PubMed Health⌕ Search

Biomedical subjects

H Kaizer

Publications and source records attributed to H Kaizer.

At least 37 records · Page 2Linked to original sources
PubMed1992

A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation.

BACKGROUND AND METHODS: Superficial and systemic fungal infections are a major problem among severely immunocompromised patients who undergo bone marrow transplantation. We performed a double-blind, randomized, multicenter trial in which patients receiving bone marrow transplants were randomly assigned to receive placebo or fluconazole (400 mg daily). Fluconazole or placebo was administered prophylactically from the start of the conditioning regimen until the neutrophil count returned to 1000 per microliter, toxicity was suspected, or a systemic fungal infection was suspected or proved. RESULTS: By the end of the treatment period, 67.2 percent of the 177 patients assigned to placebo had a positive fungal culture of specimens from any site, as compared with 29.6 percent of the 179 patients assigned to fluconazole. Among these, superficial infections were diagnosed in 33.3 percent of the patients receiving placebo and in 8.4 percent of the patients receiving fluconazole (P less than 0.001). Systemic fungal infections occurred in 28 patients who received placebo as compared with 5 who received fluconazole (15.8 percent vs. 2.8 percent, P less than 0.001). Fluconazole prevented infection with all strains of candida except Candida krusei. Fluconazole was well tolerated, although patients who received it had a higher mean increase in alanine aminotransferase levels than patients who received placebo. Although there was no significant difference in overall mortality between the groups, fewer deaths were ascribed to acute systemic fungal infections in the group receiving fluconazole than in the group receiving placebo (1 of 179 vs. 10 of 177, P less than 0.001). CONCLUSIONS: Prophylactic administration of fluconazole to recipients of bone marrow transplants reduces the incidence of both systemic and superficial fungal infections.

Bone Marrow Transplantation↗
PubMed1992

Peripheral blood stem cell transplantation: impact on procedure load and workload in an apheresis unit.

Peripheral blood stem cells (PBSC) reinfusion appears to hasten hematologic reconstitution following myeloablative therapy. While procurement of PBSC adds apheresis procedures, rapid engraftment could decrease the demand for platelet transfusions. To determine the impact of PBSC collection on workload in our apheresis unit, we studied 3 consecutive groups of patients with metastatic breast cancer given comparable high-dose chemotherapy and autologous bone marrow transplant, with or without PBSC or granulocyte-colony stimulating factor (G-CSF). Forty-one transplants were performed with bone marrow cells only: 31 patients (Group A) did not receive G-CSF, while the following 10 patients (group B) received daily G-CSF until neutrophil engraftment. Bone marrow cells and PBSC were used for the most recent 11 transplants (group C), followed by daily G-CSF until engraftment. PBSC were mobilized with cyclophosphamide (4 g/m2) and etoposide (1 g/m2), followed by G-CSF, 8 micrograms/kg/day. PBSC collection was carried out on a Fenwal CS3000+ cell collector, using modified procedure 1, to obtain a minimum of 5 x 10(8) mononuclear cells/kg. The times to neutrophil count over 500/microL, platelet count over 20,000/microL, and discharge from the hospital after transplant were significantly shorter for patients in group C (medians of 8, 8, and 21 days, respectively) compared to group A (medians of 14, 14, and 29 days; P = 0.001) or group B (medians of 11, 24, and 32 days; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Determination of the maximum tolerated dose of idarubicin when used in a combination chemotherapy program of reinduction of childhood ALL at first marrow relapse and a preliminary assessment of toxicity compared to that of daunorubicin: a report from the Childrens Cancer Study Group.

An escalating-dose trial of idarubicin, used weekly for 3 doses in combination with vincristine, prednisone, and L-asparaginase (VPLI), to reinduce remission of childhood ALL at first bone marrow relapse was conducted by the Childrens Cancer Study Group (CCSG). The maximum tolerated dose (MTD) of idarubicin, used in the manner, was determined to be 12.5 mg/m2/dose. Twelve of 16 (75%) evaluable patients in first marrow relapse of ALL treated at a dose of 10 or 12.5 mg/m2 entered a second complete remission, compared to 41 of 69 evaluable patients (59%) treated in a comparable way with daunorubicin (30 mg/m2) (VPLD). Prolonged myelosuppression was observed in both groups, but the frequency of documented bacterial sepsis and the duration of required hospitalization were greater among patients treated with idarubicin. No additional toxicity, specifically attributable to idarubicin, was observed at these doses.

Adolescent↗
PubMed1992

Characterization of peripheral blood CD8/11b cells in bone marrow transplant recipients. III. Subsets of CD8/11b cells differentially regulate immunoglobulin production.

Recovering bone marrow transplant (BMT) recipients have 20-70% circulating lymphocytes which co-express CD8 and CD11b (normals = 5-15%). These CD8/11b cells comprise at least two subpopulations distinguished by their expression of CD3. The CD3+ CD8/11b cells are T lymphocytes which exhibit in vitro suppressor activity (Ts); the CD3- CD8/11b cells express CD16 and are natural killer (NK) cells. In this study, we investigated whether such cells influenced circulating levels of IgA and IgM in 18 BMT recipients who each had greater than 30% circulating CD8/11b cells. We observed that in all patients whose CD8/11b cells were Ts lymphocytes (7/7) IgM and IgA levels were less than 10% of normal. Among those patients whose CD8/11b cells were NK cells (n = 11), two groups were distinguished. In one group (n = 5), less than 35% of patient NK cells expressed CD57 and serum levels of IgM and IgA were less than 10% of normal. In the second group (n = 6) greater than 60% of the NK cells expressed CD57 and serum levels of IgM and IgA were normal. In summary, our data indicate that BMT recipients have at least three distinct subsets of CD8/11b lymphocyte populations which may differentially regulate IgM and IgA production in vivo.

Adolescent↗
PubMed1992

Evaluation of pulmonary complications after bone marrow transplantation: the role of pretransplant pulmonary function tests.

To determine whether an association exists between abnormal pulmonary function tests (PFT) before bone marrow transplantation (BMT) and the rate of pulmonary complications after BMT, we retrospectively reviewed all transplants performed in our center between March 1984 and December 1990. A total of 163 patients, 15 years of age and older, with a hematologic malignancy or a solid tumor were treated with intensive therapy and autologous (118) or allogeneic (55) BMT. Sixty patients (37%) developed a pulmonary complication which contributed to patient death in 29 transplants (18%). Patients with pulmonary metastases, prior thoracotomy, or prior radiation to the chest had a higher frequency of abnormal PFT. By univariate analysis, patients with abnormal FVC, FEV1, or TLC before BMT had a significantly increased rate of pulmonary complications (p < 0.005). By multivariate analysis, the rate of pulmonary complications was significantly associated (p = 0.004) with abnormal FEV1 only: in the first 2 months after transplantation the rate was 65% in patients with FEV1 < 70% in contrast to 34% in patients with FEV1 > or = 70% (risk ratio = 1.9). There was no association, however, between abnormal pretransplant PFT and fatal pulmonary complications. We conclude that patients with pretransplant ventilatory defects have a higher risk of pulmonary complications after BMT, but the incidence of fatal complications was not significantly increased, although we cannot exclude a diminished study power due to the sample size. We believe that patients with abnormal PFT should not be excluded from transplantation if the anticipated anti-tumor effect is estimated to be substantial, but additional preventive measures may be necessary.

Adolescent↗
PubMed1991

Clonal analysis of T-cell deficiencies in autotransplant recipients.

We have used limiting dilution culture methods to determine the frequency of mitogen-responsive T cells in peripheral blood of patients after bone marrow autotransplantation, and have compared their responsiveness to that of allotransplant recipients and normal controls. Autotransplant patients were found to have low responder cell frequencies in tests for lymphokine-secreting helper function, and for IL-2 dependent proliferator and cytotoxic function. Multiple regression analysis showed that function was lower in autotransplant patients than in allorecipients, and lower in male patients for all three functional assays. Patients with clinically significant infection tended to have lower proliferative function in both transplant groups and lower cytotoxic function in the allotransplant population. Graft-versus-host disease was associated with lower T-cell function, but was present only in the allotransplant group; therefore, it cannot account for the even lower levels of function observed in the autotransplant population. Because we observe deficits in T-cell regeneration in autotransplant recipients that are even more severe than in allorecipients, we postulate that cellular immunodeficiency after bone marrow transplantation may reflect limitations in thymic-dependent repopulation rather than an effect of genetic disparity between host and donor (eg, clinical or subclinical graft-versus-host).

Adult↗
PubMed1991

Bone marrow transplantation: clinical and radiologic aspects.

With the advent of histocompatibility typing, use of bone marrow transplantation for treating hematogenous cancer has dramatically increased. Marrow grafting is preceded by intense immunosuppressive, marrow ablative treatment, usually with high-dose chemotherapy and whole-body irradiation. Because the recipient may be immunocompromised for months after transplantation due to this regimen, complications are numerous. Complications are classified according to the following intervals: pre-engraftment (from pretransplantation treatment to engraftment), postengraftment (3 months afterward), and delayed (longer than 3 months after engraftment). Pre-engraftment complications include bacterial, fungal, and viral infections; tissue-damaging effects (eg, toxic pneumonitis); hepatic veno-occlusive disease; and graft rejection. Postengraftment complications include viral, fungal, and protozoal infections; acute graft-versus-host disease (GVHD); and pneumatosis intestinalis. Delayed complications include chronic GVHD and recurrence of cancer. As part of the follow-up team, radiologists should be familiar with clinical aspects of marrow transplantation and be alert for early, potential life-threatening complications.

Bone Marrow Transplantation↗
PubMed1991

Involved field radiation, fractionated total body irradiation, high dose cyclophosphamide, and autologous bone marrow transplantation in the treatment of malignant lymphomas.

We report the results of intensive therapy and autologous bone marrow transplantation (BMT) in 23 patients with malignant lymphoma (eight Hodgkin's disease and 15 non-Hodgkin's lymphoma) who failed primary therapy. All patients had evidence of disease prior to transplant therapy: 10 had never achieved a complete remission and 13 were in relapse. The preparative regimen included involved field radiation followed by fractionated total body irradiation and high dose cyclophosphamide. A complete remission was achieved in 15 patients, 11 of whom continue in unmaintained complete remission from 27 to 72 months after BMT (median follow-up of 52 months). Of the remaining patients, five did not achieve a complete remission and three died of early toxicity. The event-free survival of the entire group is 47%. Disease status at the time of BMT was significantly correlated with patient outcome. The event-free survival of 13 patients in whom there was no objective evidence of tumor growth on conventional dose therapy was 77% compared with only 10% in patients with tumors progressing on conventional dose therapy (p less than 0.002). All six patients transplanted in untreated relapse continue in unmaintained remission, suggesting that debulking chemotherapy may not be necessary before BMT. Alternative approaches are needed in patients whose tumors progress on conventional dose therapy.

Adolescent↗
PubMed1990

The effect of hepatic enzyme inducers on busulfan neurotoxicity and myelotoxicity.

Anticonvulsants are commonly used empirically to prevent seizures in patients receiving high-dose busulfan in preparation for bone marrow transplantation. This study evaluates the effects of two anticonvulsants with enzyme-inductive properties, phenytoin and phenobarbital, and an enzyme inducer without anticonvulsant properties, Aroclor 1254, on the myelotoxicity and acute neurotoxicity of busulfan in a murine model. To assess the neuroprotective effects of these agents, we studied the effects of a single dose of 100 mg/kg i.p. busulfan, previously shown in this model to be uniformly lethal due to neurotoxicity. A significantly greater proportion of mice survived when pretreated with phenytoin or phenobarbital as compared with Aroclor 1254 pretreatment or an untreated control group. Busulfan myelotoxicity was studied in another group of mice treated with 135-150 mg/kg given in divided doses over 6 days. The proportion of animals surviving the otherwise myeloablative effects of this regimen were significantly improved by Aroclor 1254, high-dose phenytoin, and phenobarbital pretreatment. We conclude that anticonvulsants offer protection from the acute neurotoxicity of busulfan. However, these enzyme-inducing agents may reduce the myelosuppressive effects as well. These results suggest that an inducible enzyme system such as microsomal or glutathione S-transferases plays an important role in busulfan metabolism, warranting concern over concomitant administration of agents that either induce or inhibit these enzymes.

Animals↗
PubMed1990

Ex vivo chemopurging of autologous bone marrow with 4-hydroperoxycyclophosphamide to eliminate occult leukemic cells. Laboratory and clinical observations.

The application of autologous bone marrow transplantation (ABMT) in treating acute leukemias in children has been limited by the presence of residual occult viable leukemic cells in the marrow cell suspension. One approach to this problem is the ex vivo treatment ("purging") of the autograft to eradicate these tumor cells yet spare the normal lymphohematopoietic stem cells. Initial studies of acute myeloid leukemia (AML) in a rodent model demonstrated that incubation with 4-hydroperoxycyclophosphamide (4HC), a congener of cyclophosphamide and an active alkylating agent in aqueous solution, could effectively eliminate viable AML cells from marrow cell suspensions without apparent toxicity to normal stem cells. We have conducted clinical trials of ABMT with 4HC-treated marrow in children with acute leukemia in remission; marrow was collected, treated ex vivo with 4HC (100 micrograms/ml), and cryopreserved in liquid nitrogen until reinfusion. Children received pre-ABMT conditioning with either high-dose cyclophosphamide and total body irradiation (CY-TBI) for acute lymphocytic leukemia (ALL) or high-dose busulfan and cyclophosphamide (BU-CY) for AML. Of nine children who underwent ABMT with 4HC-treated marrow for ALL in second complete remission (CR2), all relapsed (eight in the marrow, one in the central nervous system) at a median of 5 months (range, 2-17) after ABMT and all have died with relapsed ALL or as a consequence of its treatment. Twenty-nine children with AML (five in CR1, 24 in CR2) received autografts with chemopurged marrow at a median remission duration of 3 months (range, 2-15). Three patients died from sepsis during aplasia; 10 children (one in CR1 and nine in CR2) relapsed with AML at a median of 7 months (range, 2-23) after ABMT, for an actuarial relapse rate of 47%. Sixteen patients with AML (four in CR1, 12 in CR2) are in unmaintained remission at a median of 16 months (range, 6-102) after ABMT, for an actuarial disease-free survival of 49%. Although ABMT with 4HC-treated marrow appears to have a limited role in the treatment of children with ALL who lack a suitable related donor, the results in AML are encouraging and compare favorably with both syngeneic and allogeneic BMT in similar groups of patients.

Actuarial Analysis↗
PubMed1990

Two populations of CD56 (Leu-19)+/CD16+ cells in bone marrow transplant recipients.

Bone marrow transplant (BMT) recipients are severely immunocompromised during the early post-transplant period as their immune systems recapitulate. Among the first cells to repopulate the peripheral blood are natural killer (NK) cells. Studies in normal subjects have revealed that the majority of NK cells express CD16 and CD56 (Leu-19). Such NK cells express low density, dim, Leu-19 (Leu-19D+). A small percentage of high-density, bright, Leu-19 cells (Leu-19B+) which are CD16- have also been reported in normal subjects. In this study we observed that peripheral blood mononuclear cells (PBMC) from BMT recipients contained two distinct populations of Leu-19+ cells that co-expressed CD16 and these populations could be separated on the basis of differential Leu-19 and CD16 fluorescence intensities. Leu-19B/CD16D and Leu-19D/CD-16B cells were present in four of nine BMT patients studied. Cells from one BMT recipient with a very large expansion of the Leu-19B+ population (46% of PBMC by flow cytometry) were studied in detail. While this patient is not characteristic of all BMT recipients, the large number of Leu-19+ cells that could be isolated from him allowed extensive analysis of a previously unreported population of cells. Our data suggest that BMT recipients can be an important group of subjects to evaluate NK cell subsets as these cells mature and, presumably, differentiate in a regenerating immune system.

Adolescent↗
PubMed1988

Marginal analysis applied to the dose-response curve.

To improve on drug dosage decisions, the method of "marginal analysis," traditionally found in the economics literature, is applied to the dose-response curve. Marginal analysis is first defined and explained, next the technique is redefined for the clinical setting of dose determination subject to drug efficacy and side effects, and finally an example using adjuvant adriamycin chemotherapy in osteosarcoma is presented. By not using "marginal analysis," clinicians may not be maximizing overall therapeutic success or patient survival. Implications for future clinical trials are discussed, and a suggestion for estimating dose-response is proposed. The technique described should be readily applicable to many dosing problems, and need not be restricted to chemotherapy dosing decisions.

Bone Neoplasms↗
PubMed1988

Characterization of peripheral blood CD8/11 cells in bone marrow transplant recipients. II. Two distinct populations of CD8/11 cells.

Flow cytometric analysis of mononuclear cell surface antigens identified 2 distinct populations of CD8/11 cells in the peripheral blood of recovering bone marrow transplant (BMT) recipients. These populations were distinguished based on differential CD8 antigen expression. One population expressed high-surface density CD8 (CD8 bright/11); the other population expressed low-surface density CD8 (CD8 dim/11). The surface expression of CD11, the C3bi receptor on lymphocytes, is similar in CD8 right/11 and CD8 dim cells. Thus, although 13 BMT recipients had elevated CD8/11 cells (mean = 27% +/- 9%; normal range mean = 7.4 +/- 3.3%), the percent of CD8 bright/11 cells versus CD8 dim/11 cells varied. The majority of cells in patients with a predominant CD8 right/11 phenotype did not express CD16 (Fc gamma receptor). In contrast, the CD8 dim/11 cells coexpressed CD16. When functional studies were performed, we observed high numbers of CD8 right/11 cells correlated with low natural killer (NK) lytic activity, while patients with less than 25% CD bright/11 cells had high NK activity. Analysis of interleukin 2 (IL-2) production revealed that none of the peripheral blood mononuclear cells (PBMC) from BMT patients synthesized IL-2 at less than 1.5 months posttransplant. However, cells from some patients began to synthesize IL-2 at approximately 2 months posttransplant. It is likely that both populations of CD8/11 cells have an impact on the regeneration and regulation of the immune system in BMT recipients.

Antigens, Differentiation↗
PubMed1988

T-lymphocyte subsets in the lesional skin of allogeneic and autologous bone marrow transplant patients.

Cutaneous biopsy specimens obtained from bone marrow transplant (BMT) patients, most with graft-vs-host disease (GVHD), were analyzed for infiltration by helper, cytotoxic, and suppressor T lymphocytes and natural killer cells. Lesional skin from patients with early mild GVHD and drug reactions showed a CD4/CD8 ratio of 5.0 or more, but later biopsy specimens from patients with acute GVHD and the majority of sections from those with chronic GVHD showed a CD4/CD8 ratio of 0.8 to 3.0 due to increased numbers of presumably cytotoxic cells. Significant numbers of suppressor (CD11 +/- CD16b-) cells were found in only one patient with severe chronic GVHD. Natural killer cells were not found. Preliminary examination of lesional skin from seven autologous BMT patients showed a similar trend of decreased CD4/CD8 ratios in the three patients with a syndrome that resembled GVHD. Analysis of CD4/CD8 ratios in serial biopsy specimens from patients with GVHD may allow more accurate monitoring of the progression of cutaneous GVHD and may help to elucidate the mechanism of development of the GVHD-like reaction in autologous BMT patients.

Biopsy↗
PubMed1987

Characterization of circulating suppressor T lymphocytes in bone marrow transplant recipients.

Peripheral blood T lymphocytes from 21 bone marrow transplant (BMT) patients and normal controls were studied for surface expression of HLA-DR, HLA-DQ, and classic T cell markers, including Leu 2, Leu 3, and Leu 4. Although resting T cells from normal subjects did not express HLA-DR or HLA-DQ molecules, up to 86% (range 22-86%) of T cells from BMT recipients expressed HLA-DR. Interestingly, less than or equal to 8% of the cells expressed HLA-DQ, and less than or equal to 3% had receptors for interleukin-2 (IL-2). When T lymphocytes were harvested from BMT recipients one month postransplant, they failed to produce IL-2 constitutively or after stimulation with various mitogens. Further analysis of patient cells revealed that 20-67% of their T lymphocytes were positive for both Leu 2 and Leu 15 (2+, 15+; normal range = 5-8%). Since 2+, 15+ cells from normal subjects have potent suppressor activity, we tested whether the cells from BMT recipients would suppress production of IL-2 from normal cells. In coculture studies, we found that cells from 5/5 BMT patients suppressed normal IL-2 production up to 70%. If patient cells were irradiated (3000 rads) prior to coculture, suppressor activity was abrogated. We propose that the cells described here may play a prominent role in the slow recovery of the immune system in BMT recipients.

Anemia, Aplastic↗