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Yasuo Morishima

Publications and source records attributed to Yasuo Morishima.

61 records · Page 4Linked to original sources

Outcome of 154 patients with severe aplastic anemia who received transplants from unrelated donors: the Japan Marrow Donor Program.

We retrospectively analyzed results for 154 patients with acquired severe aplastic anemia who received bone marrow transplants between 1993 and 2000 from unrelated donors identified through the Japan Marrow Donor Program. Patients were aged between 1 and 46 years (median, 17 years). Seventy-nine donor-patient pairs matched at HLA-A, -B, and -DRB1 loci, as shown by DNA typing. Among the 75 mismatched pairs, DNA typing of 63 pairs showed that 51 were mismatched at 1 HLA locus (18 HLA-A, 11 HLA-B, 22 HLA-DRB1) and 12 were mismatched at 2 or more loci. Seventeen patients (11%) experienced either early or late graft rejection. The incidence of grade III/IV acute graft versus host disease and chronic graft versus host disease was 20% (range, 7%-33%) and 30% (range, 12%-48%), respectively. Currently, 99 patients are alive, having survived for 3 to 82 months (median, 29 months) after their transplantations. The probability of overall survival at 5 years was 56% (95% confidence interval, 34%-78%). Multivariate analysis revealed the following unfavorable factors: transplantation more than 3 years after diagnosis (relative risk [RR], 1.86; P =.02), patients older than 20 years (RR, 2.27; P =.03), preconditioning regimen without antithymocyte globulin (RR 2.28; P =.04), and HLA-A or -B locus mismatching as determined by DNA typing. Matching of HLA class I alleles and improvement of preparative regimens should result in improved outcomes in patients with severe aplastic anemia who receive transplants from unrelated donors.

Adolescent↗

The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors.

To improve the clinical outcome of allogeneic hematopoietic stem cell transplantation from an unrelated donor, the identification of human leukocyte antigen (HLA) alleles responsible for immunologic events such as graft-versus-host disease (GVHD), engraftment failure, and graft-versus-leukemia effect is essential. Genomic typing of HLA-A, -B, -C, -DRB1, and -DQB1 was retrospectively performed in 1298 donor-patient pairs in cases where marrow was donated from serologically HLA-A, -B, and -DR compatible donors. Single disparities of the HLA-A, -B, -C, or -DRB1 allele were independent risk factors for acute GVHD, and the synergistic effect of the HLA-C allele mismatch with other HLA allele mismatches on acute GVHD was remarkable. HLA-A and/or HLA-B allele mismatch was found to be a significant factor for the occurrence of chronic GVHD. HLA class I (A, B, and/or C) allele mismatch caused a significantly higher incidence of engraftment failure than HLA match. Significant association of HLA-C allele mismatch with leukemia relapse was not observed. As the result of these events, HLA-A and/or HLA-B allele mismatch reduced overall survival remarkably in both standard-risk and high-risk leukemia cases, whereas the HLA-C mismatch or HLA-class II (DRB1 and/or DQB1) mismatch did not. Furthermore, multiple mismatch of the HLA locus was found to reduce survival in leukemia cases. Thus, the role of the HLA class I allele in unrelated bone marrow transplantation was elucidated. Notably, HLA-C alleles had a different mode from HLA-A or -B alleles for acute GVHD and survival.

Adult↗

Health-related quality of life of unrelated bone marrow donors in Japan.

To promote bone marrow donation, both the safety and well-being of healthy unrelated volunteer donors must be protected. This prospective cohort study evaluated donors' health-related quality of life (HRQOL) and identified factors associated with it. Using the Medical Outcomes Study Short Form 36 Health Survey (SF-36) before bone marrow harvesting (BMH), and again 1 week and 3 months after the donors' discharge, we evaluated HRQOL of 565 donors (329 men, 236 women) registered with the Japan Marrow Donor Program (JMDP). We also examined the data routinely collected by the JMDP, such as BMH-related problems and other demographic and medical variables, to determine whether such data could be used to predict donors' HRQOL after discharge. Mean scores of all pre-BMH SF-36 subscales showed better functioning than the national norm. One week after discharge, mean scores on physical functioning (PF) and role-physical (RP) subscales, indicative of physical states, and bodily pain (BP) were approximately 1 SD lower than the national norm; however, mental health (MH) and general health perception (GH) remained above normal; the most frequent BMH-related problems were pain at the donation site and lower back pain, which were associated with lower PF, RP, and BP scores. Female gender and duration of procedure predicted lower PF, RP, and BP. Three months after discharge, mean scores of all SF-36 subscales had returned to baseline levels. These data show that the adverse effects of BMH on donors' HRQOL are transient and can be minimized by better management of pain.

Adult↗

De novo CD5+ diffuse large B-cell lymphoma: a clinicopathologic study of 109 patients.

De novo CD5+ diffuse large B-cell lymphoma (CD5+ DLBCL) is known to have phenotypically and genotypically different characteristics than CD5- DLBCL and mantle cell lymphoma (MCL). To further characterize CD5+ DLBCL, 109 patients with CD5+ DLBCL were reviewed, and the results were compared with those of 384 CD5- DLBCL and 128 cyclin D1+ MCL patients. Patients with CD5+ DLBCL showed a higher age distribution (median, 66 years; P =.0083) and a female predominance (male-female ratio, 49:60, P =.011) compared with those with CD5- DLBCL. CD5+ DLBCL was more closely associated with many aggressive clinical features or parameters than CD5- DLBCL: 69% older than 60 years (P =.039), 34% with performance status greater than 1 (P =.0016), 69% with serum lactate dehydrogenase level higher than normal (P <.0001), 62% with stage III/IV disease at diagnosis (P =.0023), 35% with more than one extranodal site (P =.023), and 40% with B symptoms (P =.0031). The overall International Prognostic Index score was thus significantly higher for the patients with CD5+ DLBCL than for those with CD5- DLBCL (P =.00005). The most frequent site of extranodal involvement was bone marrow (28%), a higher frequency than that for CD5- DLBCL (P <.0001) but lower than that for cyclin D1+ MCL (P =.0015). Histopathologically, CD5+ DLBCL showed centroblastic morphology except for 3 patients with immunoblastic disease, and interfollicular growth pattern (7%) and intravascular or intrasinusoidal infiltration (19%) were observed. Immunophenotypically, CD5+ DLBCL was characterized by a CD5+CD10-CD19+CD20+CD21-CD23- cyclin D1- phenotype and a predominance of surface IgMkappa. Of particular interest is that CD5+ DLBCL was characterized by a survival curve significantly inferior to that for patients with CD5- DLBCL (P =.0026). These findings suggest that CD5+ DLBCL may constitute a unique subgroup of DLBCL.

Adolescent↗

Retrospective study on the impact of hepatitis B and hepatitis C virus infection on hematopoietic stem cell transplantation in Japan.

We performed a retrospective survey in 62 hematopoietic cell transplantation (HCT) centers in Japan in which all HCTs performed between 1986 and 1998 were reviewed, and those involving hepatitis B virus surface antigen (HBsAg)-positive donors were identified. One hundred and thirty-five patients who underwent allogeneic HCT (alloHCT) were studied for complications related to hepatitis B virus (HBV) or hepatitis C virus (HCV). The median follow-up period was 24 months. Positivity for HBsAg was observed in 32 patients (24%) throughout the study. Twenty-six of the 32 patients were HBsAg carriers before alloHCT, whereas the remaining 6 became HBsAg(+) after alloHCT. Forty-two recipients were anti-HBs antibody (HBsAb)-positive, and 58 recipients (43%) were HCV Ab(+). Eleven of 26 (42%) HBsAg(+) recipients survived between >4 and >119 months. Six of 26 cases received transplants from HBsAg(+) donors, and, although they had not developed acute graft-versus-host disease, 4 of 6 died of hepatic and renal failure within 10 months after HCT. After transplantation, 5 patients showed serologic evidence of HBV reactivation, whereas 4 patients showed evidence of an immune response to HBV. Viral reactivation occurred during the tapering of the immunosuppressive agent. However, 3 of 5 were alive at the time of this report, suggesting that reactivation is not directly correlated with severe liver dysfunction. Seventeen patients (13%) of 135 recipients developed hepatic failure. Eight (47%) of 17 were diagnosed with fulminant hepatitis and 5 (29%) with veno-occlusive disease (VOD). VOD was observed in 12% of both HBsAg(+) and HCVAb(+) patients. In this study, the relatively high incidence of HBV events occurred after alloHCT, and, therefore, we should consider a protocol for active immunization of donors and recipients against HBV. Moreover, although the presence of HBV or HCV is not a contraindication for alloHCT, we recommend a careful follow-up of recipients after transplantation, especially during immunosuppression tapering.

Adolescent↗

Single institute experience of chemotherapy and adjuvant radiotherapy for localized aggressive non-Hodgkin's lymphoma: retrospective analysis of the clinical efficacy of radiation therapy.

We retrospectively analyzed the clinical outcome of localized aggressive lymphoma treated with chemotherapy and adjuvant radiotherapy. Between 1982 and 1998, 77 patients who were diagnosed as having aggressive lymphoma stage I-II were treated with chemotherapy followed by radiation therapy. The median radiation dose was 44.4 Gy (range, 30-64 Gy). Some patients who achieved complete response after chemotherapy received limited-field radiation to reduce toxicity. Several prognostic factors were analyzed in the overall (OAS) and relapse-free survival (RFS) by both uni- and multivariate analysis. The 5-year rates of OAS and RFS were 74.6% and 70.8%, respectively. Patient age (p = 0.016), radiation dose (p = 0.043), and prognostic score proposed by the Japan Lymphoma Radiation Therapy Group (JLRTG; p = 0.0073) were significant predictive factors for OAS. As for RFS, predictive factors were patient age (p = 0.042), elevated level of serum lactic dehydrogenase (p = 0.046), and JLRTG score (p = 0.05). At the multivariate level, only patient age greater than 60 years was a significantly adverse variable for both OAS (p = 0.0079) and RFS (p = 0.0198). Our treatment strategy was thought to be acceptable with satisfactory outcomes. Limited-field radiation may have possible advantages in toxicity if it does not lead to worsening of the outcome, although a conclusive result could not be obtained by the current analysis.

Adolescent↗

MUM1/IRF4 expression is an unfavorable prognostic factor in B-cell chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

B-Cell chronic lymphocytic leukemia (B-CLL) / small lymphocytic lymphoma (SLL) consists of heterogeneous diseases that are distinguished by morphological, immunophenotypic and molecular features. MUM1 (multiple myeloma oncogene 1) is a protooncogene that is deregulated as a result of (6;14)(p25;q32) chromosomal translocation in multiple myeloma, and is also expressed in a variety of malignant lymphoma entities. We examined the expression of MUM1 in B-CLL / SLL, and found that 2 of 4 B-CLL-derived cell lines and 14 of 29 patients' specimens expressed MUM1 by immunohistochemical analysis. MUM1 expression was not associated with CD38 expression, somatic hypermutation of immunoglobulin heavy chain gene variable region (IgV(H)), or any other clinical characteristics of the patients. Interestingly, the patients who were positive for MUM1 showed shorter overall survival times than those who were negative for MUM1 (50% survival: 22 months vs. 82 months) (P = 0.0008, log-rank test). Multivariate analysis by Cox's proportional-hazards regression model showed that MUM1 expression and unmutated IgV(H) status were independent unfavorable prognostic factors in patients with B-CLL / SLL. These findings suggest that MUM1 expression is a useful prognostic factor in B-CLL / SLL. The biological role and mechanism of action of MUM1 in B-CLL / SLL need to be clarified for the development of therapies for patients with the poor prognostic subtype.

ADP-ribosyl Cyclase↗