Three patients with relapse (two molecular and one cytogenetic relapse) after allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML) were treated with donor leukocyte transfusion (DLT). Two had complete molecular remission, which persisted 16 and 20 months after treatment. The performance status of all patients was 90∼100%. Mild chronic GVHD was observed in one patient as a side effect of DLT. One patient with cytogenetic relapse required three infusions to attain molecular remission and this suggests the importance of cell numbers to infuse in DLT. Positive anti-nuclear antibody was observed in the effective cases and elevation of IgE in all cases after DLT. These abnormal laboratory findings may suggest a relationship between GVHD and GVL. DLT may be effective therapy for patients with CML who relapse after BMT. Further controlled studies are necessary to determine the optimal number of cells to infuse, interval and frequency of DLT.

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Factor VIII (IX) inhibitors represent one of the most serious problems for the treatment of patients with hemophilia. The Blood Products Research Organization (Japan) has supported a study group for treatment of hemophiliacs with inhibitors. In 1995 the study group started a prospective matched control study of hemophiliacs with and without inhibitors and compared such factors as quality of life and economic cost. Each inhibitor patient was matched with a control patient in terms of age, type of hemophilia, and severity of hemophilia. A total of 136 patient-pairs were enrolled. Bleeding episodes were more frequent in the control group than in the inhibitor group. Days of hospitalization, days in wheelchairs, and the number of impaired joints were significantly higher for the inhibitor group. Number of blood-product infusions, days of bed rest at home, and days of brace use were the same for both groups. Blood-product expenditures were significantly higher for the inhibitor group than for the control group (¥10,872,283/patient/year vs. ¥4,327,542/patient/year). Our study highlighted the higher cost of treatment and lower quality of life for hemophiliaes with Factor VII inhibitors.

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One hundred and thirteen patients who underwent autologous or allogeneic bone marrow transplantation (BMT) were investigated for the subsequent development of hemolytic uremic syndrome (HUS). HUS developed in seven patients (four males and three females, five acute lymphocytic leukemia (ALL), one acute myelogenous leukemia, one non-Hodgkin's lymphoma) between 36∼196 days after BMT. Four patients were recipients of autologous BMT and three were those of allogeneic BMT. Six patients were preconditioned with the regimens including fractionated total body irradiation (TBI). ALL and preconditioning regimen with TBI were suspected to be the risk factors for the development of HUS. Cyclosporin A (CSP) administration was discontinued in three patients who had been given CSP for graft-versus-host disease prophylaxis. Predonisolone was given to the three patients and plasma exchange was performed in one patient. Both hemolytic anemia and thrombocytopenia were resolved in virtually all patients, while creatinine elevation has persisted along with hypertension in one patient.

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As the author found that serum ferritin is decreased below 12 ng/ml in iron deficiency anaemia (IDA) even then it is coexisting with anaemia other than IDA, an attempt was made to detect and treat IDA coexisting with anaemia other than IDA. When surveyed in a general hospital admitting 222 patients, anaemias were detected in 95 out of 190 patients aged above 60:82 inflammation anaemia, 9 IDA including 6 cases with inflammation and 4 other anaemias. According to the above results, aged patients above 60 with IDA only and IDA coexisting with inflammation were treated by injecting iron intravenously. By the treatment, haemoglobin (Hb) was increased from 9.0 to 13.8 g/dl and the ratio of Hb increase was 0.59 in 4 patients with IDA only, and Hb was increased from 7.7 to 11.5 g/dl and the ratio of Hb increase was 0.63 in 18 patients with IDA coexisting with inflammation. After the treatment, general disease states were improved in many cases. Thus, the treatment of aged patients with IDA coexisting with inflammation seems to be comparablly effective as for IDA only.

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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 I 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.

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A 22-year-old woman was admitted to our hospital with fever, generalized lymphadenopathy, and pancytopenia in February 1995. She was diagnosed as having systemic lupus erythematosus (SLE) based on positivity for anti-nuclear antibody, and polyarthritis among other findings. A diagnosis of disseminated intravascular coagulation (DIC) was made based on the increase of FDP and other data (DIC score: 7). We also detected an anti-fibrinogen antibody. Lymph node biopsy revealed subacute necrotizing inflammation and there were on signs of the hemophagocytic phenomenon in bone marrow. The DIC score improved and the anti-fibrinogen antibody disappeared in association with the response of SLE to prednisolone therapy. The onset of SLE associated with DIC has never been reported before, as far as we could determine. The mechanism of DIC associated with SLE may be related to endothelial damage caused by immune complexes.

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A 44-year-old man with CML in chronic phase was admitted for BMT from an HLA-identical sibling. Ph¹ positive cells were undetectable at 3 and 7 months after BMT but became detectable by cytogenetic analysis of bone marrow aspirates at 12 months after BMT. He was treated with IFN-α (6 million units/day, 3 times a week) without apparent effect. Donor leukocyte transfusion (DLT) was performed four times between 20 months and 23 months after BMT, transfusing 3.4×10⁸ mononuclear cells/kg. However, leukocytosis appeared and the NAP score declined at 25 months after BMT. FISH analysis revealed an increase in bcr-abl positive cells. IFN-α was restarted using the same schedule at 26 months after BMT. Three months after restarting IFN-α, the leukocyte count fell to the normal range, NAP score increased to a normal level, and bcr-abl positive cells decreased markedly. He has remained in hematological and cytogenetic remission for 20 months, and bcr-abl chimeric mRNA remained undetectable by PCR. These results suggest that CML which does not respond to DLT may be cured by subsequent IFN-α therapy, possibly by inducing anti-leukemia immune responses.

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An 80-year-old woman was admitted with anemia, jaundice and a bleeding tendency about 5 weeks after starting omeprazole. On admission, the hemoglobin was 6.4 g/dl, platelets 0.1×10⁴/μl, leukocyte count 7,500/μl, and reticulocyte count 325‰. The total bilirubin was 1.9 mg/dl, indirect bilirubin 0.6 mg/dl, lactate dehydrogenase 572 IU/l, and haptoglobin<10 mg/dl. Both the direct and the indirect Coombs' tests were positive. The platelet-associated IgG (PAIgG) was 1,100.0 ng/10⁷ cells. A decrease in the complement value was observed. There was an increase in the number of megakaryocytes and erythroblasts in the marrow film. Afrer omeprazole administration was halted, her hemoglobin and platelet levels gradually returned to normal. On the 27th hospital day, the direct Coombs' test was positive but the indirect Coombs' test became negative. The PAIgG value also returned to normal, and she was discharged on the 59th hospital day. The acute phase of the drug-induced lymphocyte stimulation test was negative, however, we detected the IgG antibody to omeprazole. In the recovery phase, the IgG value decreased. Forty days after discharge, the direct Coombs' test had become negative. This is apparently the first report of a patient with acute hemolytic anemia and thrombocytopenia due to omeprazole through an immune complex mechanism.

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A 34-year-old woman was admitted to our hospital because of pancytopenia. She had been given a diagnosis of idiopathic thrombocytopenic purpura during her first pregnancy about 7 years earlier. The patient received a diagnosis of severe aplastic anemia (AA) and was treated with methylprednisolone, cyclosporin A, and granulocyte colony-stimulating factor (G-CSF), but no hematological improvement was observed. Six months later, myeloblasts appeared in the patient's peripheral blood, and she was given a diagnosis of acute myelocytic leukemia AML (FAB:M2). No chromosomal abnormalities were found. As some dyshematopoietic features had been observed in the bone marrow when the patient was first given a diagnosis of AA, it is conceivable that she already had hypoplastic myelodysplastic syndrome (MDS) then. She was treated according to the JALSG-AML92 protocol and achieved complete remission (CR). In this case, the long-term administration of G-CSF may have played an important role in the transformation of MDS into AML. It may be difficult to strictly distinguish AA from hypoplastic MDS with slight dysplastic features, as in this case, because we have no established criteria. Recently the incidence of MDS/AML in AA patients undergoing G-CSF treatment has become a concern. We should be careful about ruling out hypoplastic MDS when diagnosing a condition as AA, especially when therapy includes G-CSF. The patient is still in CR 26 months after intensive combination chemotherapy.

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We report on a case of adenovirus hemorrhagi cystitis that developed in a 49-year-old woman during intensive chemotherapy for adult T-cell leukemia. Although rapid etiologic diagnosis is essential for the effective managment of viral hemorrhagic cystitis, the isolation of adenovirus from urine is often too time-cousuming. We detected the adenovirus antigen in the patient's urine using an Adenoclone direct sandwich ELISA kit (Cambridge Bio Science), which is commonly employed for the diagnosis of adenovirus conjunctivitis. Treatment consisted of intravenous vidarabine and bladder irrigation, which resulted in prompt clinical improvement. The Adenoclone kit was useful for the rapid etiologic diagnosis of adenovirus hemmorrhagic cystitis.

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An 80-year-old woman was referred to our hospital because of irregular genital bleeding. An abnormal mass was found in the uterine cervix, and diagnosed as non-Hodgkin's lymphoma, diffuse large B cell type. Soon after admission, the patient became anuric and was given a diagnosis of acute renal failure due to obstruction of the ureter. She was immediately placed on dose-reduced CHOP and radiotherapy of 15 Gy. As a result, not only did the malignant lymphoma go into remission, but diminished renal function was alleviated. Because malignant lymphoma of the uterus is extremely rare, its exact biocharacteristics are not well understood. We are unaware of any previous report concerning uterine lymphoma complicated by renal failure.

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A 53-year-old female case of cytogenetically relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation (BMT) who achieved remission by withdrawal of immunosuppressant is reported. On day 690 of this presentation she is well and alive with performance status of 100%. She had episodes of cyclic oscillation of her neutrophil count during hydroxyurea therapy lasting 1 year before transplantation. Increase of the neutrophils at the time of BMT might have contributed to her early relapse on day 207. Withdrawal of immunosuppressant was successful at least in this case.

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