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K Ezaki
Gan to kagaku ryoho. Cancer & chemotherapy 06/2000; 27 Suppl 2:279-84.
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ABSTRACT: We retrospectively analyzed treatments and outcomes for 83 acute myelogenous leukemia (AML) patients aged 60 years or more (median age 71) admitted to our hospital between August 1984 and January 1998. Complete remission was achieved in 36% of 78 patients who received anti-leukemic therapy, and median overall survival was 227 days. In addition to abnormal karyotypes involving chromosome 5 or 7, administration of less than 120 mg/m2/course of daunorubicin (DNR) during the initial treatment phase was an unfavorable prognostic factor for both CR and survival. Only 41% of all patients received 120 mg/m2/course of DNR or more, and had a significantly higher CR rate (56%) and longer survival, with a median of 389 days. It was suggested that intensive chemotherapy was effective for selected elderly AML patients who were relatively younger and had good performance status, although the number of such patients was limited in our study.
[Rinshō ketsueki] The Japanese journal of clinical hematology 05/2000; 41(4):303-9.
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ABSTRACT: In order to characterize clinical and biological characteristics of elderly patients with acute myelogenous leukemia (AML), we retrospectively analysed 83 elderly patients aged 60 years or more and, as a control, 114 younger patients aged 15 to 59 years who were admitted to our hospital between August 1984 and January 1998. There was a significantly higher incidence of preceding myelodysplastic syndromes in the elderly patients. They also had a significantly higher incidence of unfavorable cytogenetic abnormalities (loss or partial deletion of chromosome 5 or 7) and a significantly lower incidence of favorable cytogenetic abnormalities, such as t(15:17), t(8:21), or inv(16). With regard to FAB subtypes in de novo AML, the incidence of M3 subtype was significantly lower in the elderly group. Myeloperoxidase positivity of AML cells in the elderly group was lower than that in the younger group. Laboratory data at presentation disclosed a lower peripheral leukemic cell count, a higher fibrinogen level, a lower serum protein level, and a higher serum creatinine level in the elderly group. They also had poorer performance status and more frequent concomitant diseases at presentation, including liver diseases, heart diseases, or documented infections. It was concluded that elderly AML patients 60 years or older had a higher incidence of poor prognostic factors compared to younger patients.
[Rinshō ketsueki] The Japanese journal of clinical hematology 05/2000; 41(4):296-302.
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ABSTRACT: A 53-year-old man with severe aplastic anemia developed sporadic Vibrio vulnificus septicemia 1 day after eating raw fish and shellfish. Although V. vulnificus infection is potentially fatal, he was saved by immediate and sensitive antibiotic administration. Patients with chronic hematologic disease are susceptible to infection by this organism and are prone to developing septicemia when they eat raw seafood. It is necessary for a patient with this infection to be given effective antibiotics as quickly as possible.
International Journal of Hematology 03/1998; 67(2):175-8. · 1.27 Impact Factor
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M Tsuzuki, K Ezaki,
F Maruyama,
T Ino,
H Kojima,
M Okamoto,
T Yamaguchi,
T Nomura,
H Miyazaki,
M Wakita,
T Matsui,
M Hirano
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ABSTRACT: The response of human acute myelogenous leukemia (AML) cells to four different hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 beta (IL-1beta), interleukin-3 (IL-3), and stem cell factor (SCF)) and the relationship of the proliferative response of the AML cells to treatment outcome were studied. Proliferative responses were analyzed in 79 patients with de novo AML and 19 patients with AML arising from myelodysplastic syndrome (MDS). In de novo AML, a positive proliferative response (stimulation index >2) was seen in 65 to 75% of cases. AML cells arising from MDS had a much higher incidence of proliferative response to each growth factor (79 to 90%) and a much higher level of 3H-TdR incorporation. The relationship to treatment outcome was evaluated in 79 patients with de novo AML. The patients whose leukemic cells had a positive proliferative response to any growth factor, especially IL-3 and SCF, had a poorer outcome, ie a lower complete remission (CR) rate, shorter CR duration, and shorter survival. The outcome was particularly poor in patients whose leukemic cells had proliferative responses to all four or any of the growth factors, compared to patients whose leukemic cells had no response. This increased response may be a marker of poor prognosis in patients with AML.
Leukemia 01/1998; 11(12):2125-30. · 9.56 Impact Factor
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ABSTRACT: We report a case of severe aplastic anemia (SAA) treated with granulocyte colony-stimulating factor (G-CSF), cyclosporin A and danazole, in which myelodysplastic syndrome (MDS) with monosomy 7 developed eight months later. A 24-year-old woman was diagnosed as having SAA and was initially treated with G-CSF, cyclosporin A and danazole. At initial presentation, bone marrow aspirate revealed marked hypocellularity with a normal karyotype (46, XX [20]) and no MDS features. Eight months after initial treatment, leukocytosis and reticulocytosis were observed and bone marrow aspirate showed hypercellular marrow with morphological and cytogenetic features (45, XX, -7 [16]/46, XX [4]) characteristic of MDS (refractory anemia). A total of 75 mg (1.25 mg/kg) of G-CSF had been administered during the preceding eight months. Among seven previous reports published in Japan since 1992, in which MDS/acute myelogenous leukemia (AML) developed from SAA treated with G-CSF, six showed monosomy 7. Careful observation for leukemic transformation is therefore indicated in patients with SAA who are treated with G-CSF.
[Rinshō ketsueki] The Japanese journal of clinical hematology 10/1997; 38(9):745-51.
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ABSTRACT: Recently various cytokines have been introduced into the clinic and have played important therapeutic roles in the treatment of hematological malignancies. Among these cytokines, we have focused on interferon (IFN) and granulocyte (G) or granulocyte-macrophage (GM) colony stimulating factor (CSF), which are currently the most useful cytokines in this review. IFN-a is one of most useful and wide-ranging antitumor agents in hematological malignancies. The most striking effects have been studies in chronic phase CML. Cytogenetic responses are seen in 30-40% of the treated patients, and a complete cytogenetic response can be seen in about 10%. Long-term survival can be expected in these patients. Considering the risk of graft-versus-host disease-associated mortality in allogeneic bone marrow transplantation, the most appropriate category of treatment is difficult to determine in IFN-responsive patients. Elucidation of the antitumor mechanism of IFN, as a prototype for other biological response modifiers, may revolutionize cancer treatment. G- and GM-CSF (CSFs) have reduced the duration of neutropenia, incidence of infectious episodes and days of hospitalization following cancer chemotherapy or stem cell transplantation. CSFs have also been used to mobilize peripheral blood stem cells and to increase the dose intensity of chemotherapeutic agents. Leukemic cells from many patients with acute myelogenous leukemia (AML) have surface receptors for CSFs and may proliferate in response to CSFs. However, several randomized studies showed that CSFs can be used safely and effectively in augmenting neutrophil recovery in patients with AML when given after induction chemotherapy. Various trials have been conducted to sensitize leukemic cells by CSFs, making them more susceptible to chemotherapy; but no convincing evidence has been obtained.
Gan to kagaku ryoho. Cancer & chemotherapy 06/1997; 24 Suppl 1:182-94.
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T Ino,
T Yamaguchi,
M Tsuzuki,
T Nomura,
H Miyazaki,
F Maruyama,
H Kojima,
M Okamoto,
T Matsui, K Ezaki,
M Hirano
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ABSTRACT: Thirty-two adults (median age 48 years) with acute myelogenous leukemia (excluding M3) have been treated with short-term intensive therapy (M90 therapy). After induction therapy with daunorubicin, cytosine arabinoside (araC), 6-mercaptopurine, prednisolone, mitoxantrone (MIT) and etoposide (VP16), three regimens of post-induction chemotherapy were conducted as short an intercycle time as possible. The first regimen was with MIT and VP16, the second with behenoyl-araC and aclarubicin and the third with VP16, araC, vincristine and vinblastine. No further therapy was given. Complete remission was achieved in 24 (75%) of 32 patients and 24% of all patients were projected to remain free of disease at 5 years. The median duration of the entire therapy was 120 days with a range of 95 to 157 days. Post-induction regimens resulted in severe myelosuppression and their toxicity included treatment-related death in one patient. The treatment results of this short-term therapy were comparable to a former treatment protocol, M84 therapy with a median duration of the entire treatment therapy of 515 days. To confirm the advantages of such short-term therapy, prospective randomized comparisons with conventional post-induction therapy may be required.
[Rinshō ketsueki] The Japanese journal of clinical hematology 04/1997; 38(3):209-16.
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K Ezaki
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ABSTRACT: Recently various cytokines have been introduced into the clinic and have played important therapeutic roles in the treatment of hematological malignancies. Among these cytokines, I have focused on interferon (IFN) and granulocyte (G) or granulocyte-macrophage (GM) colony stimulating factor (CSF), which are currently the most useful cytokines, in this review. IFN-alpha has been approved for chronic myelogenous leukemia (CML), multiple myeloma and hairy cell leukemia. In addition, IFN-alpha has therapeutic potentials for low grade non-Hodgkin's lymphoma, cutaneous T cell lymphoma and adult T cell leukemia/lymphoma. Thus, IFN-alpha is one of the most useful and wide-ranging antitumor agents in hematological malignancies. Most striking effects have been studied in chronic phase CML. Cytogenetic responses are seen in 30-40% of the treated patients and a complete cytogenetic response can be seen in about 10%. Long-term survival can be expected in these patients. Considering the risk of graft-versus-host disease-associated mortality in allogeneic bone marrow transplantation, the category of treatment is difficult to choose in IFN-responsive patients. Elucidation of the antitumor mechanism of IFN, as a prototype for other biological response modifiers, may revolutionize cancer treatment. G- and GM-CSF (CSFs) have reduced the duration of neutropenia, incidence of infectious episodes and days of hospitalization following cancer chemotherapy or stem cell transplantation. CSFs have also been used to mobilize peripheral blood stem cells and to increase dose intensity of chemotherapeutic agents. Leukemic cells from many patients with acute myelogenous leukemia (AML) have surface receptors for CSFs and may proliferate in response to CSFs. However, several randomized studies showed that CSFs can be used safely and effectively in augmenting neutrophil recovery in patients with AML when given after induction chemotherapy. Various trials have been made to prime leukemic cells by CSFs to make them more susceptible to chemotherapy, but no convincing evidence has been obtained.
International Journal of Hematology 01/1997; 65(1):17-29. · 1.27 Impact Factor
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ABSTRACT: A 53-year-old woman was admitted to our hospital in April 1995, because of nasal obstruction, bloody rhinorrhea and hearing disturbance. She had no lymphadenopathy or skin eruptions. Laboratory examinations revealed a WBC count of 2.7 x 10(9)/L without abnormal cells, positive serum anti-HTLV-I antibody, normal lactate dehydrogenase and normal calcium level. MRI showed an epipharyngeal mass. No involvement was detected by CT scanning of the chest and abdomen, 67Ga scintigraphy and bone marrow biopsy. The pathological diagnosis of the biopsied specimen from the epipharyngeal mass was T-cell diffuse lymphoma, pleomorphic type. Monoclonal integration of HTLV-I proviral DNA was detected in lymphoma cells, which confirmed a diagnosis of extranodal adult T-cell leukemia lymphoma primarily involving the epipharynx. She was treated with CAMBO-VIP regimen followed by adjuvant involved-field radiotherapy and she continues to be in complete remission as of April 1996.
[Rinshō ketsueki] The Japanese journal of clinical hematology 12/1996; 37(11):1331-3.
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ABSTRACT: A 51-year-old man with non-Hodgkin's lymphoma in his third remission received autologous PBSCT. He had had a couple of flat warts on his right hand since admission, which showed no progression during conventional dose chemotherapy. On day 15 of PBSCT, however, the warts began to develop and spread to his forehead, face, neck and arms over several days. The diagnosis of flat warts was made and human papilloma virus type 3 was detected by PCR analysis. Severe immunosuppression associated with PBSCT may have caused this rapid and disseminated growth of flat warts.
Bone Marrow Transplantation 12/1996; 18(5):1009-11. · 3.75 Impact Factor
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T Ino,
M Hirano,
H Kojima,
M Tsuzuki,
T Yamaguchi,
T Nomura,
H Miyazaki,
M Wakita,
F Maruyama,
M Okamoto,
T Matsui, K Ezaki
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ABSTRACT: In order to analyse the clinical characteristics and outcome in acute myelogenous leukemia, 129 consecutive adult patients admitted to our hospital over a 10-year period, from August 1984 to July 1994, were studied. Their median age was 51 years, 17 (13.2%) of them had antecedent myelodysplastic syndrome (MDS) and 9 (7.0%) had secondary leukemia. Seventy-eight patients (60.5%) were considered eligible for cure-oriented intensive chemotherapy. Forty-four patients were ineligible of one or more of the following; age over 70, antecedent MDS or secondary leukemia. Additional 7 patients were excluded due to concurrent severe diseases. The median survival of the 129 patients was 441 days with an actuarial 5-year survival of 28.6 +/- 4.4%, and the disease-free survival (DFS) decreased with the increasing age of the patient. In 78 patients who were eligible for intensive chemotherapy, complete remission was achieved in 84.6% and overall DFS was 41.1 +/- 5.9% at 5 years, and their survival was longer than that of ineligible patients. It was suggested that considerable selection of patients, for example, due to old age, already existed before visiting our hospital. Analysis of clinical data of unselected patients might enable the development of a rational approach to the management of elderly patients.
[Rinshō ketsueki] The Japanese journal of clinical hematology 10/1996; 37(9):817-24.
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M Wakita,
T Matsui,
M Tsuzuki,
T Nomura,
H Miyazaki,
H Kojima,
F Maruyama,
M Okamoto,
T Ino, K Ezaki,
T Sugihara,
A Kanzaki,
Y Yawata,
M Hirano
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ABSTRACT: Five cases of hereditary high red cell membrane phosphatidylcholine hemolytic anemia in three families were described. All cases were clinically manifested by jaundice and splenomegaly. Hemolysis was evident from indirect hyperbilrubinemia, reticulocytosis and decrement of serum haptoglobin. Red blood cells showed morphological abnormalities such as poikylocytosis, anisocytosis and target cells on blood smears. Both direct and indirect Coombs' tests were negative. Ham test, sugar water test and hemoglobin electrophoresis showed no abnormalities. Osmotic fragility test showed decreased membrane fragility. Lipid analysis of red cell membrane showed increment of phosphatidylcholine content and decrement of sphingomyelin content, although plasma lipids were essentially normal. Influx and efflux of sodium through the red cell membrane were both increased. Splenectomy was performed without effect on one patient and the mother of other patients.
[Rinshō ketsueki] The Japanese journal of clinical hematology 04/1996; 37(3):265-70.
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ABSTRACT: A 44 year-old woman with acute myeloid leukemia (AML, FAB, M4E) developed heart failure during treatment with anthracyclines for AML. She had not experienced heart disease and her left ventricular ejection fraction (LVEF) was 59% at the end of a successful remission induction therapy. Because her LVEF decreased to 33% after early consolidation therapy, the chemotherapy for AML was discontinued. The cumulative dose of daunorubicin, aclarubicin and mitoxantrone was 486 mg/m2, 135 mg/m2 and 55 mg/m2, respectively. In October 1990, four months after the end of the chemotherapy, heart failure (class III, NYHA) developed and did not improve by treatment consisting of dobutamin, digoxin and diuretics. Anthracycline cardiomyopathy was histologically confirmed by endomyocardial biopsy. Then we administered selective beta 1-antagonist, metoprolol (Seloken), with an initial dose of 5 mg/day which was doubled 3 times every 4 or 8 weeks to 40 mg/day, according to the treatment schedule of dilated cardiomyopathy. She recuperated satisfactorily (Class I, NYHA), and was discharged on February '91. Her LVEF gradually improved and it has been maintained at above 50% on an outpatient basis. The patient has been in complete hematological remission during this period. It seems that low dose selective beta 1-antagonist therapy has a potential to improve myocardial function in some patients with anthracycline cardiomyopathy.
[Rinshō ketsueki] The Japanese journal of clinical hematology 12/1995; 36(11):1305-10.
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ABSTRACT: A 41-year-old woman with follicular lymphoma developed sporadic respiratory syncytial virus (RSV) pneumonia shortly after allogeneic bone marrow transplantation from an HLA-matched sibling. RSV pneumonia is potentially fatal in immunosuppressed patients, but she improved along with the recovery of bone marrow function without specific treatment. Early recovery of myelosuppression supported by granulocyte colony-stimulating factor may have helped to control RSV pneumonia.
International Journal of Hematology 11/1995; 62(3):189-92. · 1.27 Impact Factor
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ABSTRACT: A 49-year-old man with myelodysplastic syndrome (MDS, RAEB in T) who relapsed following allogeneic bone marrow transplantation (allo BMT) was treated with infusions of donor buffy coat leukocytes. He sustained hematologic and cytogenetic remission, but severe graft-versus-host disease (GVHD) developed for which cyclosporin A and prednisolone were required. This therapeutic approach appears to be valuable for relapsed MDS following allo BMT as well as for chronic myelogenous leukemia (CML).
Bone Marrow Transplantation 10/1995; 16(3):487-9. · 3.75 Impact Factor
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Gan to kagaku ryoho. Cancer & chemotherapy 03/1995; 22(2):297-300.
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ABSTRACT: We evaluated the in vitro proliferative response to exogenous IL-1 beta in terms of tritiated thymidine (3H-TdR) incorporation in leukemic cells obtained from 119 patients with various types of acute leukemia. The content of IL-1 beta in leukemic cells was measured by enzyme-amplified sensitivity immunoassay. We observed a significant proliferative response to exogenous IL-1 beta in leukemic cells from 27/66 patients with de novo AML, 1/29 patients with ALL, 2/3 patients with AUL, 8/12 patients with AML arising from MDS, 4/7 patients with myeloid crisis of CML, and 0/4 patients with lymphoid crisis of CML. Proliferation was marked in myeloid leukemic cells of a more premature stem cell origin. There were no significant differences in proliferative responses among the different FAB classes of de novo AML. The IL-1 beta content of leukemic cells was low in patients with lymphoid leukemia, but there was no significant difference among the various types of myeloid leukemia. There was no correlation between the proliferative response to exogenous IL-1 beta and the IL-1 beta content of leukemic cells. When we correlated the proliferative response to exogenous IL-1 beta with treatment outcome in patients with de novo AML, we found the rate of complete remission (CR) to be lower in those with a high proliferative response. We noted a longer duration of CR (p = 0.07) and of survival (p < 0.05) in patients with a low proliferative response. Thus, a high proliferative response to IL-1 beta in the cells of AML patients may indicate a poor prognosis.
Leukemia Research 01/1995; 19(1):35-41. · 2.92 Impact Factor
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ABSTRACT: We investigated the expression of P-glycoprotein (P-gp) in 52 adults with de novo acute myelogenous leukemia (AML) at the initial diagnosis. We tested 52 patients by flow cytometry using the MRK16 monoclonal antibody (MoAb). To investigate the phenotype for multidrug resistance, 41 of the patients were analyzed using rhodamine 123 (Rh123). We found that 14 (27%) of the 52 patients were positive for P-gp expression by MRK16 MoAb using a cutoff of 5% positive cells. There was a significant correlation between the results of the two analyses (p < 0.01). We suggest that flow cytometry using MRK16 MoAb is acceptable for use in detecting P-gp expression in clinical samples. Among the 52 patients, 43 (83%) obtained a complete remission (CR) and 45% of remitters were predicted to be alive and in a CR after 8 years. Although the rate of CR on the MRK16-positive patients was comparable to that of the MRK16-negative patients, the MRK16-positive patients were prone to relapse. We conclude that determination of P-gp expression of de novo AML at initial presentation did not significantly influence the outcome of treatment.
Leukemia 10/1994; 8(9):1492-7. · 9.56 Impact Factor
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ABSTRACT: We present a case of severe rhabdomyolysis developing after peripheral blood stem cell transplantation (PBSCT) in a 17-year-old woman with Ki-1 lymphoma. Severe muscle weakness, myoglobinemia and acute renal failure developed on day 23 following PBSCT associated with painful peripheral neuropathy. Cytomegalovirus infection may have been a contributory factor.
Bone Marrow Transplantation 10/1994; 14(3):481-2. · 3.75 Impact Factor
