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Biomedical subjects

Philip Kuriakose

Publications and source records attributed to Philip Kuriakose.

5 recordsLinked to original sources

Targeted therapy for hematologic malignancies.

BACKGROUND: The introduction of monoclonal antibodies, either as native molecules or conjugated to radioisotopes or other toxins, has led to new therapeutic options for patients with hematologic malignancies. In addition, the use of small molecules against specific cell surface receptors, enzymes, and proteins has become an important strategy in the treatment of such disorders. METHODS: The author reviewed the published clinical trials of monoclonal antibody and other targeted therapies in hematologic malignancies. RESULTS: Results from several trials demonstrate a therapeutic benefit for the use of monoclonal antibodies (either native or conjugated) and other targeted therapies, used alone or in combination with standard cytotoxic chemotherapy. CONCLUSIONS: Targeted therapy of hematologic malignancies seems to be an effective and less toxic approach to the treatment of such disorders. Nevertheless, additional studies are needed to determine where and when such management fits into a therapeutic regimen for any given disorder, whether upfront or as salvage therapy, alone or in combination with chemotherapy (concurrent or sequential).

Antibodies, Monoclonal↗

Hematologic malignancies with primary retroperitoneal presentation: clinicopathologic study of 32 cases.

CONTEXT: The retroperitoneum is an uncommon location for primary lymphomatous involvement. Initial presentation of disease in this site (primary retroperitoneal lymphoma) is considered to be rare. Because of the uncommon anatomic location, the diagnosis and subsequent management of these patients tend to be difficult for both pathologists and clinicians. OBJECTIVE: This report describes our experience during a period of 6 years 4 months with patients with hematologic malignancies primarily presenting in the retroperitoneum. DESIGN: A retrospective search of our medical records generated 32 patients who presented initially with abdominal pain or discomfort as their predominant symptom and who were found by imaging studies to have retroperitoneal mass or masses. All the histopathology slides were reviewed and classified based on the World Health Organization classification. RESULTS: There were 13 male and 19 female patients. Tumor types included diffuse large B-cell lymphoma (n = 12); grade 1 follicular lymphoma (n = 4); grade 3 follicular lymphoma (n = 1); B chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 2); multiple myeloma (n = 1); mixed-cellularity Hodgkin lymphoma (n = 1); nodular sclerosis Hodgkin lymphoma (n = 1); aggressive B-cell lymphoma (n = 4); low-grade B-cell lymphoma (n = 4); lymphoblastic lymphoma, null cell type (n = 1); and precursor B-lymphoblastic lymphoma/leukemia (n = 1). More than half of the cases (17/32) were diagnosed on needle biopsy with immunophenotyping. CONCLUSIONS: Although open lymph node biopsy is a preferred method for diagnosis, needle biopsy plays a significant role in this setting, and, coupled with other information such as flow cytometry and immunohistochemistry, it is considered a practical and reliable method.

Adult↗

Translocation (8;14)(q24;q32) as the sole cytogenetic abnormality in B-cell prolymphocytic leukemia.

B-cell prolymphocytic leukemia is a relatively rare lymphoproliferative disorder. No specific cytogenetic abnormality has yet been associated with it. The most common translocation reported in patients with this disease is t(11;14)(q13;q32). We describe the case of a patient with B-cell prolymphocytic leukemia and a hitherto unreported genetic translocation (8;14)(q24;q32) as the sole genetic abnormality, classically seen in patients with B-cell acute lymphoblastic leukemia/Burkitt lymphoma. This patient presented with an asymptomatic leukocytosis and splenomegaly. Her marrow showed lymphoid hyperplasia, with immunophenotyping consistent with prolymphocytic leukemia; however, t(8;14)(q24;q32) was the only cytogenetic aberration with both standard karyotyping and fluorescence in situ hybridization analysis.

Aged↗

Risk of deep venous thrombosis associated with chest versus arm central venous subcutaneous port catheters: a 5-year single-institution retrospective study.

PURPOSE: To determine the risk of deep venous thrombosis (DVT) in patients undergoing placement of central (chest) versus peripheral (arm) ports. MATERIALS AND METHODS: Between January 1996 and December 2000, a total of 440 implantable chest or arm ports were placed in 422 patients. Data pertaining to the first port placed for each patient was analyzed. Ports were placed for chemotherapy (n = 415) or blood transfusion (n = 7). Subset analysis was performed, taking into consideration whether patients received prophylactic or therapeutic doses of warfarin sodium (Coumadin), to determine if there was any difference in the incidence of DVT between patients undergoing some form of anticoagulation versus those undergoing none. The medical records of these patients were reviewed to determine outcome with reference to development of DVT. RESULTS: In 273 chest ports placed, there were 13 (4.8%) instances of DVT; in 149 peripheral ports, there were 17 (11.4%). Censoring data on patients receiving some form of anticoagulation, the respective incidences were eight of 245 (3.3%) and 14 of 129 (10.9%). With use of Kaplan-Meier analysis and log-rank tests to examine comparisons of interest, the probability of thrombosis occurring over a period of 180 days was higher with peripheral ports irrespective of Coumadin use (P =.007 for all patients considered, P =.002 when analyzed only for those not receiving Coumadin). The difference in incidence of thrombosis for all ports between patients receiving Coumadin versus those not receiving Coumadin was not significant. CONCLUSIONS: Compared to chest ports, peripheral ports are associated with a significantly higher incidence of DVT.

Adolescent↗

Phase I trial of edatrexate in advanced breast and other cancers.

Edatrexate (EDX) (10-ethyl-10-deazaaminopterin or 10-EDAM) is an analogue of methotrexate with improved pre-clinical antitumor activity, more selective cellular uptake, and with more extensive formation of intracellular polyglutamate metabolites. A phase I trial in advanced cancer using EDX was initiated to determine the toxicities associated with the use of a biweekly schedule of intravenous EDX, and to carry out a dose escalation to define the maximum tolerated dose employing this schedule. Thirty-four patients were enrolled in this phase I trial. Thirty-three patients were treated in cohorts of at least three patients (except at one dose level, 210 mg m-2, where there were only two patients). Dose escalations of EDX were administered starting with 100 mg m-2, and progressing through 120, 140, 160, 180, 210, 240, and 270 mg m-2. Edatrexate was administered by intravenous infusion over 20 min, and cryotherapy using ice chips was given prophylactically for 5 min before, during, and 15 min after each EDX treatment. The dose-limiting toxicity could not be reached in this study because it had to be closed on account of competing protocols using EDX in combination regimens. Of note though, was that the delivered dose intensity at the 160 mg m-2 week-1, was higher than the previously used or recommended phase II doses. Anemia was mild and white blood corpuscle toxicity was mostly of grade 1 or 2. One patient had grade 4 neutropenia and one had grade 3 thrombocytopenia. Of the non-hematological toxicities, nausea, vomiting, and diarrhea were mild and tolerable. Mucositis, which was the dose-limiting toxicity in previous studies, was seen in 30% of the patients, but was predominantly a grade 1 toxicity. This could have been due to either the different schedule of EDX used in this study or the use of cryotherapy. Substantial antitumor effects were noted, with two near-complete complete responses at the 120 and 160 mg m-2 levels. Additionally, six partial responses and one minor response were observed, and stable disease was observed in seven patients. Despite achieving antitumor activity at different dose levels, a clear-cut dose response was not evident at the levels tested. We feel that the biweekly EDX schedule is a tolerable regimen, which allows a higher dose intensity than weekly administration, and that EDX is an active agent for the treatment of patients with metastatic cancer.

Adult↗