Search

Treatment-free remission (TFR) is a new goal for patients with chronic myeloid leukemia in chronic phase (CML-CP) with a sustained deep molecular response (DMR) to treatment with tyrosine kinase inhibitors (TKIs). However, optimal conditions for successful TFR in patients treated with second-generation (2G)-TKIs are not fully defined. In this D-FREE study, treatment discontinuation was attempted in newly diagnosed CML-CP patients treated with the 2G-TKI dasatinib who achieved BCR-ABL1 levels of ≤ 0.0032% (MR4.5) on the international scale (BCR-ABL1IS) and maintained these levels for exactly 1 year. Of the 173 patients who received dasatinib induction therapy for up to 2 years, 123 completed and 60 (48.8%) reached MR 4.5. Among the first 21 patients who maintained MR4.5 for 1 year and discontinued dasatinib, 17 experienced molecular relapse defined as loss of major molecular response (BCR-ABL1IS > 0.1%) confirmed once, or loss of MR4 (BCR-ABL1IS > 0.01%) confirmed on 2 consecutive assessments. The estimated molecular relapse-free survival rate was 16.7% at 12 months. This study was prematurely terminated according to the protocol's safety monitoring criteria. The conclusion was that sustained DMR for just 1 year is insufficient for TFR in CML-CP patients receiving dasatinib for less than a total of 3 years of treatment. [ABSTRACT FROM AUTHOR]

Fludarabine with intravenous busulfan (6.4 mg/kg; FB2) and fludarabine with intermediate-dose melphalan (140 mg/m2; FM140) are the most widely used reduced-intensity conditioning (RIC) regimens for allogeneic hematopoietic stem cell transplantation. FM140 generally has a lower relapse rate and higher non-relapse mortality (NRM), resulting in overall survival (OS) comparable to that seen with FB2. To evaluate the effect of reducing the melphalan dose, we retrospectively compared transplant outcomes in 156 patients who received FB2 (n = 103) or FM80 (n = 53) at our center (median age: 63 years; range 27–72 years). All patients received 4-Gy total body irradiation. Three-year OS, the cumulative incidence of relapse, and NRM were comparable between groups (FB2 vs. FM80, 58% vs. 47%, p = 0.24; 30% vs. 36%, p = 0.57; 17% vs. 21%, p = 0.44, respectively). There was no significant difference in the cumulative incidence of graft-versus-host disease (GVHD) at day 100, chronic GVHD at 3 years, or the 3-year GVHD-free/relapse-free survival rate. In the high-risk disease group, patients receiving FM80 tended to have lower 3-year OS (FB2 vs. FM80, 48% vs. 17%, p = 0.06). In summary, transplant outcomes following FB2 or FM80 were comparable except in patients with high-risk disease. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients are at high risk of developing invasive pneumococcal disease (IPD) with substantial morbidity and mortality. Pneumococcal polysaccharide vaccine (PPSV23) and pneumococcal conjugate vaccine (PCV13) are the primary prevention strategy. The difference between the Japanese and international guidelines is limited except when to start PCV13. However, Japanese data regarding the incidence of IPD after allo-HSCT that include vaccination status are limited. Therefore, we aimed to study the clinical characteristics of patients with IPD following allo-HSCT, focusing on unvaccinated patients. We retrospectively reviewed allo-HSCT recipients between April 2005 and December 2018 at Komagome Hospital. Among 1,091 recipients, 11 (1008/100,000 recipients) developed 13 episodes of IPD. The median period from the first allo-HSCT to the first IPD episode was 686 days (10–3040 days). Ten patients developed IPD before vaccination, and seven of these unvaccinated patients with late-onset IPD were ineligible for vaccination based on domestic guidelines. Although appropriate treatments resulted in a good short-term prognosis, most episodes of IPD developed in unvaccinated allo-HSCT recipients. Our data support the promotion of better adherence to the current guidelines and the importance of pneumococcal vaccination even years after allo-HSCT to protect against late-onset IPD. [ABSTRACT FROM AUTHOR]

Bone turnover markers (BTMs) are useful parameters for assessing fracture risk and unlike bone mineral density (BMD), can be measured at any institution. However, BTM values have not been established in patients post-allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the practicality of BTMs in patients who underwent allo-HSCT by measuring levels of the serum bone resorption marker, tartrate-resistant acid phosphatase-5b (TRACP-5b), and the bone formation marker, bone-specific alkaline phosphatase (BAP), together with BMD, 1 month before and 6 months after allo-HSCT. Patients were classified into either the alendronate group (n = 14) if alendronate treatment (35 mg orally per week) was administered before allo-HSCT or within 1 month after allo-HSCT, or the control group (n = 16), in which patients did not receive alendronate treatment. Despite the high frequency of corticosteroids users in the alendronate group (71.4 vs. 18.9%; p < 0.01), the mean percentage changes in BMD at the lumbar spine (− 2.9 vs. − 3.1%; p = 0.44) and femoral neck (− 3.2 vs. − 4.1%; p = 1.00), TRACP-5b levels (− 4.8 vs. 9.9%; p = 0.45), and BAP levels (6.9 vs. 1.0%; p = 0.85) during 6 months did not differ significantly between the alendronate and control groups. Additionally, the percentage changes in BMD at the lumbar spine were negatively associated with the TRACP-5b levels 6 months after allo-HSCT (p = 0.03, r = 0.40). Our results indicate the possible effectiveness of alendronate treatment in allo-HSCT patients. BTM levels could be useful to monitor the BMD changes. [ABSTRACT FROM AUTHOR]

Treatment outcomes for chronic myeloid leukemia (CML) have dramatically improved with the development of tyrosine kinase inhibitors (TKI). However, due to the improved prognosis for CML, problems have arisen from long-term administration of TKI. The present study sought to verify whether more patients could achieve treatment-free remission (TFR) after stopping the administration of dasatinib using dasatinib as frontline treatment. Treatment-naïve chronic phase CML cases were treated with dasatinib as frontline treatment. Dasatinib treatment was stopped for 26 patients who achieved deep molecular response (DMR) within 24 months and were able to maintain DMR for an additional 2 years. Ten patients (38.5%) achieved DMR maintenance after 12 months. Recurrence was confirmed in 16 patients, and the median recurrence-free survival time was 5.1 months. The cumulative DMR rates at six and 12 months after restarting treatment were 84.6% and 100%, respectively. The results of this study demonstrated that the DMR maintenance rate after 12 months was 38.5%, which was not significantly different from previous TKI stop trials. The 2-year dasatinib administration period after reaching DMR did not contribute to improve TFR rates. These results suggest that the type of TKI is not associated with better TFR rates. [ABSTRACT FROM AUTHOR]

To investigate the use of high-dose therapy and autologous stem cell transplantation (ASCT) for relapsed or high-risk diffuse large B-cell lymphoma (DLBCL) between 1990 and 2007, we conducted a nationwide survey using the registry database of the Japan Society for Hematopoietic Cell Transplantation. Of the 1222 patients in the database, 576 (47%) received ASCT in first complete remission (CR1), 140 (12%) in first partial remission, 281 (23%) in sensitive relapse, 150 (12%) in resistant or sensitivity-unknown relapse, and 75 (6%) in primary refractory status. With a median follow-up of 22 months, the 2-year overall survival (OS) and progression-free survival rates were 71% and 68%, respectively. The cumulative incidences of 2-year non-relapse mortality and relapse/progression were 6% and 26%, respectively. Relapse/progression after ASCT in the rituximab era (2002-2007) was significantly lower than that in the pre-rituximab era (1990-2001; P < 0.001). Older age, male gender, poor performance status at ASCT, non-CR1 at ASCT, ASCT performed in 1990-2001, and LEED or MCEC regimen were adverse predictors of OS. Because ASCT for newly diagnosed high-risk DLBCL has not been performed recently, a registry database study to assess the impact of ASCT for relapsed or refractory DLBCL in the rituximab era is warranted. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (HSCT) could be the only curative therapy for patients with relapsed/refractory acute leukemia (RRAL). Many reports have described unmanipulated haploidentical HSCT (HID-HSCT) using high-dose antithymocyte globulin (ATG). However, the transplant outcomes of HID-HSCT using very low-dose ATG (thymoglobulin, 2-2.5 mg/kg) and methylprednisolone (mPSL, 1 mg/kg) for patients with RRAL have not been reported. We compared the outcomes of 46 patients with RRAL who underwent HID-HSCT using very low-dose ATG (thymoglobulin) and mPSL with the outcomes of 72 patients who underwent non-HID-HSCT. Patient characteristics differed regarding conditioning intensity (myeloablative; 19.6% in HID-HSCT vs. 61.1% in non-HID-HSCT, P < 0.001) and having undergone multiple HSCT (26.1% vs. 11.1%, P = 0.045). However, we found no significant differences in the 1-year overall survival (OS, 31.7% vs. 29.1%; P = 0.25), disease-free survival (DFS, 20.5% vs. 23.7%; P = 0.23), cumulative incidence of relapse (CIR, 40.0% vs. 42.8%; P = 0.92), non-relapse mortality (NRM, 39.5% vs. 33.5%; P = 0.22), or 100-day grade II-IV acute graft-versus-host disease (32.6% vs. 34.7%; P = 0.64) following HID-HSCT vs. non-HID-HSCT, respectively. Subgroup analysis stratified by disease and intensity of conditioning regimen demonstrated the same results between HID-HSCT and non-HID-HSCT. Furthermore, multivariate analysis showed that HID-HSCT was not an independent prognostic factor for OS (hazard ratio (HR) = 0.95 [95% confidence interval (CI), 0.58-1.58]), DFS (HR = 1.05 [95%CI, 0.67-1.68]), CIR (HR = 0.84 [95%CI, 0.48-1.47]), or NRM (HR = 1.28 [95%CI, 0.66-2.46]). In summary, transplant outcomes for RRAL were comparable in the HID-HSCT and non-HID-HSCT groups. HID-HSCT using very low-dose ATG and mPSL for RRAL may be a viable alternative to non-HID-HSCT. [ABSTRACT FROM AUTHOR]

Autologous stem-cell transplantation is an effective procedure for the treatment of multiple myeloma, and involves the collection of hematopoietic stem cells (HSCs). However, in some patients, HSCs in the bone marrow fail to mobilize. Pomalidomide upregulates CXCR4 in hematopoietic stem cells, in a manner similar to that of lenalidomide, and is, thus, likely to have a negative impact on hematopoietic stem-cell mobilization in multiple myeloma patients. Here, we report the two cases in which hematopoietic stem cells were mobilized using plerixafor plus granulocyte-colony stimulating factor after exposure to lenalidomide and pomalidomide. Use of plerixafor with a sufficient washout period may lead to successful mobilization following pomalidomide use, although further study of this potential use is needed. [ABSTRACT FROM AUTHOR]

Recent studies have described various impacts of obesity and being overweight on acute myeloid leukemia (AML) outcomes in adult patients, but little is known about the impact of being underweight. We compared the outcomes of underweight patients to those of normal weight and overweight patients. Adult patients with AML who registered in the JALSG AML201 study (n = 1057) were classified into three groups: underweight (body mass index [BMI] < 18.5, n = 92), normal weight (BMI 18.5-25, n = 746), and overweight (BMI ≥ 25, n = 219). With the exception of age and male/female ratio, patient characteristics were comparable among the three groups. Rates of complete remission following induction chemotherapy were similar among the three groups (p = 0.68). We observed a significant difference in overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) between underweight and normal weight patients (3-year OS 34.8 vs. 47.7%, p = 0.01; DFS 28.6 vs. 39.8%, p = 0.02; 1-year NRM 6.2 vs. 2.6%, p = 0.05), but not between underweight and overweight patients. In multivariate analysis, underweight was an independent adverse prognostic factor for OS (p < 0.01), DFS (p = 0.01), and NRM (p = 0.04). During the first induction chemotherapy, the incidences of documented infection (DI) and severe adverse events (AEs) were higher in underweight patients than those in normal weight patients (DI 16 vs. 8.1%, p = 0.04; AE 36 vs. 24%, p = 0.05). In conclusion, underweight was an independent adverse prognostic factor for survival in adult AML patients. [ABSTRACT FROM AUTHOR]

Background: With the introduction of imatinib, a first-generation tyrosine kinase inhibitor (TKI) to inhibit BCR-ABL1 kinase, the outcome of chronic-phase chronic myeloid leukemia (CP-CML) has improved dramatically. However, only a small proportion of CP-CML patients subsequently achieve a deep molecular response (DMR) with imatinib. Dasatinib, a second-generation TKI, is more potent than imatinib in the inhibition of BCR-ABL1 tyrosine kinase in vitro and more effective in CP-CML patients who do not achieve an optimal response with imatinib treatment. Methods: In the present study, we attempted to investigate whether switching the treatment from imatinib to dasatinib can induce DMR in 16 CP-CML patients treated with imatinib for at least two years who achieved a major molecular response (MMR) with detectable levels of BCR- ABL1 transcripts. Results: The rates of achievement of DMR at 1, 3, 6 and 12 months after switching to dasatinib treatment in the 16 patients were 44% (7/16), 56% (9/16), 63% (10/16) and 75% (12/16), respectively. The cumulative rate of achieving DMR at 12 months from initiation of dasatinib therapy was 93.8% (15/16). The proportion of natural killer cells and cytotoxic T cells in peripheral lymphocytes increased after switching to dasatinib. In contrast, the proportion of regulatory T cells decreased during treatment. The safety profile of dasatinib was consistent with previous studies. Conclusion: Switching to dasatinib would be a therapeutic option for CP-CML patients who achieved MMR but not DMR by imatinib, especially for patients who wish to discontinue TKI therapy. [ABSTRACT FROM AUTHOR]

From January 2012 to September 2015, 49 patients received biosimilar filgrastim (BF) after allogeneic bone marrow transplantation (BMT, n = 31) or peripheral stem cell transplantation (PBSCT, n = 18) in our institution. To evaluate the clinical impact of BF on transplant outcomes of these patients, we compared hematological recovery, overall survival (OS), disease-free survival (DFS), transplantation-related mortality (TRM), cumulative incidence of relapse (CIR), and acute and chronic graft-versus-host disease (GVHD) with those of control patients who received originator filgrastim (OF) after BMT (n = 31) or PBSCT (n = 18). All cases were randomly selected from a clinical database in our institution. In both the BMT and PBSCT settings, neutrophil recovery (17 vs. 19 days in BMT; 13 vs. 15 days in PBSCT) and platelet recovery (27 vs. 31 days in BMT; 17 vs. 28 days in PBSCT) were essentially the same between BF and OF. They were also comparable in terms of OS, DFS, TRM, CIR, and the incidence of acute GVHD and chronic GVHD. On multivariate analysis, the use of BF in both BMT and PBSCT was not a significant factor for adverse transplant outcomes. Although BF significantly reduced filgrastim costs in both BMT and PBSCT, total hospitalization costs were not significantly different between BF and OF. [ABSTRACT FROM AUTHOR]

Cyclophosphamide (CY) cardiotoxicity induces a rare lethal complication associated with its use. The minimum dose for cardiac toxicity is still not known, although there are no reports of CY toxicity at doses of less than 100 mg/kg. There are few studies of CY cardiotoxicity that included a large number of patients who received high-dose CY for conditioning for allogeneic stem cell transplant (allo-HSCT). To elucidate the clinical course, complications, true incidence, and risk factors, the cardiac events of 811 patients who received more than a total of 100 mg/kg of CY as conditioning for allo-HSCT were analyzed. Twelve of 811 recipients (1.5 %) developed fatal cardiac failure induced by CY at a median of 4 (range 2-8) days after the first administration of CY. Regarding the dose of CY, 8.5, 1.2, and 0 % of the patients developed cardiac failure among the patients treated with a total of 200, 120, and 100 mg/kg CY, respectively. On echocardiography, the E/A ratio shows diastolic dysfunction but not the ejection fraction changed in the early course. Moreover, a short time to the first symptom after the administration of CY tended to be associated with early death (p = 0.09). Eleven patients died from progressive acute cardiac failure at day 7 (5-30) after the first administration of CY, and only one patient survived. In summary, fatal CY cardiotoxicity with allo-HSCT is a rare complication, but it is associated with high mortality. The possibility of CY-induced cardiotoxicity must be considered early after the administration of CY. [ABSTRACT FROM AUTHOR]

A high-flow nasal cannula (HFNC) is a newly developed device that enables high-flow oxygen therapy for patients with serious cardiopulmonary problems, but there are few data regarding its use in patients with hematological disease. The efficacy and tolerability of HFNCs for patients who developed ARF during the treatment of various hematological diseases was evaluated. Fifty-six patients underwent HFNC therapy during the last 2 years, and the causes of ARF were mainly pneumonia (n = 37) or acute congestive heart failure (n = 7). Only 11 patients (20 %) showed a good response to HFNC therapy, and remaining 45 patients (80 %) failed to respond to the initial HFNC therapy and, therefore, underwent second-line therapy including endotracheal intubation with mechanical ventilation (n = 15), non-invasive positive pressure ventilation (n = 1), or narcotic palliation alone (n = 29). Thus, HFNC appear not to be a viable treatment option in 4 out of 5 patients in this cohort of patients with hematological disease, but it was well tolerated in most patients (96 %); no major complications except for nasal soreness (n = 2) were observed. Multivariate analysis showed that the cause of ARF (pneumonia, odds ratio 11.2, 95 % CI 1.76-71.5, p = 0.01) was the only risk factor for treatment failure. [ABSTRACT FROM AUTHOR]

This nationwide, retrospective study compared the efficacy of cyclosporine and tacrolimus with methotrexate (CsA/MTX and TAC/MTX) for acute graft-versus-host disease (aGVHD) prevention and transplant-related outcomes. Data were obtained from the Transplant Registry Unified Management Program of the Japan Society for Hematopoietic Cell Transplantation for ≥ 16-year-old leukemia patients who received CsA/MTX or TAC/MTX after bone marrow transplantation and peripheral blood stem cell transplantation from serological HLA-matched related donors (MRD), HLA 8/8 allele-matched, or one allele-mismatched unrelated bone marrow (UBM), or 0-2 antigen-mismatched unrelated cord blood (UCB) transplantation between January 2005 and December 2009. Separate analyses were performed for each cohort. Adjusted multivariate analyses indicated that in the MRD (n = 1524) and the UBM (n = 1466) cohorts, TAC/MTX significantly reduced grade II-IV aGVHD risk (HR 0.58, P = 0.006 and HR 0.77, P = 0.015, respectively) without affecting the other transplant-related outcomes. In the UCB cohort (n = 925), TAC/MTX significantly reduced the risk of non-relapse mortality (HR 0.63, P = 0.027) and chronic GVHD (HR 0.60, P = 0.02) without significant effects on grade II-IV aGVHD (HR 0.83, P = 0.21). Our results may provide the most up-to-date data regarding GVHD prevention in Japan. [ABSTRACT FROM AUTHOR]

Increased levels of normal B cell precursors, termed hematogones (HGs), are observed in regenerating bone marrow after chemotherapy or hematopoietic stem cell transplantation (HSCT). Recent reports suggest that emergence of HGs is associated with better outcomes following allogeneic HSCT (allo-HSCT). We reviewed the emergence of HGs and the clinical features of 192 patients after allo-BMT. Patients undergoing allo-BMT from related donors were more likely to develop HGs at day 30 compared to unrelated donors. Furthermore, patients undergoing allo-BMT from HLA-mismatched donors were less likely to develop HGs at day 30. The emergence of HGs at day 30 was an independent prognostic factor among patients who underwent BMT. We found no difference in the relapse rate between HG-positive (+) and HG-negative (-) patients undergoing BMT. HG (-) patients had high non-relapse mortality, grade II to IV acute graft-versus-host-disease (GVHD), fungal infection, and lower IgG levels compared to HG (+) patients. The emergence of HGs at day 30 among patients undergoing BMT may be a very useful indicator of subsequent survival outcomes or acute GVHD in common clinical practice. [ABSTRACT FROM AUTHOR]

The article discusses the research on the effectiveness of mycophenolic acid (MPA), an active metabolite of mycophenolate mofetil, in skin cells of acute graft-versus-host disease patients. It mentions the measurement of treatment responses from patients who have undergone hematopoietic stem cell transplantation. It also mentions a graph on the response rate of MPA in skin, liver, and intestinal cells.

We retrospectively compared transplant outcomes for related bone marrow transplantation (rBMT), related peripheral blood stem cell transplantation (rPBSCT), unrelated bone marrow transplantation (uBMT), and unrelated cord blood transplantation (CBT) in 1,062 patients with chronic myeloid leukemia (CML) aged 20 years or over between January 1, 2000 and December 31, 2009 in Japan. The disease status was as follows: chronic phase 1 (CP1, n = 531), CP 2 or later including accelerated phase (CP2-AP, n = 342) and blastic crisis (BC, n = 189). Graft sources (GS) were rBMT ( n = 205), uBMT ( n = 507), rPBSCT ( n = 226) or CBT ( n = 124). In multivariate analysis in CP1, lower overall survival (OS) (relative risk [RR]: 6.01, 95 % confidence interval [CI]: 1.20-29.97, P = 0.029) and leukemia-free survival (LFS) (RR: 4.26, 95 % CI: 1.24-14.62, P = 0.021) were observed in uBMT compared with those in rBMT. For patients in the advanced phase of CML beyond CP1, GS had no significant impact on OS or LFS. Our results support the use of rBMT for adults with CML in CP1, but in contrast to previous reports, the superiority of rPBSCT in advanced stage of CML was not confirmed in our cohorts. [ABSTRACT FROM AUTHOR]

Recently, the presence of CEBPA mutation was identified as an important prognostic factor for normal karyotype (NK) acute myeloid leukemia (AML). Because AML with CEBPA mutation is closely associated with CD7, CD15, CD34, and HLA-DR expression, we investigated the prognostic implications of CD7+ CD15+ CD34+ HLA-DR + immunophenotype in NK-AML. We analyzed the immunophenotype of 329 patients with NK-AML from the Japan Adult Leukemia Study Group (JALSG) AML97 population. NK-AML with the CD7+ CD15+ CD34+ HLA-DR + immunophenotype was classified as the CEBPA type, and NK-AML that did not meet this criterion was considered as the non-CEBPA type. The influence of the CEBPA status on event-free survival (EFS) and overall survival (OS) was assessed using log-rank test and a multivariate Cox proportional hazard regression model. Furthermore, the surface antigen expression profile in AML according to the CEBPA mutation status (monoallelic or biallelic) was also investigated. Of the 329 NK-AML patients that were studied, 39 and 243 were classified as having CEBPA and non-CEBPA type NK-AML, respectively. Patients with CEBPA type NK-AML had significantly better EFS and OS than those with non-CEBPA type NK-AML. Multivariate analysis showed that the CEBPA type and white blood cell (WBC) counts of >20 × 10/L were independent prognostic factors for EFS and OS. Moreover, NK-AML with the biallelic CEBPA mutation was more closely associated with CD34 positivity than that with the monoallelic CEBPA mutation. NK-AML with the CD7+ CD15+ CD34+ HLA-DR + immunophenotype is a clinically discrete entity, and this may have a possible role in risk stratification. [ABSTRACT FROM AUTHOR]

Lymphocytosis in response to dasatinib for chronic myelogenous leukemia (CML) may be associated with favorable response. However, it occurs at varying times and in a limited subset of patients. To identify early clinical markers for favorable responses applicable to all patients with or without lymphocytosis, we prospectively analyzed lymphocyte profiles of 50 Japanese CML patients treated with dasatinib after intolerance/resistance to imatinib. Although absolute lymphocyte counts did not differ significantly until 3 months between patients with complete molecular response (CMR) at 12 months and those without it, relative increases in lymphocyte compared with baselines differed significantly from 1 month. Patients with relative lymphocyte counts >150 % at 1 month or >200 % at 3 months had higher CMR rates at 12 months than others (57.9 vs. 23.3 %, P = 0.015, and 76.5 vs. 16.1 %, P < 0.0001, respectively). A relative increase in lymphocyte subset of CD57CD14, CD8T, or NK cells >200 % at 1 month was also significantly associated with a higher CMR rate. There were significant negative correlations between relative lymphocyte increases and BCR/ABL transcript levels. CD57CD14 cells were a highly specific focus of proliferation. Relative increases in lymphocyte count and its subsets from 1 month are reliable early markers of favorable responses to dasatinib. [ABSTRACT FROM AUTHOR]

Background: Patients with resolved hepatitis B virus (HBV) infection undergoing chemotherapy or immunosuppressive therapy are potentially at risk of HBV reactivation. However, it remains unclear how liver disease develops after HBV reactivation. To compare the host immune response against HBV, we performed immunological analyses of six HBV reactivation patients.Methods: The numbers of peripheral HBV-specific CD8+ T cells were investigated longitudinally in six HLA-A2- and/or A24-positive patients with HBV reactivation. In addition, 34 patients with resolved HBV, 17 patients with inactive chronic hepatitis B (ICHB), 17 patients with chronic hepatitis B (CHB) and 12 healthy controls were analyzed. The number and function of HBV-specific CD8+ T cells were assessed by flow cytometry using tetramer staining and intracellular IFN-γ production. Furthermore, the numbers of CD4+ CD25+ or CD4+ Foxp3+ T cells and serum inflammatory cytokine levels were analyzed.Results: The frequency of HBV-specific CD8+ T cells was significantly increased in HBV reactivation patients compared with ICHB and CHB patients. In addition, the number of HBV-specific CD8+ T cells was increased in resolved HBV patients compared with ICHB patients. PD-1 expression was decreased in HBV reactivation patients compared with ICHB and CHB patients. The numbers of HBV-specific CD8+ T cells and CD4+ CD25+ or CD4+ Foxp3+ T cells were negatively correlated following onset of HBV reactivation.Conclusions: During HBV reactivation, the frequency of HBV-specific CD8+ T cells increased even though the administration of immunosuppressive drugs and interactions with CD4+ regulatory T cells may be important for the onset of liver disease. [ABSTRACT FROM AUTHOR]

Anti-T lymphocyte globulin (ATG) is commonly used as prophylaxis for graft-versus-host disease (GVHD), especially in patients who are at high risk of GVHD. The appropriate dosage of ATG in Japan has not yet been assessed. We therefore conducted a nationwide survey of patients who received ATG-Fresenius as GVHD prophylaxis for unrelated bone marrow transplantation (uBMT). A total of 86 patients were identified (median age 31 years, range 1-68). The median total dose of ATG was 10 mg/kg. The cumulative incidence of neutrophil engraftment was 90 %. The probability of 2-year overall survival (OS) was 67 %. The cumulative incidence of 2-year non-relapse mortality was 25 %. The incidences of grade II-IV and grade III-IV acute GVHD were 20 and 8 %, respectively. The incidences of chronic and extensive chronic GVHD were 19 and 8 %, respectively. In adult patients, there was a reduction of acute GVHD with high-dose ATG (>10 mg/kg), which did not reach statistical significance. In conclusion, the addition of low-dose ATG to GVHD prophylaxis in Japanese patients who received uBMT resulted in decreased incidences of both acute and chronic GVHD without compromising OS. The effects of low-dose ATG should be assessed in a prospective clinical trial. [ABSTRACT FROM AUTHOR]

Background: Real-time quantitative polymerase chain reaction (RQ-PCR) has been widely used for molecular monitoring for patients with chronic myeloid leukemia (CML). Currently, RQ-PCR is not based on the concept of international scale (IS) in Japan; mainly because none of the domestic laboratories have obtained their own conversion factor (CF) which makes it possible to convert locally scaled BCR- ABL ( BCR- ABL) value to the IS ( BCR- ABL). To join the global trend of molecular assessment of BCR- ABL in CML patients, we have tried to obtain a CF in Japan. Methods: Samples from 55 patients were exchanged between the Japanese laboratory and the reference laboratory in Adelaide, and BCR- ABL and internal control gene transcripts of the samples were measured using RQ-PCR. The patient bias conversion method was used to determine the CF for the IS using the Bland and Altman method. Results: The local CF in the Japanese laboratory was determined to be 0.87. Based on this CF, 0.1% BCR- ABL, defined as major molecular response, becomes equivalent to 731 copy/μg RNA BCR- ABL. Conclusion: This study is the first to introduce a laboratory-specific CF for harmonizing RQ-PCR methodology for detecting BCR- ABL transcripts to Japan, which may open new windows for molecular assessment of CML patients in Japan. [ABSTRACT FROM AUTHOR]

The aim of this retrospective study was to evaluate the toxicity profiles of dasatinib in patients with Philadelphia chromosome positive chronic myeloid leukemia (CML) or acute lymphatic leukemia (ALL) who were intolerant to imatinib, and who had been enrolled in our previous clinical trials to evaluate efficacy of dasatinib in patients resistant or tolerant to imatinib therapy. Twenty-four patients with CML and four with ALL were enrolled in the clinical studies to evaluate the efficacy according to the eligibility criteria related to intolerance to imatinib therapy. The toxicities reported during imatinib therapy were non-hematological toxicities in 23 patients and hematological toxicities in six patients. Patients were administered dasatinib 50-70 mg BID or 100 mg QD. Cross intolerance was observed in four patients who showed hematological toxicity after dasatinib treatment. However, it was possible to successfully continue therapy with only temporary interruption. No cross intolerance in non-hematological toxicity was found with the exception of one patient who showed cross intolerance, which did not result in treatment interruption. Dasatinib can be safely administered to imatinib-intolerant CML or Ph-positive ALL patients. [ABSTRACT FROM AUTHOR]

Bronchiolitis obliterans (BO) after allogeneic stem cell transplantation (allo-SCT) is a late-onset, life-threatening respiratory complication that significantly reduces a patient's quality of life. We retrospectively analysed the incidence of and risk factors for BO in allo-SCT recipients. In 2087 patients who underwent allo-SCT between January 1994 and June 2005 and survived >90 days after transplantation, 57 patients developed BO with a 5-year cumulative incidence of 2.8%. The median time interval from transplantation to BO diagnosis was 335 days (range 83-907 days). The 5-year cumulative incidence of BO was 1.62% in bone marrow transplantation (BMT) from related donors, 3.83% in peripheral blood stem cell transplantation (PBSCT) from related donors (R-PBSCT), 2.91% in BMT from unrelated donors and 2.65% in unrelated cord blood transplantation. The incidence of BO after R-PBSCT was significantly higher than that after any other type of allo-SCT (p = 0.02). R-PBSCT (p = 0.019) and preceding chronic graft-versus-host disease (GVHD) (p < 0.001) were BO-associated risk factors. Overall 5-year survival of patients with BO from the time of diagnosis was 45.4%, significantly less than those without (77.5% from day 335, p < 0.001). R-PBSCT recipients with existent chronic GVHD have a high risk of developing BO, and need extensive care and repeated pulmonary function tests. [ABSTRACT FROM AUTHOR]

We analyzed the incidence and prognosis of bacteremia/fungemia and pneumonia during remission induction therapy of a newly diagnosed acute myelogenous leukemia (AML) in the Japan Adult Leukemia Study Group treated with individual protocols of AML-87/-89 (1987-1991), AML-92 (1992-1995), AML-95 (1995-1997), and AML-97 (1997-2001). Bacteremia/fungemia was present in 251 of 2585 cases (9.7%); the causative microorganism was gram-positive bacteria (GPB) in 122 cases (49%), gram-negative bacteria (GNB) in 90 cases (36%), fungi (F) in 31 cases (12%), and polymicrobes (P) in 8 cases (3%). Particularly prevalent were Pseudomonas aeruginosa in 49 cases (20%), Staphylococcus epidermidis in 29 cases (12%), and Staphylococcus aureus in 25 cases (10%). With AML-87/-89, incidence of bacteremia/fungemia was 11.8% while it was 9.4% with AML-92, 8.7% with AML-95, and 9.2% with AML-97. The proportion of GPB, GNB, F, and P was 40, 41, 16, and 3% in AML-87/-89, 46, 40, 11, and 3% in AML-92, 48, 39, 11, and 2% in AML-95, and 59, 26, 11, and 4% in AML-97. The mortality rate by period was 26.5, 16.4, 14.0, and 6.8%, respectively. Pneumonia was found in 433 cases (16.8%); microbiological research covered 359 cases of AML-87/-89, AML-92, AML-97 and excluded AML-95 as there was no listing for the causative microorganism on questionnaires. Microbiologically documented pneumonia was found in 123 cases (34.3%), with GPB in 33 cases (27%), GNB in 28 cases (23%), F in 44 cases (36%), and P in 18 cases (15%); particularly prevalent were Aspergillus in 23 cases (19%), Staphylococcus aureus in 16 cases (13%), and Pseudomonas aeruginosa in 15 cases (12%). The incidence of pneumonia overall was 24.6% with AML-87/-89, 16.9% with AML-92, 13.9% with AML-95, and 12.9% with AML-97, with a mortality rate of 28.9, 33.3, 16.7, and 16.7%, respectively. Incidence of bacteremia/fungemia and pneumonia complicating AML has tended to decline in recent years, and mortality has also tended to improve. [ABSTRACT FROM AUTHOR]

Foscarnet is an active agent against cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT), as well as ganciclovir. We investigated the usefulness of foscarnet in patients who underwent related allogeneic HSCT. Foscarnet was used in 320 patients with a median age of 45 years (range 15-72). The purpose of administration was CMV disease in 65, preemptive use in 248 and prophylaxis in 7. Totally, 194 patients had a history of prior ganciclovir treatment. The reason for foscarnet use was insufficient therapeutic effect of prior ganciclovir in 99, and adverse event including myelosuppression in 95. The response rate in symptom was 52% for the CMV disease patients. Antigenemia disappeared in 77% of the preemptive treatment and improved in 13% of the patients. No outbreak of CMV disease was recognized. The total effectiveness of therapeutic and preemptive use was significantly higher for patients without prior ganciclovir (91 vs. 76%, P = 0.001). Adverse events of grade 3 or higher were recognized in 24%, including electrolyte abnormalities in 11%, neutropenia in 8%, and thrombocytopenia in 8%. Renal damage was only observed in 3% of patients. Foscarnet was concluded to be a safe and effective anti-CMV agent and to be a suitable alternative to ganciclovir. [ABSTRACT FROM AUTHOR]

During follow-up of leukocyte counts in 20 consecutive patients (age range 29-81 years) treated with dasatinib, 9 patients (7 chronic myeloid leukemia in chronic phase, 2 Philadelphia chromosome-positive acute lymphoid leukemia in complete remission) developed lymphocytosis (>3,000/microl). Peripheral blood smears revealed a population of large granular lymphocytes. Large granular lymphocytosis (LGL) was first noted between 1 and 8 months after initiation of dasatinib, and it has persisted up to 33 months from the onset of LGL in one patient. Peak numbers of large granular lymphocytes ranged from 2,915 to 17,425/microl. The occurrence of LGL might interfere with achieving molecular response (MR, real-time quantification of major BCR-ABL1 mRNA less than 50 copies/microg RNA) in our small cohort; 8 (89%) of 9 patients with LGL attained MR, while only 6 (55%) of 11 patients without LGL eventually achieved MR. With respect to the relationship between LGL and pleural effusion (PE), 3 (27%) of 11 patients without LGL developed PE, while 5 (56%) of 9 patients with LGL developed PE. Moreover, the mean peak number of LGL was 9,215/microl, which was much higher than the mean peak number (4,635/microl) of LGL in patients without PE. These results may suggest possible association of both events in our cohorts. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Recent studies have shown that high BAALC expression predicts an adverse prognosis and may define an important risk factor in acute myeloid leukemia patients with normal karyotype. We performed, using real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR), the molecular analysis of BAALC gene as a possible minimal residual disease (MRD) marker in 45 patients with newly diagnosed acute leukemia. BAALC transcript levels in 32 patients with CD34 expressed in leukemic blasts were 2-3 logs higher than background levels, and the copy number was reduced in patients achieving hematological remission. Comparative monitoring of MRD by RQ-PCR for the Wilms' tumor gene 1(WT1) or specific translocation markers demonstrated that BAALC had similar kinetics as WT1, AML1/ETO and minor BCR/ABL, but not PML/RARA. Quantitation of BAALC gene expression made it possible to assess MRD in patients with CD34-positive acute leukemia. To our knowledge, this is the first report concerning the use of BAALC mRNA expression for MRD monitoring. [ABSTRACT FROM AUTHOR]

We retrospectively reviewed the medical records of 75 allogeneic hematopoietic transplant recipients and evaluated cystatin C as a potential marker of subsequent renal dysfunction. Acute kidney injury developed in 31 of 75 patients after a median of 46 days post-transplantation (range 1-502 days), while worsening of chronic kidney disease (CKD) was observed in 21 patients during the observational period. Cystatin C level was significantly elevated after allogeneic transplantation (P < 0.001). Multivariate analysis revealed the use of calcineurin inhibitors as a major cause of cystatin C elevation (odds ratio 7.26, P = 0.04). A strong inverse correlation was also noted between cystatin C and estimated glomerular filtration rate (r = -0.682, P < 0.001). Cystatin C measurement could provide a useful clinical tool to identify hematopoietic stem cell transplantation recipients at an increased risk for CKD. [ABSTRACT FROM AUTHOR]

We describe herein the clinical courses and outcomes of 26 patients who received oral mycophenolate mofetil (MMF) for the treatment of steroid-resistant refractory or steroid-dependent acute or chronic graft-versus-host disease (GVHD) in a single institution. In most cases, 1,500 mg/day of MMF is a median dose (range 500-3,000 mg/day) and administered for 116.5 days (range 9-584 days) along with calcineurin inhibitors and steroids. Although 20 patients (77%) showed rapid improvement of GVHD symptoms, of 15 patients, 13 (87%) showed acute GVHD; of 11 patients, 7 (64%) showed chronic GVHD; most patients (54%) experienced infection during MMF administration, including 5 cases with life-threatening infection. Positive cytomegalovirus (CMV) antigenemia was also observed in 19 patients (73%), but no patients developed CMV infection. Within the median follow-up of 12.5 months (range 0.5-67 months), 10 patients (39%) died. This small study demonstrates that MMF offers an alternative tool for rescuing steroid-refractory or steroid-dependent GVHD, but increases the risk of developing life-threatening infection. [ABSTRACT FROM AUTHOR]

We describe the first reported case, in an 82-year-old man, of erythrocytosis caused by an erythropoietin (EPO)-producing thymic carcinoma. The patient underwent computed tomography-guided fine-needle aspiration of a 6-cm anterior mediastinal mass, and histological findings revealed thymic squamous cell carcinoma. The existence of EPO was confirmed immunohistochemically using the tumor tissue. Postoperative clinical improvement of erythrocytosis and the decline of EPO suggest a paraneoplastic nature of erythrocytosis as seen in this patient. [ABSTRACT FROM AUTHOR]

We prospectively compared allogeneic hematopoietic stem cell transplantation (allo-HSCT) with chemotherapy as a post-remission therapy in a multicenter trial (JALSG AML97) of adult patients with intermediate or poor risk acute myeloid leukemia (AML). Of 503 patients aged 15-50 years old registered between December 1997 and July 2001, 392 achieved complete remission (CR). CR patients classified in the intermediate or poor risk group using a new scoring system were tissue typed. Seventy-three with and 92 without an HLA-identical sibling were assigned to the donor and no-donor groups. Of 73 patients in the donor group, 38 (52%) received allo-HSCT during CR1 and 17 (23%) after relapse. Intention-to-treat analysis revealed that the relapse incidence was reduced in the donor group (52 vs. 77%; p = 0.008), and the disease-free survival (DFS) improved (39 vs. 19%; p = 0.016), but overall survival (OS) was not significantly different (46 vs. 29%; p = 0.088). The OS benefit was seen in the patients aged 36-50 years old (49 vs. 24%; p = 0.031), suggesting an advantage of allo-HSCT among older patients with leukemia that is more resistant to chemotherapy than that among younger patients. [ABSTRACT FROM AUTHOR]

We report the first case of Mikulicz's disease (MD) occurring 2 years after autologous peripheral blood stem cell transplantation (PBSCT) for multiple myeloma (MM). A 70-year-old man developed bilateral enlargement of parotid and submandibular glands. The patient had previously received 2 courses of autologous PBSCT for IgG-kappa type MM, and had been stable for 2 years. This salivary gland enlargement was initially felt to represent a recurrence of MM, since along with gland swelling, IgG was also elevated. However, repeated biopsy of the left submandibular gland revealed chronic sclerosing sialadenitis rather than plasmacytoma. Results of salivary gland scintigraphy, serological testing, and absence of sicca symptoms also supported the diagnosis of MD. Concurrently, the patient developed severe thrombocytopenia (0.8 x 10(4)/microl). Bone marrow biopsy showed abundant megakaryocytes, suggesting enhanced platelet destruction. After high-dose steroid and immunoglobulin therapy, the platelet count gradually returned to normal with complete resolution of the salivary gland enlargement. No apparent signs of MM recurrence were documented during these clinical events. [ABSTRACT FROM AUTHOR]

We recently developed an Invader assay combined with reverse transcriptase polymerase-chain-reaction in order to quantify T315I bcr-abl transcripts. Using this assay, we serially monitored T315I bcr-abl transcripts in chronic myeloid leukemia (CML) patients whose bcr-abl transcripts were still detectable at 6 months after starting imatinib therapy. Although, we continued to monitor bcr-abl transcripts in 14 CML patients (13 chronic phases and 1 accelerated phase) for up to 12 months, there were no patients who were apparently resistant to imatinib due to the T315I mutation. In contrast, in a case of Philadelphia chromosome-positive acute lymphoid leukemia being treated with chemotherapy including imatinib, we monitored both wild-type and T315I bcr-abl transcripts, and found increased levels of T315I transcripts during relapse (0% at the time of diagnosis and 54.8% at relapse). Thus, our new approach could be a useful tool to study the kinetics of mutant clones and the pharmacokinetics of drug resistance with regard to the T315I mutation. [ABSTRACT FROM AUTHOR]

A phase 1/2 study was conducted to assess the safety and efficacy of dasatinib in Japanese patients with chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) resistant or intolerant to imatinib. In phase 1, 18 patients with chronic phase (CP) CML were treated with dasatinib 50, 70, or 90 mg twice daily to evaluate safety. Dasatinib

Pulmonary leukemic infiltration (PLI) is more common than generally recognized, but accurate antemortem diagnosis with pathological proof is rarely achieved. We describe herein the clinical courses of two patients with PLI following hematopoietic stem cell transplantation (HSCT). One case is a male patient with acute biphenotypic leukemia, and the other is a female patient with myelodysplastic syndrome. In both cases, hyperleukocytosis did not proceed to PLI. Moreover, the former case presented PLI as the initial manifestation of relapsed leukemia and the latter was accompanied with the fungal pneumonia. High-resolution computed tomography (HRCT) of the chest at onset of PLI showed diffuse small nodular lesions along peribronchovascular bundle, and diagnosis of leukemic infiltration was made based on pathological findings obtained from transbronchial lung biopsy. Biopsy specimens further revealed leukemic infiltration along the lymphatic surrounding the peribronchial or perivascluar regions, which corresponded well with HRCT findings. Thus, radiological and pathological corroborating assessment was important to reach the correct diagnosis. [ABSTRACT FROM AUTHOR]

We reviewed and categorized 638 of 809 patients who were registered in the Japan Adult Leukemia Study Group acute myeloid leukemia (AML)-97 protocol using morphological means. Patients with the M3 subtype were excluded from the study group. According to the WHO classification, 171 patients (26.8%) had AML with recurrent genetic abnormalities, 133 (20.8%) had AML with multilineage dysplasia (MLD), 331 (51.9%) had AML not otherwise categorized, and 3 (0.5%) had acute leukemia of ambiguous lineage. The platelet count was higher and the rate of myeloperoxidase (MPO)-positive blasts was lower in AML with MLD than in the other WHO categories. The outcome was significantly better in patients with high (>or=50%) than with low (<50%) ratios of MPO-positive blasts (P < 0.01). The 5-year survival rates for patients with favorable, intermediate, and adverse karyotypes were 63.4, 39.1, and 0.0%, respectively, and 35.5% for those with 11q23 abnormalities (P < 0.0001). Overall survival (OS) did not significantly differ between nine patients with t(9;11) and 23 with other 11q23 abnormalities (P = 0.22). Our results confirmed that the cytogenetic profile, MLD phenotype, and MPO-positivity of blasts are associated with survival in patients with AML, and showed that each category had the characteristics of the WHO classification such as incidence, clinical features, and OS. [ABSTRACT FROM AUTHOR]

To clarify the clinical features of adult patients with acute leukemia (AL) with 11q23 abnormalities, we performed a retrospective analysis of data from 58 adult Japanese patients: 51 with acute myeloid leukemia (AML), and 7 with acute lymphoblastic leukemia (ALL). The incidences according to fusion partners in AML were: t(9;11), 31.3%; t(11;19), 27.4%; t(6;11), 21.5%. The incidence of patients with t(11;19) was higher than those in the US and Europe, and the incidence of t(4;11) was lower than that in childhood. The results indicated the poor prognosis of AML with 11q23 abnormalities regardless of the fusion partners. AML patients with 11q23 aged <60 years in the first CR who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) showed a more favorable outcome than those treated without allo-HSCT, although the differences were not statistically significant (P = 0.322 for DFS, P = 0.138 for OS). This result suggests that treatment strategies including allo-HSCT may be considered in the first CR in cases of AML with 11q23 abnormalities. However, further studies involving a large number of cases are required to assess the effect of allo-HSCT on adult AL with 11q23 abnormalities. [ABSTRACT FROM AUTHOR]

We describe a rare case of recurrent pulmonary nocardiosis (PN) in a hematopoietic stem cell transplant recipient. The patient developed Nocardia farcinica infection while receiving corticosteroid and cyclosporine for the treatment of bronchiolitis obliterans, probably due to chronic graft-versus-host disease (cGVHD). The patient responded well to the initial treatment with meropenem, but PN recurred 3 times during oral maintenance therapies using different antibiotics, which were chosen on the basis of the results of in vitro susceptibility testing against N farcinica Minocycline, amoxicillin/clavulanate, and levofloxacin were not effective as oral maintenance therapies. Frequent exacerbation of PN was considered to have resulted from the low blood concentration of these antibiotics, and decreased gastrointestinal absorption, probably due to cGVHD, might have been the underlying problem. [ABSTRACT FROM AUTHOR]

We describe the clinical outcome of autologous bone marrow transplantation (ABMT) for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL). Between 1985 and 2000, 14 patients in first complete remission underwent transplantation. In all cases, harvested marrow was purged with a cocktail of complement and monoclonal antibodies to common acute lymphoblastic leukemia antigen (CALLA). Eight patients died following BMT: 2 patients from interstitial pneumonia and 6 from disease recurrence. For the 6 surviving patients in continuous remission, the median follow-up period was 96 months. The probability of disease-free survival and the rate of relapse at 5 years were 41.7% and 51.4%, respectively. Minimal residual disease (MRD) was assayed quantitatively with patient-specific D-JH probes in 6 of 14 cases. A higher residual tumor burden at marrow harvest was associated with subsequent relapse. Efforts to reduce the MRD burden before harvesting stem cells should improve the clinical outcome of ABMT. [ABSTRACT FROM AUTHOR]

We report a case of immune-mediated myelopathy occurring 4 months after unrelated bone marrow transplantation for myelodysplastic syndrome. After the tapering of cyclosporine for graft-versus-host disease prophylaxis, the patient developed several neurological symptoms mimicking the clinical features of multiple sclerosis (MS). Although neurological exacerbation was well stabilized with a bulk dose of corticosteroid, sustained improvement of neurological deficits occurred after the patient developed hematopoietic mixed chimerism (HMC). This experience may provide clinical evidence supporting the current therapeutic concept, in which HMC induction can potentially cure several immune diseases, including MS. [ABSTRACT FROM AUTHOR]

We hypothesized that reducing the dosage of prophylaxis for graft-versus-host disease (GVHD) would reduce the risk of relapse and toxicity after bone marrow transplantation (BMT) from human leukocyte antigen (HLA)-identical siblings. In a prospective phase II trial, 21 patients with leukemia and myelodysplastic syndrome underwent BMT from HLA-identical siblings and received GVHD prophylaxis consisting of low-dose (1.5 mg/kg per day) cyclosporin A (CSP) with short-term methotrexate (MTX) treatment. This low-dose group was compared with a group of retrospective control patients (n = 22) who received a standard CSP dosage (3.0 mg/kg per day) and MTX. One patient died of transplantation-related causes within 100 days. The regimen-related toxicity was quite tolerable. Although acute GVHD of grades II to III was more frequent in the low-dose group (47.6%) than in the control group (22.7%), the increase in acute GVHD did not significantly contribute to morbidity or mortality. There were no differences between the groups in the incidence and severity of chronic GVHD. The probabilities of relapse and survival of the groups were similar according to the risk for relapse at the time of transplantation. A prospective randomized study is required to determine whether low-dose or standard-dose CSP in combination with MTX is optimal for Japanese patients who undergo allogeneic BMT from HLA-identical siblings. [ABSTRACT FROM AUTHOR]

A retrospective study was performed to determine the prevalence of Helicobacter pylori (H pylori) infection, the effect of H pylori eradication on platelet counts, and the characteristic clinical features of chronic immune or idiopathic thrombocytopenic purpura (ITP) with H pylori infection. H pylori infection was found in 300 patients, a group that was significantly older (P < .005) and had more cases of hyperplastic megakaryocytes in the bone marrow (P = .01) than patients without H pylori infection. H pylori eradication therapy was performed in 207 H pylori-positive ITP cases, and the platelet count response was observed in 63% of the successful eradication group and in 33% of the unsuccessful eradication group (P < .005). In the successful group, the complete remission and partial remission rates were 23% and 42%, respectively, 12 months after eradication. In the majority of responders, the platelet count response occurred 1 month after eradication therapy, and the increased platelet count continued without ITP treatment for more than 12 months. H pylori eradication therapy was effective even in refractory cases, which were unresponsive to splenectomy. In conclusion, H pylori infection was involved in most ITP patients older than 40 years in Japan, and eradication therapy should be the first line of treatment in H pylori-positive ITP patients. [ABSTRACT FROM AUTHOR]

On the basis of transplantation data from the Japan Society for Hematopoietic Cell Transplantation, we retrospectively analyzed the impact of cytogenetics at diagnosis on the outcome of transplantation in 628 patients with acute myeloid leukemia who underwent autologous (n = 200), allogeneic related (n = 363), or allogenic unrelated (n = 65) stem cell transplantation (SCT) at first complete remission. For autologous SCT, patients at good cytogenetic risk had a significantly lower relapse rate (P = .017) and a significantly higher event-free survival (EFS) (P = .013) compared with those at intermediate risk. For allogeneic SCT, patients at good cytogenetic risk had a significantly lower relapse rate (P = .019) and insignificantly higher EFS (P = .093) than those at poor risk. For unrelated SCT, there was no significant difference in relapse rate or EFS between patients at good risk and those at intermediate risk. Comparison of the 3 transplantation modalities revealed that autologous SCT patients had a significantly higher incidence of relapse compared with related or unrelated SCT patients in the intermediate-risk group but not in the good-risk group. However, there were no significant differences in EFS among the 3 transplant modalities in either of these 2 risk groups. In multivariate analysis, cytogenetics was found to be an independent predictor of relapse as well as of treatment failure. [ABSTRACT FROM AUTHOR]

The cases of 3 patients with pyomyositis associated with hematological disorders are reported. A 40-year-old man in the blastic phase of chronic myelogenous leukemia and 2 men aged 46 and 71 years with neutropenia due to myelodysplastic syndromes all reported high fever and severe local myalgia and had marked elevation of C-reactive protein. Magnetic resonance imaging revealed muscle abscesses or fasciitis, and the findings led to the diagnosis of pyomyositis. Methicillin-resistant Staphylococcus aureus was isolated from the abscesses of 2 patients, and surgical drainage proved more effective than did antimicrobial agents. It should be recognized that pyomyositis is a possible source of infection in patients with hematological disorders. [ABSTRACT FROM AUTHOR]