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Background This study evaluated the glucocorticoid (GC)-sparing effect of mepolizumab (MEP) in severe eosinophilic granulomatous polyangiitis (EGPA). Methods Participants were patients diagnosed with EGPA according to Watts’ algorithm and who underwent outpatient care at Juntendo Hospital between November 2017 and January 2023. This longitudinal, observational study consisted of a retrospective analysis of medical records. Results Thirty-five patients were analyzed. The reasons for receiving MEP, by numbers of patients, were as follows: eosinophilia, 3; neuropathy exacerbation, 3; persistent neuropathy, 3; GC-sparing effect, 3; asthma exacerbation, 2; and skin ulcer exacerbation, 1. Compared with the MEP (−) group, the MEP (+) group had higher rates of remission and concomitant azathioprine treatment, and lower peripheral blood eosinophil count and GC dosage at last observation. The median GC dose after MEP was 2.8 (0.0–4.3) mg/day as prednisolone equivalent dose less than before. Conclusions The addition of MEP may be considered for patients with severe EGPA, with or without the use of azathioprine.

Objectives The objective of this study is to provide evidence for the revision of clinical practice guidelines for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis by the Japan Research Committee for Intractable Vasculitis. Methods PubMed, CENTRAL, and the Japan Medical Abstracts Society databases were searched for articles published between 2015 and 2020 to update the systematic review for existing clinical questions, while PubMed, CENTRAL, EMBASE, and the Japan Medical Abstracts Society were searched for articles published between 2000 and 2020 to conduct a systematic review for newly developed clinical questions. The certainty of evidence was assessed with the GRADE approach. Results For remission induction, when used in conjunction with cyclophosphamide or rituximab, reduced-dose glucocorticoid lowered the risk of serious adverse events compared to standard-dose glucocorticoid. Avacopan improved sustained remission at 12 months compared to high-dose glucocorticoid. Addition of plasma exchange to remission induction therapy did not reduce the risk of death, end-stage kidney disease, or relapse. For remission maintenance, rituximab reduced the risk of relapse compared to azathioprine. Long-term rituximab or azathioprine reduced the risk of relapse compared to short-term rituximab or azathioprine, respectively. Conclusions This systematic review provided evidence required to develop the 2023 clinical practice guideline for the management of ANCA-associated vasculitis.

This study reports two cases of dasatinib-associated lymphadenopathy (DAL). Case 1 involved a 58-year-old man diagnosed with chronic myelogenous leukemia (CML). After 13 months of starting on dasatinib treatment, a molecular response (MR) 4.5 was achieved. Due to the loss of MMR, dasatinib was discontinued at 39 months but restarted at 42 months. Right cervical lymphadenopathy appeared 51 months after starting the treatment. DAL was diagnosed based on the findings of a cervical lymph node biopsy. After dasatinib was switched to ponatinib, the lymphadenopathy disappeared without recurrence. In case 2, a 54-year-old man was diagnosed with CML. He was started on dasatinib and MR 4.5 was achieved after 6 months. Left cervical lymph node adenopathy appeared 21 months later, and a diagnosis of DAL was made based on the findings of a cervical lymph node biopsy. After discontinuation of dasatinib, cervical lymph node adenopathy disappeared without recurrence. The possibility of DAL should be considered if lymphadenopathy is observed during dasatinib treatment.

Objectives Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive DM is characterized by rapidly progressive interstitial lung disease and has a poor prognosis. We aimed to investigate whether anti-MDA5 antibody titres and cytokine levels predict clinical course, and evaluate changes in both parameters before and after diagnosis. Methods This was a retrospective, single-centre study in 38 patients with anti-MDA5 antibody-positive DM. We compared clinical characteristics and laboratory data at diagnosis between patients in the treatment response (n = 23) and non-response (n = 15) groups, and between those in the relapse (n = 5) and non-relapse (n = 24) groups. We also measured serum anti-MDA5 antibody titres and cytokine levels before and after diagnosis. Results The non-response group was older, had a higher ground-glass opacity score, lower PaO2/FiO2, higher CRP level, and higher anti-MDA5 antibody titre than the response group. No cytokines significantly differed between groups at diagnosis. The relapse group had a significantly higher anti-MDA5 antibody titre than the non-relapse group. In the survivor group, the anti-MDA5 antibody titre and levels of IFN-α, IFN-γ, monocyte chemotactic protein-1 (MCP-1), IL-6, IL-33, CRP, and ferritin were significantly lower 6 months post-treatment than at diagnosis. Macrophage-associated cytokines such as IL-6, IL-8, IL-18 and MCP-1 increased after anti-MDA5 antibody positivity in three patients who were anti-MDA5 antibody-positive before diagnosis. Conclusion The anti-MDA5 antibody titre at diagnosis may predict the clinical course. Levels of macrophage-associated cytokines significantly declined at 6 months post-treatment, and they may have increased after anti-MDA5 antibody titre positivity.

We analyzed clinical cutoffs for defining computed tomography (CT) methods for sarcopenia and examined the prognostic value of CT for allogeneic hematopoietic stem cell transplantation (allo-HCST) outcomes of patients with myeloid malignancy. One hundred twenty-five adult patients with acute myeloid leukemia and myelodysplastic syndrome who underwent first allo-HSCT between 2000 and 2017 were included. Sarcopenia was assessed using CT-based skeletal muscle index (SMI) and mean muscle attenuation at L3. A statistical difference in SMI was confirmed between sarcopenia (n = 52) and nonsarcopenia (n = 73) patients. There were no significant correlations of muscularity with age, performance status, or other characteristics of HSCT. After 2 years, overall survival (OS) was 43.5% and 70.1%, disease-free survival was 52.9% and 68.6%, nonrelapse mortality (NRM) was 20.8% and 8.4%, incidence of acute GVHD (≥ grade 2) was 38.8% and 39.1%, that of chronic GVHD was 53.2% and 37.3%, and median duration of hospitalization was 88 days and 74 days (P = 0.026), respectively, in the sarcopenia and nonsarcopenia groups. Multivariate analysis showed that presence of sarcopenia is a novel adverse factor for high NRM and poor OS. Pretransplant CT-defined sarcopenia is correlated with decreased OS, increased NRM, and prolonged hospitalization.

A soluble form of suppression of tumorigenicity 2 (sST2) has emerged as a biomarker for acute graft-versus-host disease (GVHD) and non-relapse mortality (NRM). We prospectively monitored sST2 levels during the early phase of hematopoietic stem cell transplantation (HSCT) and evaluated the clinical association with transplant-related complications including acute GVHD.Thirty-two adult Japanese patients who received a first allogeneic HSCT were enrolled in this study. Levels of sST2 were measured at fixed time points (pre-conditioning, day 0, day 14, day 21, and day 28).The median age was 50.5 years (range=16-66). With a median follow-up of 21.5 months (range=0.9-35.4), 9 patients developed grade II-IV acute GVHD. Median sST2 levels on the day of HSCT were higher than baseline and reached the maximum value (92.7 ng/mL; range=0-419.7) on day 21 after HSCT. The optimal cut-off value of sST2 on day 14 for predicting grade II-IV acute GVHD was determined as 100 ng/mL by ROC analysis. The cumulative incidence of acute GVHD was 56.7% and 16.5% in the high- and low-sST2 groups, respectively (p0.01). Multivariate analyses showed that high sST2 levels at day 14 were associated with a higher incidence of acute GVHD (hazard ratio=9.35, 95% confidence interval=2.92-30.0, p0.01). The cumulative incidence of NRM was increased in the highs-ST2 group (33% vs 0%, p0.01), but all the patients died of non-GVHD complications. Among 6 patients in the high-sST2 group without grade II-IV GVHD, 5 patients developed veno-occlusive disease (VOD) and one also had thrombotic microangiopathy (TMA).The early assessment of sST2 after HSCT yielded predictive values for the onset of acute GVHD and other transplant-related complications including VOD and TMA.Akut graft-konakçı hastalığı (GVHD) ve relaps dışı mortalite (NRM) için bir biyobelirteç olarak, tümör oluşumu 2’nin baskılanmasının (sST2) çözünür bir formu ortaya konulmuştur. Hematopoietik kök hücre transplantasyonunun (HSCT) erken safhasında sST2 düzeylerini prospektif olarak izledik ve akut GVHD dahil transplantla ilişkili komplikasyonlarla klinik ilişkisini değerlendirdik.Bu çalışmaya ilk allojenik HSCT’si olan 32 yetişkin Japon hasta alındı. sST2 seviyeleri sabit zaman noktalarında (hazırlık rejimi öncesi, 0. gün, 14. gün, 21. gün ve 28. gün) ölçüldü.Ortanca yaş 50,5 idi (aralık=16-66). Ortalama 21,5 aylık takip süresi (aralık= 0,9-35,4) ile 9 hastada Grade II-IV akut GVHD gelişti. Nakil gününde ortanca sST2 seviyeleri bazal değerlerden daha yüksekti ve HSCT’den sonraki 21. günde maksimum değere (92,7 ng/mL; aralık=0-419,7) ulaştı. Grade II-IV akut GVHD’yi tahmin etmek için 14. günde sST2’nin optimal eşik değeri, ROC analizi ile 100 ng/mL olarak belirlenmiştir. Akut GVHD’nin kümülatif insidansı yüksek ve düşük sST2 gruplarında sırasıyla %56,7 ve %16,5 idi (p0,01). Çok değişkenli analizler 14. günde yüksek sST2 düzeylerinin daha yüksek akut GVHD insidansı ile ilişkili olduğunu göstermiştir (tehlike oranı=9, 35, %95 güven aralığı=2,92-30,0, p0,01). NRM’nin kümülatif insidansı yüksek sST2 grubunda artmıştır (%33’e karşı %0, p0,01), ancak tüm hastalar GVHD dışı komplikasyonlardan öldü. Yüksek sST2 grubunda grade II-IV GVHD olmayan 6 hastadan 5’inde veno-oklüzif hastalık (VOD) gelişti ve birinde trombotik mikroanjiyopati (TMA) vardı.HSCT sonrası sST2’nin erken değerlendirmesi, akut GVHD’nin başlangıcı ve VOD ve TMA dahil transplantla ilişkili diğer komplikasyonlar için prediktif değerler vermiştir.

We evaluated the kinetics of immune reconstitution (IR) after allogeneic hematopoietic cell transplantation (HSCT) and analyzed the clinical effect of IR on posttransplant outcomes. Absolute lymphocyte and its subset counts were measured using flow cytometry on days 28, 100, 180, 365, and 730 after transplantation in 358 adult patients who underwent HSCT between 2009 and 2017. On day 100 after HSCT, 310 surviving patients were analyzed. Bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT), and cord blood transplantation (CBT) were performed in 119, 55, and 136 patients, respectively. Mature B-cell and differentiated natural killer (NK) cell subset counts significantly increased after CBT. The 2-year overall survival (OS), nonrelapse mortality (NRM), cumulative incidence of relapse, and chronic GVHD in BMT, PBSCT, and CBT were 62%, 67%, and 76% (P = .021); 17%, 17%, and 13% (P = .82); 33%, 40%, and 27% (P = .063); and 43%, 45%, and 28% (P = .025), respectively. Multivariate analysis showed that higher CD16+CD57− NK cell counts correlated with lower disease relapse, whereas higher CD20+ B-cell counts correlated with lower NRM. OS-favoring factors were higher CD16+CD57− NK cell count (hazard ratio, 0.36; 95% confidence interval, 0.22-0.60; P < .001) and CD20+ B-cell count (hazard ratio, 0.53; 95% confidence interval, 0.30-0.93; P < .001) and lower Disease Risk/HCT-Specific Comorbidity index score. Collective contribution of graft source-specific and event-related immune reconstitution might yield better posttransplant outcomes in CBT.

Cytomegalovirus (CMV) reactivation and natural killer (NK) cell reconstitution are well-recognized immunologic events occurring after allogeneic stem cell transplantation (allo-SCT). We aimed to study the outcome of CMV reactivation (CMVR) and NK cell reconstitution in patients with hematologic malignancies after allo-SCT. We retrospectively studied 246 adult patients (152 men, 94 women; median age, 51 years [range, 18 to 69]) who underwent allo-SCT for hematologic malignancies at the Kanagawa Cancer Center. CMVR was defined as initiation of preemptive CMV therapy after pp65 antigenemia surveillance. All patients' lymphocyte subsets were monitored by flow cytometry at 180, 365, and 730 days post-transplant. The median follow-up period was 3.2 years (range, .8 to 9.6 years). CMVR occurred in 141 patients (57%) at a median of 45 days (range, 15 to 93). In patients without CMVR (CMVR-) versus those with CMVR (CMVR+), 5-year overall survival (OS), nonrelapse mortality (NRM), and cumulative incidence of relapse (CIR) were 79% versus 55% (P.001), 3% versus 16% (P = .012), and 28% versus 38% (P = .09), respectively. CD8

Smoking is associated with a high risk for different diseases including respiratory tract infections in immunocompetent patients. However, data about the effects of cigarette smoking on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are limited. Therefore, we retrospectively investigated 608 patients aged ≥20 years with hematological disorders who received their first allo-HSCT at our group of hospitals between 2000 and 2015, and evaluated the impact of cigarette smoking before allo-HSCT on clinical outcomes by dividing patients into two groups according to the Brinkman index (BI) (nonsmokers or light smokers [BI: 0-500] and heavy smokers [BI: ≥ 500]). Multivariate analyses showed that heavy smoking was associated with a high 5-year cumulative incidence of chronic graft-versus-host disease (cGVHD) (hazard ratio [HR]: 1.73, 95% confidence interval [CI]: 1.15-2.61, p 0.01). The 5-year overall survival (HR: 1.16, 95% CI: 0.86-1.58, p = 0.33) and disease-free survival (HR: 1.12, 95% CI: 0.83-1.52, p = 0.45) were similar between the two groups. Hence, cigarette smoking is correlated with cGVHD, although prospective studies must be conducted to further verify this result.

This single-center retrospective study was performed in consecutive patients with acute lymphoblastic leukemia who relapsed after allogeneic hematopoietic cell transplantation (HCT) and received salvage therapy using inotuzumab ozogamicin (InO). Ten patients (median age: 27 years) treated between June 2018 and July 2020 who met the eligibility criteria were included in this study. Nine patients received InO in one cycle and seven of these patients achieved complete hematological remission after salvage chemotherapy including InO. Negative minimal residual disease was confirmed in all four evaluable patients. Eight patients were successfully bridged to the subsequent HCT. After HCT, veno-occlusive disease (VOD) developed in three patients, and caused the death of one. No patient received maintenance therapy. At present, five patients are disease-free and alive, and the overall and progression-free survival rates at 1 year were 60% and 40%, respectively. High rates of disease remission and bridging to HCT with comprehensive treatments including InO may have contributed to favorable outcomes. However, further investigation is needed to reduce post-HCT complications including VOD.

Aim Primary malignant lymphomas arising from the female genital tract are very rare, with an incidence rate of 0.5%. Because of its rarity, its clinical characteristics, prognosis and optimal treatment are still unclear. Here, we retrospectively evaluated female patients with uterine lymphoma. Methods Between January 2000 and October 2016, 4362 patients were newly diagnosed with malignant lymphoma by the participating institutions of YACHT. Among these 4362 patients, we retrospectively evaluated 14 adult patients with primary uterine lymphoma. Results The median follow up time was 41 months. The median age at diagnosis was 68 years. Of 14 patients, 10 (72%) were diagnosed with diffuse large B-cell lymphoma. Seven patients presented with vaginal bleeding and three with abdominal pain. Eleven patients (79%) had advanced stages at diagnosis. Three patients (21%) had ovarian involvement and 2 (14%) had vaginal involvement. Induction chemotherapy regimens were R-CHOP in seven patients (50%), CHOP in three (21%) and other regimens in four (29%). Among 14 patients, 12 patients (86%) achieved a complete response and 2 (14%) experienced disease progression. Three patients (21%) showed relapse. Five patients (36%) died because of malignant lymphoma. The 3-year overall survival rate was 57.9%. Soluble interleukin-2 receptor levels > 5000 U/mL, anemia, a bulky mass and the presence of > 1 extranodal sites, B symptom at diagnosis were associated with a poor prognosis. Conclusion Female genital lymphoma is very rare, and further study of more cases is warranted.

Body mass index (BMI), which represents the proportion of weight to height, is a controversial prognostic factor for acute myeloid leukemia (AML). We evaluated prognostic value of BMI in Japanese AML. The study included 369 adult patients with newly diagnosed AML who were administered either daunorubicin or idarubicin with cytarabine as induction chemotherapy. The patients were categorized into two groups according to their BMI: the NW group (BMI

Objective. To determine mortality and predictive factors for lower intestinal perforation (LIP) among patients with autoimmune rheumatic diseases.Methods. This retrospective, single-center, observational study analyzed mortality rates in 31 autoimmune rheumatic disease patients with LIP who were admitted to our hospital from January 2002 to June 2017. The primary outcome was the mortality rate during hospitalization.Results. The median age at the time of LIP was 61 years, and the survival rate at discharge was 64.5%. Eleven patients died of sepsis during hospitalization. Cox univariable analysis for mortality during hospitalization showed that absence of abdominal pain (hazard ratio (HR) 5.61, 95% confidence interval (CI) 1.38–22.9), higher age (HR 1.06, 95% CI 1.01–1.11), chronic kidney disease (HR 6.89, 95% CI 1.85–25.7), systemic vasculitis (HR 3.95, 95% CI 1.14–13.6), higher blood urea nitrogen (HR 1.02, 95% CI 1.01–1.04), higher serum creatinine (HR 1.41, 95% CI 1.06–1.87), and LIP due to malignancy (HR 14.3, 95% CI 1.95–105.1) significantly increased mortality.Conclusion. Abdominal pain was absent in 16% of LIP patients with autoimmune rheumatic diseases, and this absence was a poor prognostic factor in this cohort. Moreover, higher age, chronic kidney disease, systemic vasculitis, and LIP due to malignancy were associated with significantly increased mortality. Physicians should be aware of LIP in autoimmune disease patients with higher age, chronic kidney diseases, or systemic vasculitis even if patients reveal mild abdominal symptoms.

We hypothesized that treatment-related weight loss is associated with worse outcomes following HSCT. Overall, 184 patients with AML who underwent induction therapy were classified according to d-BMI (BMI at transplant minus BMI at diagnosis) (kg/m2) as + 2. At 1 year, OS was 67.9% (95% CI, 60.7–74.2), DFS was 64.1% (95% CI, 56.7–70.6), and GRFS was 40.2% (95% CI, 33.1–47.2). For d-BMI groups + 2, GRFS at 1 year was 16.1% (95% CI, 5.1–31.4), 45.4% (95% CI, 36.4–53.7), and 41.7% (95% CI, 22.2–60.1), respectively (P = 0.0067). Multivariate analysis showed that both worse OS (HR, 1.78; 95% CI, 1.02–3.14; P = 0.007) and GRFS (HR, 2.34; 95% CI, 1.26–4.35; P = 0.007) were associated with reduced BMI (d-BMI

Objective: Pneumocystis pneumonia (PCP) is a serious complication in patients with rheumatic diseases who are receiving immunosuppressive therapy. These patients have a higher mortality from PCP th...

Useful prognostic biomarkers for diffuse large B-cell lymphoma (DLBCL) patients have been reported. To determine the prognostic value of hemoglobin (Hb) level in DLBCL patients, we performed a retrospective study.We evaluated disease outcome, progression-free survival (PFS), overall survival as the endpoint, and clinical and laboratory factors affecting the outcome of 185 DLBCL patients who had received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy during 2004-2014.The study group included 121 men and 64 women with a median age of 66 years minimum-maximum: 21-83 years. In univariate analysis, factors independently associated with worse PFS were Eastern Cooperative Oncology Group performance status ≥2, Ann Arbor stage III or IV, anemia with Hb levels of10 g/dL, and serum albumin of3.5 g/dL. In multivariate analysis, anemia with Hb levels of10 g/dL and Ann Arbor stage III or IV were found to be international index-independent prognostic factors (hazard ratio: 2.4; p=0.04).Anemia is an independent prognostic marker of poor outcome in DLBCL patients. Hb can be an easily available prognostic marker for risk stratification in these patients.Diffüz büyük B hücreli lenfoma (DBBHL) hastaları için yararlı prognostik belirteçler bildirilmiştir. DBBHL hastalarında hemoglobin (Hb) düzeyleri ile prognoz ilişkisini araştırmak amacıyla retrospektif bir çalışma yaptık.2004-2014 yılları arasında rituksimab, siklofosfamid, doksorubisin, vinkristin ve prednizolon tedavisi almış olan 185 DBBHL hastasının klinik ve laboratuvar bulguları değerlendirildi ve bunların hastalık sonuçlarına, ilerlemesiz sağkalım (PFS) ve toplam sağkalıma (TS) etkileri araştırıldı.Araştırma grubunda 121 erkek ve 64 kadın vardı, ortanca yaş 66 yıldı (minimum-maksimum: 21-83 yıl). Tek değişkenli analizde Eastern Cooperative Oncology Group performans durumunun ≥2 olması, Ann Arbor evre III veya IV olması ve Hb değerinin10 g/dL ile anemi olması PFS ve TS’yi etkileyen bağımsız değişkenler olarak bulundu. Çok değişkenli analizde ise Hb değerinin10 g/dL ile anemi ve Ann Arbor evre III veya IV olması uluslararası indeks-bağımsız prognostik faktörler olarak bulundu (Hazard ratio: 2,4; p=0,04).Anemi, DLBCL hastalarında kötü sonuçların bağımsız prognostik bir göstergesidir. Hb, bu hastalarda risk sınıflandırması için kolayca bulunabilen bir prognostik belirteç olabilir.

Background: A soluble form of suppression of tumorigenicity 2 (ST2) has emerged as a biomarker for acute graft-versus-host disease (GVHD) and non-relapse mortality (NRM), whereas a clinical role of ST2 during the early phase of hematopoietic stem cell transplantation (HSCT) has not been fully elucidated. In addition, recent studies have demonstrated that high ST2 levels are associated with the development of thrombotic microangiopathy (TMA) and veno-occlusive disease (VOD) after HSCT. Therefore, we prospectively monitored soluble ST2 levels during the early phase of HSCT and evaluated the clinical association with transplant-related complications including acute GVHD, TMA, and VOD. Methods: Thirty-two adult Japanese patients who received first allogeneic HSCT for hematological diseases were enrolled consecutively between February 2014 and July 2015 at our university hospital or medical center that participate in Yokohama Cooperative Study Group for Hematology (YACHT). The selection of donor source and conditioning regimen was based on patients' hematological diagnosis, donor availability, and patients' clinical status. Soluble ST2 were measured by ELISA at fixed time points (before conditioning, on the day of HSCT (day 0) and days 14, 21, and 28 after HSCT). Serum IL-33 (the ligand of ST2), ferritin and C-reactive protein (CRP) levels were compared with ST2. Results: The median age was 50.5 years (range: 16-66). Acute myeloid leukemia was the main underlying disease (56%). Median soluble ST2 levels on the day of HSCT were higher than baseline and reached the maximum value (92.7 ng/mL (range: 0-419.7)) on day 21 after HSCT. ST2 levels were strongly correlated with ferritin and CRP levels in all samples (r = 0.456 and 0.615). Mainly, ST2 was well correlated with CRP at days 0, 14, and 21 (r = 0.717, 0.630, and 0.628). Serum IL-33 levels were under detection limits in most of the patients, resulting in no correlation of IL-33 with ST2 levels. With a median follow-up of 21.5 months (range: 0.9-35.4), nine patients developed grade II-IV acute GVHD. The optimal cut-off value of soluble ST2 on day 14 for predicting grade II-IV acute GVHD was determined as 100 ng/mL by the ROC analysis. We focused on day 14 ST2 levels as the earliest time point for predicting acute GVHD. The cumulative incidence of acute GVHD was 56.7% and 16.5% in the high and low-ST2 group, respectively (P < 0.01). Multivariate analyses showed that high-ST2 levels at day 14 were associated with a higher incidence of acute GVHD (hazard ratio: 9.35, 95% confidence interval: 2.92-30.0, P < 0.01). Although post-transplant CRP and ferritin levels were correlated with ST2, these markers did not influence the cumulative incidence of acute GVHD. Based on analyses for GVHD severity and the target organ involvement, ST2 levels were not associated with the grade of GVHD, whereas the cumulative incidence of gastrointestinal GVHD was significantly increased in the high-ST2 group (50% vs. 15%, P = 0.03). Finally, we evaluated the association of ST2 levels with other transplant-related complications and mortality. Severe non-GVHD complications were observed in 10 patients, including TMA (n = 2), VOD (n = 5), graft failure (n = 1), engraftment syndrome (n = 4), sepsis (n = 3), and pneumonia (n = 1), which were often overlapped. The cumulative incidence of NRM was increased in the high-ST2 group (33% vs. 0%, P < 0.01), but all the patients died of non-GVHD complications (sepsis, graft failure, TMA, and pneumonia, all of them overlapping with VOD). The two patients who had TMA and five who had VOD were all included in the high-ST2 group. Conclusion: Our detailed analysis regarding serial monitoring of ST2 following HSCT suggests that the early assessment of ST2 may be a predictive indicator for the onset of acute GVHD. Furthermore, we revealed that ST2 levels increased not only in patients with acute GVHD but also in those with other life-threatening complications, such as TMA and VOD, identified during patient monitoring. Although these complications often overlapped each other in the clinical settings for HSCT, gastrointestinal GVHD, TMA, and VOD, all of which are linked to endothelial injury, may be key complications related to high ST2 release. Further studies with larger sample sizes are needed to clarify the clinical value of ST2. Disclosures No relevant conflicts of interest to declare.

A patient with severe lupus nephritis developed thrombocytopenia during treatment with high-dose steroids. In addition to viral- or disease-induced cytopenia, the pathology was believed to arise from diverse contributing factors, such as thrombotic microangiopathy and heparin-related thrombocytopenia (HIT). By combining plasma exchange therapy and intravenous cyclophosphamide, we successfully controlled the SLE activity and improved the thrombocytopenia. An antecedent bacterial infection or SLE activity is believed to have contributed to the concurrent HIT.

Background: Immune reconstitution after allogeneic stem cell transplantation (SCT) is a complicated process influenced by factors such as preconditioning regimens, graft-versus-host disease (GVHD) prophylaxis, and grafts. We studied the association between the kinetics of lymphocyte subsets and transplant outcome to clarify the differences in immune reconstitution after hematopoietic cell transplantation according to stem cell sources and its clinical significance. Patients and Methods: Clinical data were collected from patients' medical charts at Kanagawa Cancer Center, Yokohama, Japan. Patients with hematological malignancies aged ≥18 years old who underwent SCT between April 2009 and December 2017 were initially selected. Those who died or experienced disease relapse before day 100 post SCT were excluded. We measured absolute lymphocyte count (ALC) and lymphocyte subsets by flow cytometry with antibodies against CD2, CD3, CD4, CD8, CD11b, CD11c, CD16, CD25, CD29, CD56, CD57, CD45RA, and CD45RO on days 100, 180, 365, and 730 post SCT. Results: The final cohort included 314 patients (acute leukemia, n = 249; myelodysplastic syndrome, n = 44; chronic myelogenous leukemia, n = 9; malignant lymphoma, n = 6; and others, n = 6). The median age was 51 (range: 18- 69) years, with 184 males and 130 females. The disease risk at transplantation was standard in 209 and high in 105 patients. Myeloablative preconditioning was administered to 114 and reduced-intensity preconditioning to 200 patients. Bone marrow transplantation (BMT), peripheral blood SCT (PBSCT), and cord blood transplantation (CBT) were performed in 121, 57, and 136 patients, respectively. A calcineurin inhibitor with short-term methotrexate was mainly used for GVHD prevention. The median follow-up of surviving patients was 869 (range: 103-3074) days. The 2-year overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM) in BMT, PBSCT, and CBT were 62%, 68%, and 76% (P = 0.023); 33%, 38%, and 27% (P = 0.068); and 17%, 16%, and 13% (P = 0.82); respectively. The 2-year cumulative incidence of chronic GVHD was 43% in BMT, 45% in PBSCT, and 28% in CBT (P = 0.027). There were significant differences between lymphocyte subset recovery and stem cell sources (Table). ALC; CD20+ B cell; CD4+, CD4+CD29+, CD4+CD45RO+, CD4+CD45RO− , and CD4+CD45RA+ T cell subsets; and CD3−CD56+ and CD16+CD57− natural killer (NK) cell subsets were significantly elevated in CBT compared with BMT and PBSCT at day 100 post SCT. Conversely, CD8+CD11b+ and CD8+CD11b− T cell subsets and CD3+CD56+ NKT cells were significantly lower in CBT than in BMT and PBSCT on day 100. Univariate analysis revealed that lymphocyte subsets exhibiting higher levels of CD20+ B cell; CD16+CD57− and CD3−CD56+ NK cells; and CD4+CD25+, CD4+CD29+, CD4+CD45RA+, CD8+CD11b+, and CD8+CD11b− T cell subsets at day 100 were associated with a better 2-year OS. There were strong correlations with a lower CIR and higher CD16+CD57+ and CD16+CD57− NK cell levels . A higher incidence of chronic GVHD was associated with lower levels of CD16+CD57− NK cells and CD4+CD25+ T cells and with higher levels of CD8+CD11b+ T cells and CD8+CD11b− and CD3+CD56+ NKT cells. Further, a lower NRM correlated with higher levels of CD20+ B cells and CD8+CD11b− T cells. The lymphocyte subsets were used for multivariate analysis. Favorable factors for better OS were higher levels of CD16+CD57− NK cells [hazard ratio (HR), 0.62; 95% confidence index (CI), 0.38-0.81; P = 0.024] and CD20+ B cells (HR, 0.56; 95% CI, 0.31-0.0.98; P = 0.048). Prognostic factors for lower CIR were higher levels of CD16+CD57+ NK cells (HR, 0.51; 95% CI, 0.27-0.95; P = 0.034) and CD16+CD57− NK cells (HR, 0.52; 95% CI, 0.28-0.99; P = 0.048). A lower incidence of NRM was associated with higher levels of CD8+CD11b− T cells (HR, 0.18; 95% CI, 0.08-0.39; P < 0.001) and CD20+ B cells (HR, 0.24; 95% CI, 0.08-0.70; P = 0.0088). High levels of CD8+CD11b+ T cells were an independent predictor for a higher incidence of chronic GVHD (HR, 2.38; 95% CI, 1.22-4.95; P = 0.012). Conclusions: The distinct differences in immune reconstitution according to stem cell sources and lymphocyte subset analysis at day 100 post SCT are useful for predicting transplant outcome. Furthermore, the results suggest that characteristic immune recovery in CBT positively affects transplant outcome. Disclosures No relevant conflicts of interest to declare.

Introduction: Consistent with more direct measures of body fat, body mass index (BMI), defined as a personfs weight in kilograms divided by the square of his height in meters (kg/m2), is strongly correlated with various adverse health outcomes. Recent studies have reported the prognostic benefits of higher BMI at diagnosis in acute myeloid leukemia (AML). However, there are few reports on the prognostic impact of BMI classification and post-remission therapy, including hematopoietic stem cell transplantation (HSCT). Although some studies have reported worse outcomes related to lower BMI at transplant, there are no studies on the prognostic impact of the difference-BMI (d-BMI) between time of transplant and time of AML diagnosis. We hypothesized that lower BMI at transplant and reductions in BMI from diagnosis are associated with worse survival outcomes, including graft-versus-host disease-free survival, relapse-free survival (GRFS), which is currently defined as a novel composite endpoint in the first post-HSCT year. Patients and Methods: We identified 369 patients from January 2000 to March 2015 newly diagnosed with adult AML who had been administered daunorubicin or idarubicin in combination with cytarabine as induction chemotherapy (IC) at any of the seven Japanese hospitals that collaborate to form the Yokohama Cooperative Study Group for Hematology. Patients with acute promyelocytic leukemia, myeloid sarcoma, and aged 66 years or more were excluded from this study. For adjustment treatment intensification, patients who had over 20% reduction in actual dosage of IC were also excluded. In this study model, 184 patients were eligible for HSCT. According to the classification of obesity by the World Health Organization, underweight patients were characterized by BMI of 30 kg/m2. d-BMI was calculated as BMI at the time of transplant subtracted from BMI at the time of diagnosis, which reflects constructive changes in body structure due to intensive chemotherapy. Based on the ranges of d-BMI, patients were divided into three groups: under −2, between −2 and +2, and over +2. We analyzed overall survival (OS), disease-free survival (DFS), and GRFS in different BMI groups at transplant and in d-BMI groups. Results: This study included 115 males and 69 females, with median age of 43 years (range, 17-65 years) at diagnosis. In BMI classification at transplant, 29 patients were underweight, 116 were normal weight, 30 were overweight, and nine were obese. At transplant, median BMI was 22.1 kg/m2 (range, 14.8-33.2 kg/m2) and median d-BMI was −0.39 (range, −7.9-+10.0). There were no significant differences in basement characteristics of patients at transplant and in each BMI and d-BMI group. Survival outcomes were observed with a median follow-up period of 1081 days (range, 8-5230 days). At 1 year, OS was 67.9% (95% CI, 60.7-74.2), DFS was 64.1% (95% CI, 56.7-70.6), and GRFS was 40.2% (95% CI, 33.1-47.2). There was no significant association between BMI at transplant and survival outcomes. GRFS at 1 year for the d-BMI groups under −2, between −2 and +2, and over +2 was 16.1% (95% CI, 5.1-31.4), 45.4% (95% CI, 36.4-53.7), and 41.7% (95% CI, 22.2-60.1), respectively (P = 0.0067) (Figure 1). Multivariate analysis showed that a worse GRFS was associated with lower BMI at transplant than that at diagnosis (d-BMI < −2) (HR 2.72, 95% CI, 1.47-5.03, P = 0.015) and the other prognostic factors of performance status (PS) and disease risk. Conclusions: Our results showed that among 184 AML patients who underwent HSCT for the first time, those with d-BMI < −2 had worse GRFS. Figure GRFS of patients with newly diagnosed AML according to d-BMI. Figure. GRFS of patients with newly diagnosed AML according to d-BMI. Disclosures Fujita: Chugai Pharmaceutical Co.,LTD: Honoraria.

Background: The prevalence of obesity has more than doubled between 1980 and 2014, worldwide. In Japan, 25% of adults aged ≥20 years (29 % of males and 20% of females) were overweight in 2013. Body mass index (BMI) assesses the proportion of weight versus height, and is commonly used to stratify underweight, normal, overweight, and obesity in adults. However, the prognostic impact of BMI in acute myeloid leukemia (AML) is debatable. In this retrospective study, we aimed to assess whether BMI was associated with clinical outcomes in AML patients in Japan. Patients and Methods: We identified 374 patients with newly diagnosed AML who had been administered either daunorubicin or idarubicin in combination with cytarabine as induction chemotherapy at any of the seven Japanese hospitals that collaborate to form the Yokohama City University Hematology Group from January 2000 to March 2015. Patients with acute promyelocytic leukemia were excluded from this study. BMI is defined as a person's weight in kilograms divided by the square of his height in meters (kg/m2). All patients were categorized in one of two groups according to their BMI: underweight (BMI Results: This study included 227 males and 147 females, with median age at diagnosis of 49 years (range, 15-77 years). In BMI classification, 273 were NW (47, underweight; 226, normal weight), 101 were OW (83, overweight; 18, obese). Median BMI was 22.4 (range, 15.9-39). There were not significant differences in age, sex, Performance status (PS), cytogenetic risk, and comorbidities such as diabetes, hypertension, and ischemic heart disease requiring treatment on diagnosis of AML in the two BMI groups. In this cohort, 283 patients (75.7%) achieved CR and 81 (21.7%) experienced PIF, and 10 subjects (2.8%) had an early death (ED) as death occurring within 30 days of chemotherapy initiation. Only one patient received reduced intensity of chemotherapy ( ≥20%) because of obesity. Relapse during the first CR occurred in 173 subjects (46.3%), and death occurred in 139 patients (37.2%). There was no significant difference in CR rate between the NW and OW groups (73.3% and 82%, respectively, P = 0.079). All 10 patients who experienced ED were in NW (3.7%, P = 0.0068). Causes of ED were as follows: infection in 5 subjects; 3 from cerebral bleeding; and 2 deaths from alveolar bleeding. With a median follow-up of 42 months (1-176 months), OS was 52.4% and 64% at 3 years for the NW and OW groups, respectively (P = 0.022; Figure 1). There was no significant difference in PIF and adverse event between theNW and OW groups. Multivariate analysis showed that a better OS was associated with OW (HR 0.65, 95% CI 0.43-0.97, P = 0.033) and the other prognostic factors of age, sex, PS, and cytogenetic risk. Conclusions: The results of this study show that AML patients with BMI ≥25 had better survival. There was no difference in the toxicity of chemotherapy between the different BMI groups. Out study suggests that Increased BMI should not be a criterion for reducing the dose of chemotherapy administered to patients of newly diagnosed AML. Figure 1. Overall survival of patients with newly diagnosed acute myeloid leukemia according to BMI. Figure 1. Overall survival of patients with newly diagnosed acute myeloid leukemia according to BMI. Disclosures Fujita: Chugai Pharmaceutical CO.,LTD.: Honoraria.

A 55-year-old man was scheduled for resection of an adrenal tumor under the diagnosis of a non-functioning adrenal tumor. He was admitted for unstable angina 58 days preoperatively, and on the second hospital day, he had an episode of ventricular tachycardia for 20 seconds following epigastric pain. Abdominal computed tomography scans revealed a retroperitoneal abscess, which was subsequently drained effectively, and a right adrenal tumor. Because of the almost normal plasma catecholamine concentration, the tumor was considered a nonfunctioning tumor. However, when the surgeon manipulated the tumor during the operation, the patient's blood pressure increased suddenly to 240/120 mmHg. The hypertensive crisis was managed with nicardipine and phentolamine. After resection of the tumor, his blood pressure decreased to 80/40 mmHg, and the patient was treated with ephedrine, phenylephrine, and noradrenaline. After surgery, the tumor was confirmed histopathologically as a pheochromocytoma. The management of patients with a hypertensive crisis under suspicion of pheochromocytoma is discussed.