Shigeru Oguma

Clinical characteristics of Japanese patients with primary myelodysplastic syndromes: A co-operative study based on 838 cases

The characteristics of Japanese (JPN) patients with myelodysplastic syndromes (MDS) were investigated in 838 retrospectively collected cases. The median age of the JPN patients was 60 years, about 10 years younger than that in most of the reports based on Western patients. Median survivals were 65 months for refractory anemia (RA), 58 months for RA with ring sideroblasts (RARS), 16 months for RA with an excess of blasts (RAEB), 10 months for RAEB in transformation (RAEBT), and 20 months for chronic myelomonocytic leukemia (CMML). Cumulative leukemia-free rates at final observation were 73% for RA, 79% for RARS, 24% for RAEB, 20% for RAEBT, and 53% for CMML. When low-risk (RA and RARS) patients were divided into two groups, those 40 years of age and older, and those under 40, the cumulative leukemia-free rate was 94% for the younger patients (n = 101), compared with 66% for the older patients (n = 318). The prognostic factors for survival were different from those in Western reports, i.e., variables representing quantitative abnormalities (hemoglobin levels, granulocyte, and platelet counts) were not major prognostic factors, while variables representing qualitative abnormalities (morphological abnormalities in granulocytic and megakaryocytic series cells) were highly significant. Two scoring systems for overall survival and for leukemic transformation were developed, based on multivariate prognostic factor analysis. Neither system included variables representing the degree of cytopenia. Whatever the reason for the different prognostic factors in JPN and Western MDS patients, the use of a scoring system based on Western patients for clinical decision-making in a JPN patient could be misleading, and vice versa.

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).

Randomized controlled study of chemoimmunotherapy of acute myelogenous leukemia (AML) in adults with Nocardia Rubra cell‐wall skeleton and irradiated allogeneic AML cells

The effect of immunotherapy with Nocardia rubra cell‐wall skeleton (N‐CWS) on remission duration and survival of adults with acute myelogenous leukemia (AML) was studied in a prospective randomized controlled study. After having been induced into complete remission and having been consolidated, 73 patients were randomized either to maintenance chemotherapy or maintenance chemotherapy plus immunotherapy with N‐CWS and irradiated allogeneic AML cells. Thirty‐four patients in the chemotherapy group and 32 in the chemoimmunotherapy group were evaluable. Six months after the closure of the study, the immunotherapy showed a borderline beneficial effect on remission duration (P = 0.080) and on survival length (P = 0.098). When the data were analyzed at 30 months after the entry, there was a borderline significant difference in remission duration (P = 0.080) between the two groups, prolonging the 50% remission period by 110 days; but no significant difference in survival length (P = 0.314), although the 50% survival was 168 days longer in the chemoimmunotherapy group. However, there were 4 (18.2%) 5‐year relapse‐free survivors among 22 patients (11 in each group) who had been diagnosed more than 5 years before the time of the present analysis, and all of them belonged to the chemoimmunotherapy group (P = 0.090). Thus, immunotherapy with N‐CWS and irradiated allogeneic AML cells seems to be active in the treatment of adult AML when used for maintenance therapy in combination with chemotherapy. Cancer 57:1483–1488, 1986.

Factors influencing survival in philadelphia chromosome positive chronic myelocytic leukemia

The prognostic value of several clinical and hematologic features, recorded at diagnosis, in chronic phase Ph1 positive chronic myelocytic leukemia (CML), was analyzed in 135 patients using life‐table analysis. About one third of patients were atomic bomb survivors and they had been examined twice a year before the diagnosis of CML. In general, features representing tumor cell burden, i.e., leukocyte count, spleen sizes, and absolute differential cell counts of all granulocyte series cells except myeloblasts affected survival significantly, while sex, age, hemoglobin, platelets, and features representing quality of leukemia, i.e., neutrophil alkaline phosphatase score, percent Ph1 positive cells in bone marrow, and percent differentials of all granulocyte series cells except promyelocytes and segmented neutrophils were all insignificant. Multivariate life‐table analysis was also performed using age, sex, hemoglobin, platelets, and leukocyte count as predictor variables. The result was that leukocyte was the single most important factor in this analysis and annual death rates between low risk (risk ratio < 0.8) and high risk (risk ratio > 1.4) differed considerably up to four years from diagnosis, indicating our formula to calculate risk ratio is valid as a grading parameter of chronic phase Ph1 positive CML within four years from diagnosis.

Stable human T-lymphotropic virus type I carrier rates for 7 years among a teenaged blood donor cohort of 1986 in Kumamoto, Japan

The human T-lymphotropic virus type I (HTLV-I) carrier rates for blood donors in Kumamoto, Kyushu, Japan for 8 years, 1986-1993, are currently available. The data show that 16-19-year-olds in 1986 and 20-29-year-olds in 1993 represent nearly the same cohort, because the median age in both groups is 24.5 years in 1993. Therefore, comparison of the HTLV-I positive rate for the two groups gives an estimate of the change in the rate over 7 years within the cohort. In males, 265 of 22,143 donors (1.20%) were seropositive for HTLV-I among 16-19-year-olds in 1986, and 214 were seropositive among 20,076 (1.07%) donors in 20-29-year-olds in 1993. In females, 203 were seropositive among 20,677 (0.98%) donors in 16-19-year-olds in 1986, and there 154 were seropositive among 18,660 (0.83%) donors in 20-29-year-olds in 1993. Thus, the seropositive rates declined in both sexes. However, the average annual rate of immigration to Kumamoto Prefecture was 2.37%. If seropositive rates for 20-29-year-olds in 1993 are adjusted for the dilution effect due to immigration (under the assumption that all immigrants were HTLV-I negative), the adjusted carrier rate for males is 1.26% and that for females is 0.98%. The adjusted carrier rates for both sexes are almost the same as those for 16-19-year-olds in 1986. This indicates that horizontal transmission was negligible for those in the cohort who were in their early reproductive period. Using all 8 year carrier rates for 16-19-year-olds and 20-29-year-olds, chronological changes of 20-29-year-olds, in the near future was estimated. The best goodness of fit model indicated that the HTLV-I carrier rate will decline exponentially, and that the rate will decrease by 50% approximately every 10 years for both sexes. It is probable that in recent years south-west Japan has lost the conditions that are favorable for HTLV-I endemicity and the virus will be virtually non-endemic within a few generations.

Clinical features of long-term survivors of refractory myelodysplastic anemias. A Japanese cooperative study

Eighty-one of 473 patients with refractory myelodysplastic anemias registered by the Japanese Cooperative Study Group prior to January 1987 survived more than 5 years. At presentation, most patients had mild cytopenia, a less aggressive form of the disease (48 with refractory anemia, 23 with refractory anemia with ring sideroblasts, 10 with refractory anemia with excess of blasts), less blast cells in the marrow and blood, and onset at younger ages. Their clinical profiles 5 years after presentation showed no significant improvement. The results suggest that the long-term survivors were found in a subpopulation of patients with a favorable prognosis and that it is a part of the natural course rather than the results of treatment.

SIGNIFICANCE OF RING SIDEROBLASTS IN REFRACTORY ANAEMIA WITH EXCESS OF BLASTS

Peters. M., Jansen, E.. Ten Cate, J.W., Kahle’, L.H., Ockelford, P. K Breederveld. C. (1984a) Neonatal antithrombin Ill. British Journcil of Haemntolugy, 58, 579-587. Peters, M.. Ten Cate. J.W.. Koo. L.H. & Breederveld. C. (1984b) Persistent antithrombin I11 deficiency: risk factor for thromboembolic complications in neonates small for gestational age. Journal of Pediatrics. 105, 310-314. Teger-Nilsson. A.C. (1975) Antithrombin I11 in infancy and childhood. Acta Paediatrica Scandinavica, 64, 624-628. Antithrombin 111 Roma: a familial quantitative-qualitative AT 111 deficiency identifiable by crossed immunoelectrofocusing and by crossed immunoelectrophoresis. HaernatoIogicu, 68, 76 5-774. Leone. G.. Cotumaccio, R.. De Stefano, V.. Zanetti. L. & Bizxi. B. (1984) Different forms of AT 111 congenital defect: a study by crossed immunoelcctrofocusing. Scandinavian Journal of HflKmcitologg, 3 3 , 410-41 7. Peters. M. . Breederveld, C. &Ten Cate. J.W. ( 7 982) Daily monitoring of antithrombin 111 in premature neonates. Acta Chirurgica Scandinnvica (Suppl.) 509, 81-82.

Mode of disease progression in primary myelodysplastic syndromes: A Japanese co-operative study

Chronological changes in hematological findings were analyzed in 225 patients with myelodysplastic syndromes (MDS). They were diagnosed between 1990 and 1992. Their hematological findings, i.e. hemoglobin levels, leukocyte and platelet counts, proportions of peripheral blood (PB) blasts and monocytes, and proportion of blasts in bone marrow (BM), were recorded for up to 42 months after diagnosis, when available. BM was examined regularly in only a few patients. Therefore, it was impractical to use the French-American-British Cooperative Group criteria for subtype classification during the disease course. Thus, we used the percentage of PB blasts as the only indicator of stage evolution. We classified the disease into four stages: stage 1, less than 1% PB blasts; stage 2, 1-5% PB blasts; stage 3, 5-30% PB blasts; and stage 4, 30% or more PB blasts. There were 171 patients initially in stage 1, 37 initially in stage 2, and 17 initially in stage 3. Less than half (45%) of the patients initially in stage 1 progressed to stage 2, while 91% of the patients initially in stage 2 and all of the patients initially in stage 3 showed stage evolution. Eight variables, i.e. BM blasts 5% or more, male sex, karyotypic abnormalities, micromegakaryocytes, mononuclear large megakaryocytes, platelet counts 50 x 10(9)/l or higher, abnormal nucleus of granulocytes, and abnormal granules of granulocytes, were found to be significant risk factors for evolution from stage 1 to 2. Evolution from stage 1 to a higher stage within 15 months of diagnosis was associated with impending poor prognosis in most patients. However, of the 67 patients initially in stage 1 who died, 30 did not show stage evolution. Evolution from stage 2 to a higher stage and from stage 3 to stage 4 was also associated with impending poor prognosis. Higher levels of cytopenia were not associated with poorer prognosis in the stage 1 patients. In conclusion, our grading system proved to be useful in evaluating the chronological changes in MDS patients.