Radiotherapy with or without chemotherapy for locally advanced head and neck cancer in elderly patients: analysis of the Head and Neck Cancer Registry of Japan.

BACKGROUND: Whether concurrent chemotherapy with radiotherapy (CRT) is effective for elderly patients with head and neck cancer is a controversial topic. This study aimed to analyze the effectiveness of CRT vs. radiation therapy (RT) among elderly patients in Japan. METHODS: Data from the Head and Neck Cancer Registry of Japan were extracted and analyzed. Patients with locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, or larynx who received definitive CRT or RT between 2011 and 2014 were included. RESULTS: CRT was administered to 78% of the 1057 patients aged ≥ 70 years and 67% of the 555 patients aged ≥ 75 years. For the patients aged ≥ 75 years, the overall survival (OS) rate was significantly better in the CRT group than in the RT group (P < 0.05), while the progression-free survival (PFS) rate was not significantly different (P > 0.05). The add-on effect of CRT was significantly poor in elderly patients (P < 0.05), and it was not a significant factor in the multivariate analysis for patients aged ≥ 75 years. After propensity score matching, there were no significant differences in the OS and PFS rates between the patients aged ≥ 70 years and those aged ≥ 75 years (all, P > 0.05). CONCLUSION: Although aggressive CRT is administered to elderly patients in Japan, its effectiveness is uncertain. Further prospective randomized trials are needed to verify whether CRT is superior to RT alone for elderly patients.

EGFR inhibition in EGFR-mutant lung cancer cells perturbs innate immune signaling pathways in the tumor microenvironment.

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) elicit potent cell cycle arrest in EGFR-mutant non-small-cell lung cancer (NSCLC) cells. However, little is known about the mechanisms through which these drugs alter the tumor phenotype that contributes to the immune escape of EGFR-mutant cells. Using EGFR-mutant NSCLC cell lines and tissue samples from patients, we investigated the changes in immune checkpoints expressed in tumor cells following EGFR inhibition. Subsequently, we also analyzed the role of soluble factors from the dying tumor cells in the activation of immune signaling pathways involved in therapy resistance. Upon EGFR-TKI treatment, we found that EGFR-mutant cells upregulated the expression of innate immune checkpoint CD24 in vitro. We then analyzed biopsy samples from six patients who developed resistance to a first-generation EGFR-TKI without the acquired T790M mutation. Immunohistochemistry revealed that levels of tumor CD24 expression were increased upon treatment compared with those from pre-treatment samples. Monocyte-derived macrophages facilitated antibody-dependent cellular phagocytosis when EGFR-TKI-treated EGFR-mutant cells were incubated with anti-CD24 antibodies in vitro, suggesting that CD24 may be a therapeutical target for EGFR-mutant lung cancer. Moreover, EGFR inhibition accelerated the release of cell-free DNA (cfDNA) from dying tumor cells, which activated the type I interferon signaling pathways in human THP-1 monocytes in a stimulator of interferon genes-dependent manner. Our study indicates that EGFR inhibition in EGFR-mutant NSCLC cells fosters a tumor microenvironment associated with immune escape. Thus, CD24 targeted therapy and cfDNA monitoring may contribute to improved treatment outcomes in patients with EGFR-mutant NSCLC.

Live attenuated VZV vaccination induces antitumor immunity in ATLL patients.

Adult T cell leukemia/lymphoma (ATLL) is a CD4-positive peripheral T cell lymphoma caused by human T cell lymphotropic virus type 1 (HTLV-1). Although ATLL is quite difficult to be cured, up-regulation of cellular immunity such as HTLV-1 Tax-specific cytotoxic T lymphocytes (CTLs) has been proved to be important to obtain long-term survival. At present, no efficacious method to activate ATLL-specific cellular immunity is available. This study aimed to investigate whether live attenuated varicella-zoster virus (VZV) vaccination to ATLL can activate HTLV-1 Tax-specific cellular immune response. A total of 3 indolent- and 3 aggressive-type ATLL patients were enrolled. All aggressive-type patients had the VZV vaccination after completing anti-ATLL treatment including mogamulizumab, which is a monoclonal antibody for C-C chemokine receptor 4 antigen, plus combination chemotherapy, whereas all indolent-type patients had the VZV vaccination without any antitumor treatment. Cellular immune responses including Tax-specific CTLs were analyzed at several time points of pre- and post-VZV vaccination. After the VZV vaccination, a moderate increase in 1 of 3 indolent-type patients and obvious increase in all 3 aggressive-type patients in Tax-specific CTLs percentage were observed. The increase in the cell-mediated immunity against VZV was observed in all indolent- and aggressive-type patients after VZV vaccination. To conclude, VZV vaccination to aggressive-type ATLL patients after mogamulizumab plus chemotherapy led to the up-regulation of HTLV-1 Tax-specific CTLs without any adverse event. Suppression of regulatory T lymphocytes by mogamulizumab may have contributed to increase tumor immunity in aggressive-type ATLL patients. Japan Registry of Clinical Trials number, jRCTs051180107.

Sepsis following acute pyelonephritis caused by Trueperella bernardiae: a case report and literature review.

BACKGROUND: Trueperella bernardiae is a coryneform, gram-positive bacterium that is a commensal of the skin and upper respiratory tract. It is treated as a contaminant and rarely causes infections. Blood, urine, and abscesses have been previously reported as the most common sites of infection. Infections caused by T. bernardiae are rarely reported in bedridden very old patients with reduced activities of daily living (ADL). In this report, we describe a case of sepsis due to acute pyelonephritis caused by T. bernardiae in a very old patient with impaired ADL. CASE PRESENTATION: A 94-year-old woman had a home visit from her local physician. She was bedridden and used diapers. On the day of admission, she presented with fever and dyspnea and was admitted with a diagnosis of sepsis associated with acute pyelonephritis. T. bernardiae was detected in blood and urine cultures; furthermore, multiple bacteria were detected in a urine culture. She was treated with ampicillin/sulbactam 3 g every 12 h on the day of admission. The fever was controlled, and inhaled oxygen 1 L/min via a nasal cannula was administered for dyspnea until hospitalization day 2. On hospitalization day 2, her fever resolved to 36 °C. Antimicrobials were de-escalated and changed to cephazolin and then to cephalexin on hospitalization days 9 and 16, respectively, and were continued until day 22. On hospitalization day 28, the urinary tract infection flared up; however, her fever resolved by hospitalization day 38 after the re-administration of antimicrobial agents. She was discharged on hospitalization day 60. CONCLUSIONS: We encountered a rare case of sepsis following acute pyelonephritis caused by T. bernardiae infection. When bedridden, diaper-using, very old patients present with urinary tract infections caused by multiple bacteria, the presence of rare opportunistic organisms, such as T. bernardiae, should be considered.

Oral histone deacetylase inhibitor tucidinostat (HBI-8000) in patients with relapsed or refractory adult T-cell leukemia/lymphoma: Phase IIb results.

This multicenter, prospective phase IIb trial evaluating the efficacy and safety of tucidinostat (HBI-8000) in patients with relapsed or refractory (R/R) adult T-cell leukemia/lymphoma (ATLL) was undertaken in Japan. Eligible patients had R/R ATLL and had failed standard of care treatment with chemotherapy and with mogamulizumab. Twenty-three patients received tucidinostat 40 mg orally twice per week and were included in efficacy and safety analyses. The primary end-point was objective response rate (ORR) assessed by an independent committee. The ORR was 30.4% (95% confidence interval [CI], 13.2, 52.9]. Median progression-free survival was 1.7 months (95% CI, 0.8, 7.4), median duration of response was 9.2 months (95% CI, 2.6, not reached), and median overall survival was 7.9 months (95% CI, 2.3, 18.0). All patients experienced adverse events (AEs), which were predominantly hematologic and gastrointestinal. Incidence of grade 3 or higher AEs was 78.3%; most were laboratory abnormalities (decreases in platelets, neutrophils, white blood cells, and hemoglobin). Tucidinostat was well tolerated with AEs that could be mostly managed with supportive care and dose modifications. Tucidinostat is a meaningful treatment option for R/R ATLL patients; further investigation is warranted.

Expression of Karyopherin Alpha 2 and Karyopherin Beta 1 Correlate with Poor Prognosis in Gastric Cancer.

INTRODUCTION: Karyopherin alpha 2 (KPNA2) and karyopherin beta 1 (KPNB1) constitute nuclear transport protein complexes involved in nuclear import and are significant in tumor progression. Although high KPNA2 expression was associated with poor prognosis in solid tumors, the relationship between KPNA2 and KPNB1 expression and their prognostic role in gastric cancer (GC) remains unclear. METHODS: Immunohistochemistry was used to correlate the expression of KPNA2 and KPNB1 with various features, including clinicopathological characteristics in 130 patients with GC and survival in 94 patients with invasive lesions extending to the submucosa or deeper. RESULTS: High expression of KPNA2 and KPNB1 was found in 25% and 36% of the patients, respectively. Both were significantly related to tumor depth, lymph node metastasis, lymphatic invasion, venous invasion, and Ki-67 expression. KPNA2 expression was significantly related to that of KPNB1 (p < 0.001). Patients with high KPNB1 expression had poorer prognosis than those with low expression (p = 0.027), as was also observed in case of KPNA2 (p < 0.001). Patients with high expression of both KPNA2 and KPNB1 accounted for 18% and had a poorer prognosis than those with high expression of either and those with low expression of both (p = 0.001). Multivariate analysis revealed that high expression of both KPNA2 and KPNB1 was an independent prognostic factor in patients with GC (hazard ratio, 3.46; 95% confidence interval, 1.64-2.73, p = 0.001). CONCLUSION: KPNA2 expression was correlated with KPNB1 expression, and high co-expression of KPNA2 and KPNB1 may represent a strong prognostic biomarker in GC.

Changes in cerebral blood flow before, during, and after forward and backward walking in stroke patients trained using virtual reality walking videos with deliberately induced inaccuracies in walking speed estimations.

[Purpose] The aim of this study was to examine the effects of virtual reality (VR) training, with deliberately induced inaccuracies in walking speed estimations, on brain activity. [Participants and Methods] The study participants were 21 stroke patients, and the walking tasks involved forward and backward walking. While the VR walking speed was set at 3 km/h, estimation errors were induced by using an actual walking speed of 1 km/h during the walking tasks. Cerebral blood flow was measured using two functional near-infrared spectroscopy (fNIRS) channels located over the left and right prefrontal cortices, to determine changes in oxyhemoglobin levels from the resting state. Cerebral hemodynamics were compared during and after the VR training. [Results] The backward walking task induced a significant increase in cerebral blood flow in the right prefrontal cortex during and after the VR training. No significant changes were observed during the forward walking task. [Conclusion] In the backward walking condition, greater activation of the right prefrontal cortex was observed during and immediately after the VR training. Watching VR may have led to inaccurate walking-speed estimations, necessitating postural control (which may be attributed to the activation of the prefrontal cortex) during walking.

Phase II trial of combination treatment with S-1/cetuximab in patients with platinum-ineligible recurrent and/or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: The standard of care for first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) in patients who cannot tolerate platinum-based regimens has not been clarified. We aimed to develop a new treatment regimen for patients with R/M SCCHN who are ineligible for platinum-based therapy, by evaluating the effects and safety of tegafur/gimeracil/oteracil (S-1) and cetuximab. METHODS: Platinum-ineligibility was defined as: elderly (aged ≥ 75 years), poor PS, comorbidity, platinum resistance and refusal to undergo platinum-based therapy. Patients received S-1 (80 mg/m2/day for 14 days followed by a seven-day break) and cetuximab (initial dose, 400 mg/m2, followed by 250 mg/m2 weekly) until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). RESULTS: Between September 2014 and September 2018, we enrolled 23 patients. Among the 21 patients who were evaluable, 20 were male [median age, 69 years (range 49-82)]. The ORR was 9 (43%) of 21 patients [95% confidence interval (CI) 22-66]. One and eight patients achieved complete response (CR) and partial response (PR), respectively. The median overall survival (OS) was 13.7 months (95% CI 9.0-18.3) and progression-free survival (PFS) was 5.7 months (95% CI 3.1-8.2). Grade 3/4 adverse events included acneiform rash and skin reactions (33%), hypomagnesemia (19%), hand-foot syndrome (14%), fatigue (14%), mucositis (10%), and anorexia (10%). CONCLUSIONS: Combination treatment with S-1 and cetuximab was effective and tolerated well by patients with platinum-ineligible R/M SCCHN. Registered clinical trial number: UMIN000015123.

Changes in cerebral blood flow during forward and backward walking with speed misperception generated by virtual reality.

[Purpose] The purpose of this study was to investigate the effect of speed misperception on brain activity, created by a speed difference between actual walking and virtual reality walking videos. [Participants and Methods] The participants were 20 healthy young people. The walking speed in the video was set to 3 km/h to induce an error, while the actual walking speed was 1 km/h. Cerebral blood flow was measured using an optical imaging brain function measurement device. Left and right prefrontal cortices were analyzed using two channels and oxyhemoglobin level change from rest was used as a cerebral blood flow index. A t-test compared the cerebral blood flow dynamics before, during, and after the virtual reality video viewing under forward and backward walking conditions. [Results] Regarding changes in oxyhemoglobin levels during walking after watching the virtual reality video, cerebral blood flow increased especially in the backward walking state, where the difference was large in the right prefrontal cortex. [Conclusion] The backward walking that caused misperception by virtual reality is an extraordinary movement compared to forward walking. Thus, it is necessary to voluntarily adjust the movement by the cerebral cortex, and it is thought that activation of the prefrontal cortex occurs.

No clear survival benefit of azacitidine for lower-risk myelodysplastic syndromes: A retrospective study of Nagasaki.

The efficacy of azacitidine (AZA) on survival of lower risk (LR) - myelodysplastic syndromes (MDS) is controversial. To address this issue, we retrospectively evaluated the long-term survival benefit of AZA for patients with LR-MDS defined by International Prognostic Scoring System (IPSS). Using data from 489 patients with LR-MDS in Nagasaki, hematologic responses according to International Working Group 2006 and overall survival (OS) were compared among patients that received best supportive care (BSC), immunosuppressive therapy (IST), erythropoiesis-stimulating agents (ESA), and AZA. Patients treated with AZA showed complete remission (CR) rate at 11.3%, marrow CR at 1.9%, and any hematologic improvement at 34.0%, with transfusion independence (TI) of red blood cells in 27.3% of patients. and platelet in 20% of patients, respectively. Median OS for patients received IST, ESA, BSC, and AZA (not reached, 91 months, 58 months, and 29 months, respectively) differed significantly (P < .001). Infection-related severe adverse events were observed in more than 20% of patients treated with AZA. Multivariate analysis showed age, sex, IPSS score at diagnosis, and transfusion dependence were significant for OS, but AZA treatment was not, which maintained even response to AZA, and IPSS risk status at AZA administration was added as factors. We could not find significant survival benefit of AZA treatment for LR-MDS patients.

Treatment with mogamulizumab or lenalidomide for relapsed adult T-cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation: The Nagasaki transplant group experience.

Mogamulizumab (Mog) and lenalidomide (Len) are new therapeutic candidates for relapsed adult T-cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the present study, we retrospectively analyzed 12 patients who received Mog or Len monotherapy for relapsed ATL after allo-HSCT. Eight and three patients received Mog and Len, respectively. The remaining patient received Mog for the first relapse and Len for the third relapse. A complete response was achieved by three and two patients who received Mog and Len, respectively, two and one of whom remained alive with a complete response for more than 20 months. In terms of adverse events, the emergence or progression of graft-versus-host disease was observed in three out of four patients treated with Len and in none of the patients treated with Mog. The development or progression of cytomegalovirus reactivation was detected in four out of eight patients treated with Mog and in none of those treated with Len. The present results suggest that Mog and Len would be promising treatment options for relapsed ATL after allo-HSCT and need to be selected based on adverse event profiles.

The outcome and characteristics of patients with relapsed adult T cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation.

Treatment options for patients with adult T cell leukemia/lymphoma (ATLL) who have relapsed disease after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are limited. To clarify which patients with ATLL are likely to benefit from these treatment options and to define patient populations for novel treatments, we performed a nationwide retrospective analysis of 252 Japanese patients who had relapsed ATLL after allo-HSCT. Some long-term survivors remained after tapering and withdrawal of immunosuppressive agents. Thirty-six patients who received donor lymphocyte infusion had a better overall survival (OS) in comparison to those who did not [hazard ratio (HR), 0.63; 95% confidence interval (CI), 0.43-0.93; P = .02], suggesting the efficacy of a graft-versus-ATLL (GvATLL) effect even after relapse. Multivariate analysis demonstrated that skin lesions at initial relapse of ATLL were independently associated with higher OS (HR, 0.41; 95% CI, 0.22-0.74; P = .003), indicating that the skin is a susceptible target organ of GvATLL. This study suggested that enhancement of a GvATLL effect is a potential therapeutic option for relapsed disease after allo-HSCT. Further investigations of incorporation of immune-based approaches with new molecular target drugs into the therapeutic options of patients with ATLL before and after transplantation are warranted.

Diagnostic Utility of Cytomegalovirus Nucleic Acid Testing during Antigenemia-Guided Cytomegalovirus Monitoring after Hematopoietic Stem Cell Transplantation or Liver Transplantation.

Cytomegalovirus (CMV) is an opportunistic pathogen, and careful monitoring of CMV is important for immunocompromised patients. Antigenemia-based CMV monitoring is a standard test used for managing CMV infection in transplant recipients; however, in Japan, there are no reports of CMV monitoring using the standardized test. The utility of a standardized CMV nucleic acid test (NAT) was evaluated during antigenemia-based CMV monitoring after hematopoietic stem cell transplantation (HSCT) or liver transplantation. Blood collection for CMV monitoring was performed under the physician's instructions depending on the condition of the patient, and CMV NAT and antigenemia was evaluated. For HSCT recipients, blood collection only for NAT was additionally performed during the pre-engraftment phase. The results of the NAT were blinded to those evaluating the results. A total of 34 patients were enrolled (11 HSCT recipients and 23 liver transplant recipients). NAT detected the first CMV episode no later than antigenemia in 2 (18.2%) HSCT recipients and 3 (13.0%) liver transplant recipients, earlier than antigenemia in 3 (27.3%) HSCT recipients and 7 (30.4%) liver transplant recipients, and later than antigenemia in 1 (9.1%) HSCT recipient and 1 (4.3%) liver transplant recipient. In 5 HSCT recipients, NAT was positive during the pre-engraftment phase. Among the 468 blood samples which were evaluated by both NAT and antigenemia, 124 (26.7%) were positive in NAT and 51 (10.9%) were positive in antigenemia. The standardized CMV NAT is useful for accurately diagnosing CMV infection and determining appropriate therapeutic interventions for HSCT recipients and liver transplant recipients.

[Gingival squamous cell carcinoma diagnosed on the occasion of osteonecrosis of the jaw in a patient with chronic GVHD].

A 44-year-old male was diagnosed with acute myeloid leukemia with a complex karyotype. He underwent bone marrow transplantation using an HLA 6/6 antigen-matched sibling donor, but developed chronic graft-versus-host disease (cGVHD) with skin erythema and oral and esophageal lichen planus changes. Treatment with a combination of prednisolone and cyclosporine was initiated on day 646 after transplantation, but oral symptoms persisted. The patient developed bilateral osteonecrosis of the lower jaw after extraction of the lower left and right molars on days 2,861 and 3,339, respectively. As the disease gradually progressed, segmental mandibular osteotomy was performed. Biopsy specimens demonstrated proliferation of squamous epithelial carcinoma cells in the bilateral gingiva and lower jaw bone, which confirmed the diagnosis of bilateral gingival squamous cell carcinoma. Thus, gingival squamous cell carcinoma should be considered as a differential diagnosis in post-transplant patients with refractory osteonecrosis of the jaw during the course of cGVHD.

Efficacy and Long-Term Outcomes of Autologous Stem Cell Transplantation in POEMS Syndrome: A Nationwide Survey in Japan.

POEMS syndrome is a rare plasma cell dyscrasia presenting with polyneuropathy, λ-type M protein, vascular endothelial growth factor elevation, and systemic manifestations. The standard treatment has not been established, but autologous stem cell transplantation (ASCT) has exhibited effectiveness in this syndrome. However, the efficacy and long-term outcomes of ASCT have not been systematically studied. To clarify the efficacy and long-term outcomes of ASCT-treated patients in Japan, we performed a multicenter retrospective study assessing the clinical course of patients registered to the Japan Society for Hematopoietic Cell Transplantation Transplant Registry Unified Management Program (TRUMP) database. Between January 2000 and December 2011, 95 patients (58 men) were registered to the TRUMP database with a median age of 53 years (range, 28 to 72). The conditioning regimen was melphalan in 93 of 94 patients (99%), and 69 patients (74.2%) received a melphalan dose ≥ 200 mg/m2. The median CD34 cell dose was 2.47 × 106/kg (range, .31 to 20). After ASCT, patient performance status was dramatically improved (Eastern Cooperative Oncology Group performance status 0 to 1: 20.0% versus 71.6%, P < .0001). Over a median follow-up of 46.6 months 10 patients died, and 5-year overall survival was 88.8% (n = 95). Progression-free survival at 3 years was 78.3% (n = 70; median follow-up, 54.4 months). These data support the promising role of ASCT in patients with POEMS syndrome for both prolonging survival and improving quality of life. However, disease recurrence remains a major issue for long-term survivors.

Chromosomal analysis of myelodysplastic syndromes among atomic bomb survivors in Nagasaki.

The myelodysplastic syndromes (MDS) are clonal haematopoietic disorders that develop de novo and also secondary to chemotherapy and/or radiation therapy. We previously demonstrated that the risk of MDS is increased among atomic bomb survivors with significant correlation to radiation dose; however, the clinical characteristics of these survivors have not been well analysed. In this study, we investigated chromosomal abnormalities of MDS among survivors. The frequency of abnormal karyotypes was significantly higher, with more very poor risk karyotypes, according to the revised International Prognostic Scoring System, among those exposed close to the hypocentre compared with unexposed cases. However, abnormal karyotype frequency did not reflect the prognosis of exposed cases with respect to distance from the hypocentre. In addition, there was no difference in prognosis between exposed and unexposed cases. Among proximally exposed cases (<1·5 km from the hypocentre), chromosomal translocations and inversions were more frequent, and the frequency of structural alterations in chromosomes 3, 8, and 11 was significantly increased compared with unexposed cases. These results suggest that chromosomal alterations in MDS among survivors have different features compared with those in de novo or therapy-related MDS. Detailed molecular study is warranted.

[Durable remission attained with plasmapheresis and intravenous immunoglobulin therapy in a patient with acute exacerbation of GVHD-related myasthenia gravis].

A 17-year-old male underwent a second bone marrow transplantation using a 6/8 allele HLA-matched unrelated donor. On day 100 after transplantation, steroid treatment for chronic graft-versus-host disease (GVHD) was started. On day 766, the patient experienced general fatigue, followed by double vision, ptosis, and dysphagia on day 810. Based on the positivity of the acetylcholine receptor antibody and a waning electromyography pattern, he was diagnosed with GVHD-related myasthenia gravis (MG). On day 861, we initiated plasmapheresis (PE), followed by the administration of intravenous immunoglobulin (IVIg) ; this treatment attenuated the bulbar symptoms of MG. Although the steroid treatment was continued, we restarted the administration of tacrolimus. On day 2,739 after transplantation, we stopped the steroid treatment, and the patient remained in remission for MG following the cessation of the steroid treatment on day 2,897. This case suggests that PE followed by IVIg could be an effective therapeutic alternative for MG associated with GVHD.

Long-term survival following autologous and allogeneic stem cell transplantation for blastic plasmacytoid dendritic cell neoplasm.

We sought to clarify the role of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) to treat blastic plasmacytoid dendritic cell neoplasm (BPDCN). We retrospectively identified 25 BPDCN patients (allo-HSCT, n = 14; auto-HSCT, n = 11) from registry data of the Japan Society for Hematopoietic Cell Transplantation and analyzed clinicopathologic data and clinical outcomes after transplantation. The median age at HSCT was 58 years (range, 17-67 years). All 11 patients who underwent auto-HSCT were in the first complete remission (CR1). With a median follow-up of 53.5 months, the overall survival rates at 4 years for patients who underwent auto-HSCT and allo-HSCT were 82% and 53% (P = .11), respectively, and progression-free survival rates were 73% and 48% (P = .14), respectively. Auto-HSCT for BPDCN in CR1 appears to provide promising results and deserves further evaluation in the setting of prospective trials.

Development of a modified prognostic index for patients with aggressive adult T-cell leukemia-lymphoma aged 70 years or younger: possible risk-adapted management strategies including allogeneic transplantation.

Adult T-cell leukemia-lymphoma is a distinct type of peripheral T-cell lymphoma caused by human T-cell lymphotropic virus type I. Although allogeneic stem cell transplantation after chemotherapy is a recommended treatment option for patients with aggressive adult T-cell leukemia-lymphoma, there is no consensus about indications for allogeneic stem cell transplantation because there is no established risk stratification system for transplant eligible patients. We conducted a nationwide survey of patients with aggressive adult T-cell leukemia-lymphoma in order to construct a new, large database that includes 1,792 patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma who were diagnosed between 2000 and 2013 and received intensive first-line chemotherapy. We randomly divided patients into two groups (training and validation sets). Acute type, poor performance status, high soluble interleukin-2 receptor levels (> 5,000 U/mL), high adjusted calcium levels (≥ 12 mg/dL), and high C-reactive protein levels (≥ 2.5 mg/dL) were independent adverse prognostic factors used in the training set. We used these five variables to divide patients into three risk groups. In the validation set, median overall survival for the low-, intermediate-, and high-risk groups was 626 days, 322 days, and 197 days, respectively. In the intermediate- and high-risk groups, transplanted recipients had significantly better overall survival than non-transplanted patients. We developed a promising new risk stratification system to identify patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma who may benefit from upfront allogeneic stem cell transplantation. Prospective studies are warranted to confirm the benefit of this treatment strategy.

Clinical features and prognosis of patients with myelodysplastic syndromes who were exposed to atomic bomb radiation in Nagasaki.

There is evidence that radiation exposure is a causative factor of myelodysplastic syndromes (MDS). However, little is known about whether radiation exposure is also a prognostic factor of MDS. We investigated the impact of radiation exposure on the prognosis of MDS in Nagasaki atomic bomb survivors using the International Prognostic Scoring System (IPSS) and the revised version (IPSS-R). Subjects were 140 patients with primary MDS diagnosed between 1985 and 2011 and evaluable for IPSS, IPSS-R, and exposure distance. Of those, 31 were exposed at <1.5 km, 35 at 1.5-2.99 km, and 74 at ≥3.0 km. By the end of March 2014, 47 patients (34%) progressed to overt leukemia and 106 (75.7%) died. By comparing with patients exposed at ≥3.0 km, those exposed at <1.5 km had significantly higher frequencies of abnormal chromosome (P = 0.02), intermediate/poor IPSS, and intermediate/poor/very poor IPSS-R cytogenetic category (P = 0.0001, and P < 0.0001, respectively). As with de novo MDS, multivariate Cox regression analyses revealed that cytogenetic abnormalities, IPSS karyotype, and IPSS-R cytogenetics were significantly associated with poor survival, and cumulative incidence of leukemic transformation in MDS among atomic bomb survivors, but exposure distance was not associated with any poor outcomes. These suggest that exposure to the greater dose of atomic bomb radiation is associated with developing poor cytogenetic abnormalities in MDS, which might consequently lead to overt leukemia among atomic bomb survivors.