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Peter Maslak

Publications and source records attributed to Peter Maslak.

10 recordsLinked to original sources

Grading follicular lymphomas in fine-needle aspiration biopsies: the role of ThinPrep slides and flow cytometry.

BACKGROUND: The World Health Organization (WHO) recommends a 3-tier grading system (Grades 1-3) for follicular lymphomas (FLs) based on the absolute number of centroblasts per high-power microscopic field (HPF) in 10 neoplastic follicles. Grades 1 and 2 FL are still managed as indolent FLs, whereas Grade 3 FL is thought to behave more aggressively. In this study, the feasibility of grading FL using ThinPrep (TP) slides and flow cytometry (FC) was evaluated. METHODS: Fifty-three cases of lymph node fine-needle aspiration (FNA) from patients with histologically confirmed FL (20 Grade 1, 17 Grade 2, and 16 Grade 3) were included. The number of centroblasts present in 300 lymphoid cells and in 10 HPF in TP Papanicolaou-stained slides was evaluated. The percentage of CD10-positive small cells was calculated with FC results. Statistical analysis was performed with the Jonckheer-Terpstra nonparametric trend test and the Wilcoxon rank sum test. RESULTS: The statistical analysis demonstrated a significant upward trend in the number of centroblasts as the grades increased. Also, all 3 methods had statistically significant results to distinguish different grades of FL, except when FC was used to distinguish Grade 2 from Grade 3 FL. CONCLUSIONS: Counting centroblasts, either in 300 lymphoid cells or per 10 HPF in TP slides, represented a statistically significant method to separate different grades of FL in FNA samples. Analysis of cell size by FC was not as reliable to distinguish different grades of FL, especially Grade 2 from 3.

Adult↗

Acanthocytes.

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Abetalipoproteinemia↗

Pentostatin, cyclophosphamide, and rituximab is an active, well-tolerated regimen for patients with previously treated chronic lymphocytic leukemia.

PURPOSE: Purine analogs and alkylators are important agents for treating chronic lymphocytic leukemia (CLL). Early studies combining fludarabine and chlorambucil were abandoned owing to increased toxicity from overlapping myelosuppression and immunosuppression. Of the purine analogs active in CLL, pentostatin appears to be the least myelosuppressive. We previously reported that pentostatin and cyclophosphamide (PC) is active and well-tolerated in patients with relapsed or refractory CLL. Subsequently, we added rituximab, and now report on this three-drug combination. PATIENTS AND METHODS: We treated 46 patients with either previously treated CLL (32 patients) or other low-grade B-cell neoplasms (14 patients). Patients received pentostatin 4 mg/m2, cyclophosphamide 600 mg/m2, and rituximab 375 mg/m2 (PCR). All drugs were administered on the same day (rituximab omitted from cycle 1), and patients received six cycles at 3-week intervals. Filgrastim, sulfamethoxazole/trimethoprim, and acyclovir were administered prophylactically. RESULTS: The median age was 62 years (range, 30 to 80 years). The median number of prior regimens was two (range, one to seven). For CLL patients, there were 24 responses (75%), including eight complete responses (25%). In fludarabine-refractory patients, 75% responded. Toxicity was acceptable, with grade 3/4 infections (including fever of unknown origin) in 28%. The regimen was well tolerated, with 72% of patients receiving the planned treatment at full dose. CONCLUSION: PCR is safe and effective in previously treated patients with CLL. In comparison with our prior two-drug regimen, we find that rituximab did not seem to add significantly to the toxicity, but did appear to confer a survival advantage. Based on these results, we are currently studying PCR as initial therapy for patients with CLL.

Adult↗

Pegylated interferon plus rituximab in advanced stage, indolent lymphoma: is there CD20 antigen upregulation?

The anti-CD20 monoclonal antibody, rituximab, and interferon alpha (IFN) are active agents in advanced stage, indolent lymphoma. Some data obtained in vitro suggest upregulation of CD20 by IFN, and clinical trials have reported additive or synergistic activity of IFN with rituximab. A prospective phase II study in advanced stage, follicular and non-follicular indolent lymphoma was performed. Peginterferon alpha 2b (pegIFN) 0.5 microg/kg s.c. weekly x 6 and rituximab 375 mg/m2 i.v. weekly x 4 (beginning on week 3 of pegIFN) was administered. Quantitative CD20 antigen was measured pre-treatment and pre-rituximab in lymph node aspirates. Nine patients were treated: one complete response and three partial responses; however, all relapsed within 12 months and two were withdrawn for grade 3 toxicity (both with serum sickness). No up-regulation of CD20 was documented in seven patients studied (median change in CD20: decrease by 11.9%). PegIFN plus rituximab as delivered in this study is not recommended. PegIFN does not appear to upregulate CD20 expression in peripheral lymph node tumor cells.

Aged↗

Clinical applications of molecular monitoring in leukemia.

Molecular analyses of the leukemias have been able to identify unique markers that can be used as "molecular signatures" for the various diseases. In acute promyelocytic leukemia, qualitative polymerase chain reaction (PCR) has helped define the clinical syndrome and has been used to guide therapy. Quantitative modifications of the PCR technique have been investigated in chronic myelogenous leukemia and acute lymphocytic leukemia and found to correlate with clinical outcomes. These assays may soon be incorporated into standard clinical management and may result in a new definition of response.

Humans↗

Phase I study of the cyclin-dependent kinase inhibitor flavopiridol in combination with paclitaxel in patients with advanced solid tumors.

PURPOSE: Preclinical studies indicate that the cyclin-dependent kinase inhibitor flavopiridol potentiates the induction of apoptosis by paclitaxel, provided paclitaxel is followed by flavopiridol. We therefore designed a phase I clinical trial of sequential paclitaxel and flavopiridol. PATIENTS AND METHODS: Paclitaxel was administered at a fixed dose, as either a 24- or 3-hour infusion on day 1, followed by a 24-hour infusion of flavopiridol on day 2. Doses of flavopiridol were escalated in successive cohorts according to a modified Fibonacci design. Flavopiridol pharmacokinetics were obtained on all patients. RESULTS: Dose-limiting neutropenia developed with 24-hour paclitaxel doses of 135 and 100 mg/m(2) and flavopiridol doses of 10 and 20 mg/m(2), respectively. With 3-hour paclitaxel at 100 mg/m(2), flavopiridol could be escalated to 70 mg/m(2) without dose-limiting toxicity. With 3-hour paclitaxel next escalated to 135 mg/m(2), dose-limiting neutropenia and pulmonary toxicity occurred when flavopiridol was escalated to 94 mg/m(2). This did not correlate with any change in flavopiridol or paclitaxel pharmacokinetics. At a 3-hour paclitaxel dose of 175 mg/m(2), dose-limiting pulmonary toxicity occurred in only one patient at flavopiridol doses under 94 mg/m(2). Clinical activity was observed in patients with esophagus, lung, and prostate cancer, including patients who had progressed on paclitaxel. CONCLUSION: The recommended phase II doses will be a 3-hour infusion of paclitaxel at 175 mg/m(2) on day 1 followed by a 24-hour infusion of flavopiridol at 70 mg/m(2) on day 2. Flavopiridol dose escalations to 80 mg/m(2) are possible. At these doses, toxicities are manageable and clinical activity is promising.

Adult↗