[Blast crisis of chronic myelocytic leukemia that was difficult to differentiate from Ph+ acute lymphoblastic leukemia].

We encountered a 44-year-old woman with suspected chronic myelocytic leukemia (CML) in the acute phase that was difficult to be differentiate from Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). At disease onset, her bone marrow showed an increase in blasts that were negative for myeloperoxydase (MPO) and Positive for CD10, 19, 34, and HLA.DR. Standard type Ph was detected by chromosome analysis, and both major and minor BCR/ABL m-RNA were detected by reverse-transcriptase polymerase chain reaction (RT-PCR) methods. Neutrophil alkaliphosphatase (NAP) score was normal, and neither eosinophilia nor basophilia was observed in peripheral blood. Under a presumptive diagnosis of Ph-positive ALL (L2), the patient was given AdVP (doxorubicin, vincristine, and prednisolone) therapy followed by a regimen of LMVP (L-asparaginase, mitoxantrone, and VP), and obtained a complete remission 2 months later. At that time, FISH analyses of her bone marrow and blood cells no longer detected bone marrow Ph or BCR/ABL fusion gene. A month later, however, the leukemia relapsed with an increase in MPO-positive blasts in bone marrow, and the patient died soon thereafter. We finally concluded that her leukemia was not Ph-positive ALL, but CML in the acute phase at disease onset.

[Hemophagocytic syndrome due to miliary tuberculosis in the course of aplastic anemia].

We report a 63 year-old female with aplastic anemia (AA) who was complicated with hemophagocytic syndrome induced by systemic miliary tuberculosis. Two years before admission to our hospital, she was diagnosed as AA and had been treated with granulocyte colony-stimulating factor, erythropoietin and methenolone acetate. In May, 1996, She was transferred to our hospital because of high fever and exacervation of pancytopenia. She showed severe pancytopenia, and an increase in macrophages showing remarkable erythrophagocytosis and decrease in hemopoietic cells in the bone marrow. In initial examination, high titer of IgM antibody to herpes simplex virus type I was identified and methylprednisolone pulse therapy was started under the diagnosis of virus associated hemophagocytic syndrome. Ten days later, however, she died for intestinal hemorrhage followed by multiorgan failure. In autopsy, multiple epitheloid cell granulomas with acid-fast bacilli were found in bone marrow, lungs, liver, spleen and kidneys.

[Early establishment of bone marrow hypoplasia by antileukemic chemotherapy with concurrent rhG-CSF in a case of acute myelogenous leukemia complicated with intestinal perforation].

We report a case of 53-year-old man with acute myelogenous leukemia (M2) showing a karyotype of t(7;11) (p15;p15), del(10) (q11;q12), who was complicated with perforation of a duodenal ulcer during the antileukemic chemotherapy using behenoyl ara-C, daunorubicin, 6-mercaptopurine and prednisolone. As his bone marrow still showed high cell density and leukemic proliferation at the time of intestinal perforation, the therapeutic regimen was changed to a combination of behenoyl are-C and mitoxantrone, and daily rhG-CSF was concurrently administered for the purpose of early establishment of bone marrow hypoplasia. On the 8th day after the therapeutic regimen had been changed, his bone marrow became nearly aplastic, and complete remission was obtained on the 24th day. This case may indicate that the concurrent administration of cell-cycle specific antileukemic drugs and rhG-CSF is available for AML patients with emergent need of leukemic cell reduction.

A combination chemotherapy with low doses of cytarabine and etoposide for high risk myelodysplastic syndromes and their leukemic stage. A pilot study.

BACKGROUND: Even now, no definitely effective therapy is inducted to high risk myelodysplastic syndromes (MDS) and their leukemic stage (MDS-AML) except bone marrow transplantation. METHODS: Ten patients with high risk MDS and 6 with MDS-AML were treated with daily low doses of cytarabine (10 mg/m2/12h, infused over 2h) etoposide (50 mg/m2/day, infused over 2h). RESULTS: Fourteen of these patients were finally evaluated among whom 6 with high risk MDS and 3 with MDS-AML (64.3%) had complete remission, and 2 with high risk MDS (14.3%) achieved partial remission after this chemotherapy for 9 to 21 days. Three of 11 responders were resistant to the prior chemotherapies with single and low dose cytotoxic agents including cytarabine, etoposide, or aclarubicin. Although all of the patients who could be assessed developed severe marrow hypoplasia after chemotherapy, the nonhematologic side effects were mild enough to be tolerated. CONCLUSIONS: This combination chemotherapy must be effective and useful in high risk MDS and MDS-AML not only without prior chemotherapy but in cases which have been resistant to single and low dose oncostatic agent.

[Interleukin-3 therapy in patients with aplastic anemia refractory to prior therapies].

A therapeutic trial of interleukin-3 (IL-3) was carried out in four patients with aplastic anemia refractory to the prior therapies. Daily subcutaneous doses of 2.5, 5.0 or 7.5 micrograms/kg was given for 7 or 14 days. In a patient who had co- and immediate boost-administration of granulocyte colony-stimulating factor (G-CSF) and/or erythropoietin (Epo) and another who had sequential administration of G-CSF and Epo two weeks after IL-3, definite hematological response was obtained during the course after IL-3. In one patient, moderate to severe side effects consisting of facial edema, conjunctival bleeding, chills and fever, were observed after two days' administration of IL-3. Co- or sequential administration of other hemopoietic factor(s) may be essential in IL-3 therapy for aplastic anemia.

[Hematological stability under ubenimex monotherapy in a patient with acute myelogenous leukemia developing marrow karyotypic changes during the course].

We encountered a 71-year-old female with acute myelogenous leukemia (AML, M1), who maintained a steady hematological state for 22 months under ubenimex monotherapy. At the first medical examination in our hospital, the marrow cellularity was approximately 40% containing leukemic myeloblasts of 41.4% in the total nucleated cells, and the marrow cytogenetic study revealed 47, XX, + 8 in 13 of 20 cells analyzed. Nineteen months later, the bone marrow showed definite hypoplasia with leukemic blasts of 39.8% and chromosome finding of 46, XX, ins (10;?) (q11;?) in all cells analyzed. During the course, the patient has been doing well without transfusion of red blood cells or platelets.

[Morphological observation of a process of bone marrow hypoplastic formation in a case of aplastic anemia].

Bone marrow morphological change was consecutively analyzed form the disease onset to the formation of bone marrow aplasia in a patient with post-hepatitic aplastic anemia. In this case, the mean bone marrow cellularity and absolute numbers of erythroids and megakaryocytes were continuously higher than those in normal subjects for 3 weeks after the appearance of peripheral pancytopenia. During this stage, administration of recombinant human granulocyte colony-stimulating factor (G-CSF) improved marrow myeloid hypoplasia and peripheral neutropenia. During the period in which the marrow cellularity transformed from hyperplasia to hypoplasia, the bone marrow showed a mixture of hyper-, normo- and hypocellular portions, and the decrease in the megakaryocytes was the faster than myeloid and erythroid cells. These findings indicate that (1) ineffective hematopoiesis might be present in the early stage of the disease, (2) G-CSF responsive granulocytic precursors remained during the early stage of the disease, and (3) the marrow aplasia progressed in the manner of aplastic nest formation during the period in which the marrow cellularity declined to hypoplasia. We experienced another case of aplastic anemia showing the same progress of bone marrow findings and speculated that this might be one of the ways of the progression of bone marrow hypoplastic formation in aplastic anemia.

[Initiation of hematopoietic recovery by recombinant human granulocyte-macrophage colony-stimulating factor in a case of severe aplastic anemia induced by gold salt].

A 65-year-old female with severe aplastic anemia induced by gold salt, whose hematopoietic recovery was initiated by rhGM-CSF therapy, was reported. The patient has been given a total of 500 mg of gold-sodium thiomalate for treatment of her rheumatoid arthritis. Two months after the final administration of it, she was admitted to our hospital with complaints of palpitation and shortness of breath. The hemogulobin was 5.9 g/dl, the platelet count was 0.5 x 10(4)/microliter, and the leukocyte count was 800/microliters with 19% neutrophils. Her bone marrow showed aplasia, and both of Ham and sugar-water tests were positive. Three times of bolus-methylprednisolone treatment, with or without methenolone acetate, resulted in no definite improvement of peripheral pancytopenia and marrow aplasia. Subsequent subcutaneous rhGM-CSF, 300 micrograms daily for 28 days with oral prednisolone 5 mg and methenolone acetate 40 mg daily, initiated hematopoietic recovery of all three cell lineages in both peripheral blood and bone marrow. The same doses of prednisolone and methenolone acetate were continued after rhGM-CSF administration, and three months later peripheral cytopenia and positive Ham and sugar-water tests disappeared completely.