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Congenital factor VII (FVII) deficiency is a bleeding disorder that requires optimal hemostatic management for each case due to its wide variety of bleeding symptoms. We experienced a patient with inherited FVII deficiency who demonstrated different FVII activities depending on tissue thromboplastins used for assays. An 82-year-old woman without any episodes of abnormal bleeding was found to have different FVII activities of 1.4% and 32% when assayed using thromboplastins from rabbit brain and human placenta, respectively. DNA sequencing analysis revealed a homozygous missense mutation of G10828A (FVII Padua) that caused an amino acid substitution of Arg304 to Gln (R304Q). Carriers of 304Q alleles are usually clinically asymptomatic and do not require FVII replacement therapies even in cases of homozygotes. In case a prolonged prothrombin time or reduced FVII activity is detected, re-examination using thromboplastins of other sources can be helpful for preliminary diagnosis of R304Q, in order to prevent unnecessary FVII replacement therapies.

A 64-year-old woman visited our hospital in December 2005 because of general malaise. Her hemoglobin level was 9.0 g/dl. Gastrointestinal fiberscopy detected a hemorrhagic gastric ulcer, which was considered as etiology of anemia. Abdominal ultrasonography showed bilateral hydronephroses and hydroureters. A urine test revealed pyuria and macroscopic hematuria, and urine culture revealed 10(8) colony-forming units of Escherichia coli per ml. Pelvic MRI showed thickening of the posterior wall and trigone of the urinary bladder. Transurethral resection was peformed, and biopsy of the mucous of the bladder gave a diagnosis of primary mucosa-associated lymphoid tissue (MALT) lymphoma of the urinary bladder. Ann Arbor clinical stage was IEA. It was planned to administer irradiation at a total dose of 36 Gy to the whole bladder and part of the tumor; however, radiotherapy was discontinued at a dose of 26 Gy because of the development of pollakisuria. Pelvic MRI and pathologic examination of the urinary bladder after radiotherapy showed that the lymphoma was in complete remission; however, she received retuximab therapy at a dose of 375 mg/m2/week, 8 times additionally, because of the reduced radiotherapy. The patient has remained in complete remission for 14 months.

In performing cancer chemotherapy, it is essential to know the expression of multidrug resistant (MDR) P glycoprotein (p-gp) on cancer cells. In the present study, in order to clarify the relationship between MDR of leukemic cells and cytologic, immunological and clinical features of acute nonlymphocytic leukemia (ANLL), leukemic cells in peripheral blood and/or bone marrows obtained from 28 ANLL patients were examined. Each smear was stained with C219 monoclonal antibody against P-gp by the APAAP method, and then 1,000 ANLL cells in each smear were observed. Among the FAB subtypes, M4 showed the highest proportion of leukemic cells expressing P-gp. Concerning the response to chemotherapy, five of seven patients (71%) having 1.0% or more of P-gp positive leukemic cells and 11 of 19 patients (58%) having less than 1.0% of those cells achieved complete remission. However, there was no significant correlation between P-gp expression and clinical outcome. There was also no significant correlation between P-gp expression and CD7 or CD34. Furthermore, no significant correlation between chromosome 7 abnormality and P-gp expression was observed. From these results, if we can clarify the mechanism of MDR and the relationship between MDR and cytogenetic or clinical features of ANLL with further study, P-gp expression may become a useful marker for predicting the outcome of ANLL.

A 67-year-old woman was treated with MP-P therapy and combination chemotherapy for multiple myeloma IgG-lambda type. After the therapy for about three years, pancytopenia developed. Bone marrow aspiration study revealed a few of myeloma cell and many atypical cells showing promyelocytic feature. Chromosomal abnormality was 46, X, -X, +8, -13, +mar. CD33 and CD56 were positive, but CD16 and HLA-DR were negative. We diagnosed as multiple myeloma complicated with secondary myeloid/natural killer (NK) cell acute leukemia. After she had been treated with low dose etoposide for leukemia, she obtained complete remission. But since myeloma progressed and the amount of M protein was increased, she was treated with dexamethasone and low dose etoposide, resulting in a decrease in the amount of M protein. After that, because of leukemic cell re-proliferation, she was treated with etoposide. However, she died of sepsis due to severe myelosuppression. This case was interesting one in coexist of multiple myeloma and secondary myeloid/NK cell acute leukemia, and those affecting her clinical course each other.

We treated two patients with thrombotic thrombocytopenic purpura (TTP) with multiple plasma exchanges for a short period. Following 6 plasma exchanges during 11 days in patient 1 and the 8 exchanges during 13 days in patient 2, consciousness disturbance and thrombocytopenia improved with a decrease in serum lactate dehydrogenase (LDH) levels in both patients. However, thrombocytopenia rapidly progressed with a rise of serum LDH levels after a few days from cessation of the treatment. They received a few rounds of plasma exchange without beneficial effects and eventually died of massive hemorrhage. The clinical course of these patients indicates that some patients with TTP are refractory to repeated plasma exchanges for a short period. It seems important to determine the target point in blood chemistry values such as the LDH level for plasma exchange at which the treatment could be discontinued without causing relapse of TTP.

We treated 14 patients with aplastic anemia (6 severe, 8 moderate) who did not respond to high dose methylprednisolone, antilymphocyte globulin, or anabolic steroid with cyclosporin (CyA) for more than 4 weeks. Four of them (29%) showed clinical improvement to transfusion-independence. The response rate of patients who received CyA more than 5 weeks was 50% (4 out of 8). The dose of CyA given to the 4 patients who improved after the therapy was 5 to 9 mg/kg/day. One patient needed 11 weeks until the first sign of response (increase of reticulocytes) appeared. In the other three patients, platelets increased first in response to CyA within 5 weeks. Side effects such as hypertricosis and gingival hyperplasia were frequently seen during the CyA therapy, but since they were not so severe or transient, almost all patients tolerated the therapy. These results indicate that CyA can be an efficacious drug for patients with refractory aplastic anemia. Long term treatment with a relatively low dose of CyA may be important for obtaining a high response rate.

The clinical data of 53 patients with Stage III-IV Hodgkin's disease collected from 9 institutions in Japan were analyzed for the efficacy of chemotherapy. CR rate (78%) and five-year relapse-free survival (RFS) rate (61%) were higher in the patients treated with VEPA/CHOP regimen than those in patients with VEMP/BONP or MOPP/C-MOPP regimen, although the difference was not statistically significant because of the small number of the patients. As to 14 patients treated with CHOP regimen, CR rate was 87% and RFS curve trend toward plateau at 67% after 2 years and 3 months from the initiation of chemotherapy. Salvage therapy with adriamycin-based combination chemotherapy achieved CRs in 9 of 14 (64%) patients who had been treated with VEMP, BONP, modified MOPP or C-MOPP regimen. The CHOP regimen was effective in the treatment of III-IV Hodgkin's disease but an alternative multidrug chemotherapy with ADM, CPM, VCR, BLM, etoposide and procarbazine is recommended for achieving a higher CR rate and a better RFS. Prospective study is needed to establish the standard chemotherapy for Hodgkin's disease in Japan.

At Kanazawa University 28 patients with Hodgkin's disease were treated between 1975 and 1988. Ten patients underwent staging laparotomy by which we had to change the pathological stage in 3 patients because occult splenic lesions were detected histologically. Patients with early disease were treated mainly with radiotherapy (RT) and those with advanced disease received modified MOPP chemotherapy with or without RT. Twenty-six patients entered complete remission, and relapse occurred in 7 including 5 patients with stage III disease. Four patients died of the disease and 4 of other causes. The actuarial survival at 5 and 10 years were 80.1% and 47.1% respectively. The actuarial relapse free rate at 10 years was 65.8%. Fourteen patients are in good health after completion of treatment, and 9 healthy babies were born to 5 patients including 3 female patients. The goal of therapy in Hodgkin's disease is cure. Treatment strategy must be based on proper staging and consideration of iatrogenic morbidity such as sterility and second malignancy.