We reported the use of recombinant factor VIII (rF VIII) On two consecutive occasions of percutaneous nephrolithotripsy (PNL) for treatment of nephro-urethrolithiasis in a patient, a Jehovah's Witness, with hemophilia A. The patient refused blood transfusions but reluctantly accepted treatment with plasma-derived factor VIII concentrates. rF VIII was administered intravenously; 50U/kg just prior to PNL followed by a total dose of 37,500U of rF VIII within a week on each PNL. Hemostasis was complete on two occasions of PNL. The inhibitor to F VIII did not develop. rF VIII is considered to be an extremely useful for management of hemostasis during invasive surgery for patients with hemophilia A who refuse transfusions for religious reasons.

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A 9-year-old girl was admitted to Mie University Hospital June 25, 1992, complaining of fever, skin rash and pallor. Physical examination revealed anemia and hepatosplenomegaly. Laboratory findings showed normocytic normochromic anemia, increased reticulocyte counts and remarkably decreased haptoglobin level. Red blood cells had no morphological abnormality. Bone marrow examination showed erythroid hyperplasia without abnormal cells. Hemoglobin electrophoresis showed an abnormal band. The amino acid structure and sequence of the abnormal hemoglobin was determined to be an unstable hemoglobin, Hb Buenos Aires [β85 (F1) Phe→Ser]. Sequence of genomic DNA and cDNA was compatible to Hb Buenos Aires. Parvovirus B19 infection was thought to have caused severe anemia due to hemolytic crisis in this patient because its IgM antibody was positive on admission. She recovered soon without any treatment and has been followed in the outpatient clinic. Her parents and brother showed no hemoglobin abnormality.

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Two patients with severe aplastic anemia received combination therapy consisting of granulocyte colony-stimulating factor (G-CSF) and erythropoietin (EPO) by subcutaneous injection. During the first 8 weeks, we administered only G-CSF, but subsequently we administered EPO with G-CSF. Administration of G-CSF caused rapid increase in neutrophil counts in each case. In the first case, a 23-year-old woman, the first sign of improvement of anemia appeared in the 12th week but 50 more weeks elapsed before improvement of platelet count. In the second case, a 59-year-old woman, marked increase of reticulocytes appeared in the 32nd week, and the RBC count become normal in the 46th week. Minor improvement of platelet count was obtained in the 40th week. After 53 weeks of treatment, we stopped administration of G-CSF and EPO, and all of peripheral blood cell counts decreased. Therefore G-CSF and EPO were given to her again, and she showed the same response as first administration. It showed that she was dependent upon G-CSF and EPO. Finally she obtained normalization of all blood cell counts. In both cases, no serious side effects were observed. Combination therapy consisting of G-CSF and EPO may be beneficial for patients with aplastic anemia.

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In December 1993, a 76-year-old Japanese male presented with general fatigue. Peripheral blood (PB) examination indicated marked leukocytosis (WBC count, 19.8×10⁴/μl; leukemic blast differential, 89.5%). Leukemic blasts were positive for CD33, and negative for lymphoid antigens, with 2% of the blasts being positive for myeloperoxidase staining. On admission, chromosome analysis of leukemic cells in PB showed 45, X, -Y, t(9;22) [12/15]/46, XY, t(9;22) [3/15]. Southern blot analysis of the DNA from PB showed a rearrangement at the M-BCR region and germline configurations of both TCRβ and IgH chain genes. The patient was diagnosed as Philadelphia-positive chronic myelogenous leukemia (CML) in blast crisis. We commenced treatment with daunorubicin (DNR; 20 mg/day×1 IV) and daily prednisolone (PSL; 60 mg/day PO). Leukemic blasts disappeared rapidly from PB, while the promyelocytes showed a transient increase, peaked 7 days after the start of therapy, and then disappeared. Myelocytes and metamyelocytes also showed transient increases. Without a period of severe myelosuppression, the patient reverted to the chronic phase of CML and karyotypic analysis of bone marrow cells showed 45, X, -Y, t(9;22) [33/35]/46, XY, [2/35]. Consolidation chemotherapy with DNR and BHAC was started, but the patient's condition deteriorated due to bacterial infection and he died of hepatic failure on March 1994. In this case, reversion to the chronic phase of CML in blast crisis may be accomplished by the cytodifferentiating effects of small-dose DNR and oral PSL to the leukemic blasts.

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We report a case of AML with diabetes insipidus (DI). A 68-year-old female was admitted to our hospital because of fever and leukocytosis. The WBC was 197,000/μl with 98% blasts positive for myeloperoxidase, CD33, CD34 and HLA-DR. While, on admission, urine volume was more than 6 liters daily. Blood vasopressin level was 0.3 μg/ml. The patient was diagnosed as having AML with DI. By chemotherapy consisting of BHAC, DNR, 6-MP and PSL and intrathecal administration of AraC, MTX and PSL, and nasal drip of DDAVP, complete remission was attained and the urine volume was reduced to normal. Finally DDAVP became unnecessary. Although the exact cause of DI cannot be ascertained, rapid increase of leukemic blasts and leukostasis in small vessels might be associated with hypothalamus-pituitary system damage. Reportedly, DI is a rare complication of leukemia and administration of DDAVP could be halted in only two patients with leukemia and DI.

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A 58-year-old woman complicated with rheumatoid arthritis (RA) was admitted to our hospital with right axillar lymphadenopathy and splenomegaly in November 1992. She was diagnosed as an anaplastic large-cell lymphoma (Ki-1 +) (stage IIIB) on the histological findings of the right axillar lymph nodes. She was treated with 11 courses of CHOP regimen between February 1992 and May 1993, and with mitoxantrone, etoposide (VP-16) and predonisolone in April 1992 and May 1993. The right axillar lymph nodes and spleen were irradiated at a dose of 36Gy in October 1992 and May 1993 respectively. In May 1993, peripheral blood showed WBC 89,000/μl with 96% myeloblasts, Hb 8.3 g/dl, and Plt 124,000/μl. Bone marrow aspirate revealed hypercellularity with 90% myeloblasts, which were positive for CD13 and HLA-DR. She was diagnosed as AML (M1). The karyotype showed normal. Southern blot analysis did not reveal the rearrangement of the MLL gene. She received the BHAC-DMP regimen and obtained complete remission. However, she relapsed during consolidation therapy, and died of cerebral bleeding. An autopsy revealed absence of a residual tumor. The mean interval from exposure to alkylating agent to the onset of secondary leukemia has been reported to be about 5 years, in contrast to a shortened interval of about 2 years for VP-16-induced leukemia. In our patient, it took only 1 year to have AML following chemotherapy for Ki-1 lymphoma. This suggests that her AML might be induced not only by treatments for RA and Ki-1 lymphoma, but also by immunological background such as RA.

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