Successful resection of sigmoid colon cancer in a patient with factor XI deficiency.

A 42-year-old-women with sigmoid colon adenocarcinoma was found to have isolated prolonged activated partial thromboplastin time (aPTT 102.5 s, normal range 24-36 s) preoperatively. Her medical history included an episode of prolonged postdelivery uterine bleeding 16 years previously. A mixed aPTT test showed immediate correction of the prolonged aPTT, indicating a coagulation factor deficiency in the intrinsic pathway. Factor assays showed factor XI was below 1% of average normal value whereas factor VIII, IX and XII activities were normal. Family screening revealed one sister among the three siblings also had isolated prolonged aPTT. The patient was transfused with four units (5mL/kg) of fresh frozen plasma the day before surgery, then with two units during surgery. The operation was uneventful with no bleeding problems. The patient recovered smoothly and is currently undergoing adjuvant chemotherapy. This is the first formal report of a patient with factor XI deficiency undergoing major surgery in Taiwan. Careful monitoring of aPTT, with fresh frozen plasma transfusion, when needed, may safely overcome bleeding problems during surgery.

Development of an enzyme-linked immunosorbent assay (ELISA) for detecting IgA antibodies to the Epstein-Barr virus.

A 3-step enzyme-linked immunosorbent assay (ELISA) was developed for detecting IgA antibodies to purified Epstein-Barr virus (EBV) polypeptides. The 3-step procedure included the use of a mouse anti-human IgA monoclonal antibody (MAb) to amplify the IgA reaction. The 2 major EBV proteins used in this assay were the 125-kDa component (gp125) associated with the viral capsid antigen (VCA) complex and a major glycoprotein (gp250/200) associated with the membrane antigen (MA) complex. Eighty-two sera were tested on ELISA plates containing either both of the glycoproteins or each one separately. These included 45 IgA antibody-positive sera from patients with nasopharyngeal carcinoma (NPC). With these sera, there was a good correlation, both qualitatively and quantitatively, between results with the immunofluorescence (IF) and ELISA procedures. Although most IgA antibody-positive sera contained antibodies reactive with both gp125 and gp250/200, a number of sera contained antibodies reactive with one of the glycoproteins but not with both. The data indicated that both of these glycoproteins should be used in assays for detecting IgA antibodies to EBV, to avoid false-negative results. This assay should be useful for screening large populations for IgA antibodies to EBV and also possibly for monitoring disease course in patients with NPC.

Characteristic clinicopathologic features of Epstein-Barr virus-associated peripheral T-cell lymphoma.

BACKGROUND: The authors previously reported the existence of a unique subtype of peripheral T-cell lymphoma (PTCL) characterized by a clonotypical proliferation of Epstein-Barr virus (EBV) in the tumor cells (Blood 1991; 77:799). Detailed clinicopathologic features of this newly recognized entity remain to be clarified. METHODS: A retrospective study was done in 23 patients receiving consecutive diagnoses at National Taiwan University Hospital by methods previously described. RESULTS: There were 13 male and 10 female patients, with a median age of 40 years. Seventeen patients had Stage III/IV disease, and 15 patients had fever as a presenting B symptom. Initial extranodal involvement occurred in skin (10 patients), lung (4 patients), bone marrow (4 patients), brain (3 patients), and nasal cavity (1 patient) and was evidenced by hepatosplenomegaly (6 patients). Sixteen patients had specific histopathologic features including characteristics similar to angioimmunoblastic lymphadenopathy with dysproteinemia (3 patients), angioinvasive-type features (6 patients), Hodgkin disease-like features (2 patients), hepatosinusoidal-type features (2 patients), Lennert lymphoma (2 patients), and malignant histiocytosis-like features (1 patient). Six (37.5%) of the 16 patients who received a standard regimen with cyclophosphamide, doxorubicin, vincristine, and prednisone or an equivalent regimen as induction chemotherapy achieved complete remission. The median survival time was only 8 months. Six (42.8%) of the 14 patients who have died at this report ended up with a terminal hemophagocytosis syndrome. All five relapsed tumors were found to have a strong expression of P-glycoprotein (P-gp). CONCLUSIONS: The authors suggest that EBV-associated PTCL should be regarded as a separate entity of non-Hodgkin lymphoma showing characteristic histopathologic features, frequent expression of P-gp in relapsed tumor, a terminal hemophagocytosis syndrome, and a generally ominous outcome.

Systemic chemotherapy alone for patients with non-acquired immunodeficiency syndrome-related central nervous system lymphoma: a pilot study of the BOMES protocol.

BACKGROUND: Anecdotal reports have suggested that systemic chemotherapy with agents that better cross the blood-brain barrier may result in long term disease remission in some patients with central nervous system (CNS) lymphoma. This treatment strategy has the advantage of sparing patients the late neurologic complications from brain irradiation. METHODS: Eligible patients were required to 1) have tissue-proven and measurable non-acquired immunodeficiency syndrome (AIDS)- related primary or metastatic CNS lymphoma; 2) have normal hemogram, renal function, and hepatic function; 3) be age < or = 75 years; and 4) have provided informed consent. Patients with lymphoblastic lymphoma or patients who previously had been exposed to nitrosoureas, etoposide, or high dose methotrexate were not eligible. The systemic chemotherapy (BOMES regimen) included carmustine, 65 mg/m2/day, intravenously (i.v.) on Days 1-2; vincristine, 2 mg/day, i.v. on Days 1 and 8; methotrexate, 1.5 g/m2, i.v. on day 15 followed by leucovorin rescue; etoposide, 50 mg/m2/day, i.v. on Days 1-5; and methylprednisolone, 200 mg/day, i.v. on Days 1-7; repeated every 4 weeks (BOMES regimen). Four doses of intrathecal methotrexate were given to patients who had involvement in the cerebrospinal fluid. RESULTS: Between March 1991 and March 1997 a total of 19 patients were enrolled on the study. There were 13 men and 6 women, with a median age of 57 years. Fourteen patients had primary CNS lymphoma and 5 patients had concurrent extra-CNS lymphoma. Nine patients previously had been treated by radiotherapy (four patients), chemotherapy (three patients), or both (two patients). There were 11 complete remissions (CR) (57.9%) and 5 partial remissions (26.3%), with a total remission rate of 84.2%. One patient had had progressive brain lymphoma during systemic chemotherapy with the conventional cyclophosphamide, doxorubicin, vincristine, and prednisolone regimen, but achieved CR soon after the regimen was changed to BOMES. The median time to progression of the responders was 6 months. At last follow-up, 4 patients were alive without lymphoma at 10, 47, 64, and 66 months, respectively. There were two treatment-related deaths due to sepsis. Another two patients died of fulminant hepatitis that most likely was chemotherapy-related reactivation of chronic B viral hepatitis. CONCLUSIONS: The authors believe systemic chemotherapy alone may result in long term disease remission in some select patients with non-AIDS-related CNS lymphoma. Further investigation for better protocols is mandatory.

Clinicopathological spectrum of haemophagocytic syndrome in Epstein-Barr virus-associated peripheral T-cell lymphoma.

Haemophagocytic syndrome (HS) is frequently observed in Epstein-Barr virus-associated peripheral T-cell lymphoma (EBV-PTCL) and represents a major cause of death. In this communication we have further analysed the spectrum of HS in 12 patients with EBV-PTCL. The patients could be divided into three groups according to the time of onset of HS during the clinical course of PTCL. Group I patients (four cases) had HS as the initial clinical manifestation. All four patients were initially suspected to have malignant histiocytosis (MH) but a MH-like PTCL was later diagnosed. Group II patients (six cases) developed HS at the time of lymphoma relapse. Four of them belonged to the angioinvasive type PTCL. Group III patients (two cases) developed HS at clinical remission; both were angioinvasive type PTCL. Nine patients had serological evidence suggesting active EBV infection. The clinical course after the onset of HS was generally fulminant in each group with a median survival of only 44d despite combination chemotherapy and/or empirical therapy with high-dose immunoglobulin and corticosteroids in six patients. In conclusion, HS represents a severe complication of EBV-PTCL. Although most patients develop HS at a time of active lymphoma, the syndrome may occur when the lymphoma is in remission. Because of the poor outcome, early diagnosis and a new modality of treatment for HS associated with EBV-PTCL should be pursued in future.

A phase II study of piritrexim in patients with advanced squamous head and neck cancer.

Piritrexim (PTX) is a newly developed lipid-soluble folate antagonist that crosses the cell membrane by a simple, rapid, carrier-independent diffusion process. A Phase II study was conducted to evaluate the activity of PTX in 34 patients with previously chemotherapy-naive squamous cell cancer of the head and neck area (SCCHN). Among them, 30 patients had received previous radiation therapy and/or surgery. Of 33 patients who could be examined, 3 had a complete response (CR), 6 had a partial response (PR), 11 had no change, and 13 had disease progression. The overall response rate (CR + PR) was 27% (9 of 33; 95% confidence interval, 13% to 46%). The response duration ranged from 36 to 360 + days (median, 162) and was similar to the best studies reported with methotrexate. The three most severe side effects (Grades 3 and 4 by World Health Organization criteria) were leukopenia, thrombocytopenia, and mucositis. These occurred in 41%, 26%, and 15% of the 34 patients, respectively. This study established PTX as an agent with some activity in SCCHN. The use of PTX in combination chemotherapeutic regimens needs to be explored.

Aggressive peripheral T-cell lymphomas containing Epstein-Barr viral DNA: a clinicopathologic and molecular analysis.

The Epstein-Barr virus (EBV) has been shown to be associated with posttransplant lymphoma, Hodgkin's disease, and T-cell lymphoma, in addition to African Burkitt's lymphoma. In a retrospective study of 56 consecutive cases of T-cell lymphoma, EBV DNA was found by Southern blot and in situ DNA hybridization in 10 (20%) of 50 peripheral T-cell lymphomas, but in none of six cases of T-lymphoblastic lymphoma. Peripheral T-cell lymphomas containing EBV DNA could be subclassified into three categories according to histology and immunophenotypic studies: (1) T-cell lymphoma of the helper phenotype, five cases. Two cases had histologic features resembling angioimmunoblastic lymphadenopathy (AILD). (2) T-cell lymphoma of the cytotoxic/suppressor phenotype, four cases. AILD-like features could also be recognized in two cases. Reed-Sternberg-like giant cells were identified in three cases designated Hodgkin-like T-cell lymphoma. (3) Angiocentric T-cell lymphoma or lymphomatoid granulomatosis in one case, initially affecting the skin and nose; no T-cell subset could be defined. Six of the eight EBV DNA-positive patients tested for serum EBV antibodies had elevated titers of IgG antiviral capsid antigen (greater than 640) and/or early antigen (greater than 10). From combined studies of Southern blot hybridization by using EBV termini fragment probe and in situ DNA hybridization, the EBV genomes appeared to be clonotypically proliferated in the neoplastic T cells. The patients in all three groups usually had prolonged fever preceding the diagnosis, hepatosplenomegaly, an aggressive clinical course, and poor response to chemotherapy; nine died with a median survival of only 8 months. We propose that these EBV-associated aggressive T-cell lymphomas, like human T-cell leukemia/lymphoma virus-positive T-cell lymphoma, have characteristic clinicopathologic features and should be treated as a separate disease entity.

Cutaneous angiocentric T-cell lymphoma associated with Epstein-Barr virus.

BACKGROUND: Two unusual cases of cutaneous angiocentric T-cell lymphoma were found to be associated with Epstein-Barr virus infection. OBJECTIVE: The objective was to study the clinical course and the response of the disease to conventional chemotherapy. METHODS: Histologic specimens from both patients were studied. Clonal proliferation was assessed by Southern blot hybridization. RESULTS: The disease in both patients was rapidly progressive and responded poorly to aggressive treatment. Biopsy specimens showed infiltration of atypical lymphoid cells with angiocentricity and angiodestruction, which probably resulted in the observed tissue necrosis. Clonal proliferation of Epstein-Barr virus DNA was detected in tissue from primary skin lesions and disseminated nasal lesions. CONCLUSION: Epstein-Barr virus-associated angiocentric T-cell lymphoma in our patients was characterized by an aggressive course and resistance to conventional chemotherapy. A search for Epstein-Barr virus and the human T-lymphotropic virus should be performed in patients with atypical features of cutaneous T-cell lymphoma.