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Biomedical subjects

H M Lazarus

Publications and source records attributed to H M Lazarus.

At least 127 records · Page 7Linked to original sources
PubMed1994

Role of upper endoscopy in evaluation of upper gastrointestinal symptoms in patients undergoing bone marrow transplantation.

We reviewed our upper endoscopy (esophagogastroduodenoscopy, EGD) experience in a group of 65 consecutive patients receiving carmustine (BCNU) 600 mg/m2, cisplatin 200 mg/m2, VP-16 2400 mg/m2, and autologous bone marrow transplantation (BMT) for relapsed or refractory non-Hodgkin's lymphoma or Hodgkin's disease. Forty-one patients (33 with chest irradiation) underwent 48 EGDs for the following symptoms: upper gastrointestinal bleeding (melena and/or hematemesis) (12/48); persistent nausea and vomiting (7/48); odynophagia (25/48); and dysphagia (14/48). All patients who had dysphagia or odynophagia had endoscopic evidence of severe esophagitis, with confluent erosions or ulcerations. Gastrointestinal bleeding, which presented as melena or hematemesis, was caused by severe esophagitis in 11 of 12 patients. Yeasts were detected in 11/42 histological, or cytological specimens and were isolated in 4/26 cultures. No bleeding or infectious complications occurred in any patient as a result of the EGD procedure. We conclude that severe esophagitis documented by EGD is common in lymphoma patients receiving autologous BMT. Use of EGD, however, did not affect the decision to initiate empirical therapy with amphotericin B for persistent fever.

Adolescent↗
PubMed1994

Hepatic dysfunction in patients with carcinoma who are severely thrombocytopenic and immunosuppressed.

BACKGROUND: The use of intensive cytotoxic drug therapy for malignant disorders often results in hepatic dysfunction. It is important to determine the cause of hepatic injury to institute appropriate therapy; however, neutropenia and thrombocytopenia may prevent performance of hepatic biopsy to establish a cause. STUDY DESIGN: We prospectively evaluated the cause of hepatic dysfunction using laparoscopic biopsy of the liver in 20 consecutive patients who were receiving intensive cytotoxic therapy, with or without bone marrow transplantation, or who were being treated for severe aplastic anemia. One to three direct-vision laparoscopic biopsies were performed in each patient during general anesthesia and bleeding was controlled with spatula electrocautery. Platelet concentrate transfusions were given before, during, and immediately after the biopsy. RESULTS: Platelet and leukocyte counts at the time of hepatic biopsy ranged from 1,000 to 83,000 per microL (median of 23,500 per microL) and zero to 14,300 per microL (median of 2,200 per microL), respectively. Nineteen of 20 patients had platelet counts of less than 68,000 per microL. Bleeding at biopsy site was controlled during the procedure without evidence of bleeding or complications after biopsy. Biopsy specimens revealed graft-versus-host disease (n = 2), hepatic veno-occlusive disease (n = 1), steatosis (n = 5), cholestasis (n = 19), hemosiderosis (n = 19), and granuloma (n = 1). CONCLUSIONS: In several patients, the knowledge derived from hepatic biopsy results altered the therapeutic strategy. The use of laparoscopic hepatic biopsy to assess the cause of hepatic dysfunction should be encouraged because it is a safe procedure, even in patients who are severely thrombocytopenic and immunocompromised.

Adolescent↗
PubMed1994

Phase I trial of high-dose melphalan, high-dose etoposide and autologous bone marrow re-infusion in solid tumors: an Eastern Cooperative Oncology Group (ECOG) study.

The purpose of this work was to determine the maximum tolerated (phase II) dose of melphalan and etoposide that can be given in conjunction with autologous BM re-infusion in patients who have refractory or relapsed solid tumors. Twenty-six patients with refractory or relapsed breast cancer (n = 15), small cell lung cancer (n = 1), ovarian cancer (n = 3), colorectal cancer (n = 3) or malignant melanoma (n = 4) were enrolled and treated in this phase I study. Patients ranged in age from 31 to 60 years (median 44.5 years). Melphalan 180 mg/m2 (60 mg/m2/day for 3 consecutive days i.v. over 30 min) and etoposide 1200-3600 mg/m2 (400-1200 mg/m2/day for 3 consecutive days i.v. over 4 h) were given followed by autologous BM infusion 60-72 h after completion of chemotherapy. Ten patients received GM-CSF or G-CSF therapy after marrow re-infusion. Regimen-related toxicities included fever, pancytopenia, mucositis, nausea, vomiting, diarrhea, esophagitis, hepatic dysfunction and infection. Neutrophils recovered to > 500 x 10(6)/l and platelets recovered to > 20 x 10(9)/l (without transfusions) a median of 17 days and 20.5 days after marrow infusion, respectively. Dose-limiting toxicity occurred at an etoposide dose of 3600 mg/m2, since 4 of 6 patients treated at this dose level experienced grade 4 NCI Common Toxicity Criteria (mucositis (n = 3) and infection (n = 1)). Complete responses were noted in 7 patients (breast cancer (n = 5), colorectal cancer (n = 1) and melanoma (n = 1)); partial responses were observed in 5 patients. Melphalan 180 mg/m2 and etoposide 3000 mg/m2 is a potent high-dose chemotherapy regimen with significant antineoplastic activity, particularly for breast cancer, and has acceptable toxicity when administered in conjunction with autologous BM re-infusion.

Adult↗
PubMed1993

Detection and viability of tumor cells in peripheral blood stem cell collections from breast cancer patients using immunocytochemical and clonogenic assay techniques.

Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and BM from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 x 10(5) mononuclear cells. Immunostained tumor cells were detected in 9.8% (13/133) PBSC specimens from 9/48 (18.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < .005). The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/10(5) mononuclear cells (range 0.33 to 2.0/10(5)) compared with 22.9/10(5) mononuclear cells in BM (range 1 to 3,000/10(5), P < .0001). In culture experiments, clonogenic tumor colonies grew in 21/26 immunocytochemically positive specimens. No tumor colony growth was detected in 30/32 immunocytochemically negative specimens. Immunocytochemical detection of tumor involvement in BM and PBSC correlated significantly with in vitro clonogenic growth (P < .0001). We conclude that PBSC contain fewer tumor cells than paired BM specimens from patients with advanced breast cancer and that these tumor cells appear to be capable of clonogenic growth in vitro.

Adult↗
PubMed1993

Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double-blind, multicenter trial.

OBJECTIVE: To evaluate the efficacy and safety of fluconazole for prevention of fungal infections. DESIGN: A randomized, placebo-controlled, double-blind, multicenter trial. PATIENTS: Adults (257) undergoing chemotherapy for acute leukemia. INTERVENTION: Patients were randomly assigned to receive either fluconazole (400 mg orally once daily or 200 mg intravenously every 12 hours) or placebo. The study drug was started at initiation of chemotherapy and continued until recovery of neutrophil count, development of proven or suspected invasive fungal infection, or the occurrence of a drug-related toxicity. MEASUREMENTS: Fungal colonization, proven superficial or invasive fungal infection, empiric antifungal therapy with amphotericin B, drug-related side effects, and mortality. MAIN RESULTS: Fluconazole decreased fungal colonization (83 of 122 [68%] placebo patients compared with 34 of 119 [29%] fluconazole patients colonized at end of prophylaxis, P < 0.001) and proven fungal infections (27 of 132 [21%] placebo patients compared with 11 of 123 [9%] fluconazole patients infected, P = 0.02). Superficial fungal infections occurred in 20 of 132 (15%) placebo patients but in only 7 of 123 (6%) fluconazole patients (P = 0.01), whereas invasive fungal infections developed in 10 of 132 (8%) placebo patients and in 5 of 123 (4%) fluconazole patients (P = 0.3). Fluconazole was especially effective in eliminating colonization and infection by Candida species other than Candida krusei (66 of 122 [64%] placebo patients colonized at end of prophylaxis compared with 11 of 119 [9%] fluconazole patients, P < 0.001; 22 of 132 [17%] placebo patients infected compared with 7 of 123 [6%] fluconazole patients, P = 0.005). Aspergillus infections were infrequent in both fluconazole (3 cases) and placebo groups (3 cases). The use of amphotericin B, the incidence of drug-related side effects, and overall mortality were similar in both study groups. CONCLUSION: Prophylactic fluconazole prevents colonization and superficial infections by Candida species other than Candida krusei in patients undergoing chemotherapy for acute leukemia and is well tolerated. Fluconazole could not be clearly shown to be effective for preventing invasive fungal infections, reducing the use of amphotericin B, or decreasing the number of deaths.

Acute Disease↗
PubMed1993

Rashes in immunocompromised cancer patients. The diagnostic yield of skin biopsy and its effects on therapy.

BACKGROUND AND DESIGN: Rashes in immunocompromised cancer patients can be important, and skin biopsies are often recommended for their evaluation. The objectives of this study were to determine how often skin biopsy in these patients is performed and how often it alters diagnosis and therapy. Records of all immunocompromised adults with cancer and acute rash seen by dermatology consultants on a hematology-oncology ward of a university hospital for 39 months were reviewed to determine patients' course and outcome (190 episodes of rash in 123 patients). RESULTS: Skin biopsies were performed on 108 rashes (57%); 82 rashes (43%) were evaluated without biopsy. Among the 108 patients who underwent a biopsy of their rashes, the biopsy findings supported the prebiopsy diagnosis in 51% (95% confidence interval [CI], 42% to 60%), altered it in 44% (95% CI, 35% to 53%), and did not contribute to the final diagnosis in 6% (95% CI, 2% to 12%). Fifteen of 108 biopsies (14%) (95% CI, 7% to 21%) changed systemic therapy. Most treatment changes were for cutaneous reactions to drugs; biopsy never resulted in the diagnosis of untreated systemic infection. Biopsy findings that altered diagnoses were not more likely to change therapy. Among the 82 rashes in which biopsies were not performed, review of the chart revealed no adverse sequelae (0%) (95% CI, 0% to 5%), which would have made a biopsy advisable. CONCLUSIONS: Skin biopsy findings often changed dermatologic diagnoses in immunocompromised cancer patients, but treatment changes based on biopsy results were much less common, and altered diagnoses in patients who underwent biopsy often did not change therapy. Untreated systemic infection was never diagnosed by means of a skin biopsy. Skin biopsies of these rashes may not be mandatory for either diagnostic or therapeutic reasons.

Adolescent↗
PubMed1993

Does in vitro bone marrow purging improve the outcome after autologous bone marrow transplantation?

High-dose therapy with bone marrow rescue is now regarded as an effective treatment for a variety of malignancies. In an attempt to circumvent the scarcity of HLA-matched donors, autologous marrow has been successfully used as the source of cells for hematopoietic reconstitution. There has been considerable controversy as to whether any malignant cells present in the graft could contribute to relapse of disease post-transplant. In this paper we review clinical results obtained by using autologous transplantation and present evidence on how ex vivo tumor purging may contribute to the outcome.

Acute Disease↗
PubMed1993

Corynebacterium striatum: a diphtheroid with pathogenic potential.

Although nondiphtherial corynebacteria are ubiquitous in nature and commonly colonize the skin and mucous membranes of humans, they rarely account for clinical infection. Corynebacterium striatum has rarely been reported to be a pathogen, causing pleuropulmonary infections and bacteremia in only immunocompromised or anatomically altered patients. We noted C. striatum to be the infecting pathogen or copathogen in six patients. To our knowledge, this report describes the first cases of C. striatum causing infection of exist sites of central venous catheters, thrombophlebitis associated with central venous catheters, conjunctivitis, and chorioamnionitis as well as a possible pathogen contributing to peritonitis and pyogenic granuloma. Unlike Corynebacterium jeikeium, which is highly resistant to beta-lactam agents, aminoglycosides, and quinolones, all strains of C. striatum isolated from the patients described in this report were susceptible to vancomycin and aminoglycosides, and all strains except one were susceptible to penicillin G, imipenem, and ciprofloxacin. C. striatum should be recognized as a potential pathogen in both immunocompromised and normal hosts in the appropriate circumstances, and appropriate antimicrobial therapy can quickly lead to resolution of infection.

Adult↗
PubMed1993

Defective and normal haematopoietic stem cells in paroxysmal nocturnal haemoglobinuria.

The expression of decay-accelerating factor (DAF or CD55) and CD59 during haematopoietic cell development in bone marrow aspirates of two patients with paroxysmal nocturnal haemoglobinuria (PNH) was compared with that in normal bone marrow by five-dimensional flow cytometry. In contrast to early uncommitted haematopoietic progenitor cells (CD34+, CD38-) in normal bone marrow which uniformly express DAF and CD59, the majority of CD34+, CD38- cells in both patients' marrow exhibited the absence of the two proteins. In both specimens, however, subpopulations of CD34+, CD38- cells expressing DAF and CD59 were detectable, indicative of the presence of two lines of haematopoiesis, one abnormal and the other normal. Concurrent abnormal and normal haematopoietic development was further evident by the presence of subpopulations of DAF-, CD59- and DAF+, CD59+ cells along the differentiation and maturation pathways of the myeloid (CD33+, CD15(-)-->CD33+-->++, CD15+), the erythroid (CD45dim, CD71dim-->CD45-, CD71++), and the B-lymphoid cell lineages (CD10++, CD20(-)-->CD10-, CD20++). While the majority of cells differentiating into and maturing along each cell lineage lacked DAF and CD59, the majority of mature B (CD20++, CD10-) and T-lymphocytes lymphocytes (CD3+) expressed both proteins suggestive of the presence of lymphocytes with a long life span which were generated from normal haematopoietic progenitors before the onset of the disease. The detection of distinct sets of CD34+, CD38(-)--> + progenitor cells which are DAF+, CD59+ or DAF-, CD59- in marrow of PNH patients has relevance for the treatment of PNH. Cells with the phenotype CD34+, CD38-, DAF+, CD59+ are capable of self renewal and represent potential candidates for autologous bone marrow transplantation following depletion of CD34+, CD38-, DAF-, CD59- cells.

Adult↗
PubMed1993

Autologous bone marrow transplant in acute myeloid leukemia in first remission.

PURPOSE: The Eastern Cooperative Oncology Group conducted a prospective study of postremission high-dose chemotherapy and autologous bone marrow transplantation (autoBMT) in a group of uniformly treated adults with de novo acute myeloid leukemia (AML) to evaluate whether intensive, myeloablative therapy in first complete remission (CR) could improve the disease-free survival. PATIENTS AND METHODS: After initial CR was induced by the combination of daunorubicin, cytarabine, and thioguanine, patients not eligible for allogeneic bone marrow transplantation (alloBMT) were offered autoBMT. Within a median of 2 months after CR, and without intervening postremission therapy, bone marrow was obtained, purged by exposure to 4-hydroperoxycyclophosphamide (4-HC), and cryopreserved. High-dose therapy consisted of oral busulfan over 4 days (16 mg/kg total) followed by intravenous (IV) cyclophosphamide 50 mg/kg daily for 4 days. The cryopreserved marrow was then reinfused. RESULTS: Of the 39 patients scheduled for autoBMT, four relapsed before transplantation. Two of the 35 (6%) transplant patients died of transplant-related complications, and 11 (33%) relapsed a median of 8 months after marrow reinfusion. No relapse has occurred after 24 months posttransplant. With a median follow-up of 31 months, the median disease-free survival period for all 39 patients has not been reached; however, 54% +/- 16% of patients are projected to be alive and disease-free at 3 years. CONCLUSION: Long-term, disease-free survival after autoBMT in AML seems to be better than the outcome after conventional-dose postremission therapy and rivals the results of alloBMT.

Adolescent↗
PubMed1993

Antimicrobial activity and in vitro corneal epithelial toxicity of antimicrobial agents for gram-positive corneal pathogens.

We assessed in vitro the antimicrobial activity of four agents (vancomycin, teicoplanin, mupirocin, and imipenem) which are effective against Gram-positive cocci causally associated with bacterial keratitis, as well as their corneal epithelial cytotoxicity. Minimal inhibitory concentrations inhibiting 90% of strains (MIC90s) against 10 strains each of methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis, penicillin-susceptible and -resistant Streptococcus pneumoniae, and viridans group streptococci were as follows: vancomycin (MIC90s 0.25-2 micrograms/ml), teicoplanin (MIC90s 0.25-4 micrograms/ml, mupirocin (MIC90s 0.12-4 micrograms/ml), and imipenem (MIC90s 0.008-0.25 micrograms/ml, except for methicillin-resistant staphylococci with MIC90 of 16 micrograms/ml). Cytotoxicity was assayed by uptake of 3H-thymidine by rabbit corneal epithelial cell cultures at drug concentrations of 12.5-100 mg/ml for vancomycin and teicoplanin, 1-8 mg/ml for mupirocin and 0.125-8 mg/ml for imipenem, with exposure times of 5, 30 and 60 min. Cytotoxicity was as follows: imipenem < mupirocin < vancomycin < or = teicoplanin. Resistance to methicillin-resistant S. aureus and S. epidermidis for imipenem and resistance to S. epidermidis and cytotoxicity for teicoplanin limit their consideration for suspected Gram-positive keratitis. On the other hand, vancomycin and mupirocin, because of their excellent therapeutic indices, should be considered for this indication.

Animals↗
PubMed1993

Autologous bone marrow transplantation for the treatment of lung cancer.

Non-small cell lung cancer is extremely difficult to treat in all stages, and small cell lung cancer patients are cured rarely despite initial responsiveness to conventional chemoradiation therapy, even when diagnosed in limited stage. Intensive cytotoxic therapy has been explored in both small cell and non-small cell lung cancer patients, since a number of agents showed an increased response when given in high dose followed by autologous bone marrow reinfusion. The antitumor responses of single-agent high-dose trials were short-lived, but set the stage for combination chemotherapy trials given in earlier disease stages, ie, as consolidation or intensification therapy in lung cancer. In 11 published trials, 204 small cell lung cancer patients have undergone autologous bone marrow transplants. Although the transplant-related mortality rate in these studies was 7%, the long-term disease-free survival rate was 14% in a heterogeneous group of patients receiving a variety of regimens. The data gleaned from these studies suggested that a subpopulation of lung cancer patients may benefit from the use of this approach if it were to be administered at a time when the tumor burden was low. Because of the great cost of this procedure, however, third-party payers seldom provide financial coverage for these procedures. Hence, while great strides have been made in the therapy of other solid tumors, such as breast, testicular, and ovarian cancers, the role of autologous stem cell transplantation in small cell and non-small cell lung cancer remains yet to be defined.

Antineoplastic Agents↗
PubMed1993

High-dose cyclophosphamide-induced myocardial damage during BMT: assessment by positron emission tomography.

Despite its potential to cause myocardial damage, high-dose CY in doses up to 200 mg/kg is an integral part of preparative regimens for BMT. Conventional tests, such as an electrocardiogram or echocardiogram, have lacked sensitivity in prediction of cardiotoxicity in this patient population. We prospectively compared serial electrocardiograms and positron emission tomography scans before and after CY administration to investigate the possible changes in 13N-ammonia perfusion and 18F-2-deoxyglucose metabolism after CY administration in 12 consecutive patients undergoing BMT. Neither global nor regional changes in myocardial N-13 ammonia and 18-fluorodeoxyglucose were significant when compared with baseline studies and control studies (p < 0.05). In a single patient, however, a substantial increase in 13N-ammonia perfusion was seen in the inferior region simultaneously with electrocardiographic T wave inversions in the inferior leads. These changes may be due to alterations in myocardial blood flow or membrane permeability. PET scanning may be a useful adjunct in evaluating CY cardiotoxicity, although further investigations are needed to elucidate its role in clinical practice.

Adult↗
PubMed1992

Reticulocyte quantification by flow cytometry, image analysis, and manual counting.

Reticulocyte counting by flow cytometry with thiazole orange was compared to manual or automated counting of new methylene blue stained blood smears. Forty-nine samples were compared for manual counting from randomly chosen clinical samples. Two hundred and eighty-nine samples from bone marrow transplant patients were compared during the period before and through chemo-irradiation and engraftment. The slopes of correlation plots were less than 1 when flow cytometric data were the dependent variable, suggesting that thiazole orange is less sensitive than new methylene blue. In a third study, 407 samples from bone marrow transplant patients were compared after increasing the thiazole orange concentration. The reticulocyte fluorescence distribution was divided into four groups of the brightest (youngest) 40, 60, 80, and 100% of reticulocytes. The slopes from regression analysis were 0.25, 0.49, 0.78, and 1.14, respectively. This demonstrates that thiazole orange is more sensitive than new methylene blue because the window of analysis includes an increased fraction of mature reticulocytes. In addition, the precision of each assay as measured. The rank order of precision from high to low was flow cytometry > image analysis >> manual counting.

Benzothiazoles↗
PubMed1992

Expression of the DAF (CD55) and CD59 antigens during normal hematopoietic cell differentiation.

Expression of decay-accelerating factor (DAF or CD55) and of CD59 during hematopoietic cell development in normal bone marrow and on peripheral blood leukocytes were characterized by three-color immunofluorescence experiments. With this technique cell subsets were identified by forward light scatter, orthogonal light scatter, and two cell-surface antigens. For each cell lineage, specific combinations of two monoclonal antibodies labeled with different fluorochromes were used. DAF or CD59 were then quantitated on the defined cell subsets from the fluorescence signal of the respective antibody conjugated with a third fluorochrome. Early uncommitted hematopoietic progenitor cells (CD34+, CD38-) all expressed both proteins homogeneously. Initial commitment to the erythroid (CD71+, CD45dim), myeloid (CD33+), or B lymphocyte (CD10+) lineages was not associated with changes in DAF or CD59 levels. With erythroid development, i.e., after loss of CD45 and decrease of CD71, expression of both proteins decreased. With myeloid maturation, expression of CD59 remained constant and expression of DAF varied. During neutrophil maturation, DAF decreased initially and then reemerged on maturing neutrophils concurrently with the appearance of CD16 (Fc gamma RIII), whereas during monocyte maturation, DAF increased concurrently with up-regulation of CD14. With B cell development, expression of DAF increased concurrently with down-regulation of CD10 and up-regulation of CD20, whereas expression of CD59 diminished slightly late in B cell maturation. Analysis of peripheral blood elements showed that monocytes, neutrophils, and B lymphocytes expressed both proteins homogeneously, but that in contrast to other cell subsets, which all expressed CD59, only a subset of (CD3+) T lymphocytes and (CD16+) Natural killer cells expressed DAF. The absence of DAF was not related to CD4 or CD8 expression or to the presence of activation markers (CD25+, CD38+), memory cell markers (CD58+, CD45RO+), or virgin T cell markers (CD45RA+), but was correlated with expression of CD11b (CR3) and CD11c (gp150/95). Although CD21+ (CR2) and CD35+ (CR1) cells all expressed DAF, CD11a (LFA-1) levels correlated inversely with those of DAF. Although the presence of CD55 and CD59 on early progenitor cells and throughout hematopoietic cell development is consistent with the requirements for both proteins in protection of host cells from complement-mediated injury, the physiological relevance of the unique patterns of variation for each cell lineage is unclear. Nevertheless, the availability of a detailed DAF and CD59 expression map in normal marrow will facilitate analyses of alterations during hematopoietic development that may occur in hematological disorders including paroxysmal nocturnal hemoglobinuria (PNH).

Adult↗
PubMed1992

Fluctuation of serum phenytoin concentrations during autologous bone marrow transplant for primary central nervous system tumors.

We reviewed our experience for adult patients receiving oral anticonvulsant therapy during high-dose chemotherapy and autologous bone marrow re-infusion for primary malignant tumors of the central nervous system. Nineteen patients received either iv carmustine (BCNU) 900-1050 mg/m2 and 6120 cGy cranial irradiation (N = 10), iv carmustine 900-1050 mg/m2 and iv cisplatin 200 mg/m2 (N = 8), or iv carmustine 600 mg/m2, iv cisplatin 200 mg/m2, and iv etoposide 2400 mg/m2 (N = 1). Anticonvulsant therapy consisted of phenytoin alone (N = 8), phenobarbital alone (N = 4), carbamazepine alone (N = 2), phenytoin and carbamazepine (N = 2), carbamazepine and phenobarbital (N = 1), and no anticonvulsant therapy (N = 2). Serum anticonvulsant concentrations were monitored frequently and doses adjusted to keep values in the therapeutic range. While phenobarbital and carbamazepine doses remained relatively stable, all patients required increased doses of phenytoin anticonvulsant therapy after beginning chemotherapy (mean onset 3.7 days after initiation of chemotherapy). The increase in phenytoin dose ranged from 50% to 300% above baseline (mean 134%). By the time of discharge from the hospital (approximately 3-4 weeks after the start of chemotherapy) anticonvulsant dose was decreased to near pre-therapy levels. These swings coincided with the initiation of dexamethasone therapy for antiemetic effect and were more pronounced in patients also receiving cisplatin therapy. Due to close monitoring of serum phenytoin concentrations, no instances of toxicity due to excessive drug concentration, or seizures due to subtherapeutic doses, were noted in patients with primary CNS malignancies. Serum phenytoin concentrations fluctuate markedly during high-dose chemotherapy and must be analyzed frequently during the course of therapy.

Adult↗