Comparison of the anti-EBV titer and the EBV-associated membrane reactive and precipitating antibody levels in the sera of Burkitt lymphoma and nasopharyngeal carcinoma patients and controls

Comparisons were made between 151 sera from 131 donors with Burkitt's lymphoma, nasopharyngeal carcinoma and other tumors of the head and neck area, from patients having had infectious mononucleosis and from healthy controls, in three EBV-associated serological tests: intracellular immunofluorescence on fixed smears of EBV-carrying lymphoblastoid cell lines (“anti-EBV-reaction”), blocking of membrane fluorescence on similar lines and immunoprecipitation against the soluble antigen extracted from the EBV-carrying P3J culture line. Anti-EBV and membrane blocking antibody levels showed concordant patterns in 122 sera (81%) and discordant in 29 (19%), in agreement with previous results. If the anti-EBV and the precipitin tests are compared, 81.5% of the sera gave concordant and 18.5 discordant results. Blocking of membrane reactivity gave concordant results with the precipitin test in 71.5% of the sera whereas 28.5% were discordant. All three tests gave concordant results in 67% of the serum material; this figure fits expectations if it is assumed that the probability of an association between the anti-EBV titer and the membrane blocking antibody level is independent of the probability of an association between the anti-EBV titer and the antibody detected by the precipitin test. Analysis of the serological patterns in relation to disease categories shows that the sera of patients with head and neck tumors other than carcinoma of the post-nasal space or Burkitt's lymphoma fell mainly within the low reactive categories. Sera from nasopharyngeal carcinoma and African Burkitt lymphoma patients showed the opposite behavior, with a majority of highly reactive sera according to all three tests. Most control sera were negative or low in all three tests. In one Burkitt patient, the serological findings could be related to the clinical course of the disease; high membrane reactive antibody levels were seen in the course of tumor regression, but fell to low levels before and immediately after recurrence. Precipitating antibodies showed the opposite pattern, being absent during regression and highly positive after recurrence.     

Recurrence of infantile supratentorial ependymoma after 23-year remission following surgical removal and radiation therapy

We report on a patient with ependymoma who had a recurrence after long-term remission. The patient developed frontoparietal ependymoma at the age of one year and ten months. The tumor was radically removed and postoperative radiation therapy was performed. A calcified area adjacent to the area of surgical removal remained unchanged until the patient was 18 years old. The patient was healthy except for mild hemiparesis until an MRI scan performed when he was 25 years old showed regrowth of the tumor. The patient underwent surgery with additional radiation therapy and was discharged. The 23-year interval until tumor recurrence in this case is far beyond the so-called risk period of "Collins' law". Immunohistochemical study with MIB-1 and anti-p53 antibody showed a high proliferative potential of the primary and recurrent tumors and possible p53 mutation in the primary tumor. This is the first report to describe the detailed clinical course and histological features of a recurrent infantile ependymoma that progressed after Collins' risk period. It seems that follow-up of ependymoma patients after initial treatment should be performed regularly for a longer period in cases showing radiological evidence of a residual lesion.     

Monoclonal antibodies produced by immunization with neoglycoproteins containing Gal alpha 1-4Gal beta 1-4Glc beta-O and Gal alpha 1-4Gal beta 1-4GlcNAc beta-O residues: useful immunochemical and cytochemical reagents for blood group P antigens and a differentiation marker in Burkitt lymphoma and other B-cell malignancies

Several monoclonal antibodies (MAbs) directed to blood group P1 (Gal alpha 1-4Gal beta 1-4GlcNAc beta-O) and Pk (Gal alpha 1-4Gal beta 1-4Glc beta-O) determinants were produced with high efficiency by using synthetic neoglycoproteins as immunogens. The specificity of IgM and IgG1 MAbs was characterized by binding to defined oligosaccharides and glycoconjugates. Antibodies that bound equally well to P1 and Pk determinants and to Gal alpha 1-4Gal beta 1-O-derivatives were obtained, together with others that showed selective recognition of the entire trisaccharide chain. Selected antibodies were shown to be useful as reagents for detection of the blood group P antigens in glycolipid extracts of erythrocytes and on the surface of erythrocytes of different P phenotypes, demonstrated both by radioimmune assays and hemagglutination. Six IgM MAbs directed to the Pk determinant bound selectively to Burkitt lymphoma cells and 2 of these antibodies (424/3D9 and 424/6A2) could be used as auxiliary reagents in immunofluorescence for diagnosis and classification of B-cell lymphomas and leukemias using flow cytometric analysis. Eight normal individuals and 37 patients with lymphoma or leukemia were studied. Tumor cells of 2/2 patients with "Burkitt-like" lymphoma, 1 patient with centroblastic lymphoma and 2 patients with acute leukemia were strongly stained for the Pk antigen. The staining patterns for differentiation markers classified the tumor cells to a developmental stage closely related to the Burkitt cell type.     

SH2D1A and SLAM protein expression in human lymphocytes and derived cell lines

The gene defect responsible for the X-linked lymphoproliferative disease (XLP) is associated with an impaired control of Epstein-Barr virus (EBV) infection. The gene has been recently identified and the encoded protein (designated SH2D1A, DSHP or SAP) was characterized. It is a 128 amino acid (aa) protein, containing a single Src homology 2 (SH2) domain. It interacts with signaling lymphocytic activation molecule (SLAM) expressed on the surface of activated T and B cells. We show that activated T, but not activated B, cells express the SH2D1A protein. NK cells express the protein as well. Tumor lines originating from B, T or NK cells exhibited similar SH2D1A protein expression as the corresponding normal cells, with some notable exceptions. EBV-carrying, tumor phenotype representative (type I), but not EBV-carrying lymphoblastoid cell line (LCL)-like (type III) or EBV-negative Burkitt lymphoma (BL) lines expressed SH2D1A. The phenotypic switch from type I to type III in the EBV-carrying BL line Mutu was associated with a down-regulation of SH2D1A and up-regulation of SLAM. In contrast to normal ex vivo and long-term activated NK cells, 2 of 3 NK leukemia lines expressed SLAM. All 3 lines expressed SH2D1A, like their normal counterparts.     

A case of local recurrence of colon cancer responding to chemotherapy with low-dose oxaliplatin, 5-FU and l-LV

A 68-year-old woman underwent right colectomy for cancer of the ascending colon, followed by a local recurrence 26 months after surgery. She presented with fever and right lower abdominal pain, and was admitted to the hospital for locally recurrent colorectal cancer and tumor rupture. The patient was treated with a modified (reduced-dose) FOLFOX 4 regimen (mFOLFOX 4). In the four course of this regimen, the serum level of CEA decreased from 268 to 2.3 ng/mL. Even after 8 course, the serum CEA level remained within the normal range (4.7 ng/mL). Our case suggests that the mFOLFOX 4 regimen is effective for advanced or recurrent colorectal cancer with less toxicities including neuropathy,thus enabling patients to undergo long-term therapy.     

Results of xenogeneic I-RNA therapy in patients with metastatic renal cell carcinoma

Six patients with metastatic renal cell carcinoma were treated with five intravenous infusions (every other day) of autologous lymphocytes incubated in vitro with I-RNA extracted from the lymphoid tissue of guinea pigs immunized with the patient's own tumor. No toxicity was evident. One patient showed regression of multiple pulmonary metastases beginning three months after therapy with complete remission by six months. She remained without evidence of disease until 18 months after therapy. Two other patients had more than 50% regression of measurable metastases lasting eight and ten months after therapy. Two patients showed stabilization of previously growing renal cell carcinoma pulmonary metastases. A single patient with renal cell carcinoma metastatic to brain had progressive tumor growth after a single I-RNA treatment. Serial peripheral blood lymphocyte samples obtained from each of the patients during I-RNA therapy demonstrated progressive increase in in vitro cytolysis of allogeneic renal cell carcinoma targets. Boosts in cytolytic effect were shown in all patients during I-RNA treatment regardless of their subsequent clinical course. These results seem to justify a randomized, prospective trial of xenogeneic I-RNA therapy in renal cell carcinoma patients with lesser tumor burden.     

Obstructive biliary symptomatology as the first sign of HIV-infection

A 41-year-old white homosexual man presented with epigastric pain and jaundice. Physical examination showed enlargement of bilateral axillar and left inguinal lymph node, while ERCP and a CT scan suggested interruption of bile flow in the intrapancreatic tract of the common bile duct. An endoprosthesis was positioned in the common bile duct during the ERCP. Blood tests (both ELISA and Western blot techniques) showed positivity for anti-HIV antibodies and a CD4 count of 780/mmc (normal: 900-1,200/mmc). A few days later, a dramatic increase of the size of a lymph node in this right axilla occurred, rapidly reaching 5 cm of diameter. A biopsy was performed at this level, and histological examination revealed a high grade B-cell Burkitt type lymphoma. Bone marrow biopsy was negative, as well as lumbar puncture. Aggressive chemotherapy with adriamycin, cyclophosphamide, bleomycine, eldesine and prednisone, together with intratechal administration of methotrexate, was attempted. However, after a marginal and transient regression, the NHL rapidly progressed and the patient eventually died seven months after the diagnosis of NHL. A post mortem examination confirmed the diagnosis of Burkitt lymphoma of the peripancreatic and axillar lymph nodes, with diffusion to the leptomeninges, subaracnoideal spaces and encephalus. No signs of lymphoma were detected in other nodal or extra nodal areas.     

Regression of a plasmablastic lymphoma in a patient with HIV on highly active antiretroviral therapy

We describe an HIV-infected 44-year-old man who presented 1 month after discontinuation of HAART therapy with a large mass extending from the mediastinum, enclosing the heart and extending through the diaphragm to the epigastric region. Biopsies subsequently revealed a highly aggressive non-Hodgkin's lymphoma (NHL) producing sheets of cells with an organoid distribution. The cells had abundant basophilic cytoplasm and a plasmacytic appearance. Although immunohistochemistry failed to show either B- or T-cell markers, antigens consistent with plasma cells were found. An immunoglobulin heavy chain clonal rearrangement was identified by PCR analysis. These studies were supportive of a diagnosis of a plasmablastic lymphoma. While awaiting the results of these tests, the patient was reinitiated on his HAART regimen. He was found on follow-up a month later to have complete resolution of his bulky mediastinal mass. He remained free of disease for 3 months with subsequent rectal and abdominal recurrence. Treatment with CHOP chemotherapy with filgrastim support was begun which resulted in another remission. Plasmablastic lymphoma is now reported in some studies to account for 2.6% of all HIV-related NHL. Originally described in 1997 in a series of 16 patients, this entity is highly associated with HIV infection in its later stages. Often, patients present with oral or jaw lesions with a rapidly progressive course. The tumors have the morphologic appearance of a plasmacytoid tumor with high proliferative index. Markers are positive mainly for LCA, CD79a, VS38C, and CD138. Co-infection with HHV-8 and EBV has not been consistently reported. Therapy with standard regimens has variable response. One case has been reported with a 3.5 year disease free survival. The regression of disease after resumption of HAART therapy alone in this patient suggests that HAART has an important role in the treatment of lymphoma in the HIV infected patient.     

Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and highly active antiretroviral therapy for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma/leukemia

BACKGROUND: Patients with acquired immunodeficiency syndrome (AIDS)-associated lymphoma/leukemia have a poor prognosis and are frequently treated with low-intensity therapy. The authors investigated the feasibility and efficacy of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD), a dose-intensive chemotherapy regimen, in patients with AIDS-associated Burkitt lymphoma/leukemia, as well as the possible impact of highly active antiretroviral therapy (HAART) in these patients. METHODS: Thirteen patients with AIDS-associated Burkitt lymphoma (six patients) or leukemia (acute lymphoblastic leukemia; seven patients) were treated with hyper-CVAD alternating with high-dose methotrexate and ara-C for a total of eight cycles. Nine patients received HAART from the start of induction chemotherapy (seven patients) or later in the course of chemotherapy (two patients). The median patient age was 43 years (range, 32-55). Nine patients were diagnosed with human immunodeficiency virus (HIV) infection at the time of diagnosis of Burkitt lymphoma/leukemia; the other 4 patients had been diagnosed with HIV infection for a median of 37 months (range, 18-137) prior to the diagnosis of Burkitt lymphoma/leukemia. The median absolute CD4 count from the 9 patients with evaluable counts was 77 cells/microL (range, 9-544); only one patient had a count > 200/microL. RESULTS: Twelve patients (92%) achieved a complete remission (CR) and one achieved a partial response (PR). Eight patients continued in CR after a median of 31 months (range, 7-45) at the time of writing. Five patients were alive and in CR over two years later. The median survival was 12 months, with 48% of patients alive after 2 years. Six of seven patients who received HAART from the start of chemotherapy were alive and in CR after a median of 29 months (range, 7-45). The four patients who did not receive HAART died. The regimen was universally myelosuppressive, but the toxicity profiles, recoveries from myelosuppression, and incidences of infectious complications were similar to that of non-HIV patients with Burkitt lymphoma/leukemia treated with the same regimen. CONCLUSIONS: Hyper-CVAD is an effective regimen for patients with AIDS-associated Burkitt lymphoma/leukemia, with acceptable toxicity. The combination of hyper-CVAD and HAART is associated with long-term survival in patients with the two diseases, which, until recently, were both considered invariably fatal and almost futile to treat medically.     

Interdisciplinary approach to abdominal Burkitt’s lymphoma

Burkitt’s lymphoma is a high-grade, rapidly growing B-cell neoplasm. It is recognized by its aggressive course, brief median survival, and low rates of long-term survival. The authors discuss the case of a patient who acutely presented with intraabdominal complications from a new onset of Burkitt’s lymphoma. The clinical and pathological features, staging, treatment options, and survival data are reviewed. In addition, the role of surgical intervention is carefully analyzed.     

Antibodies against malaria and Epstein-Barr virus in childhood Burkitt lymphoma: a case-control study in Uganda

Burkitt lymphoma, a childhood tumor common in parts of sub-Saharan Africa, has been directly associated with Epstein-Barr virus (EBV) and indirectly with prevalence of malaria. We studied antibodies to both EBV and malaria in children diagnosed with this cancer in Uganda. We performed a case-control study of HIV-seronegative children (相似文献   

Direct membrane fluorescence reaction of EBV-carrying human lymphoblastoid cells: blocking tests with xenogeneic antisera

The direct membrane fluorescence reaction obtained between a fluorescein-conjugated reference antiserum of a Burkitt lymphoma patient (Mutua) and the EBV-associated membrane antigen complex carried on lymphoblastoid cell lines of Burkitt lymphoma or infectious mononucleosis origin was evaluated with regard to its ability to distinguish between anti-species and anti-EBV antibodies in heterologous (rabbit) antisera. The serum of a rabbit immunized with EB virus concentrate gave fair to very good blocking of the direct membrane reaction with the Mutua conjugate. The sera of rabbits immunized with chronic lymphatic leukemia cells were free of significant blocking activity. Sera of three rabbits immunized with Burkitt lymphoma biopsies gave significant blocking in several tests. It is concluded that the EBV-determined surface antigen receptors can be distinguished from species-specific membrane antigen sites and that this type of approach may be helpful to study the mutual relationships of antigenic structures identified by auto-, allo- and heteroantibodies, respectively.     

Variations in serum alkaline DNase activity in rats during growth and treatment of tumors sensitive or resistant to therapy

Serum alkaline DNase activity (SADA) was investigated in rats receiving s.c. transplants of tumor cells sensitive or resistant to chemotherapy. Serum samples from each animal were collected before transplantation, during the development of tumors and after therapy. Within a few days after transplantation of both tumor lines (sensitive or resistant), SADA levels decreased progressively to 52% of the normal pre-transplantation level (p less than 0.01). This decrease in SADA preceded by 4 to 5 days the appearance of any palpable tumor mass. In all untreated animals as well as in treated rats bearing resistant tumors, SADA remained at a low level until death. In rats bearing tumors sensitive to therapy a progressive increase in SADA was observed after treatment, paralleling tumor regression. When tumor regression was complete, SADA resumed the levels of activity measured prior to transplantation.     

Cyclophosphamide-induced immunologically mediated regression of a cyclophosphamide-resistant murine tumor: a consequence of eliminating precursor L3T4+ suppressor T-cells

It was shown that it is possible to use cyclophosphamide (Cy) to cause immunologically mediated regression of the immunogenic, Cy-resistant L5178Y lymphoma in syngeneic and semisyngeneic mice. In order to cause tumor regression it was necessary to give Cy shortly before or shortly after tumor implantation. However, regardless of whether Cy was given before or after tumor implantation, tumor regression did not commence until 10 days of progressive tumor growth, by which time the tumor was 1 cm in diameter. Tumor regression was associated with the presence in the spleen of an increased number of Lyt-2+ T-cells capable of passively transferring immunity to tumor-bearing recipients. This augmented level of immunity was sustained throughout the period of tumor regression. In contrast, a lower level of concomitant immunity generated by control tumor bearers decayed after Day 12 of tumor growth. Because the therapeutic effect of Cy could be inhibited by passive transfer of L3T4+ T-cells from normal donor mice it is apparent that the therapeutic effect of Cy is based on its ability to preferentially destroy L3T4+ suppressor T-cells. These putative precursor suppressor T-cells were regenerated 4 days after being destroyed by Cy. Taken together the results represent a striking example of the negative regulatory influence of suppressor T-cells on the immune response to an immunogenic tumor.     

A case of peritoneal dissemination of postoperative primary duodenal cancer successfully treated by TS-1 therapy

A 62-year-old man reported to our hospital with serious complaints of abdominal pain, vomiting, and weight loss. An endoscopic examination detected a type 2 tumor of the descending limb of the duodenum. With a diagnosis of adenocarcinoma based on the biopsy finding, the patient was subjected to surgery. Laparotomy revealed the presence of a duodenal tumor disseminating to the omentum at the site where the transverse colon is attached. Pancreatoduodenectomy and partial resection of the transverse colon were carried out. CT conducted 6 months after surgery did not show any signs of tumor recurrence; but one year later, extensive tumor dissemination was noted on the hepatic surface. Upon consultation with the patient, a regimen of 80 mg/day of TS-1 given for 4 weeks followed by 2 weeks of a drug-free period was initiated. Six months later, the growth of tumor became arrested, improving his QOL. Nine months later, the tumor growth was progressive and the patient died two years after operation. The patient could gain long-term survival after operation. The TS-1 regimen applied in the present case may constitute a therapeutic strategy to be considered for similar conditions in future.     

A case of long-term survival after curative resection of advanced rectal cancer treated by pre-operative chemoradiotherapy

We report a long-term survival case of rectal cancer that was initially thought unresectable treated with chemoradiotherapy (CRT). The patient was a 50s female with advanced rectal cancer and liver metastasis. The primary tumor was expanded locally and made abscess around the rectum. We evaluated the primary lesion as unresectable, and we performed CRT after colostomy. After radiation therapy (total 60 Gy) and chemotherapy with S-1 (3 courses), the primary tumor was remarkably reduced. The liver metastasis showed a progressive growth in size but not in number. She underwent complete resection of rectal tumor and partial resection of metastatic liver tumor. Postoperative course was uneventful, and she is alive without a recurrence for 5 years after the surgery.     

Stabilization of a Progressive Hemangioblastoma under Treatment with Thalidomide

After the second recurrence of spinal seeding in hemangioblastoma not associated to von-Hippel-Lindau disease, we treated an adult female patient with thalidomide 200 mg orally/day at night for longer than 1 year. The patient reported subjective relief of symptoms after 1 month. Magnetic resonance imaging (MRI) controls 1,6 and 11 months after begin of thalidomide treatment did not show further tumor progression. She remained wheelchair-bound, but mobility of her arms continuously improved. There was no thalidomide associated side-effect in this patient until her death from pneumonia due to legionnaire's disease. Antiangiogenic treatment with interferon (IFN) alpha-2a and IFN alpha-2b and with SU 5416 has been reported to be effective and well tolerated in several patients with previously progressive angioblastomas and hemangioblastomas. This case adds further evidence of the efficacy of an antiangiogenic treatment concept in a progressive hemangioblastoma.     

Elevated Serum CA-125 in a Patient with Follicular Lymphoma and a History of Ovarian Cancer

A patient with a previous history of epithelial ovarian cancer presented to her physician with diffuse adenopathy. On subsequent evaluation, she was found to have a follicular lymphoma. Work-up revealed an elevated serum CA-125 antigen level, raising the question of whether the laboratory abnormality represented evidence of recurrence of the original epithelial cancer. The subsequent major decline in this tumor marker following treatment directed to the lymphoma provided strong support for the conclusion that the elevated CA-125 was secondary to this malignant process and not ovarian cancer.     

Immunological studies on a case of recurrent Burkitt's lymphoma during immune stimulant treatment

Antibodies against several EBV- and non-EBV-associated antigens were titrated in serial sera from a patient with Burkitt's lymphoma who was given immune stimulants during chemotherapeutically induced tumor regression. EBV-associated membrane reactive antibodies gradually declined during BCG treatment 3–4 months prior to triple (pertussis-diphtheria-tetanus, PDT) vaccination, after which they rapidly increased simultaneously with the appearance of multiple recurrent tumors. Prior to vaccination, antibodies to the R component of the EBV-induced early antigen complex became detectable and increased further before the recurrences became evident. Antibodies to EB viral capsid antigens and to the D component of the early antigen complex also increased starting after triple vaccination, whereas most other antibodies studied remained stable during the observation period. Possible interpretations of the serological changes are discussed.     

Expression of the BLA antigen, defined by the monoclonal 38.13 antibody, on Burkitt lymphoma lines, lymphoblastoid cell lines, their hybrids and other B-cell lymphomas and leukemias

The BLA expression of eight Burkitt lymphoma lines was high, whereas it was negative in four, including the two IgG producers tested. Most lymphoblastoid cell lines (LCL) of normal origin had only a low percentage of positive cells, not significantly above background, although a few had up to 30% positives. EBV conversion of the EBV-negative Burkitt lymphoma line Ramos destabilized the high BLA expression, leading to a decrease in the average number of positive cells in the majority of the converted sublines in parallel with considerable fluctuation in antigen expression within each subline. Our group has previously shown that EBV-conversion of Ramos cells can induce certain differentiation steps (Spira et al., 1981 a). EBV-converted sublines of another EBV-negative Burkitt lymphoma, BJAB, showed a much greater stability previously and remained unchanged with regard to BLA expression in our present experiments. Eight T-cell leukemias, three myeloid leukemia lines and two diffuse histiocytic lymphomas were negative for BLA, whereas two myeloma lines were 30-40% positive. A histiocytic tumor had marginal reactions. Hybrids derived from the fusion of high with low BLA-reactive parental lines showed all three possible patterns (high, intermediate and low), provided that B-cell lines were fused with each other. Fusion of two Burkitt lymphoma lines with the K562 erythroleukemia line led to the extinction of BLA expression, as well as to the eclipse of other B-cell markers. B-lymphoma and leukemia (CLL) cells harvested directly from the patient showed a heterogeneous reactivity pattern. Strong to intermediate BLA expression was found among CLL cells and in most histological groups of B-CLL lymphomas except the centroblastic group (3/3 negatives). IgG-expressing follicular lymphomas were less reactive than IgM +/- IgD lymphomas of the same group. Immunocytomas were also low-reactive. BLA can be thus expressed on a variety of B-cell neoplasms; the degree of its expression appears to be related to the stage of differentiation.