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Little is known about stem cell transplantation in solid organ transplantation (SOT) recipients. We conducted a nationwide retrospective survey of Japan Society for Hematopoietic Stem Cell Transplantation centers. A total of 19 patients who underwent 22 hematopoietic stem cell transplantations (HSCTs) after SOT were identified: 5 autologous HSCTs and 17 allogeneic HSCTs were performed. Patients who underwent autologous HSCT received a liver (n = 4) or kidney (n = 1) transplant. All 5 patients achieved neutrophil engraftment, and 2 of 3 patients with hepatoblastoma were alive at 1 year after HSCT. Allogeneic HSCT was performed in 16 patients (7 liver transplant recipients and 9 kidney transplant recipients). Among these, 2 donors were identical for both transplantations. All but 1 patient achieved neutrophil engraftment. The 5-year overall survival rate was 41.7%, but that in patients with malignant disease (n = 13) was much lower than the overall rate (23.1%). Only 1 patient with malignant disease underwent allogeneic HSCT in nonremission. In allogeneic HSCT after kidney transplantation, post-transplantation (1 year) kidney function in 5 evaluable patients was significantly lower than that before allogeneic HSCT, and 3 patients experienced renal rejection. However, no severe hepatic rejection was noted. In SOT recipients, HSCT is a potentially curable treatment for hematologic disorders, but it must be performed with caution, especially in patients with malignancy.

Almost comparable transplantation outcomes have been reported with HLA-matched unrelated donor transplantation (UDT) and cord blood transplantation (CBT). We conducted a prospective phase 2 study to assess the efficacy and safety of single-unit myeloablative CBT in adult leukemia and myelodysplastic syndrome. Because the day 180 survival of UDT was approximately 80%, we determined the alternative hypothesis of expected day 180 survival with a successful engraftment rate of 80% and set the null hypothesis of threshold rate at 65%. Sixty-two patients (median age, 37 years) were registered, including 28 with acute myelogenous leukemia, 25 with acute lymphoblastic leukemia, and 9 with myelodysplastic syndrome. Of 61 eligible patients, 52 were successfully engrafted and survived at day 180 (85%; 95% confidence interval, 74% to 93%). Single-unit CBT was judged to be effective because the null hypothesis was rejected (P.001). Furthermore, neutrophil engraftment was observed in 57 patients (92%); the incidences of grade II-IV acute and chronic graft-versus-host disease were 30% and 32%, respectively; and the cumulative incidences of nonrelapse mortality and relapse at 2 years were 18% and 13%, respectively. The present study showed favorable survival outcomes with single-unit CBT. Therefore, this method may be considered if a well-HLA-matched UDT cannot be obtained.

Background Despite recent progress in blood systems, transfusion errors can occur at any time from the moment of collection through to the transfusion of blood and blood products. This study investigated the actual statuses of blood transfusion errors at institutions of all sizes in Aichi prefecture. Materials and methods We investigated 104 institutions that perform 98 % of the blood transfusions in Aichi prefecture, and investigated the errors (incidents/accidents) that occurred at these facilities over 6 months (April to September, 2017). Incident/accident data were collected from responses to questionnaires sent to each institution; these were classified according to the categories and risk levels. Results Ninety-seven of the 104 institutions (93.3 %) responded to the questionnaire; a total of 688 incidents/accidents were reported. Most (682 cases; 99.2 %), were classified as risk level 2; however, 6 were level 3 and over, which included problems with autologous transfusion and inventory control. Approximately one-half of the incidents/accidents (394 cases; 57.3 %), were related to verification and the actual administration of blood products at the bedside; more than half of these incidents/accidents occurred at large-volume institutions. Meanwhile, a high frequency of incidents/accidents related to transfusion examination and labeling of blood products was observed at small- or medium-sized institutions. The reasons for most of these errors were simple mistakes and carelessness by the medical staff. Conclusions Our results emphasize the importance of education, operational training, and compliance instruction for all members of the medical staff despite advances in electronic devices meant to streamline transfusion procedures.

Ganciclovir (GCV) and foscarnet (FCN) are effective anti-cytomegalovirus (CMV) preemptive therapies; however, the impact of the 2 agents on various clinical outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) remains unclear. We retrospectively analyzed data on 532 patients undergoing allogeneic HSCT from unrelated donors and administered FCN (n = 86) or GCV (n = 446) as first-line anti-CMV preemptive therapy. Overall survival, relapse, and nonrelapse mortality (NRM) did not differ between the FCN and GCV groups, whereas the GCV group had a higher risk of chronic graft-versus-host disease (cGVHD) (hazard ratio [HR], 2.38; 95% confidence interval [CI], 1.28 to 4.39; P = .006) and extensive cGVHD (HR, 3.94; 95% CI, 1.43 to 10.9; P = .008). All 13 patients with cGVHD in the FCN group survived. Switching to the other agent was done mainly due to hematologic adverse events in the GCV group and mainly due to insufficient efficacy in the FCN group. The incidence of end-organ CMV disease was similar in the 2 groups. Selection of FCN or GCV as first-line preemptive anti-CMV therapy did not affect survival, relapse, or NRM. Physicians can select either of the agents, depending on the clinical situation; however, the selection may influence the cGVHD-related clinical course in HSCT recipients.

Little is known regarding the chimerism status after reduced-intensity conditioning transplantation when bone marrow is used as a stem cell source. We prospectively analyzed lineage-specific chimerism and retrospectively evaluated clinical outcomes in 80 adult patients who underwent unrelated donor bone marrow transplantation (URBMT) with fludarabine plus melphalan (FM) as the conditioning regimen. Mixed donor chimerism (MDC) was seen in 43 and 10 % of patients at days 14 and 28, respectively. Melphalan at ≤130 mg/m(2) was associated with an increased incidence of MDC at day 28 (P = 0.03). Patients with MDC at day 14 showed a marginally increased risk of primary graft failure and a marginally decreased risk of graft-versus-host disease. In multivariate analysis, MDC at day 14 was associated with higher overall mortality (hazard ratio (HR) = 2.1; 95 % confidence interval (CI), 1.1-4.2; P = 0.04) and relapse rate (HR = 3.0; 95 % CI, 1.2-7.5; P = 0.02), but not with non-relapse mortality (HR = 1.8; 95 % CI, 0.70-4.6; P = 0.23). Thus, the FM regimen yields prompt complete donor chimerism after URBMT, but the melphalan dose significantly impacts the kinetics of chimerism. Chimerism status evaluation at day 14 may be instrumental in predicting relapse after URBMT with the FM regimen.

Inotuzumab ozogamicin (CMC-544), an antibody-targeted chemotherapeutic agent composed of an anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic antibiotic, specifically targets the CD22 antigen present in >90% of B-lymphoid malignancies, rendering it useful for treating patients with B-cell non-Hodgkin lymphoma (B-NHL). This phase I study evaluated the safety, tolerability, efficacy, and pharmacokinetics of inotuzumab ozogamicin in Japanese patients. Eligible patients had relapsed or refractory CD22-positive B-NHL without major organ dysfunction. Inotuzumab ozogamicin was administered intravenously once every 28 days (dose escalation: 1.3 and 1.8 mg/m(2)). All 13 patients had follicular lymphoma, were previously treated with > or =1 rituximab-alone or rituximab-containing chemotherapy, and were enrolled into two dose cohorts (1.3 mg/m(2), three patients; 1.8 mg/m(2), 10 patients). No patient had dose-limiting toxicities, and the maximum tolerated dose, previously determined in non-Japanese patients (1.8 mg/m(2)), was confirmed. Drug-related adverse events (AEs) included thrombocytopenia (100%), leukopenia (92%), lymphopenia (85%), neutropenia (85%), elevated AST (85%), anorexia (85%), and nausea (77%). Grade 3/4 drug-related AEs in > or =15% patients were thrombocytopenia (54%), lymphopenia (31%), neutropenia (31%), and leukopenia (15%). The AUC and C(max) of inotuzumab ozogamicin increased dose-dependently with pharmacokinetic profiles similar to non-Japanese. Seven patients had complete response (CR, 54%) including unconfirmed CR, four patients had partial response (31%), and two patients had stable disease (15%). The overall response rate was 85% (11/13). Inotuzumab ozogamicin was well tolerated at doses up to 1.8 mg/m(2) and showed preliminary evidence of activity in relapsed or refractory follicular lymphoma pretreated with rituximab-containing therapy, warranting further investigations. This trial was registered in ClinicalTrials.gov (NCT00717925).

Graft failure and nonrelapse mortality (NRM) are major obstacles after the first unrelated-donor bone marrow transplantation (UD-BMT) with reduced-intensity conditioning. We evaluated UD-BMT with fludarabine (5 x 25 mg/m2) and melphalan (2 x 90 mg/m2) treatment combined with short-term methotrexate and tacrolimus (n = 20) or cyclosporine (n = 2) therapy for 22 patients with hematologic malignancies who were ineligible for conventional conditioning. Only 9 patients were in remission at transplantation. Seventeen patients underwent HLA-matched or DRB1 allele-mismatched transplantation, and 5 patients underwent HLA-A allele-mismatched or serologically HLA-DR-mismatched transplantation. Regimen-related toxicities were tolerable, although transient oral mucositis, hepatobiliary enzyme elevation, and diarrhea were observed frequently. All evaluable patients achieved sustained neutrophil engraftment, and all patients tested showed complete donor chimerism on day 28. With a median follow-up of 16 months, NRM and overall survival rates at 1 year were 19% and 81%, respectively, among the patients who underwent HLA-matched or DRB1 allele-mismatched transplantation. Acute graft-versus-host disease (GVHD) of grades II to IV occurred in 26% of the patients. The cumulative incidence of chronic GVHD was 44%. Despite the small number of patients and the short follow-up period, this reduced-intensity regimen enabled satisfactory engraftment and achievement of rapid complete donor chimerism with tolerable toxicities in the patients, including those who underwent HLA-mismatched UD-BMT.

We analyzed donor-type chimerism in CD3+, CD14.15+ and CD56+ cells from 36 patients who had undergone conventional-intensity allogeneic stem cell transplantation (CST) and 34 patients who had undergone non-myeloablative allogeneic stem cell transplantation (NST) for hematological malignancies. On day 28 after transplantation, all fractions in NST patients and CD3+ cells in CST patients who received a non-total body irradiation (TBI) regimen showed more frequent mixed chimerism (

We conducted a nationwide survey to define incidence of deep fungal infections and fungal prophylaxis practices after HSCT. In all, 63 institutions responded. Total number of in-patient transplantations was 935: 367 autologous, 414 allogeneic myeloablative, and 154 allogeneic reduced-intensity (RIST) (n=154). Number of patients who were cared for in a clean room at transplant was 261 (71%) in autologous, 409 (99%) in conventional and 93 (66%) in RIST, respectively. All patients received prophylactic antifungal agents; 89% fluconazole. Number of patients who received the dosage recommended in the CDC guidelines (400 mg/day) was 135 (42%) in conventional transplant and 34 (30%) in RIST (P=0.037). Number of patients who received fluconazole until engraftment and beyond day 75 in conventional transplant vs RIST was, respectively, 324 (100%) vs 109 (97%), and 39 (12%) vs 18 (16%), with no significant difference between the two groups. A total of 37 patients (4.0%) were diagnosed with deep fungal infections; autologous transplantation (0.03%), conventional transplantation (6.0%) and RIST (7.1%). Wide variations in antifungal prophylaxis practice according to the type of transplant and the institutions, and deep fungal infection remain significant problems in RIST.

Background: The aim of the study was to determine factors affecting the toxicity and efficacy of rituximab monotherapy in relapsed patients with indolent B-cell lymphoma and mantle cell lymphoma (MCL). Patients and methods: A total of 90 patients were enrolled and treated with rituximab infusions at 375 mg/m 2 once weekly for 4 weeks. Central pathology review revealed that histologically, 81 patients had indolent B-cell lymphoma or MCL: 59 with follicular lymphoma, 17 with MCL, four with marginal zone lymphoma and one with lymphoplasmacytoid lymphoma. Of these, four were ineligible due to violation of other eligibility criteria. Pre-treatment variables affecting toxicities were analyzed for all 90 patients, and those affecting response and progression-free survival (PFS) were analyzed for 77 eligible patients with confirmed indolent B-cell lymphoma or MCL. The relationship between serum rituximab levels and efficacy was also analyzed for 66 eligible patients. Results: Hematological toxicities (grade ≥3) occurred more frequently in females (P

We established a real-time PCR method that can simultaneously detect 10 different fusion transcripts (major, minor and micro BCR/ABL, AML1/MTG8, PML/RARalpha, CBFbeta/MYH11, TEL/AML1, E2A/PBX1, MLL/AF4, and MLL/AF9) together with Wilms' tumor gene (WT1) transcripts. This screening method allowed the processing of six specimens concomitantly and required only one working day from RNA extraction to final results. Fifty-seven bone marrow (BM) samples from patients with acute leukemia were retrospectively screened for the presence of fusion and WT1 transcripts without knowledge of the cytogenetic data, and the fusion transcripts were detected in 20 of 57 samples (35.1%). The concordance between the present method and cytogenetic analysis was examined in 38 samples in which the cytogenetic data were available. In 12 of 38 samples, the PCR results agreed with the cytogenetic data, whereas in 4 of the remaining 26 samples, the translocations were detected by real-time PCR alone because of the insufficient number of metaphases obtained and presumably the submicroscopic or masked translocations. The WT1 levels ranged from 400 to 690,000 copies/microg RNA in BM from leukemia patients, whereas 0-470 copies/microg RNA were found in BM cells from BMT donors. This real-time PCR method enables rapid and efficient characterization of acute leukemia in addition to subsequent evaluation of minimal residual diseases.

Multiple myeloma (MM) developing after renal transplantation is rare. From January 1972 to December 2011, a total of 1,485 patients underwent renal transplantation in Nagoya Daini Red Cross Hospital; 14 (0.9%) of these recipients developed post-transplantation lymphoproliferative disorders (PTLDs) including two plasma cell neoplasms. Here, we report the clinical course of a 35-year-old male with immunoglobulin G k-type MM of recipient origin that developed 5 years after renal transplantation from a human leukocyte antigen (HLA)-haploidentical female sibling donor, which was performed to address dialysis-dependent chronic glomerulonephritis. Cytogenetic analysis revealed significant del(17p) abnormalities in myeloma cells. After non-response to bortezomib treatment, the patient achieved partial response with a thalidomide-containing salvage regimen and underwent successful tandem autologous/reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated male donor matched for seven of eight HLAs. At the 8-month follow-up time point, the patient's performance status remained good, and the transplanted kidney remains functional without rejection. To the best of our knowledge, this is the first report of a successful use of allogeneic HSCT for a patient who developed MM as a PTLD after renal transplantation. This patient has a transplanted kidney and transplanted hematopoietic cells that currently coexist without rejection.

The management of myelodysplastic syndrome (MDS) remains challenging. We performed a phase I/II study to evaluate the safety and efficacy of decitabine in patients with MDS in Japan. Patients with MDS with red cell transfusion dependence or 5-30% blasts in marrow and with an International Prognostic Scoring System score of intermediate-1 or higher were eligible. Patients received intravenous decitabine at 15 or 20 mg/m(2) daily for 5 days every 4 weeks. A total of 37 patients were enrolled. Three patients received 15 mg/m(2) and experienced no dose limiting toxicity during the first cycle. Thirty-four patients received 20 mg/m(2) . Grade 3 or greater non-hematologic toxicities included cerebral infarction (n = 1), subdural hematoma (n = 1), elevated blood glucose (n = 1), and pulmonary hypertension (n = 1). At 20 mg/m(2) , complete response, partial response, and hematologic improvement were observed in 7 (20.6%), 2 (5.9%), and 7 (20.6%) patients, respectively. Complete cytogenetic response was observed in 30% of evaluable 20 patients. The median number of cycles to clinical response was 4 (range 4-8), and duration of remission was 474+ days (range 294-598+). The 2-year rate of acute myeloid leukemia-free survival was 52%. Correlative studies revealed hypomethylation in multiple genes in peripheral blood cells after treatment. Hypomethylation was generally more profound in CD15 + peripheral blood cells, which reflects myeloid cells, than in peripheral blood mononuclear cells. In summary, decitabine was safe and demonstrated efficacy in Japanese patients with high-risk MDS. This trial was registered at ClinicalTrials.gov (NCT00796003).

The response criteria proposed by European Leukemia Net are useful to predict the prognosis of de novo chronic myeloid leukemia (CML) patients in the chronic phase (CP) treated with imatinib. However, the clinical significance of late suboptimal response, which is defined as the achievement of CCgR without MMR after 18 months, is controversial. In this study, we retrospectively analyzed the clinical courses of 16 CML-CP patients, who satisfied the criteria for late suboptimal response. The median duration of imatinib treatment was 62 (25∼87) months. The median starting dose of imatinib was 400 mg/day. Imatinib dose was escalated to 600∼800 mg/day in 10 patients for various reasons. Among 4 patients who continued high-dose imatinib for late suboptimal response, 2 patients subsequently achieved MMR, and BCR-ABL mRNA transcript levels were decreasing in 2 patients. However, imatinib was kept at 300 or 400 mg/day in 6 patients. Among these six patients, 4 patients achieved MMR, while 2 failed to achieve MMR. None of 16 patients progressed to the acute phase or blast phase. Imatinib dose escalation was effective for late suboptimal response. Furthermore, a second tyrosine kinase inhibitor such as nilotinib may be more potent to reduce the risk of disease progression by achieving earlier MMR.

To identify factors to improve the outcomes of related and unrelated allogeneic stem cell transplantations (allo-SCT) for Philadelphia chromosome–negative acute lymphocytic leukemia (Ph− ALL) in the first complete remission (CR1), we retrospectively analyzed 1139 Ph− ALL patients using the registry data, particularly the details of 641 patients transplanted in CR1. Overall survival was significantly superior among patients transplanted in CR1, but no significant difference was observed between related and unrelated allo-SCTs (related vs unrelated: 65% vs 62% at 4 years, respectively; P = .19). Among patients transplanted in CR1, relapse rates were significantly higher in related allo-SCT compared with unrelated allo-SCT, and multivariate analysis demonstrated that less than 6 months from diagnosis to allo-SCT alone was associated with relapse. On the other hand, nonrelapse mortality (NRM) was significantly higher in unrelated allo-SCT compared with related allo-SCT, and multivariate analysis demonstrated that 10 months or longer from diagnosis to allo-SCT, human leukocyte antigen mismatch, and abnormal karyotype were associated with NRM. In conclusion, our study showed comparable survival rates but different relapse rates, NRM rates, and risk factors between related and unrelated allo-SCTs. After a close consideration of these factors, the outcome of allo-SCT for adult Ph− ALL in CR1 could be improved.

Bendamustine is a cytotoxic agent with a novel mechanism of action. This phase I, dose-escalation study evaluated the safety, tolerability, efficacy, and pharmacokinetics of bendamustine in Japanese patients with relapsed/refractory indolent B-cell non-Hodgkin lymphoma (B-NHL) or mantle cell lymphoma (MCL) without major organ dysfunction. Bendamustine 90 or 120 mg/m(2) (dose escalation) was administered intravenously over 60 min on days 1 and 2 every 3 weeks for up to three cycles. Nine patients (eight indolent B-NHL and one MCL) received per-protocol treatment, three at 90 mg/m(2) and six at 120 mg/m(2) . No dose-limiting toxicities were observed; thus, the maximum-tolerated dose was not reached. Grade 3/4 hematologic toxicities were neutropenia (33%) and leukopenia (33%). Non-hematologic toxicities were grade 1/2 and included gastrointestinal events and fatigue. Peak plasma concentrations of bendamustine occurred near the end of infusion in both dose groups and were equivalent to therapeutic concentrations observed in vitro. Bendamustine was rapidly eliminated, with a mean elimination half-life (t(1/2) ) of 29 min. Plasma concentrations of active metabolites M3 and M4 were approximately 4 and

We have analysed the expression of HLA-G in 40 leukaemia samples of various subtypes [seven cases of acute lymphoblastic leukaemia (ALL), 28 cases of acute myelogenous leukaemia (AML), three cases of chronic myelogenous leukaemia (CML) and two cases of chronic lymphocytic leukaemia (CLL)] by flow cytometry using HLA-G-specific monoclonal antibody. No leukaemia samples expressed HLA-G without incubation with interferon (IFN)-gamma. However, six out of 28 (21%) AML samples expressed HLA-G upon incubation with IFN-gamma. These six samples derived from one out of seven M2, two out of eight M4 and three out of five M5. The results indicated that AML cells, especially myelomonocytic leukaemia samples, are capable of expressing the HLA-G molecule.

We retrospectively analyzed the results of 707 adult patients who underwent myeloablative peripheral blood stem cell transplantation (PBSCT) (n = 365) and myeloablative bone marrow transplantation (BMT) (n = 342) for leukemia from HLA-identical sibling donors between 2000 and 2005 using the propensity score method. The results were obtained from the Japan Society for Hematopoietic Cell Transplantation registry. Multivariate Cox analysis showed that PBSCT was associated with lower overall survival (OS) in standard-risk patients [adjusted hazard ratio (aHR) = 1.83; 95% confidence interval (CI) 1.04–3.23; P = 0.036], but not in high-risk patients (aHR = 1.11; 95% CI 0.76–1.61; P = 0.599). Hematopoietic recovery was significantly faster after PBSCT. The risk of acquiring grade III–IV acute graft-versus-host disease (GVHD) (aHR = 2.23; P = 0.040) and extensive chronic GVHD (aHR = 1.93; P = 0.001) were significantly higher after PBSCT. PBSCT was associated with higher non-relapse mortality in standard-risk patients (aHR = 2.30; 95% CI 1.08–4.88; P = 0.030), but not in high-risk patients (aHR = 1.29; 95% CI 0.65–2.54; P = 0.468). Relapse after transplantation did not differ between PBSCT and BMT either in standard-risk group or in high-risk group (aHR = 1.17; 95% CI 0.55–2.52; P = 0.684 and aHR = 0.81; 95% CI 0.52–1.28; P = 0.370, respectively). In this retrospective analysis, OS was significantly lower after PBSCT in standard-risk patients, but not in high-risk patients. PBSCT was associated with significant risks of grade III–IV acute GVHD and extensive chronic GVHD.

We retrospectively surveyed the data of 233 patients who underwent myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) for non-Hodgkin lymphoma (NHL). Donors were HLA-matched relatives in 154 patients (66%) or unrelated volunteers in 60 (26%). Ninety patients (39%) were in complete remission. One hundred ninety-three (83%) received a total body irradiation (TBI)-based regimen, and 40 (17%) received a non-TBI-based regimen. Acute graft-versus-host disease (GVHD) occurred in 155 (67%) of the 233 evaluable patients; grade II to IV in 90 (39%), and grade III to IV in 37 (16%). Treatment-related mortality (TRM) was observed in 98 patients (42%), and 68% of them were related to GVHD. In a multivariate analysis, chemoresistance, prior autograft, and chronic GVHD were identified as adverse prognostic factors for TRM. Relapse or progression of lymphoma was observed in 21%. The 2-year overall survival rates of the patients with indolent (n = 38), aggressive (n = 111), and lymphoblastic lymphoma (n = 84) were 57%, 42%, and 41%, respectively. In a multivariate analysis, chemoresistance, prior autograft, and prior radiotherapy were identified as adverse prognostic factors for overall survival. Although myeloablative allo-HSCT represents an effective therapeutic option for patients with NHL, more work is still needed to decrease TRM and relapse. (Blood. 2006;108:382-389)

Noninfectious pulmonary dysfunction (NIPD) is a common and often fatal complication associated with allogeneic hematopoietic stem cell transplantation (HSCT). An insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE) gene has been extensively studied in relation to cardiovascular and renal disease, and lung fibrosis. In pulmonary fibrosis, D-allele frequency is significantly higher than in the control population. We hypothesized that a similar mechanism exists between post-HSCT NIPD and pulmonary fibrosis in the absence of HSCT. We retrospectively analyzed the incidence of NIPD and the ACE genotype polymorphism in 118 Japanese patients who underwent HSCT from HLA-identical sibling donors. NIPD occurred in 17 cases. Deletion/deletion genotype carriers were more common in the NIPD group than in the other 101 patients (41.2 vs 11.9%; hazard ratio, 5.19; 95% confidence interval, 1.67-16.21). There were no significant relationships between the clinical characteristics of patients and the development of NIPD. These findings suggest that the ACE genotype is associated with the development of NIPD following HSCT. This study is the first to report the relationship between genetic background and NIPD.

We report a patient who developed chronic renal failure 11 months after an allogeneic hematopoietic stem-cell transplantation (HSCT) for Ph1(+) acute lymphocytic leukemia. Renal biopsy showed typical pathological findings compatible with a bone marrow transplant nephropathy (BMT nephropathy). The general course of BMT nephropathy is slowly progressive, eventually reaching endstage renal failure. Intervention therapy with an angiotensin-converting enzyme inhibitor (ACE-I), temocapril, was started for this patient, based on several experimental reports showing the protective effects of ACE-Is on BMT nephropathy. After the induction of ACE-I in this patient, the rate of regression of renal function was significantly reduced and his serum creatinine was maintained at almost the same level for 18 months. Although the course of observation in this patient was short, we clearly showed the effects of an ACE-I on preventing BMT nephropathy from progressing to endstage renal failure in a human rather than in an experimental model.

A reduced incidence of graft versus host disease (GvHD) has been documented among Japanese allogeneic bone marrow transplantation (BMT) patients, as the Japanese are genetically more homogeneous than western populations. To clarify whether this ethnic difference affects the results of allogeneic peripheral blood stem cell transplantation (PBSCT), we conducted a nationwide survey to compare clinical outcomes of allogeneic PBSCT (n = 214) and BMT (n = 295) from a human leucocyte antigen-identical-related donor in Japanese patients. The cumulative incidence of grades II-IV acute GvHD was 37.4% for PBSCT and 32.0% for BMT. The cumulative incidence of extensive chronic GvHD at 1 year was significantly higher after PBSCT than BMT (42% vs. 27%; P0.01). The organ involvement patterns of GvHD were different between the two groups. By multivariate analyses, the incidence of chronic GvHD was significantly increased in PBSCT, whereas the stem cell source did not affect the incidence of acute GvHD, transplant-related mortality, relapse or survival. We concluded that Japanese PBSCT patients have an increased risk of chronic GvHD compared with BMT patients, but the incidence of acute GvHD was still lower than in western populations. Thus, the choice of haematopoietic stem cell source should be considered based on data for individual ethnic populations.

The effect of graft-versus-host disease (GVHD) on relapse incidence and survival has been analyzed in several studies, but previous studies included heterogeneous patients. Therefore, we analyzed the data of 2114 patients who received unmanipulated bone marrow graft from an HLA-identical sibling donor with a GVHD prophylaxis using cyclosporin A and methotrexate. Among the 1843 patients who survived without relapse at 60 days after transplantation, 435 (24%) developed grade II-IV acute GVHD. Among the 1566 patients who survived without relapse at 150 days after transplantation, 705 (47%) developed chronic GVHD. The incidence of relapse was significantly lower in patients who developed acute or chronic GVHD, but disease-free survival (DFS) was significantly inferior in patients who developed acute GVHD. A benefit of 'mild' GVHD was only seen in high-risk patients who developed grade I acute GVHD. The strongest association between GVHD and a decreased incidence of relapse was observed in patients with standard-risk acute myelogenous leukemia/myelodysplastic syndrome. In conclusion, the therapeutic window between decreased relapse and increased transplant-related mortality due to the development of GVHD appeared to be very narrow.

Acute promyelocytic leukemia (APL) is specifically associated with a reciprocal translocation, t(15; 17)(q22; q21), leading to the formation of a fusion of the retinoic acid receptor-alpha (RARA) gene and the promyelocytic leukemia (PML) gene. However, there are several reports describing APL cases lacking the t(15; 17). Many such cases are those bearing variant translocations involving chromosomes 15 or 17, and those with no chromosomal aberrations have rarely been reported. We have studied a patient with APL showing an apparently normal karyotype which was confirmed by spectral karyotyping (SKY). A submicroscopic PML-RARA fusion was identified by reverse transcriptase-polymerase chain reaction (RT-PCR) and fluorescent in situ hybridization (FISH). All-trans retinoic acid (ATRA) was effective as the initial therapy for remission induction and as the reinduction therapy after a relapse. The present study shows the key role of the fusion of PML-RARA in the responsiveness to ATRA as well as in the leukemogenesis of APL.

Background: Contradictory results have been reported in terms of detecting bcr/abl transcripts in patients with essential thrombocythemia. The aim of this study was to investigate whether the bcr/abl transcript could be found in patients with essential thrombocythemia (ET). Methods: The bcr/abl transcript was amplified by the RT-nested PCR method using RNA extract from leukocytes taken from 14 essential thrombocythemia patients. The amplified DNAs were electrophoresed in 1% agarose and visualized with ethidium bromide. The DNA bands associated with the bcr/abl transcript were then extracted and followed by DNA sequence analysis. Results: Major bcr/abl transcripts of the b3a2 type and minor ones of the e1a2 type were found in one and two ET patients, respectively. The incidence of bcr/abl transcripts was 21.4% (three of 14 patients). Conclusion: Our experiments confirmed that bcr/abl transcripts are present in some patients with essential thrombocythemia.