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K Hirashima

Publications and source records attributed to K Hirashima.

At least 19 recordsLinked to original sources
PubMed2002

Serum thymidine kinase and soluble interleukin-2 receptor predict recurrence of malignant lymphoma.

Before and after therapy, serum thymidine kinase (TK) and soluble interleukin-2 receptor (sIL-2R) were serially determined in 28 patients with malignant lymphoma (ML). In 15 patients achieving and maintaining complete remission (CR) for more than 2 years, serum TK and sIL-2R were unchanged or decreased gradually. In contrast, logarithmic linear increases of TK and sIL-2R were observed in 13 relapsed patients. The increments of the serum markers occurred more than 10 months before the relapse. A significant positive correlation between the slope of the line for TK and that for sIL-2R was noted. The doubling time for TK estimated from the slope also showed a positive correlation with that for sIL-2R. Taken together, serum TK and sIL-2R were shown to be quite sensitive and interrelated serum markers for the recurrence of ML. Slopes of logarithmic linear increase, which are proper and specific for the individual patients, are inversely correlated with the doubling time and reflect proliferation of ML. We conclude that serum TK and sIL-2R are better predictors of relapse than LDH and the international prognostic index (IPI).

Adult↗
PubMed2001

Clinical benefits of lenograstim in patients with neutropenia due to chemotherapy for multiple myeloma (MM).

The object of this study was to determine the efficacy and safety of glycosylated recombinant human granulocyte colony-stimulating factor (rHuG-CSF; lenograstim) after combination chemotherapy consisting of ranimustine, vindesine, melphalan and prednisolone (MCNU-VMP). One hundred thirty-nine consecutive patients with newly diagnosed multiple myeloma (MM) were allocated at random to a lenograstim group (n = 70) or a placebo group (n = 69). Patients were treated with two cycles of MCNU-VMP, and either lenograstim (2 microg/kg daily, s.c.) or placebo was administered from the day neutrophils decreased to less than 1.000/microl and was discontinued when neutrophils exceeded 5,000/microl. The median duration of neutropenia (neutrophils under 1,000/microl) was significantly shorter for the lenograstim group than the placebo group (2 days vs 9 days in the first cycle; 1 day vs 13 days in the second cycle). The incidence of febrile neutropenia in the first cycle was significantly lower in the lenograstim group than in the placebo group (9.2% vs 30.4%). No life-threatening infections were observed in either group. The two cycles of MCNU-VMP therapy were completed in 90.8% of the patients, and a higher average relative dose intensity (ARDI; 0.94) was achieved in the lenograstim group. The tumor response rate of the lenograstim group (57.8%) was higher than that of the placebo group (43.1%), but the difference was not statistically significant (chi2 = 2.634, df = 1, P = 0.105). Lenograstim was well tolerated, and no unexpected adverse events occurred. Lenograstim proved effective in controlling chemotherapy-induced neutropenia in MM patients under MCNU-VMP therapy.

Adjuvants, Immunologic↗
PubMed2001

Tobamovirus replicase coding region is involved in cell-to-cell movement.

Tobacco mosaic virus (TMV) encodes a 30-kDa movement protein (MP) which enables viral movement from cell to cell. It is, however, unclear whether the 126- and 183-kDa replicase proteins are involved in the cell-to-cell movement of TMV. In the course of our studies into TMV-R, a strain with a host range different from that of TMV-U1, we have obtained an interesting chimeric virus, UR-hel. The amino acid sequence differences between UR-hel and TMV-U1 are located only in the helicase-like domain of the replicase. Interestingly, UR-hel has a defect in its cell-to-cell movement. The replication of UR-hel showed a level of replication of the genome, synthesis, and accumulation of MP similar to that observed in TMV-U1-inoculated protoplasts. Such observations support the hypothesis that the replicase coding region may in some fashion be involved in cell-to-cell movement of TMV.

Genes, Viral↗
PubMed2001

[CD7(+) acute myeloid leukemia (M0) associated with a mediastinal bulky mass lesion].

A 41-year-old man visited his doctor in May 2000 because of a sore throat and high fever. His symptoms did not improve, despite administration of antibiotics and nonsteroidal anti-inflammatory drugs. Since a chest X-ray examination revealed an anterior mediastinal bulky tumor, he was referred and admitted to our hospital on June 21, 2000. The peripheral white blood cell count was 44,540/microliter with 74% myeloblasts. Bone marrow aspiration revealed a hypercellular marrow with 82% myeloblasts, which were negative for peroxidase and alpha-naphthyl butylate esterase staining. Blast cells were positive for CD7, CD13, CD33, CD34, and HLA-DR, and negative for CD56. A needle biopsy specimen of the mediastinal tumor consisted of myeloblasts. We diagnosed the patient as having CD7 (+) acute myeloid leukemia (AML) (M0) with a bulky mediastinal mass based on the surface marker analysis, although the clinical features resembled myeloid/NK precursor acute leukemia. The patient achieved a complete remission after two courses of induction therapy. We are planning an allogeneic stem cell transplantation during his first remission because of the high risk of relapse.

Adult↗
PubMed2000

Expression of functional granulocyte colony-stimulating factor receptors on human B-lymphocytic leukemia cells.

We analyzed the expression of cell surface antigens and granulocyte colony-stimulating factor (G-CSF) receptors using flow cytometry, the expression of G-CSF mRNA receptor, using reverse transcription (RT)-PCR, and tested the effect of G-CSF on leukemia colony formation. A total of 14 lymphocytic leukemia patients were examined, seven with acute lymphocytic leukemia (ALL), two with adult T-cell leukemia (ATL), two with B-chronic lymphocytic leukemia (CLL), two with chronic myelocytic leukemia in lymphoid blastic crisis (CML-LBC), and one with plasma cell leukemia (PCL). The presence of G-CSF receptors was demonstrated in 4/14 (29%) patients, two with ALL, one with CLL, and one with CML-LBC, and was associated with stimulation of leukemia clonogenic cell growth by G-CSF. In addition, all four positive leukemia cell types expressed typical B-cell antigens. Our results indicated that G-CSF receptors are expressed on some portion of B-lymphoid leukemia and that their receptors are functional as growth stimulators.

Adolescent↗
PubMed2000

Granulocyte-colony stimulating factor induced intranuclear endonuclease in murine leukemia cell line.

We have reported that murine leukemia cell line (C2M-A5) induced apoptosis by G-CSF. To clarify the mechanism, mRNA expression of apoptosis-related genes was studied. It revealed transient over-expression of c-myc, H-ras and p53 and down-expression of bcl-2. These changes were known as triggers of endonuclease induction. After 96 h culture with G-CSF, apoptosis was occurred simultaneously with endonuclease (37 kd) activation. This endonuclease induced the digestion of double-strand DNA and might be associated with caspase3. Although G-CSF accelerates cell growth and prevents apoptosis in general, it is a contradictory effect. We concluded that G-CSF induced endogenous endonuclease activity in C2M-A5.

Animals↗
PubMed1999

Fusion of TEL/ETV6 to a novel ACS2 in myelodysplastic syndrome and acute myelogenous leukemia with t(5;12)(q31;p13).

We identified a novel human long fatty acyl CoA synthetase 2 gene, ACS2, as a new ETV6 fusion partner gene in a recurrent t(5;12)(q31;p13) translocation in a patient with refractory anemia with excess blasts (RAEB) with basophilia, a patient with acute myelogenous leukemia (AML) with eosinophilia, and a patient with acute eosinophilic leukemia (AEL). ACS2 is expressed in the brain and bone marrow and is highly conserved in man and rats. The resulting ETV6/ACS2 fusion transcripts showed an out-frame fusion of exon 1 of ETV6 to exon 1 of ACS2 in the AEL case, an out-frame fusion of exon 1 of ETV6 to exon 11 of ACS2 in the AML case, and a short in-frame fusion of ETV6 exon 1 to the 3' untranslated region of ACS2 in the RAEB case. Reciprocal ACS2/ETV6 transcripts were identified in two of the cases. Fluorescence in situ hybridization (FISH) analysis with ETV6 cosmids on 12p13, and BACs and P1s on 5q31, demonstrated that the 5q31 breakpoints of the AML and AEL cases involved the 5' portion of the ACS2 gene, and that the 5q31, breakpoint of the RAEB case involved the 3' portion of the ACS2 gene. None of the resulting chimeric transcripts except for the ACS2/ETV6 transcript in the RAEB case led to a fusion protein. Disruption of the second ETV6 allele by t(12;19) was detected in the AML case by FISH analysis. These observations suggest that the disruption of ETV6 and/or ACS2 may lead to the pathogenesis of hematologic malignancies with t(5;12)(q31;p13).

Adult↗
PubMed1999

Hair dye use and occupational exposure to organic solvents as risk factors for myelodysplastic syndrome.

To investigate the relationships of personal hair dye use and environmental factors to myelodysplastic syndromes (MDS), we conducted a case-control study in Japan. A total of 111 MDS cases and 830 controls randomly selected from the residents in the same prefecture of cases using telephone directories responded to a health questionnaire. The odds ratio (OR) for ever having used hair dye was 1.99 (95% confidence interval (CI) 1.17-3.38) and there were statistically significant trends in risk with increasing duration and number of hair dye use. Occupational exposure to organic solvents was marginally associated with the risk of MDS (OR = 1.99; 95% CI 0.97-4.10).

Adult↗
PubMed1999

New system for assessing the prognosis of refractory anemia patients.

Refractory anemia (RA) is a very heterogeneous disease regarding biological and clinical features. The International Prognostic Scoring System (IPSS) was useful for assessing the prognosis in the whole group of 219 myelodysplastic syndrome (MDS) patients. However, the IPSS was not sufficient in 132 RA patients. To predict survival and freedom from acute myeloid leukemia (AML) evolution, we investigated individual prognostic factors based on the clinical parameters (age, gender, morphologic features, cytopenias and cytogenetics) of 132 RA patients using univariate and multivariate analyses. Based on the results, we devised a new system for assessing the prognosis of RA patients. In our system, RA patients with pseudo-Pelger-Huët anomalies >/=3% were classified as high risk (12 patients); of patients without pseudo-Pelger-Huët anomalies >/=3%, those with intermediate/poor karyotype according to IPSS, Hb </=6 g/dl or mMgk >/=10% were classified as intermediate risk (57 patients); and those without high or intermediate risk were classified as low risk (67 patients). In our system, the analyses of both survival times and leukemia-free survival times revealed significant differences among the three groups (P < 0.0001).

Acute Disease↗
PubMed1999

[Non-Hodgkin's lymphoma complicated by recurrent intractable generalized herpes zoster responsive to long-term acyclovir therapy].

A 34-year-old male with a history of chickenpox developed primary abdominal non-Hodgkin's lymphoma (diagnosed in August 1995). Treatment with cyclophosphamide, doxorubicin, vincristine, and prednisolone achieved a partial remission. In July 1996, the disease recurred, and the patient received chemotherapy with carboplatine, etoposide, mitoxantrone, and prednisolone, but no response was noted. Involvement of the central nervous system and meninges was diagnosed on September 12, 1997. Blast cells were detected in the peripheral blood on September 26. Based on these findings, he was diagnosed as having leukemia. On September 27, painless vesicles developed on the left gluteal region. On October 13, the patient was hospitalized because the vesicles had spread over his entire body. Pathologic examination of the roofs of the blisters showed masses of inclusion bodies. Based on this, a diagnosis of varicella-zoster infection was made. Treatment with acyclovir (750 mg/day) for seven days failed to form crusts. New vesicles developed after the drug was discontinued, but crusts formed after acyclovir therapy was resumed. He died of interstitial pneumonia on December 21. Autopsy could not be performed. Histopathologic examination of pulmonary tissue obtained by necropsy did not reveal the presence of inclusion bodies characteristic of herpes simplex or varicella-zoster infection. Varicella-zoster virus (VZV) antigen was negative by an immunochemical staining method using monoclonal antibodies against VZV. Continuous long-term administration of acyclovir has been reported to be effective for non-Hodgkin's lymphoma complicated by recurrent intractable herpes zoster.

Acyclovir↗
PubMed1999

Effect of granulocyte-colony stimulating factor on empiric therapy with flomoxef sodium and tobramycin in febrile neutropenic patients with hematological malignancies. Kan-etsu Hematological Disease and Infection Study Group.

The clinical effects of concomitant use of granulocyte-colony stimulating factor (G-CSF) on empiric antibiotic therapy in febrile neutropenic patients were evaluated in a randomized fashion. Two hundred and fourteen neutropenic febrile episodes (neutrophil counts < 1.0 x 10(9)/l) were treated with flomoxef sodium and tobramycin with or without G-CSF. The resolution of fever at day 4 (excellent response) or at day 7 (good response) was deemed effective. Among 157 evaluable episodes, the observed excellent responses were 31 (38.8%) and the good responses were 20 (25.0%) in the G-CSF group; those in the control group were 26 (33.8%) and 25 (32.5%), respectively. The overall efficacy rate was 63.8% (51/80) in the G-CSF group and 66.2% (51/77) in the control group (not significant). The initial neutrophil count was 0.186 +/- 0.249 x 10(9)/l in the G-CSF group and 0.235 +/- 0.290 x 10(9)/l in the control group, and rose to 2.889 +/- 4.198 x 10(9)/l and 0.522 +/- 0.844 x 10(9)/l, respectively, at day 7. These results indicate that G-CSF does not affect the rate of response to empiric antibiotic therapy in febrile neutropenic patients, although a significant effect of G-CSF was observed on neutrophil recovery.

Adolescent↗
PubMed1999

[Atypical chronic myeloid leukemia presenting with trilineage dysplasia and IgG (lambda) type monoclonal gammopathy].

A 78-year-old man was diagnosed as leukocytosis in February 1994. Physical examination revealed marked hepatosplenomegaly. A peripheral blood examination disclosed 95,090/microliter leukocytes without hiatus leukemicus, 6.5 g/dl Hb, and 15.0 x 10(4)/microliter platelets. The neutrophil alkaline phosphatase score was 27, and serum VB12 was above 1,600pg/ml. IgG was identified as monoclonal immunoglobulin of type lambda. Bone marrow specimens demonstrated marked granulocytic hyperplasia. Neither the Philadelphia chromosome (Ph1) nor BCR gene rearrangement was detected; hence, the diagnosis of Ph1 (-) chronic myeloid leukemia (CML) was made. The patient was treated with hydroxyurea and low-dose VP-16 with no improvement, and died of pneumonia and sepsis in June 1995. This case was considered to be consistent with atypical CML (aCML) according to the FAB classification because monocytosis was not observed. It seems likely and interesting that the coexistent monoclonal gammopathy and aCML might have arisen from common abnormal hematopoietic stem cells.

Aged↗
PubMed1998

A long term follow-up of a randomized trial comparing interferon-alpha with busulfan for chronic myelogenous leukemia. The Kouseisho Leukemia Study Group.

To evaluate the long-term effectiveness of interferon-alpha (IFN-alpha) therapy in patients with chronic myelogenous leukemia (CML) in chronic phase, we examined the updated outcomes of 159 patients who had been enrolled between 1988 and 1991 into a randomized trial comparing IFN-alpha with busulfan. At a median follow-up of 73 months, the median survival was 71 months in the IFN-alpha group and 55 months in the busulfan group (P=0.0563), and the median time of remaining in chronic phase was 58 months in the IFN-alpha group and 39 months in the busulfan group (P=0.4676). Landmark analysis showed a significant advantage in survival (P=0.009) and duration of chronic phase (P=0.0001) in patients with any cytogenetic response among the IFN-alpha group. About half patients were discontinued IFN-alpha administration in spite of cytogenetic response in this study. It appears that continuation of IFN-alpha might possibly confer a survival advantage. Pretreatment factors associated with cytogenetic response included high hemoglobin level, low percentage of peripheral basophils and low leukocyte counts. Multivariate analysis identified lower percentage of bone marrow basophilia (P=0.007) for survival advantage. If a group with a very good prognosis is predicted by a new prognostic model, it might be an option to wait for bone marrow transplantation.

Adult↗
PubMed1998

Therapy-related AML after successful chemotherapy with low dose etoposide for virus-associated hemophagocytic syndrome.

A 19-year-old male patient with virus associated hemophagocytic syndrome (VAHS) began receiving chemotherapy including etoposide (cumulative dose of 900 mg/m2 intravenously) and Ara-C (cumulative dose of 360 mg/m2 intravenously) in July 1994. He achieved complete remission, but developed acute myelomonocytic leukemia (AML, FAB M4) with t(9;11)(p22;q23) in March 1997 and a rearrangement of the MLL gene was also recognized. The MLL gene rearrangement is closely associated with secondary leukemia with an 11q23 translocation. It is highly likely that this case of AML was caused by the cytostatic treatment the patient received, including etoposide for VAHS.

Adult↗
PubMed1998

Refractory anemia with severe dysplasia: clinical significance of morphological features in refractory anemia.

Refractory anemia (RA) in myelodysplastic syndromes (MDS) are very heterogeneous diseases regarding their morphology, clinical features and survival. We proposed the new designations 'RA with severe dysplasia (RASD)' and 'RA with minimal dysplasia (RAminiD)'. In our criteria, RASD is considered present if a bone marrow (BM) examination shows Pseudo-Pelger-Huet anomalies of mature neutrophils > or =3% and/or micromegakaryocytes (mMgk) of megakaryocytes > or =10% in RA patients. RAminiD is defined as RA cases other than RASD. After the reclassification of 58 primary RA patients, the group was composed of 45 RAminiD and 13 RASD patients. The blast percentage in the BM and the frequency of cytogenetic abnormalities observed in the RASD patients were intermediate between those in the RAminiD and RAEB patients. The analysis of survival curves revealed differences among the three groups; the RASD patients had lower survival probabilities than those of the RAminiD group, and significantly higher probabilities than those of the RAEB group. (RAminiD vs RASD, P=0.06; RASD vs RAEB, P=0.004.) Our data indicate that in RA patients, RASD is a distinct subset of RA with an unfavorable clinical outcome.

Adult↗