Current status of hematopoietic cell transplantation for adult patients with hematologic diseases and solid tumors in Japan.

A nationwide survey of hematopoietic cell transplantation (HCT) was started in Japan in 1991, and the analyzed survey data have been presented as the annual report of the Japan Society for Hematopoietic Cell Transplantation. The 10-year overall survival (OS) rates after HCT for each disease are as follows: acute myelogenous leukemia, 44.2%; acute lymphocytic leukemia, 33.7%; adult T-cell leukemia, 24.6%; chronic myelogenous leukemia, 53.3%; myelodysplastic syndrome, 37.3%; non-Hodgkin's lymphoma, 41.5%; Hodgkin's lymphoma, 50.8%; aplastic anemia, 72.5%; breast cancer, 37.1%; germ cell tumor, 52.6%; and ovarian cancer, 44.2%. The 5-year OS rates for multiple myeloma and lung cancer were 40.6% and 23.6%, respectively. Except in cord blood transplantation, engraftment was accomplished in more than 90% of patients. The respective frequencies of acute graft-versus-host disease (GVHD) and chronic GVHD were 41.1% and 34.9% for related bone marrow transplantation (BMT), 66.8% and 34.5% for unrelated BMT, 52.9% and 36.0% for allogeneic peripheral blood stem cell transplantation, and 53.3% and 32.1% for allogeneic cord blood transplantation. OS for each disease was analyzed by patient age, stem cell source, donor type, disease status, and disease type. These data provide objective and valuable information for hematologists as well as for patients who need HCT.

[Role of polymorphic adhesion molecules in the development of graft-versus-leukemia effect after HLA-matched allogeneic stem cell transplantation].

Mismatches of minor histocompatibility antigens (mHas) between HLA-identical stem cell donors and recipients are known as a major risk factor for graft-versus-host disease (GVHD). We determined the alleles of 5 polymorphic molecules including HA-1 and 4 adhesion molecules in 102 patients who had undergone stem cell transplantation from HLA-identical donors and investigated the association of their mismatches with the relapse rate and incidence of GVHD. We observed relapse rates of 16.1% in patients with at least one or more incompatibilities and 39.4% in patients without incompatibilities (p = 0.018). The respective relapse rates of patients with CD62L, HA-1, CD31 exon 563, CD31 exon 125 and 49b incompatibilities were 6.1%, 14.3%, 11.7%, 20% and 40%. Only patients with CD62L incompatibilities showed a lower relapse rate than patients who received a compatible graft. Since there was no difference between patients with and without incompatibilities as far as the appearance of acute GVHD (> or = 2) was concerned, we conclude that the polymorphic CD62L molecule contributes to graft-versus-leukemia rather than the development of GVHD after HLA-identical stem cell transplantation.

Graft-versus-leukemia effect of allogeneic stem cell transplantation; a Japanese single center study.

To clarify graft-versus-leukemia effect of graft-versus-host disease, we studied 166 patients treated with allogeneic stem cell transplantation for hematologic malignancies. The cumulative incidence of relapse in patients with acute GVHD was significantly lower than that in patients without acute GVHD, but there was no similar GVL effect for chronic GVHD.

Epstein-Barr virus (EBV)-associated post-transplantation lymphoproliferative disorder simultaneously affecting both B and T cells after allogeneic bone marrow transplantation.

Post-transplantation lymphoproliferative disorder (PTLD) is usually an aberrant proliferation of EBV-infected B cells. We report the case of a 31-year-old man with severe aplastic anemia who suffered PTLD 42 days post-BMT from an unrelated donor. At the onset of PTLD, peripheral blood lymphocytes were comprised of 40% CD20(+) cells, 3% CD4(+) cells, and 56% CD8(+) cells. A highly sensitive in situ hybridization (ISH) method was used to detect EBV-encoded small non-polyadenylated RNA 1 (EBER-1) in 33.9% of sorted CD20(+) cells, 4.4% of CD4(+) cells, and 1.4% of CD8(+) cells. Each T-cell fraction contained less than 0.034% of contaminated EBV-infected B cells. Clonal proliferation of both B and T cells was demonstrated by Southern blotting. The patient did not respond to donor leukocyte infusion and died due to deterioration of PTLD. At autopsy, examination of multiple organs revealed B-cell (rather than T-cell) infiltration. This case clearly indicates that EBV can simultaneously infect B and T cells and can induce clonal proliferation of both lymphocyte subsets in severely immunocompromised patients.

High-dose chemotherapy with peripheral blood stem cell transplantation for advanced testicular cancer.

BACKGROUND: The aim of this study was to investigate the efficacy and safety of high-dose chemotherapy (HDCT) for the treatment of patients with advanced testicular cancer. METHODS: Fourteen patients were treated with high-dose carboplatin, etoposide and cyclophosphamide (with or without THP-adriamycin) followed by peripheral blood stem cell transplantation. The treatment was used for two refractory cases, a second relapse, and for consolidation after the first relapse in one case each. It was also used for nine cases as part of the first-line treatment following primary conventional-dose chemotherapy, and for one case as the first salvage for a late recurrent tumor of teratoma with malignant transformation. RESULTS: The first two patients who received intensive pretreatment with cisplatin-based chemotherapy did not respond to HDCT. The two patients who were treated with HDCT as the first or second salvage therapy achieved successful outcomes. The results for the subsequent nine patients (consisting of two with stage IIIC, five with IIIB2, one with IIB, and one extragonadal seminoma) were two progressive disease, three no change and four partial remission. Only three are alive with NED following salvage surgery. Finally, a case of teratoma with malignant transformation did not respond well to two cycles of HDCT. There were no marked adverse reactions except one episode of severe neutropenic colitis. CONCLUSIONS: The results demonstrated the limited efficacy of HDCT even in cases with a good to intermediate risk rating according to classification by the International Germ Cell Cancer Collaborative Group. Because treatment for relapse after HDCT is extremely difficult, new HDCT regimens consisting of drugs that are not used in induction chemotherapy need to be established.