 40) and 3 years (n = 23) after transplantation documented a continuous decrease in antibody titer; by 3 years after transplantation, another 6 patients had become seronegative. When one dose of inactivated trivalent poliovirus vaccine was administered 1 year after transplantation, 2 (25%) of 8 patients seronegative for poliovirus type 1 had an increase of at least fourfold in antibody titer; after three doses, 10 (83%) of 12 patients exhibited such an increase (P < .05). The corresponding figures were 5 (71%) of 7 and 13 (100%) of 13 for poliovirus type 2 (difference not significantly) and 2 (22%) of 9 and 14 (88%) of 16 for poliovirus type 3 (P < .01). These results indicate that at least 30% of patients undergoing autologous bone marrow transplantation including those seronegative for poliovirus before transplantation will benefit from reimmunization with three doses of inactivated trivalent poliovirus vaccine 1 year after transplantation.

Adolescent↗
PubMed1994

Releasability of human hypereosinophilic eosinophils is related to the density of the cells.

The activity of eosinophils and neutrophils with respect to the release of granule proteins was studied in 11 patients with the hypereosinophilic syndrome (HES). Granulocytes or purified eosinophils were stimulated with serumopsonized Sephadex particles (C3b-induced release), and the released amounts of eosinophil cationic protein (ECP), eosinophils protein-X (EPX) and myeloperoxidase (MPO) were measured by means of specific radioimmunoassays (RIA). Eosinophils obtained from patients with HES released significantly more ECP (P < 0.002) and EPX (P < 0.01) after 20 min of incubation than cells from the control group. The cellular content of ECP and EPX in eosinophils obtained from the patients with HES was significantly reduced to 50% and 62%, respectively, of the content of these granule proteins of eosinophils from the control group. In separated eosinophils light-density eosinophils released more of both ECP and EPX than normal density eosinophils. There was no difference in MPO release between the patients and the control group. We conclude that the eosinophils from patients with HES have an increased propensity to release their granule proteins and the releasability seems to be related to the density of the cells.

Adolescent↗
PubMed1994

The effect of rGM-CSF on neutrophil and eosinophil regeneration after ABMT as monitored by circulating levels of granule proteins.

In order to further evaluate the effects of rGM-CSF on the reconstituting granulopoiesis, plasma and serum levels of myeloperoxidase (MPO) and lactoferrin (LF), as well as serum levels of eosinophil cationic protein (ECP), were monitored daily during a period of 3-4 weeks following ABMT in a group of 22 patients treated with either rGM-CSF (n = 11) or placebo (n = 11). Despite faster increase in the neutrophil counts in the rGM-CSF group, we did not observe any difference either in P-MPO or in P-LF during the period of early engraftment (days 11-19). This finding indicates that the proliferative effect of rGM-CSF on the neutropoiesis may be overestimated when neutrophil counts alone are taken into consideration, and suggests that other mechanisms may have contributed to the increase in the number of circulating neutrophils. The ratio of the serum to plasma level of LF, but not of MPO, was higher in the rGM-CSF group, probably reflecting a specific in vivo neutrophil priming effect. In the rGM-CSF group there was a clear increase of S-ECP during the second and third week post transplant, corresponding to an increase in eosinophil counts, which indicates that rGM-CSF stimulated eosinophil reconstitution without causing excessive activation of the mature eosinophils.

Adolescent↗
PubMed1994

Pulmonary function and complications subsequent to autologous bone marrow transplantation.

Risk factors for early pulmonary complications occurring within the first 3 months after autologous bone marrow transplantation (BMT) were analysed in 158 consecutive adults. The long-term effects of autologous BMT on pulmonary function were analysed in 102 patients, who had survived free of disease for > 6 months after autologous BMT. Pulmonary function tests were performed before, at 6 and 12 months after autologous BMT and thereafter annually. The median follow-up was 12 (6-60) months. The incidence of early pulmonary complications was 16% (26 of 158). Idiopathic interstitial pneumonitis was seen in 11% of patients treated with total body irradiation (TBI). Single dose TBI was the major risk factor as regards early pulmonary complications but restrictive pulmonary disturbances and impaired diffusing capacity prior to autologous BMT were also significant risk factors. In both non-TBI and TBI-treated patients a mild restrictive ventilatory dysfunction and impaired diffusing capacity was noted 6 months after autologous BMT. In non-TBI-treated patients, these disturbances had resolved completely within 2 years whereas the lung volumes of TBI-treated patients were persistently reduced by 10% of their pre-autologous BMT values during follow-up. However, dysfunctions rarely progressed 6 months after autologous BMT. In most patients, ventilatory dysfunction was slight and had no clinical significance.

Adolescent↗
PubMed1994

Interactions between cladribine (2-chlorodeoxyadenosine) and standard antileukemic drugs in primary cultures of human tumor cells from patients with acute myelocytic leukemia.

The semiautomated fluorometric microculture cytotoxicity assay (FMCA), based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA) to fluorescein in microtiter plates, was used for in vitro evaluation of Cladribine (2-chlorodeoxyadenosine, CdA) interactions with five standard antileukemic drugs: amsacrine (Am), etoposide (VP16), daunorubicin (Dnr), cytosine arabinoside (AraC), and mitoxantrone (Mit). Samples from 31 patients with acute myelocytic leukemia (AML) were tested with continuous drug exposure. A large heterogeneity with respect to cell kill was observed for all combinations tested. An additive model provided a significantly better fit of the data compared to the effect of the most active single agent of the combination (Dmax) only for CdA+AraC. When the frequency of additive and synergistic interactions were calculated according to the multiplicative concept for drug interactions, the highest frequencies were observed for CdA+AraC and CdA+Dnr. This interaction pattern was confirmed by isobologram analysis. Cross-resistance analysis revealed high correlations between CdA and AraC whereas the correlations were weaker between CdA and the other drugs. The highest frequency of synergistic interactions was obtained for AraC+CdA, despite their cross-resistance. Of the non-cross-resistant drugs tested, Dnr appears to be the most effective adjunct to CdA in terms of interactions at the cellular level.

Adolescent↗
PubMed1994

Pulmonary function after autologous bone marrow transplantation in children.

Forty-two children receiving bone marrow autografts were studied prospectively regarding acute pulmonary complications; there was no procedure-related mortality and only one case of interstitial pneumonitis. An analysis was also made of the pulmonary function tests (PFTs) of the 27 autografted children who were disease-free and had been followed up for at least 1 year (median 4.1 years, range 1.1-7.6 years). PFTs were performed before and 6, 12, 24, 36 and 60 months after autologous BMT. The mean pre-transplant values of total lung capacity (TLC), vital capacity (VC) and forced expiratory volume in one second (FEV1) were close to predicted but 6 months after autologous BMT there was a statistically significant decrease (11, 13 and 15% below baseline, respectively) in patients receiving total body irradiation in their conditioning regimen. There was some but not complete recovery with time. DLCO remained low throughout the study, irrespective of the conditioning regimen. In summary, acute pulmonary complications were few and PFTs showed only modest changes from baseline after ABMT. At the latest follow-up no respiratory symptoms had reportedly occurred in any of the children and the chest radiographs were normal. Although the results are promising so far, long-term follow-up is necessary to evaluate the final outcome in these children.

Adolescent↗
PubMed1993

Intensive treatment in order to minimize the Ph-positive clone in chronic myelogenic leukemia.

Several studies indicate that interferon (IFN) treatment, intensive chemotherapy and autologous bone marrow transplantation (ABMT) effectively reduce the Ph-positive clone in Chronic Myelogenic Leukemia (CML). In the present study on patients < or = 55 years, we have combined these three treatment modalities. The aim of the study was to eliminate or minimize the Ph-positive clone to see whether a status of minimal residual or Ph-negative disease could be maintained for a longer period of time. After diagnosis, patients received interferon (IFN-a-2b) and hydroxyurea (HU) to keep the white blood cell (WBC) and platelet count below 2-4 and 100-150 x 10(9)/l, respectively. After six months of treatment, Ph-analysis was performed. Patients with Ph-positive cells in bone marrow then received 1-3 courses of intensive chemotherapy. In patients Ph-negative after two courses, bone marrow was harvested and used for ABMT. After a third course, patients with up to 50% Ph-positive metaphases were accepted for ABMT. As of January 1, 1993, 97 patients were registered in the study. Six months of IFN+HU reduced the percentage of Ph-positive metaphases in 57% of the patients (7% became Ph-negative). The corresponding figures after two intensive cytotherapies were 70% (40% Ph-negative). Eighteen patients were autotransplanted. Seven have relapsed with Ph-positivity 3-22 months after ABMT, while nine are Ph-negative at 1-32+ months after ABMT (two not yet analyzed). Seventeen patients are alive and well, while one died one month after ABMT due to interstitial pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Oral acyclovir as prophylaxis for bacterial infections during induction therapy for acute leukaemia in adults. The Leukemia Group of Middle Sweden.

We prospectively tested the hypothesis that prevention of herpes simplex virus infection with acyclovir might also reduce the incidence of bacterial infections in adult patients with acute leukaemia. During the first induction therapy a double-blind, randomized and placebo-controlled study was undertaken. Fifty-two patients were treated with 200 mg acyclovir orally four times daily throughout the induction period, whereas 55 patients received placebo. The groups were comparable with regard to age, cytotoxic chemotherapy and duration of neutropenia. Bacteraemias were significantly fewer in the acyclovir group (20 versus 41 episodes; P = 0.007). The number of isolated microorganisms causing bacterial or fungal infections was also lower during acyclovir prophylaxis (52 isolates, versus 93 isolates; P = 0.02). There was no significant difference between the groups with regard to the number of clinically documented infections or fevers of unknown origin. Herpes simplex virus isolations occurred only in the placebo group (P = 0.001). Thus, oral acyclovir prophylaxis was associated with reductions of all microbiologically documented infections suggesting that prevention of herpes simplex virus reactivation in acute leukaemia patients may reduce the occurrence of other infections.

Acyclovir↗
PubMed1993

Pneumococcal immunity and response to immunization with pneumococcal vaccine in bone marrow transplant patients: the influence of graft versus host reaction.

The aim of this study was to evaluate levels and subclass distribution of pneumococcal antibodies in 40 bone marrow transplant (BMT) and 42 autologous bone marrow transplant (ABMT) recipients during the first year after transplant, and response to vaccination with a polyvalent pneumococcal vaccine. Before transplantation, 35/40 recipients of allogeneic grafts, all 42 autologous BMT recipients and 38/39 donors had adult levels of anti-pneumococcal antibodies of the IgG2 subclass. During the first year after transplantation, antibody levels decreased in 29 BMT patients while 11 retained their pretransplant antibody levels. No change was noted among ABMT patients. In the 8 BMT patients who had chronic graft versus host disease (GVHD), none showed normal levels of anti-pneumococcal antibodies 1 year after BMT as compared to 11/32 without chronic GVHD. Three different response patterns were seen after vaccination of 29 BMT patients who lost immunity with a polyvalent pneumococcal vaccine. Ten patients responded with an increase in IgG2 antibodies, 8 responded with an increase in IgG1 and 11 patients did not respond at all. In the 8 patients with chronic GVHD, none responded with an increase in IgG2 antibodies and 6/8 did not respond at all. The results of this study suggest that chronic GVHD is the main factor contributing to loss of immunity to pneumococci and lack of responsiveness to vaccination with pneumococcal polysaccharides after BMT. Furthermore, the difference in capability, between BMT and ABMT recipients, of retaining anti-pneumococcal activity may explain the clinical experience of severe pneumococcal infections in these patients.

Adolescent↗
PubMed1993

Influence of prophylactic anticonvulsant therapy on high-dose busulphan kinetics.

The pharmacokinetics of high-dose busulphan was studied in 17 patients during conditioning prior to bone marrow transplantation using deuterium-labeled busulphan (d8-BU). About 50% of busulphan doses 1 and 16 was replaced with d8-BU. Patients were treated with phenytoin or diazepam as prophylactic anticonvulsant therapy. Patients who received phenytoin demonstrated significantly higher clearance (mean +/- SD, 3.32 +/- 0.99 ml min-1 kg-1), a lower area under the concentration-time curve (AUC, 5,412 +/- 1,534 ng h ml-1; corrected for dose/kilogram) and a shorter elimination half-life (3.03 +/- 0.57 h) for the last dose of d8-BU (dose 16) as compared with the first dose (2.80 +/- 0.78 ml min-1 kg-1, 6,475 +/- 2,223 ng h ml-1 and 3.94 +/- 1.10 h, respectively). No difference in the above mentioned pharmacokinetic parameters was seen in patients treated with diazepam. Moreover, a continuous decrease in the steady-state level of busulphan was observed in four of seven patients in the phenytoin-treated group, whereas in the diazepam group, such a decrease was seen in only one of eight patients. We conclude that phenytoin used as prophylactic anticonvulsant therapy alters busulphan pharmacokinetics and, most probably, its pharmacodynamics. For adequate prophylactic therapy, anticonvulsants with fewer enzyme-inductive properties than phenytoin should be used.

Adult↗
PubMed1993

Haemolytic uraemic syndrome and renal dysfunction following BEAC (BCNU, etoposide, ara-C, cyclophosphamide) +/- TBI and autologous BMT for malignant lymphomas.

Twenty-four patients autografted for malignant lymphoma have been followed. All were conditioned with BEAC (BCNU, etoposide, ara-C, cyclophosphamide), in 10 patients combined with total body irradiation (TBI) 7.5 Gy. Within 1 month of ABMT, a capillary leak syndrome was seen in four patients (one death) and isolated pericarditis in one. Nineteen patients survive disease-free at > or = 6 months, median (range) 24 (11-48) months. In 15 of 19 patients, a decrease in glomerular filtration rate (GFR) of > 20% was observed, 6 (6-24) months after ABMT. In six of these patients (five treated with TBI), the renal dysfunction was still progressing 11-36 months after ABMT. Five patients (four conditioned with TBI) developed a haemolytic uraemic syndrome (HUS) with Coombs negative haemolytic anaemia, platelet consumption and renal impairment, with onset 3-6 months after ABMT. Haemolysis and platelet consumption, but not renal impairment, were reversible in all patients. One death from HUS was seen. Because of the adverse effects described we have abandoned the combination of BEAC with TBI.

Adolescent↗