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Biomedical subjects

J D Cotelingam

Publications and source records attributed to J D Cotelingam.

At least 37 records · Page 2Linked to original sources

Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome.

PURPOSE: This phase II study was undertaken to assess the efficacy and toxicity of the addition of continuous low-dose interferon alfa-2a (IFN) to fludarabine in patients with advanced or refractory mycosis fungoides (MF) or the Sézary syndrome (SS). PATIENTS AND METHODS: Thirty-five patients were treated with fludarabine 25 mg/m2 intravenously (IV) on days 1 to 5 every 28 days along with IFN 5 x 10(6) U/m2 subcutaneously three times per week continuously for up to eight cycles. IFN doses were escalated to 7.5 x 10(6)/m2 at day 29 if constitutional toxicities were less than grade 3. Twenty-one patients had not responded to prior chemotherapy or total-skin electron-beam irradiation (TSEB), and 10 of these had received prior deoxycoformycin (pentostatin; DCF) and intermittent high-dose IFN; seven had received only topical therapies, and seven were untreated. RESULTS: Four patients achieved a complete response (CR) and 14 achieved a partial response (PR) for an overall response rate of 51% (95% confidence interval, 35% to 70%). Four of 11 patients with visceral involvement responded. The median progression-free survival duration of the patients who responded was 5.9 months, and three of the complete responders are in unmaintained response after 18 to 35 months. Grade 3 or 4 hematologic toxicity occurred in 21 patients, including two who developed persistent bone marrow aplasia. Eighteen patients developed infections during therapy, including five with herpes zoster, one with Pneumocystis carinii, one with extrapulmonary tuberculosis, and two with disseminated toxoplasmosis. CONCLUSION: The combination of fludarabine with continuous low-dose IFN is an active regimen in patients with advanced MF/SS, including patients with visceral involvement and patients who progressed after prior therapy with DCF and IFN. This regimen has induced unmaintained remissions in a small subset of patients.

Adult↗

Prognostic implications of a bone marrow histopathologic classification system in mycosis fungoides and the Sézary syndrome.

BACKGROUND: The authors devised a histopathologic classification system for interpreting bone marrow biopsy materials in patients with mycosis fungoides and the Sézary syndrome and correlated histopathologic findings with clinical stage and outcome. METHODS: Bone marrow specimens from 90 consecutively staged patients were examined for lymphoid infiltrates, benign or cytologically atypical lymphoid aggregates, and large or cytologically transformed cells. RESULTS: Thirty-seven (41%) marrows were involved, two with diffuse lymphomatous infiltrates and 35 with lymphoid aggregates. Twelve of the 35 had lymphoid aggregates consisting of cytologically normal-appearing lymphocytes, and 23 had aggregates composed of cytologically atypical lymphocytes. Eleven patients had greater than 5% large cytologically transformed cells. Patients with infiltrative disease or cytologically atypical aggregates had an inferior survival compared with those with cytologically normal lymphocytes (P2 = 0.0042), and patients with aggregates consisting of cytologically normal lymphocytes had a survival comparable with that of patients with uninvolved marrows (P2 = 0.33). Whereas most patients with cytologically atypical marrows had advanced skin and lymph node involvement, 28% had early skin stage. Bone marrow eosinophilia was noticed in 38% of patients and was not consistently associated with peripheral blood eosinophilia or clinical stage. CONCLUSIONS: These results suggest that patients with cytologically atypical lymphoid aggregates or diffuse lymphomatous infiltration of the marrow have an inferior survival regardless of clinical stage, whereas those with lymphoid aggregates consisting of cytologically normal-appearing lymphocytes have a survival indistinguishable from that of patients without lymphoid aggregates.

Adult↗

Splenic metastasis in hairy cell leukemia.

BACKGROUND: Splenic metastasis is uncommon and usually occurs in the setting of widespread visceral metastasis. Splenic metastasis as an initial manifestation of disease and sole site of metastasis has not been reported previously. METHODS: The authors describe a patient with hairy cell leukemia (HCL) with the unexpected finding of metastatic adenocarcinoma in the spleen. Direct inspection at the time of laparotomy and subsequent radiographic studies did not show a primary or additional metastatic tumor. Eventually, he manifested evidence of pulmonary and hepatic metastases and died with fungal sepsis. RESULTS: The splenectomy specimen showed HCL and metastatic adenocarcinoma. Immunohistochemical studies showed adenocarcinoma with diffuse cytoplasmic staining for prostate-specific antigen and focally positive results with prostatic acid phosphatase antigen. Postmortem examination 9 months later showed HCL and widespread metastatic adenocarcinoma. No primary tumor was identified, and multiple tissue blocks of the prostate had negative findings for tumor. CONCLUSIONS: The immunohistologic features of the metastatic adenocarcinoma were interpreted as prostatic in origin. The pattern of isolated metastatic disease in the absence of primary tumor appears to represent another possible atypical disease presentation of prostatic cancer. Hairy cell-induced structural and immunologic alterations within the splenic microenvironment may have contributed to this unique clinical presentation.

Adenocarcinoma↗

T-cell lymphoblastic lymphoma with eosinophilia associated with subsequent myeloid malignancy.

Three patients with T-cell lymphoblastic lymphoma and peripheral blood eosinophilia are reported. At the time of diagnosis, all patients had lymphadenopathy, and one had a mediastinal mass. Lymph node biopsies revealed lymphoblastic lymphoma admixed with a variable number of mature eosinophils. Immunophenotypic studies demonstrated that each lymphoma had an immature T-cell immunophenotype. Bone marrow biopsies were hypercellular with myeloid hyperplasia and eosinophilia but were negative for lymphoma. All patients received multiagent chemotherapy; one patient achieved a complete remission, and two patients had partial remissions. All patients subsequently developed a myeloid malignancy. Two died of acute myeloid leukemia within 18 months of the diagnosis of lymphoblastic lymphoma. The third patient relapsed with a lymphoma that had histologic and immunophenotypic features of both T-cell lymphoblastic lymphoma and granulocytic sarcoma and also developed a poorly defined myeloproliferative disorder. These findings suggest that T-cell lymphoblastic lymphoma associated with eosinophilia may represent a distinct clinico-pathologic entity with a high risk of subsequent myeloid neoplasia.

Acute Disease↗

Whole-body pathologic analysis of a patient with Thorotrast-induced myelodysplasia.

An autopsy was performed on a 72-y-old Caucasian female who had received a carotid artery injection of thorium dioxide in 1953. The body was dissected in such a manner as to provide for radiobiological evaluation as well as to determine histologically the distribution of Thorotrast in the tissues and its complications. Thorotrast was identified within the liver, spleen, lymph nodes, bone marrow, and surrounding the right carotid artery (the injection site). The cause of death was gastric hemorrhage complicating pancytopenia secondary to refractory anemia with excess of blasts (myelodysplastic syndrome).

Aged↗

Phase II study of pentostatin and intermittent high-dose recombinant interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome.

PURPOSE: This phase II study was undertaken to assess the efficacy and toxicity of alternating administration of pentostatin (deoxycoformycin [DCF]) and interferon alfa-2a (IFN) in patients with advanced or refractory mycosis fungoides (MF) or the Sézary syndrome (SS). PATIENTS AND METHODS: Forty-one patients underwent therapy with alternating cycles of DCF 4 mg/m2 intravenously (IV) days 1 through 3 and IFN 10 million U/m2 intramuscularly (IM) day 22, and 50 million U/m2 intramuscularly (IM) days 23 through 26. Twenty-nine patients had not responded to prior chemotherapy or total-skin electron-beam irradiation (TSEB), six had not responded to topical therapies, and six had no previous treatment. RESULTS: Two patients achieved a complete response (CR) and 15 achieved a partial response (PR), for an overall response rate of 41% (95% confidence interval, 26% to 58%). No responses were observed in the seven patients with visceral involvement. The median progression-free survival of patients who responded was 13.1 months. IFN-related constitutional symptoms were reported in 39% of patients; severe toxicities included cardiomyopathy in one patient, acute and chronic pulmonary dysfunction in four, and reversible mental status changes in two. Seven patients developed herpes zoster during therapy and six had staphylococcal bacteremia. CONCLUSION: These results suggest that the combination of DCF and IFN is an active regimen in MF patients without visceral involvement.

Adult↗

Direct intralymphatic injection of radiolabeled 111In-T101 in patients with cutaneous T-cell lymphoma.

Direct intralymphatic administration of radiolabeled monoclonal antibody in targeting antigen-bearing lymphoma cells in regional lymph nodes of patients with cutaneous T-cell lymphoma was evaluated. Seven consecutive patients undergoing staging lymphangiography received intralymphatic infusions of 111In-T101 to evaluate lymph node involvement. This procedure was accomplished without significant complication. The 111In-T101 rapidly distributed throughout the regional lymphatic compartment and passed into the systemic circulation. Tumor-bearing sites in the inguinal-femoral lymph nodes retained from 0.42 to 4.8% of the injected dose of radiolabeled antibody. Three patients were upstaged to Stage IVA based on tumor involvement found after radiolymphoscintigraphy-directed biopsy of groin lymph nodes, selected because of intense radioactivity by gamma camera imaging. Compared with previously reported s.c. antibody administration, there was a marked reduction in the radioactive exposure of normal tissues at the injection sites in the lower extremities. Direct intralymphatic delivery of 111In-T101 appears to be a feasible, efficient method for delivering therapeutic doses of radiolabeled antibody.

Adult↗

Chronic lymphocytic leukemia with coexistent Hodgkin's disease. Implications for the origin of the Reed-Sternberg cell.

The association of chronic lymphocytic leukemia (CLL) and Hodgkin's disease has been controversial. Pleomorphic lymphoreticular cells resembling Reed-Sternberg cells have been observed in Richter's syndrome. Although most observers have favored the view that these cells are a component of a pleomorphic non-Hodgkin's lymphoma, some cases of histologically typical Hodgkin's disease have been described. We have studied two cases that appear to represent composite CLL and Hodgkin's disease, providing evidence for an interrelationship of these two disorders. Classic Reed-Sternberg cells and variants (RS-H) were seen in a background that was otherwise typical of CLL. Both patients initially presented with characteristic findings of CLL in the peripheral blood and bone marrow. The first patient was found to have RS-H cells within lymph nodes at initial presentation, and ultimately progressed to develop a disseminated lymphoma characteristic of Hodgkin's disease. In the second patient, RS-H cells were not discovered until 5 years later. Immunophenotypic studies confirmed these morphologic impressions. The predominant lymphocyte population had a phenotype consistent with B-cell CLL. By contrast, the RS-H cells were strongly positive for CD15 (Leu M1) with staining of the Golgi region and cell membrane. Additionally, the RS-H cells were surrounded by rosettes of lymphocytes that marked as T cells. In both of the patients, a small percentage of RS-H cells expressed positivity for the B-cell marker L-26, which may indicate an origin from the underlying CLL. These findings support a B-cell origin for the malignant cell in some cases of Hodgkin's disease and suggest that Hodgkin's disease in some patients may be related to or derived from a coexisting lymphoid malignancy.

Antigens, Differentiation↗

Inverted papilloma of the urinary bladder with granular eosinophilic cells. An unusual neuroendocrine variant.

We report the morphologic, immunohistochemical, and electron microscopic characteristics observed in a case of an inverted papilloma that contained neuroendocrine cells resected from the urinary bladder of a 77-year-old woman. Additionally, we evaluated the incidence of neuroendocrine cells in eight cases of inverted papillomas of the urinary bladder obtained from the files of the Armed Forces Institute of Pathology, Washington, DC. To our knowledge, an in-depth study of neuroendocrine cells in this neoplasm and a comparison of the same with neuroendocrine cells observed in other conditions in the lower genitourinary tract have not been previously published, prompting this report.

Aged↗

Correlation of in vitro drug-sensitivity testing results with response to chemotherapy and survival in extensive-stage small cell lung cancer: a prospective clinical trial.

We devised a novel clinical protocol for extensive-stage small cell lung cancer (SCLC), selecting chemotherapy whenever possible on the basis of in vitro drug-sensitivity testing (DST) of individual patients' tumor specimens. Most of the specimens were obtained from metastatic sites during routine staging procedures. Increase of tumor cell number by culture in selective media usually was required before DST could be performed. We used the Weisenthal dye exclusion assay to place the seven drugs in rank order and to select the in vitro best regimen (IVBR), a three-drug combination of proved efficacy in SCLC. After initial staging and specimen acquisition, patients received etoposide and cisplatin (primary therapy) and were restaged after 12 weeks. Patients with partial or no responses and those relapsing after a complete response to primary therapy were switched to the IVBR if DST data were available. If DST data were unavailable, an empiric combination, vincristine-doxorubicin-cyclophosphamide, was administered as secondary therapy. Tumor-containing specimens were collected from 60 of the 80 patients (75%). One or more cell lines were established from 28 patients, and DST data were available from 26 patients (33% of total). Several parameters of in vitro drug sensitivity were significantly associated [two-sided P (P2) less than .05] with clinical response to primary therapy and also with response to the IVBR and were marginally associated with length of survival (.07 less than or equal to P2 less than or equal to .08). Sixteen patients (23%) received their IVBR as secondary therapy, and four of these (25%) attained a complete response, compared with three of 43 (7%) who received an empiric regimen (P2 = .16). We concluded that (a) selection of individualized chemotherapy is labor intensive but feasible in extensive-stage SCLC; (b) DST data are associated with clinical response to primary therapy and to secondary therapy with an IVBR; and (c) further observations will be required if we are to determine whether there is a modest therapeutic benefit to administering the IVBR as a secondary therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Burkitt's lymphoma: a pericardial presentation.

Described herein is a case of childhood Burkitt's lymphoma initially presenting as a pericardial effusion. A cytological diagnosis was made from a Wright's-Giemsa stained cytospin preparation. Supporting diagnostic evidence was provided by immunological surface marker analysis and electron microscopy. To our knowledge, Burkitt's lymphoma has not hitherto been diagnosed initially from the morphology of cells in pericardial fluid.

Biopsy, Needle↗

Cytomegalovirus-infected cells express Leu-M1 antigen. A potential source of diagnostic error.

The authors examined cytomegalovirus (CMV)-infected tissues and Hodgkin's Disease (HD) cases with immunohistochemical assays for Leu-M1 and CMV. The cytologic characteristics were correlated with immunostaining patterns. Cytomegalovirus-infected cells in lymph node, lung, and esophagus sections showed Cowdry type A inclusions, and many had granular cytoplasmic inclusions. All infected cells showed nuclear staining with an anti-CMV antibody. Leu-M1 reacted with CMV-infected cells in cytoplasmic areas, particularly near the nucleus simulating the characteristic staining pattern of Reed-Sternberg (R-S) cells. Cytoplasmic staining intensified as the intranuclear inclusions increased in size. Reed-Sternberg cells showed characteristic Leu-M1 positivity along the cell membrane and golgi zone. At times, Leu-M1 staining of CMV-infected cells was indistinguishable from that of R-S cells. None of the R-S cells reacted with the antibody to CMV. Recognition of the reactivity of Leu-M1 with CMV-infected cells is important in avoiding misdiagnosis of CMV lymphadenitis as HD.

Adult↗

Bilateral pigmented villonodular synovitis of the wrists.

The wrist is an unusual anatomic location for pigmented villonodular synovitis (PVNS). PVNS is generally a benign or minimally destructive process, but in our patient it resulted in progressive erosive changes in a bilateral wrist distribution. This is the first histologically documented case of bilateral PVNS in this anatomic distribution, to our knowledge. Although uncommon, PVNS should be considered a possible cause of unexplained upper extremity inflammatory arthritis.

Aged↗

Expression of interleukin-2 receptor beta subunit in hematopoietic malignancies.

The expression of the interleukin-2 (IL-2) receptor was studied in neoplastic cells derived from acute leukemias, T-cell lymphoblastic lymphomas, peripheral T-cell lymphomas, chronic lymphocytic leukemias, well-differentiated lymphocytic lymphomas, and established cell lines by both flow cytometric analysis and sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) after affinity crosslinking of radiolabeled IL-2. Cells from most acute leukemias (19 of 22), irrespective of their subtype (T, common or nonlymphoid leukemias), as well as T-cell lymphoblastic lymphomas and peripheral T-cell lymphomas expressed only the p70-75 beta subunit of the IL-2 receptor. Cells from the more mature B-cell neoplasms, chronic lymphocytic leukemia, and well-differentiated lymphocytic lymphoma, expressed predominantly alpha beta IL-2 receptors (11 of 14). In contrast to these results, most cell lines established from hematopoietic malignancies do not express either chain of the IL-2 receptor. Further studies are necessary to determine the exact function of the IL-2R p70-75 beta subunit in immature hematopoietic cells, but its wide distribution throughout the hematopoietic system suggests that IL-2 may play a role in the early stages of hematopoiesis.

Cell Line↗