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Biomedical subjects

J Gajewski

Publications and source records attributed to J Gajewski.

At least 73 records · Page 4Linked to original sources
PubMed1994

Treatment of advanced acute leukaemia with allogeneic bone marrow transplantation from unrelated donors.

Bone marrow transplantation from a histocompatible sibling donor may produce complete remission in patients with induction failure or relapsed acute leukaemia. Through the National Marrow Donor Program, histocompatible bone marrow from unrelated donors has become available for high-risk patients. In this study we analyse the results of matched unrelated bone marrow transplant in 55 patients with highly advanced acute myelogenous and acute lymphoblastic leukaemia. 28 patients with advanced acute lymphoblastic leukaemia and 27 patients with advanced acute myelogenous leukaemia, age 2-51, were treated with high-dose chemoradiotherapy and transplantation of 6/6 HLA matched (n = 46) or one antigen mismatched (n = 9) unrelated donor bone marrow. After a median follow-up of 36 months, 13 patients remain alive 17-74 months after transplant for a 2-year actuarial disease-free and overall survival of 23 +/- 12% (median disease-free survival 3.5 months). The actuarial risk of relapse is 24 +/- 16% at 1 year. Moderate to severe graft-versus-host disease occurred in 27/47 evaluable patients (57%). Significant prognostic factors for poor leukaemia-free survival include age > 21, abnormal karyotype, and active leukaemia at the time of transplant. Other pretreatment characteristics such as gender or type of leukaemia were not significant prognostic factors. Our results show that matched unrelated bone marrow transplant for patients with advanced acute leukaemia may provide long-term leukaemia-free survival, but transplant-related complications produce a significant impact on survival with older age and adverse disease characteristics predicting for poor prognosis.

Adolescent↗
PubMed1994

Etoposide, cyclophosphamide, total-body irradiation, and allogeneic bone marrow transplantation for hematologic malignancies.

PURPOSE: To determine the efficacy and toxicity of etoposide, cyclophosphamide, and fractionated total-body irradiation (TBI) as the conditioning regimen for allogeneic bone marrow transplantation (BMT) in patients with hematologic malignancies. PATIENTS AND METHODS: Seventy-nine patients underwent BMT from a human leukocyte antigen (HLA)-identical sibling using cyclosporine/methotrexate for graft-versus-host disease (GVHD) prophylaxis. Thirty-four patients had early leukemia (acute leukemia or lymphoblastic lymphoma in first remission, chronic myelogenous leukemia [CML], or refractory anemia [RA]), and 45 patients had more advanced disease. Patients received etoposide 1,500 mg/m2 on day -8, followed by cyclophosphamide 60 mg/kg/d on days -7 and -6, and 10.2 Gy of TBI administered in six fractions of 1.7 Gy given twice daily for 3 days from day -3 to -1. Donor bone marrow was harvested and infused on day 0. RESULTS: Patients with early leukemia had a disease-free survival rate of 53% +/- 9% and an overall survival rate of 57% +/- 10% at 3 years. Patients with advanced disease had a disease-free survival rate of 15% +/- 5% and overall survival rate of 17% +/- 5%. The actuarial relapse rate for the early-leukemia group is 33% +/- 9% versus 69% +/- 9% for patients with more advanced disease. Severe toxicity was most frequently manifested as pulmonary hemorrhage followed by multiorgan failure and death. The 100-day mortality rate for the early-leukemia group was 10% versus 50% for patients with more advanced disease. CONCLUSION: The combination of cyclophosphamide, etoposide, and TBI is a relatively safe and effective preparative regimen for patients with early hematologic malignancies. Controlled trials are needed to evaluate critically this combination versus other standard preparative regimens. Greater toxicity was observed in patients with advanced disease, and this program does not appear to offer any advantage over other regimens.

Adolescent↗
PubMed1994

Benefit of high-dose cytarabine-based consolidation chemotherapy for adults with acute myelogenous leukemia.

Despite consolidation and/or maintenance chemotherapy most patients with newly diagnosed acute myelogenous leukemia relapse such that only 20-30% survive free of recurrence at five years. To evaluate the long-term effects of dose-intensive consolidation, we analysed 123 consecutive patients, age 16 to 84 (median 48 years), who received high-dose cytarabine-based consolidation chemotherapy. After a median follow-up of 88 months (range 26 to 126 months), 38 patients remain alive, with 26 in continued remission from 45 to 126+ months. Median remission duration for all eligible patients is 14 months (range 1.3 to 126 months) and actuarial leukemia-free survival at five years is 24 +/- 8%. Median survival from remission is 24 months (range 1.3 to 126 months) and actuarial survival from remission is 31 +/- 9%. Eighty-two patients (67%) have relapsed with an actuarial risk of relapse of 71 +/- 9% at five years. Adverse prognostic factors were age over 45 and male gender. When compared to historical controls (P = 0.02), dose-intensive consolidation produced improved leukemia-free survival for patients age < 45, but compliance and enhanced toxicity in the older age groups may limit further dose intensification.

Acute Disease↗
PubMed1994

Forearm tremor in relation to selected physiological and body dimensional variables.

Interrelationships between forearm tremor and a number of body dimensional, muscle structure, muscular strength and training background variables were studied among 13 male students with athletic backgrounds. The subjects performed isometric dominant upper extremity elbow flexions with a 90 degrees joint angle and with the forearm held in a horizontal position. A freely hanging mass was attached via a strain gauge transducer, a metal chain and cuff to the forearm. An accelerometer attached to the cuff measured the vertical component of tremor. The power spectrum density function was calculated for a tremor acceleration signal and a bandwidth of 7-20 Hz was analysed in more detail. The right M. vastus lateralis was biopsed in order to determine the muscle fiber composition. Arm mass and muscle fiber composition were found to correlate statistically significantly with the tremor frequency characteristics. In the further analyses arm mass was found to be the only variable explaining the tremor frequency characteristics; the effects of the muscle structure variables were minor when the effects of arm mass was controlled in partial correlation analyses. Interindividual differences in motor unit firing properties were presumed to explain the dependence found between arm mass and tremor frequency.

Acceleration↗
PubMed1994

Phase I-II study of busulfan and cyclophosphamide conditioning for transplantation in advanced multiple myeloma.

We evaluated a non-radiation containing preparative regimen for persons with myeloma receiving bone marrow (BM) or blood cell transplants. Twenty-three adults with advanced multiple myeloma (15 responsive to chemotherapy, 8 resistant) received cyclophosphamide 120 mg/kg and busulfan 14-16 mg/kg followed by the infusion of BM or blood progenitor cells. Patients were followed for response by monthly skeletal radiographs, urine and serum monoclonal paraprotein measurement, BM evaluation and beta 2-microglobulin. Three of 18 evaluable patients achieved complete response, 13 patients achieved partial response and two a minimal response. Actuarial 1 year survival post-transplant for all patients is 63% (95% confidence interval, 40-86%). Disease stage and response to chemotherapy pre-transplant correlated with survival post-transplant. Actuarial survival for patients with resistant disease was 38% (4-72%); for patients with chemotherapy-responsive disease, it was 78% (48-100%, p = 0.02). Regimen-related toxicity consisted of five early deaths, three from veno-occlusive disease, one from infection and one from multiorgan failure. Fatal and non-fatal hepatic and renal toxicities were related to busulfan dose with most complications occurring at 16 mg/kg. Our studies suggest that busulfan and cyclophosphamide are an effective conditioning regimen in multiple myeloma. Toxicity precludes increasing the total dose of busulfan beyond 14 mg/kg.

Adult↗
PubMed1993

Outcome after allogeneic bone marrow transplant for leukemia in older adults.

OBJECTIVE: To determine whether age over 40 years is associated with adverse outcome after allogeneic bone marrow transplantation for leukemia. DESIGN: A retrospective analysis of outcome after bone marrow transplants for leukemia reported to the International Bone Marrow Transplant Registry (IBMTR) among recipients 30 through 39 years, 40 through 44 years, 45 through 49 years, and 50 years of age and older. SETTING: Transplantations performed in 138 institutions worldwide and reported to the IBMTR. PATIENTS: A total of 2180 recipients of HLA-identical sibling bone marrow transplants for leukemia, divided into four cohorts based on age: 30 through 39 years (n = 1282), 40 through 44 years (n = 527), 45 through 49 years (n = 291), and 50 years and older (n = 80). MAIN OUTCOME MEASURES AND RESULTS: Incidence of leukemia-free survival, graft-vs-host disease, and relapse was comparable among the four age cohorts. Patients with advanced leukemia aged 45 years or older had a slightly higher risk of treatment-related mortality, and the 45- through 49-year-old cohort had a higher risk of interstitial pneumonia. CONCLUSIONS: These data indicate that among leukemia patients over 30 years of age at the time of allogeneic bone marrow transplantation, increasing age into the fifth decade does not adversely affect outcome after transplants from HLA-identical siblings.

Adult↗
PubMed1993

Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program.

BACKGROUND AND METHODS: Allogeneic bone marrow transplantation is curative in a substantial number of patients with hematologic cancers, marrow-failure disorders, immunodeficiency syndromes, and certain metabolic diseases. Unfortunately, only 25 to 30 percent of potential recipients have HLA-identical siblings who can act as donors. In 1986 the National Marrow Donor Program was created in the United States to facilitate the finding and procurement of suitable marrow from unrelated donors for patients lacking related donors. RESULTS: During the first four years of the program, 462 patients with acquired and congenital lymphohematopoietic disorders or metabolic diseases received marrow transplants from unrelated donors. The probability of engraftment by 100 days after transplantation was 94 percent, although 8 percent of patients later had secondary graft failure. The probability of grade II, III, or IV acute graft-versus-host disease was 64 percent, and the probability of chronic graft-versus-host disease at one year was 55 percent. The rate of disease-free survival at two years among patients with leukemia and good prognostic factors was 40 percent and among patients at higher risk, 19 percent. Twenty-nine percent of the patients with aplastic anemia were alive at two years, and the rate of two-year disease-free survival among patients with myelodysplasia was 18 percent. For patients with congenital immunologic or nonimmunologic disorders, the probability of survival was 52 percent. CONCLUSIONS: The National Marrow Donor Program has benefited a substantial number of patients in need of marrow transplants from closely HLA-matched unrelated donors and has facilitated the recruitment of unrelated donors into the donor pool and the access to suitable marrow.

Adolescent↗
PubMed1993

Unrelated donor marrow transplantation therapy for chronic myelogenous leukemia: initial experience of the National Marrow Donor Program.

In the interval from December 1987 to November 1990, 196 consecutive patients with chronic myelogenous leukemia (CML) received unrelated donor marrow transplantation using marrow procured by the National Marrow Donor Program (NMDP) at 21 NMDP-affiliated marrow transplant centers. Baseline donor and recipient data as well as follow-up data were obtained systematically in all cases by the NMDP. The median interval from the initiation of a search for an unrelated donor to bone marrow transplantation was 8.4 months (range, 1.7 to 34.6 months). Median age of the recipients was 33.3 years (4.5 to 54.5 years). Seventy-five recipients were female and 121 were male. At time of transplant, 115 patients were in chronic phase, 51 in accelerated phase, 14 in blast crisis, and 16 in a second or subsequent chronic phase. In 133 cases, donors and recipients were identical at the HLA A, B, and DR loci using standard serologic typing, and in 63 cases, there was nonidentity at one HLA locus. Patients were prepared for transplantation with a combination of high-dose chemotherapy and total body irradiation (N = 169) or with high-dose chemotherapy only (N = 27). Thirty-five patients received marrow depleted ex vivo of T lymphocytes, whereas 161 patients received non-T-depleted marrow. One hundred seventy-four of 196 patients engrafted (absolute neutrophil count > or = 500/mm3 for 3 consecutive days). The median time to engraftment was 22 days (6 to 69 days). Twenty-two patients failed to engraft, and an additional 10 patients experienced late graft failure. The incidence of grades III or IV acute graft-versus-host disease (GVHD) was 0.54 +/- 0.10, and that of extensive chronic GVHD was 0.52 +/- 0.12. A lower incidence of both grades III and IV acute GVHD (P = .0003) and of extensive chronic GVHD (P = .01) were independently associated with use of T-depleted marrow. The actuarial incidence of hematologic relapse at 2 years is 0.11 +/- 0.06. The 2-year actuarial incidence of disease-free survival for patients transplanted in first chronic phase within 1 year of diagnosis is 0.45 +/- 0.21, in chronic phase more than 1 year from diagnosis is 0.36 +/- 0.11, in accelerated phase is 0.27 +/- 0.12, in second or subsequent chronic phase is 0.22 +/- 0.21, and in blast crisis is 0. Fifteen of 55 patients transplanted at 40 to 50 years of age survive.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1993

Phase II study of etoposide, ifosfamide, and mitoxantrone for the treatment of resistant adult acute lymphoblastic leukemia.

Although combination chemotherapy induces complete remission in 60-90% of adults with acute lymphoblastic leukemia, only 20-45% of patients remain in continued remission 5 years from diagnosis. For patients with a short first remission, multiple relapses, or patients with disease refractory to initial induction chemotherapy, few salvage treatments are successful. To improve the results of salvage therapy we studied the efficacy and toxicity of a combination of etoposide (100 mg/m2 IV qd x 5), ifosfamide (1.5 g/m2/d x 5), and mitoxantrone (8 mg/m2/d IV x 3) in 11 adult patients with relapsed or refractory ALL. The median follow-up of all patients completing therapy is 208 days (30-484+ days). Eight of 11 (73%; 95% confidence interval 45-92%) achieved a complete remission, two patients failed to enter remission, and one patient died of multiorgan system failure shortly after receiving therapy. Median DFS is 96 days and median survival from remission is 234 days. Five patients who achieved CR subsequently relapsed with a median time to relapse of 80 days (50-151 days). Median time to granulocyte > .5 x 10(9)/L was 28 days (21-46 days) and the median time to platelet recovery > 20 x 10(9)/L was 24 days (21-39 days). Although gastrointestinal toxicity was common, no patient developed severe cardiac, hepatic, pulmonary, or neurologic complications. These results demonstrate that the combination of etoposide, ifosfamide, and mitoxantrone can be used as an effective salvage therapy for patients with resistant ALL.

Adult↗
PubMed1993

Effect of induction cytarabine dose intensity on long-term survival in acute myelogenous leukemia: results of a randomized, controlled study.

The optimal dose and schedule of cytarabine in induction chemotherapy of newly diagnosed acute myelogenous leukemia is not established. We compared the use of cytarabine 200 mg/m2/day by continuous infusion for seven days to an intermediate-dose of cytarabine, 500 mg/m2 every 12 hours for 12 doses. Thirty-seven of 52 patients assigned to conventional-dose cytarabine achieved complete remission (71%) and the actuarial disease-free and overall survival after achieving remission were 22 +/- 16% and 31 +/- 19% respectively. Thirty-seven of 50 patients assigned to intermediate-dose cytarabine achieved remission (74%) and the actuarial disease-free and overall survival after achieving remission were 26 +/- 16% and 39 +/- 18% respectively. There were no statistically significant differences in complete remission rate, actuarial leukemia-free survival or overall survival between the groups. The most significant predictor for survival was age. Actuarial two year leukemia-free survival and overall survival for patients age > 60 were 8 +/- 15% and 20 +/- 19% respectively compared to 36 +/- 14% and 54 +/- 15% for patients age < or = 60 (P = .058 and .01, respectively). Induction regimen did not significantly affect disease free or overall survival for patients under or over age 60. We conclude that intermediate-dose cytarabine did not substantially improve results of induction for newly diagnosed acute myeloid leukemia.

Adolescent↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1990

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↗