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Marfan syndrome (MFS) is caused by mutations in the gene encoding fibrillin. A 35-year-old man with MFS visited a local physician because of a sore throat. His left tonsil gradually became swollen and he was referred to our department. Histopathological examination of tonsil biopsy specimens showed diffuse proliferation of lymphoma cells with large nuclei. The tumor cells showed CD5+, CD10+, CD20+, BCL-6+, and MUM-1-. Based on these findings, the patient was diagnosed with CD5+ CD10+ diffuse large B-cell lymphoma (DLBCL). Chemotherapy combined with rituximab was administered and complete response was achieved. CD5+ DLBCL comprises approximately 5 approximately 10% of DLBCLs. In addition, CD5+ CD10+ DLBCL comprises about 5% of CD5+ DLBCLs. There may be a relationship between MFS and B-cell lymphoma because mutations in the gene encoding the receptor of transforming growth factor-beta (TGF-beta) have been implicated in the pathogenesis of MFS and downregulation of TGF-beta receptor expression has been described in the pathology of B-cell lymphoma.

A-51-year-old woman with a sixteen-year history of mixed connective tissue disease was admitted to the Kitasato University Hospital because of hypogastric pain in September 1999. Colonofiberscopy and computed tomography in the abdomen demonstrated thickening of the intestinal wall with a hemorrhagic ulcer in the terminal ileum. The histopathologic findings of the lesion revealed diffuse infiltration of atypical T-lymphocytes. The titers of anti-HTLV-I antibody and serum soluble IL-2 receptor were elevated. The diagnosis of adult T-cell leukemia/lymphoma (ATLL) infiltrating the terminal ileum was made. Combination chemotherapy including VEPA-M was undertaken, and resulted in a partial response. ATLL became refractory about June 2000. Flaccid paralysis, dysesthesia in the left lower limb and bladder-bowel disturbance emerged in a few days, July 2000. T2-weighed MRCT images demonstrated that a lesion with a high intensity signal was present in the spinal cord around Th 7. Flower-like cells were detected in the cerebrospinal fluid. Infiltration of ATLL into the thoracic cord was diagnosed. Administration of intrathecal methotrexate and prednisolone, systemic dexamethasone and local irradiation of 30 Gy improved the paralysis and the abnormal MRCT findings. Rehabilitation restored the patient's ability to walk.

A 59-year-old man with a six-month history of chronic myelomonocytic leukemia (CMML) was admitted to the Kitasato University Hospital because of melena in September 2000. Colonofiberscopy and barium enema demonstrated an ulcerated tumorous lesion in the transverse colon. The histopathologic findings of the ulcer bed revealed diffuse infiltration of granulocytes at each stage of differentiation. The diagnosis of granulocytic sarcoma (GS) was made. Surgical resection was not indicated, because thrombocytopenia was hardly improved enough to allow surgery despite repetitive transfusion of platelet concentrates. CMML developed to refractory anemia with excess of blast in transformation in February 2001. Two courses of low dose cytarabine plus aclarubicin were ineffective on the GS in spite of a decrease in the peripheral blood blasts. Progression to acute myeloid leukemia eventually broke out, in July 2001. The patient died of leukemia complicated with pneumonia and intestinal obstruction. At present, nine cases of GS in the colon have been reported. However, these cases did not include CMML. This is the first report describing GS in the colon associated with CMML.

Primary vaginal non-Hodgkin's lymphomas (NHL) are rare, and are clinically difficult to differentiate from inflammatory diseases or vaginal cancer. Here, we present such a case in a 74-year-old woman complaining of fever and difficulty with urination. Pelvic examination revealed a tumor involving most of the vaginal wall, and pelvic MRI demonstrated vaginal wall thickening. A biopsy of this lesion confirmed NHL (diffuse large B-cell lymphoma), and the patient was admitted. Abdominal CT and MRI detected a vaginal tumor, and Ga scintigraphy confirmed accumulation in the pelvis, but no abnormalities were seen in other areas. Therefore, the patient was diagnosed as having NHL at clinical stage IB with low-intermediate risk (international prognosis index) (LDH 1,309 IU/L). The patient underwent three courses of CHOP therapy followed by radiotherapy, and complete remission was achieved. Primary vaginal NHL often affects women younger than 50 years of age, and abnormal hemorrhage is the initial symptom in many cases. There have been a number of reports of long-term survival following appropriate early chemotherapy and radiation therapy, suggesting that early diagnosis and treatment based on vaginal biopsy findings greatly influence the prognosis.

Primary non-Hodgkin's lymphoma (NHL) of bone is a rare disease, accounting for less than 1% of all NHL cases and 3-5% of all extranodal lymphoma cases. Of 512 NHL patients treated at our department, 9 patients (1.8%, median age of 54 years) had primary NHL of bone. The disease was histologically of the diffuse type in all a patient, and of the large cell type in 6. The disease was at stage 1 in 8 patients and stage II in 1. The patients all received radiotherapy of 30-40 Gy following either the CHOP or COP-BLAM chemotherapy regimens. Treatment achieved complete remission in 8 patients. Six patients still alive (median follow-up: 63 months). It has been reported that survival is longer for patients treated with a combination of chemotherapy and radiotherapy than those, treated with radiotherapy alone. Consequently, we conclude that the standard treatment course for primary NHL of bone should be chemotherapy followed by radiotherapy.

Autoimmune hemolytic anemia (AIHA) complicated with non-Hodgkin's lymphoma (NHL) is not unusual. Two cases of NHL associated with cold agglutinin disease were reported. Case 1: A 38-year-old man had diffuse medium-sized cell NHL diagnosed by cervical lymph node biopsy. The Hb was 7.6 g/dl with a cold agglutinin titer of 32,768, and the IgM level was 890 mg/dl (I-specific), so cold agglutinin disease (CAD) was suspected. After administration of COP-BLAM therapy, complete remission (CR) was achieved along with a decrease in the cold agglutinin titer and improvement of anemia. Case 2: A 68-year-old woman had follicular mixed NHL diagnosed by inguinal lymph node biopsy. The Hb was 8.2 g/dl with a cold agglutinin titer of 51,200, and an IgM level of 920 mg/dl (I specific), thus concurrent CAD was suspected. Biweekly COP-BLAM therapy was administered and CR was achieved along with a decrease in the cold agglutinin titer and improvement of her anemia. In both patients, the cold agglutinin titer decreased after CR was achieved suggesting that production of anti-erythrocyte autoantibody was due to disturbance of the antibody system by NHL.

This study investigated 72 patients (12.4%) with follicular lymphoma among 582 patients with non-Hodgkin's lymphoma admitted to our department. Treatment achieved complete remission (CR) in 83.3% of the follicular lymphoma patients, with an overall 5-year survival rate of 63.7%. The 5-year survival rate was 76.9% for the 60 patients who achieved CR, and this rate was significantly higher than that for patients who achieved only partial remission (PR) (p < 0.01). The 5-year survival rate was 40% with the CHOP regimen and 74.3% with the COP-BLAM regimen. The 3-year survival rate for biweekly COP-BLAM was 88.4%. The 5-year disease free survival rate for patients who achieved CR was 80.5%. The rate reached a plateau after 42 months, and the same survival was maintained for more than 10 years. These results suggest that intensive chemotherapy is effective even against follicular lymphoma. The 5-year survival rate for patients who achieved PR, suggesting the importance of the response to initial chemotherapy.

COP-BLAM chemotherapy with concomitant G-CSF was performed on patients 65 or older with non-Hodgkin's lymphoma (NHL), and cardiac sympathetic disorders due to the chemotherapeutic agents were studied using 123I-MIBG (metaiodobenzylguanidine) myocardial SPECT (single photon emission CT). The results showed no correlation between the ejection fraction due to echocardiography and the total dose of adriamycin (ADR). However, there was a positive correlation between the total dose of ADR and the washout rate, and the possibility of cardiac sympathetic disorders caused by ADR was suggested.

Intensive multidrug chemotherapy with concomitant IFN was performed in three hepatitis B virus (HBV) carriers with malignant lymphomas. All of the patients were HBsAg+, HBsAb-, HBcAb+, HBeAg- and HBeAb+ (mutant strain+). HBV-DNA polymerase (DNA-P) was normal at the beginning of chemotherapy, and complete response was achieved with CO-BLAM chemotherapy (without PDN) in all cases. In case 1, a slight elevation of DNA-P and normal GOT and GPT was observed after IFN-alpha was started during the third course. IFN-alpha was administered twice a week. In case 2, elevation of DNA-P and normal GOT and GTP were noted at the end of the 5th course, then daily IFN-alpha was started. In case 3, daily IFN-alpha was started during the 3rd course because of elevation of DNA-P. It was possible to prevent severe liver damage by administering IFN immediately after the elevation of DNA-P, since DNA-P elevation is noted before GOT and GPT elevation. The detection of the HBV mutant strain could be helpful in the treatment of HBsAg+ and HBeAb+ patients. In all of three patients, DNA-P, serum GOT and GPT normalized quickly after the administration of IFN-alpha. Severe hepatitis did not develop.

G-CSF was used concomitantly with the COP-BLAM regimen, and its therapeutic results and adverse effects were evaluated. A total of 104 patients with untreated non-Hodgkin's lymphoma (NHL), including 22 in stage II, 52 in stage III and 30 in stage IV. Seventy five patients had diffuse large cell type, 18 diffuse medium cell type, and 11 diffuse mixed cell type. The treatment consisted of the COP-BLAM regimen based on the method of Laurence et al., was performed every 3 weeks. Complete remission was achieved in 98 out of 104 patients (94.2%), and the 4-year survival rate was 82.4%, while at the time of evaluation the median observation period was 26 months. The survival time was significantly prolonged in patients with low LDH values, B-cells, stage II or low CRP values. The COP-BLAM regimen with concomitant G-CSF administration achieved a high remission rate and reduced the frequency of infections. Almost all of the patients could be treated in 21-day cycle and this appeared to be effective for treatment with increased dose intensity.

Combination chemotherapy regimens using multiple agents have been reported to produce long term survival in patients with non-Hodgkin's lymphoma (NHL). However, the adverse effects of those regimens, particularly pulmonary complications, have resulted in fatalities. We measured P-III-P and type IV collagen-7S level in the serum and BALF of 23 previously untreated NHL patients who underwent COP-BLAM III chemotherapy in which a high dose of bleomycin (BLM) was used, and studied the relationship between those parameters and the pulmonary functions in those patients. The parameters and pulmonary function were measured before the first course and after the completion of the fourth course of chemotherapy. As for pulmonary function, chemotherapy produced an increment of %DLCO value but no change in PaO2, %VC, and %FEV1.0. While serum P-III-P levels remained unchanged, P-III-P levels in BALF slightly decreased after the chemotherapy. Type IV collagen-7S levels both in serum and BALF showed no change after the chemotherapy. Serum P-III-P levels after the chemotherapy were significantly correlated with both total cell counts and lymphocyte counts in the BALF. But there was no correlation between serum P-III-P levels and %DLCO. Mild and early-Stage fibrosis was observed in the lungs of the patients who were treated with COP-BLAM III. Pulmonary adverse effects are not likely to be associated with the total administered dose of BLM, but are associated with individual susceptibility to BLM toxicity. Our results suggest that the chemotherapy should be discontinued or the dose of BLM should be reduced if the P-III-P level in BALF increases.

We report a case of Lennert's lymphoma complicated by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and autoimmune hemolytic anemia (AIHA). A 76-year-old female patient was admitted to our hospital because of cervical lymph node swelling. A diagnosis of Lennert's lymphoma was made by histological examination of the biopsied lymph node. She was also diagnosed as SIADH and AIHA. After the patient was treated with COP-BLAM therapy, lymph-adenopathy, SIADH and AIHA improved. However, lymph node swelling and hyponatremia became exacerbated again after the third course of COP-BLAM therapy. Then she was treated with IMV-triple P therapy. Eventually, she died of aspergillus pneumonia. The etiology of her SIADH was suggested to be an abnormal feedback mechanism of ADH secretion due to the infiltration of lymphoma cells into the diencephalic-hypophysial system.

ACVP-16 chemotherapy combined with recombinant granulocyte-colony stimulating factor (rG-CSF) was carried out on patients with malignant lymphoma which were recurrent or resistant to chemotherapy including adriamycin. Twenty patients with non-Hodgkin's lymphoma, 11 men and 9 women, with a median age of 54 years, were entered in this study. Fourteen patients had diffuse large cell lymphoma, 4 diffuse medium, and 2 diffuse mixed. The previous treatments for these patients were COP-BLAM, IMV-triple P and COP-BLAM III. The ACVP-16 regimen included ara-C at 100 mg/m2 i.v. on day 1 to 5, CBDCA at 250 mg/m2 i.v. on day 1, and VP-16 at 70 mg/m2 i.v. on day 1 to 3. Subcutaneous administration of rG-CSF at 2 micrograms/kg was started on day 7. Since complete remission was achieved in 7 patients (35%) and partial remission in 8 (40%), the total response rate was 75%. The median survival duration after the initiation of this therapy was 11 months for those who achieved CR and 4 months for those who achieved PR and those who had no response. Leukopenia (< or = 1,000/microliters) and thrombocytopenia (< or = 50,000/microliters) were observed in 15 (75%) and 12 (60%), respectively. We conclude that the ACVP-16 regimen is useful for the treatment of refractory or relapsed non-Hodgkin's lymphoma. However, the patients who are treated with this regimen should be carefully managed in order to avoid severe infection, because leukopenia was observed even when rG-CSF was administered.