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Biomedical subjects

M Ichimaru

Publications and source records attributed to M Ichimaru.

At least 73 records · Page 4Linked to original sources

[Significance of the chromosomal findings in acute myeloid leukemia with maturation (M2)].

Chromosomal banding studies were performed on 13 patients with acute myeloid leukemia with maturation (M 2). Six patients revealed t (8;21) (q22;q22), five normal karyotype, and the remaining two +8 and inv (16) (p13 q22), respectively. Apparent pseudo-Pelger-Huët anomalies in mature neutrophils were observed in all the 6 patients with t (8;21), but in only one of the 5 patients with normal karyotype. Neutrophil alkaline phosphatase (NAP) score decreased in all but one in the former group while it increased in all the patients in the latter group. The former group had a median follow-up of 20.8 months or more, whereas the latter group had a median survival of 4.4 months or more. Accordingly, it was suggested that two major chromosome subgroups may be present among patients diagnosed as having M 2: one subgroup with t (8;21) and the other with normal karyotype. One patient with M 2 and inv (16) showed almost the same hematologic features as those observed in patients with acute myelomonocytic leukemia (M 4) and inv (16) except for a small population (6.8%) of monocytoid cells in the bone marrow.

Adolescent↗

[Difference of antibody profile for human T-lymphotropic virus type-I (HTLV-I) among individuals].

Healthy carriers, patients with ATL and HTLV-I associated myelopathy (HAM) were examined for HTLV-I antibodies of IgG and IgM classes and anti-p 40x antibodies, using ELISA, western blot (WB) and particle agglutination (PA) techniques. IgG antibodies were almost always detectable in sera from all of patients with ATL and HAM and healthy carriers with high titer in the PA test (normal carriers), and the average value of OD 405 was 2.0 +/- 0.3, 1.6 +/- 0.6 and 1.3 +/- 0.7, respectively. In anti-p 40x antibodies, the detectable incidence of HAM, ATL, normal carriers and carriers with low titer of the PA (low-PA group) was 90%, 67%, 44%, and 3%; and, the average value of OD 405 of the antibodies was 2.3 +/- 1.0, 0.7 +/- 0.5, and 0.7 +/- 0.7, respectively. On the other hand, the incidence of IgM antibodies demonstrated in HAM, ATL, normal carriers and low-PA group was 90%, 41%, 33%, and 53%, respectively. Furthermore, the follow-up observation of these antibodies revealed that the antibody profile of individuals for a long time was constant, i.e. in each carrier the value with high OD remained high and the presence of anti-p 40x and/or IgM antibodies remained present. These data has demonstrated that there are considerably differences among individuals in responsivilities for HTLV-I. Then, the antibody profile is mainly classified into 3 groups; hyper-, common- and hypo-immune patterns.

Aged↗

Two major subgroups of human T-cell leukemia virus-1 in Japan.

T lymphocytes of patients with human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy (HAM) were cultured. After cultivating for several months, HAM-derived cell lines were tested for the presence of HTLV-1 proviral genome. We have found two major subgroups, the SacI type and the PstI type, of HTLV-1 by the restriction map analysis. They were almost equally distributed among HAM patients. We have also found two types of the provirus in DNA derived from fresh peripheral blood lymphocytes (PBL) or lymph node cells of adult T-cell leukemia/lymphoma (ATL) patients. The PstI type proviruses were predominant in ATL patients. It was concluded that two major subgroups of HTLV-1 exist in Japan and both types have an ability to cause either of two diseases, ATL or HAM.

Cell Line↗

Chromosomes and surface markers in lymph node cells from 2 patients with AILD and IBL-like T-cell lymphoma.

Chromosomes and surface markers in lymph node cells from 2 patients with angioimmunoblastic lymphadenopathy associated with dysproteinemia (AILD) or immunoblastic lymphadenopathy (IBL) and with IBL-like T-cell lymphoma, respectively, were examined before treatment. In the patient with AILD, a small clone with chromosome abnormality was found in lymph node cells although a surface marker study failed to demonstrate monoclonality. In this patient, the clinical and cytogenetic findings suggested a subtype of lymphoma with a mild clinical course and a benign histological appearance. In the patient with IBL-like T-cell lymphoma, a high percentage of metaphases showed chromosome abnormalities such as ring chromosomes. The clinical, immunological and cytogenetic findings suggested an aggressive type of lymphoma, even though the histologic appearance was similar to that of IBL.

Adult↗

Chemotherapeutic results and prognostic factors of patients with advanced non-Hodgkin's lymphoma treated with VEPA or VEPA-M.

One hundred sixty-three patients with advanced non-Hodgkin's lymphoma including adult T cell leukemia/lymphoma (ATL) were treated from 1981 to 1983 with VEPA (vincristine, cyclophosphamide, prednisolone, and doxorubicin) or VEPA-M (VEPA plus methotrexate) in randomized fashion after stratification by surface marker. The complete response (CR) rate and the 4-year survival rate of patients treated with VEPA-M was 62.2% and 36.9%, respectively, while for those treated with VEPA the rates were 51.9% and 26.6, respectively. The difference was not statistically significant, but pretreatment characteristics predictive for response and survival were interesting. Three factors, leukemic change, poor performance status (PS), and T cell marker, were negatively associated with both CR and survival rates, and high-grade pathology was adversely associated with survival rate in a multivariate analysis. These prognostic factors are somewhat different from those in Western lymphomas. This may be reflection of major differences in patients' characteristics between Japanese and Western lymphomas: in this study, there was a high incidence of T cell lymphoma/leukemia (50%) including ATL (33%), leukemic manifestation (34%), poor PS (34%), and a low incidence of follicular lymphoma (9%). The statistically significant three factors for both CR and survival rates were used to construct a model containing eight categories of patients at increasing risk for poor response and shortened survival. These categories were divided into four groups, with respective CR and 4-year survival rates of 91% and 73%, 67% and 35%, 27% and 7%, and 10% and 5%. Ninety-three patients in whom CR was induced by VEPA or VEPA-M therapy were evaluated for prognostic factors predictive for disease-free survival. A shorter period (less than 28 days) required to achieve CR, a clinical diagnosis of ATL, and a lower hemoglobin level were found to affect disease-free survival adversely. These results have important implications for both the design of prospective randomized therapeutic trials and the determination of optimal therapy for individual patients.

Antineoplastic Combined Chemotherapy Protocols↗

Major prognostic factors of adult patients with advanced T-cell lymphoma/leukemia.

Eighty-one adult patients with advanced T-cell lymphoma/leukemia including 54 with adult T-cell leukemia/lymphoma (ATL), who were treated between 1981 and 1983 with vincristine, cyclophosphamide, prednisolone, and doxorubicin (VEPA) or VEPA plus methotrexate (VEPA-M) in randomized fashion, were evaluated for pretreatment characteristics. The overall complete response (CR) and the 4-year survival rates were 39.5% and 19.4%, respectively, and 69% of 32 CR patients had relapses, indicating the need for development of new effective regimens for the disease. In a multiple logistic regression analysis, only three factors, leukemic manifestation, poor performance status (PS), and a high lactate dehydrogenase (LDH) level, were significantly associated with the poor response rate. In a Cox proportional hazards model analysis, shortened survival was again significantly associated with poor PS and a high LDH level, but not with a clinical diagnosis of ATL. The two factors, PS and LDH level, that were found to be significantly associated with both CR and survival rates, were used to construct a model containing six categories of patients at increasing risk for poor response and shortened survival. These categories divided the patients into three groups with respective CR and 4-year survival rates of 75% and 53% for low-risk, 45% and 15% for moderate-risk, and 15% and 0% for high-risk. The results indicate that PS and LDH levels were the most important in predicting the response and survival of an adult patient with advanced T-cell lymphoma/leukemia. The prognosis of patients with usual peripheral T-cell lymphoma, excluding ATL, was comparable with that of advanced B-cell lymphoma. These results have important implications for the design of new prospective therapeutic trials.

Antineoplastic Combined Chemotherapy Protocols↗

Reclassification of leukemia among A-bomb survivors in Nagasaki using French-American-British (FAB) classification for acute leukemia.

The concordance rate for diagnoses of atomic bomb-related cases of leukemia in Nagasaki was determined using the French-American-British (FAB) classification for acute leukemias and myelodysplastic syndromes (MDS). Two Radiation Effects Research Foundation (RERF) hematologists and one of the members (JMB) of the FAB cooperative group reviewed independently the peripheral blood and/or bone marrow smears from 193 people with leukemia or a related disorder. There was 85% agreement in the identification of types and subtypes of acute leukemia. There was almost complete agreement for the diagnoses of non-FAB disorders (chronic myeloid leukemia (CML), adult T-cell leukemia (ATL) and others) resulting in overall concordance of 88.2%. The present study suggests that the previously established leukemia types for about a quarter of the cases of acute leukemia and related disorders except CML should be changed. Considerable numbers of cases of ATL and MDS were involved in this series. The frequency of the former disease was not high in the high-dose irradiated group, but that of the latter was considerably high. All subtypes of AML except M3 and M6 were present in the high-dose group. The striking difference in CML incidence between Nagasaki and Hiroshima may continue to be a problem in relation to biological response to radiation exposure.

Acute Disease↗

[Clinical study on the effect of natural alpha-interferon (HLBI) in the treatment of adult T-cell leukemia].

The phase II trial of natural interferon-alpha (HLBI) in treatment of adult T-cell leukemia was carried out as a cooperative study. Of the 24 cases which could be evaluated, 3 cases in crisis type and 5 cases in chronic type with lymphadenopathy and/or skin infiltration achieved PR, giving a response rate of 33.3%. The anti-tumor effect of HLBI for skin lesion could be assessed in 16 cases with skin infiltration, giving a response rate of 50.0% (5 CR and 3 PR) and demonstrating a high efficacy. Of the 31 eligible patients, side effects were recognised in 27 (87.1%). Major subjective and objective symptoms were fever (38.7%), fatigue (25.8%), anorexia (12.9%) and nausea (12.9%), and leukopenia (22.6%), granulocytopenia (38.7%), thrombocytopenia (38.7), elevation of GPT (12.9%) and GOT (12.9%) were observed.

Adult↗

Growth and differentiation of circulating hemopoietic stem cells with atomic bomb irradiation-induced chromosome abnormalities.

The effects of atomic bomb irradiation on hemopoietic stem cells were studied cytogenetically using single colonies derived from hemopoietic progenitor cells. The subjects studied were 21 healthy atomic bomb survivors (10 males and 11 females) in the high dose exposure group (100+ rad) with a known high incidence (10% or more) of radiation-induced chromosome abnormalities in their peripheral blood lymphocytes (stimulated with phytohemagglutinin), and 11 nonexposed healthy controls (5 males and 6 females). Colony formation by circulating granulocyte-macrophage (GM-CFC) and erythroid (BFU-E) progenitor cells was made by the methylcellulose method using peripheral blood mononuclear cells. Chromosome specimens were prepared from single colonies by our micromethod. The total number of colonies analyzed in the exposed group was 131 for GM-CFC and 75 for BFU-E. Chromosome abnormalities were observed in 15 (11.5%) and 9 (12.0%) colonies, respectively. In the control group, the total number of colonies analyzed was 61 for GM-CFC and 41 for BFU-E. None of these colonies showed chromosome abnormalities. The difference in incidence of chromosome abnormalities was highly significant by an exact test; p = 0.003 for GM-CFC and 0.017 for BFU-E. The karyotypes of chromosome abnormalities obtained from the colonies in the exposed group were mostly translocations, but deletion and marker chromosomes were also observed. In two individuals, such karyotypic abnormalities as observed in the peripheral lymphocytes were also seen in the myeloid progenitor cells. This finding suggests that atomic bomb irradiation produced a chromosome aberration on multipotent hemopoietic stem cells common to myeloid and lymphoid lineages. These stem cells, although carrying chromosome defects, are likely to have survived for more than 30 years, continuously producing progenitor cells capable of normal-looking growth and differentiation.

Adult↗