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J Gajewski

Publications and source records attributed to J Gajewski.

At least 19 recordsLinked to original sources

Long-term outcome of high-dose cytarabine-based consolidation chemotherapy for adults with acute myelogenous leukemia.

Modern induction chemotherapy produces 60% to 80% complete remissions in adults with newly diagnosed acute myelogenous leukemia. A major challenge is to eradicate subclinical disease in remission and prevent leukemic relapse. We analyzed the long-term results of high-dose cytarabine-anthracycline consolidation chemotherapy without maintenance treatment and examined the effect of major prognostic factors, including age, sex, history of preleukemia, and cytogenetics. Two hundred twenty-seven patients with newly diagnosed acute leukemia were enrolled on two sequential studies conducted from 1982 to 1991. One hundred fifty-one patients (67%) achieved a complete remission. One hundred twenty-three patients were eligible for high-dose cytarabine-based consolidation administered in two to three courses. After a median follow-up of 4.8 years, 40 patients remain alive, with 28 in continued remission. Median remission duration for all eligible patients is 12.8 months, and actuarial leukemia-free survival (LFS) at 5 years is 26% +/- 8%. Advanced age and male sex were negative prognostic indicators for LFS. For patients < or = 45 years of age, 5-year LFS was 35% +/- 13%, as compared with 18% +/- 11% for patients greater than age 45 (P = .03). Toxicity of consolidation chemotherapy included treatment-related death in nine patients and serious neurotoxicity in five. Our results show an improved LFS for younger patients treated with high-dose cytarabine-based consolidation. There was no apparent benefit for older patients compared with reported data with less intensive regimens.

Adult

Investigation of an experimental weight-training programme.

The aim of this study was to compare the effects of conventional weight-training (control) with an experimental programme. The training programme consisted of 12 sessions, 3 a week for 4 weeks. The experimental group (n = 12) performed sets of forearm flexion with a barbell until a 20% decline in maximal force was noted. The controls (n = 11) trained according to established weight-training principles. Isometric tests were performed on both the right and left forearm flexors and during forearm flexion with a barbell: the tests were continued for a 3-week post-experimental period. The subjects were matched on all tests at the start of the experiment. Larger reductions in muscle torque within the training sessions were noted among the experimental subjects--19.8 +/- 2.0, 16.9 +/- 1.9 and 18.0 +/- 1.8% for right, left and combined elbow flexion respectively, compared to 11.8 +/- 2.7, 14.9 +/- 4.1 and 13.4 +/- 3.1% for the controls. The volume of training (number of lifts) was 30.4% higher for the experimental subjects. Muscle strength increased in both groups (P less than 0.05). The controls improved by 12.7 +/- 6.9, 24.9 +/- 22.1, 18.3 +/- 12.3 and 30.3 +/- 11.1% for right, left, combined isometric strength and the barbell test respectively. These did not differ significantly from the corresponding results for the experimental group--7.6 +/- 8.8, 17.0 +/- 12.4, 11.8 +/- 9.3 and 29.1 +/- 10.6% (P greater than 0.05). Neither the decrease in force during a single training session nor the volume of training were related to the training effect expressed as an increase in muscle force (P greater than 0.05). The effectiveness of the conventional programme in producing similar improvements in muscle strength to the experimental programme suggests that a high volume of training is unnecessary for strength gains.

Fatigue

A randomized study of intermediate versus conventional-dose cytarabine as intensive induction for acute myelogenous leukaemia.

The optimal dose of cytarabine for induction chemotherapy is unknown. Most studies have utilized doses of 100-200 mg/m2/d, although higher doses have been proposed to increase the concentration of the active metabolite ara-CTP within leukaemia cells. To address this question 101 adults with newly diagnosed acute myeloid leukaemia were randomized to receive treatment with daunorubicin and either conventional-dose cytarabine (200 mg/m2/d by continuous infusion) or an intermediate-dose of cytarabine (500 mg/m2 every 12 h). 36/51 (71%) patients assigned to conventional-dose cytarabine achieved complete remission compared to 37/50 (74%) who achieved remission with intermediate-dose cytarabine (P = 0.9). Patient age significantly affected remission rate. 8/17 patients age greater than 60 assigned to conventional-dose cytarabine and 10/17 assigned to intermediate-dose cytarabine achieved complete remission compared to 27/33 patients under age 60 assigned to the conventional dose and 28/34 patients assigned to the intermediate dose arm (P = 0.004). Actuarial 4-year disease-free survival for patients assigned to conventional-dose cytarabine was 20 +/- 16% versus 28 +/- 17% for patients assigned to intermediate-dose cytarabine (P = 0.9). We conclude that intermediate dose cytarabine did not substantially improve results of induction chemotherapy for acute myeloid leukaemia.

Adolescent

Unrelated donor marrow transplants for severe acquired aplastic anemia.

This report is divided into two parts. The first part is a retrospective analysis of 40 unrelated transplants [UD-BMT] for severe acquired aplastic anemia [SAA], performed at five transplant centers between 1981 and 1990. The second is an interim analysis of 15 UD-BMT for SAA compared with a matched cohort of 16 sibling transplants [ID-BMT] carried out since February 1989 using prospectively collected data provided by the IMUST Study Group. In the retrospective study the actuarial survival was 28% [+/- 15] with a median follow-up of 1485 [266-3890] days post BMT. Univariate analysis showed a considerable survival advantage for patients younger than 15 years at BMT [p = 0.03]. More recently patients entered in the IMUST Study showed an actuarial survival of 50% [+/- 27] for UD-BMT compared with 58% [+/- 31] for ID-BMT recipients. These data suggest that UD-BMT is a realistic option for paediatric patients with SAA. Although numbers are very small there is some indication from IMUST Study data that better patient selection and intensive BMT protocols may also improve the results of UD-BMT in young adult patients with SAA.

Adolescent

Selective depletion of CD8+ T lymphocytes for prevention of graft-versus-host disease after allogeneic bone marrow transplantation.

The effects of selectively depleting CD8+ cells from donor bone marrow were assessed in 36 patients receiving transplantation from an HLA-identical sibling as treatment for leukemia. Donor bone marrow underwent ex vivo treatment using anti-Leu-2 monoclonal antibody and complement. Patients received cyclosporine post-transplant for 6 months. Thirty-three patients had initial engraftment. Three failed to have hematologic recovery, and one patient with initial engraftment had late graft failure. The actuarial incidence of grade greater than or equal to 2 acute graft-versus-host disease was 28% +/- 18% and was usually confined to the skin. Of 33 patients with engraftment, 32 were complete chimeras and one had mixed chimerism. The tempo of hematologic and immunologic recovery was comparable with that reported with transplantation of unmodified bone marrow, although CD4+ and CD8+ T cells recovered at comparable rates. The actuarial rate of leukemia relapse was 11% +/- 10%, occurring in three patients with acute leukemia but in none of 13 patients transplanted for chronic myelogenous leukemia. Actuarial survival was 57% +/- 17% at 2 years. These data indicate that after transplantation of marrow depleted of CD8+ cells, engraftment with prompt hematologic and immunologic recovery generally occurs, with a relatively low rate of acute graft-versus-host disease. Graft failure remains a problem despite retention of CD4+ cells within the donor marrow. The lack of leukemia relapse in patients with chronic myelogenous leukemia suggests retention of a graft-versus-leukemia effect, at least for this malignancy.

Adolescent

Postremission chemotherapy for adults with acute myelogenous leukemia: improved survival with high-dose cytarabine and daunorubicin consolidation treatment.

Results of postremission chemotherapy for adults with acute myelogenous leukemia (AML) were assessed in two sequential prospective studies involving similar induction therapy and two courses of intensive consolidation treatment. Fifty-six patients achieving remission on the acute leukemia protocol (ALP3) study received high-dose cytarabine and daunorubicin as course one and standard-dose cytarabine and daunorubicin as course two. Results are compared with forty-six patients achieving remission on the ALP2 study who received azacitidine and doxorubicin as consolidation course one and standard-dose cytarabine, daunorubicin, and thioguanine as course two. The ALP3 regimen resulted in a significantly improved 5-year disease-free survival of 32% +/- 19% versus 20% +/- 11% for the ALP2 study (P = .03). Survival from remission was also improved, 40% +/- 14% versus 24% +/- 12% (P less than .01). Favorable prognostic factors for disease-free survival included receiving the ALP3 treatment regimen, absence of a prior preleukemic syndrome, and female sex. These factors and younger patient age were significant for survival following first chemotherapy and survival after achieving remission. Six of 34 patients who relapsed after receiving the ALP3 regimen successfully achieved prolonged second remissions with high-dose cytarabine-based chemotherapy and/or allogeneic bone marrow transplantation (BMT). Overall survival for adults less than or equal to 45 years of age was 58% +/- 19% with the ALP3 postremission chemotherapy regimen, comparable to most studies of BMT for AML in first remission. Actuarial 5-year survival for ALP3 patients greater than 60 years of age was 18% +/- 20% with no improvement compared with ALP2.

Adult

Red blood cells and serum antioxidant defense systems of galactosaemic children.

Many reports have pointed out that oxidative damage and disturbances in antioxidant defense systems of the lenses may play an important role in the development of cataract. In the present study the activities of glutathione peroxidase, glutathione reductase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase, catalase and the level of glutathione and lipid peroxides were measured in red blood cells of galactosaemic children with cataract and without cataract. Furthermore the serum antioxidant activity and the level of uric acid. ceruloplasmin and transferrin in serum were estimated. It was found that in red blood cells of galactosaemic children with cataract the activity of glutathione reductase was slightly lower than in a control age-matched group of children and in galactosaemic children without cataract. The increase of serum antioxidant activity in both groups of galactosaemic children was also observed. Probably it could be due to the increase of the level of ceruloplasmin. Except glutathione reductase activity no other differences were found in the investigated components of the antioxidant defense systems of red blood cells and serum between galactosaemic children with cataract and those without cataract. Therefore it seems that red blood cells and serum metabolism are no good reflections of disturbances in antioxidant defense mechanisms which may be involved in the cataract development in galactosaemic children.

Antioxidants

Insurance premium reductions. A motivating factor in long-term hypertensive treatment.

Elevated blood pressure substantially increases mortality and requires, therefore, high premium payments for life insurance coverage. Most life insurance companies are willing to reduce the cost of yearly premiums when blood pressure is successfully treated and controlled for several years. Physicians should bring these facts to their patients' attention as a motivating factor to improve adherence to therapy.

Adolescent

Experimental evidence for a central nervous system site of action in the effect of alpha-adrenergic blockers on the external urinary sphincter.

The present study was done to test the hypothesis that alpha-adrenoceptor blocking drugs (phentolamine and prazosin) could interfere with somatic control of the external sphincter through an action in the central nervous system. Stimulation of the hypogastric nerve in the chloralose-anesthetized cat caused a urethral constriction which could be antagonized by alpha-receptor blockers. However, the constriction produced by stimulation of the S1 or S2 ventral root was completely resistant to alpha blockade. The drugs therefore had the expected action against sympathetic stimulation of the urethra but had no peripheral effect on the somatic component. The central effect of these drugs was investigated by recording urethral perfusion pressure responses, or compound action potentials on the central cut end of the pudendal nerve, evoked by stimulation of the contralateral pudendal or pelvic nerve. The urethral constriction produced by stimulation of the central cut end of 1 pudendal nerve was antagonized by both prazosin and phentolamine. Action potentials evoked on the pudendal nerve by stimulation of the central cut end of the contralateral pudendal or pelvic nerve were substantially inhibited by prazosin. Phentolamine produced a more variable blockade of the pudendal-pudendal reflex. The results strongly indicate that these alpha-adrenoceptor antagonists and especially prazosin can influence pudendal nerve-dependent urethral responses through a central nervous system action and not through a peripheral mechanism.

Action Potentials

Hepatitis associated antigen, autoantibodies and serum immunoglobulin levels in patients with liver injury following administration of antituberculosis drugs.

32 patients with liver injury following the administration of tuberculosis drugs were examined for HAA, ANA, SMA and serum immunoglobulin levels. HAA was found in 38-7% of patients. SMA were detected in some HAA positive as well as in HAA negative cases. ANA except in one case were found in the HAA negative group. Serum IgM levels are significantly higher in patients with liver injury as compared to the normal values. The highest levels of IgG and IgM were found in the ANA or/and SMA-positive cases.

Adult