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Multiple myeloma (MM) is known for its immune disturbance and patients suffering from MM are thus vulnerable to opportunistic infections, including herpes zoster (HZ). As HZ infection remarkably affects patients' quality of life and poses huge economic burdens on the health system, we aim to identify the risk factors of HZ infection and evaluate the effects of different dosages, types, and durations of anti-HZ prophylaxis drugs to prevent HZ infection.551 MM patients at Taipei Veterans General Hospital in Taiwan between January 1, 2009 and August 31, 2021 were restrospectively analyzed. The patients' baseline characteristics were recorded. The primary endpoint of the study was the incidence of HZ infection among the studied patient population. Due to the lack of cost coverage from Taiwanese public health insurance on HZ prophylaxis drugs, the use of anti-HZ drugs mainly depends on physicians' preferences and patients' choices.In our study, prophylaxis was given to 283 of the patients. In the multivariate analysis, we included non-prophylaxis, age ≥ 60, corrected serum calcium ≥12 mg/dl, serum creatinine ≥2 mg/dl, serum β2-microglobulin ≥5500 mg/L, autologous stem cell transplant (SCT), and allogeneic SCT for analysis. Our results demonstrated that the non-prophylaxis group (HR: 2.37, 95% CI 1.57-3.57) and patients receiving autologous SCT (HR: 2.22, 95% CI 1.28-3.86) and allogeneic SCT (HR: 5.12, 95% CI 1.13-23.22) had higher risk of HZ infection. The difference in dosage and types of anti-HZ drugs showed similar protective effects. In patients who stopped anti-HZ prophylaxis before active cancer-related treatment, a higher risk of getting HZ infection compared to the corresponding group was also observed (adjusted HR 3.09, 95% CI 1.35-7.07, p = 0.008).We concluded that MM patients should receive HZ prophylaxis drugs while receiving active cancer-related treatment. Patients receiving SCT are also at high risk of getting HZ infection, even under prophylaxis.

Introduction: Autologous hematopoietic stem cell transplantation (ASCT) is a well-established treatment for patients with multiple myeloma (MM), and adequate stem cell collection must be assured before ASCT. However, prediction of poor mobilizers (PMs) is still difficult despite several risk factors for mobilization failure having been identified. Methods: We retrospectively analyzed MM patients at Taipei Veterans General Hospital in Taiwan who underwent stem cell collection between October 2006 and August 2020. A CD34+ cell collection of 6 cells/kg was defined as a mobilization failure. The primary endpoint was mobilization failure. The secondary endpoint was overall survival (OS). Odds ratios (ORs) and 95% confidence intervals (CIs) for mobilization failure were calculated using a logistic regression model. The cumulative incidence of mortality was estimated using the Kaplan-Meier method. Results: In the multivariate analysis, absolute monocyte count p = 0.009), platelet count p = 0.001) before mobilization, and time interval from diagnosis to stem cell harvest ≥180 days (adjusted OR 7.69, 95% CI: 1.61–36.87, p = 0.011) were risk factors for PMs. PM patients had poorer OS compared to patients with successful stem cell collection in the univariate analysis (log-rank test p = 0.027). The predicted probability of PMs was estimated by the multiple logistic regression model with a sensitivity of 84.6% and a specificity of 84.0%. Conclusion: Absolute monocyte count

Introduction Circulating monocytic myeloid-derived suppressive cells (M-MDSCs) are implicated as a poor prognostic factor and cause CAR T-cell failure in diffuse large B-cell lymphoma (DLBCL). Triggering receptors expressed on myeloid cells 2 (TREM2) are a transmembrane glycoprotein that polarize macrophages to anti-inflammation phenotype but have never been explored on M-MDSCs. This study aims to elucidate the expression and clinical impact of surface TREM2 on circulating M-MDSCs derived from DLBCL adults. Methods This prospective, observational study enrolled 100 adults with newly diagnosed and treatment-naïve DLBCL from May 2019 to October 2021. Human circulating M-MDSCs were obtained from freshly isolated peripheral blood, and each patient’s surface-TREM2 level on M-MDSCs was normalized via a healthy control at the same performance of flow-cytometry analysis. Murine MDSCs derived from bone marrow (BM-MDSCs) were adopted to assess the link between Trem2 and cytotoxic T lymphocytes. Results More circulating M-MDSCs at diagnosis of DLBCL predicted worse progression-free (PFS) and overall survival (OS). Patients with higher IPI scores, bone marrow involvement, or lower absolute counts of CD4+ or CD8+ T cells in PB had significantly higher normalized TREM2 levels on M-MDSCs. Additionally, normalized TREM2 levels on M-MDSCs could be grouped into low ( 44%) levels, and a high normalized TREM2 level on M-MDSCs was proven as an independent prognostic factor for both PFS and OS via multivariate Cox regression analysis and associated with worst PFS and OS. Interestingly, normalized levels of surface TREM2 on M-MDSCs were negatively associated with absolute counts of PB CD8+ T cells and positively correlated with levels of intracellular arginase 1 (ARG1) within M-MDSCs. Wild-type BM-MDSCs had significantly higher mRNA levels of Arg1 and showed more prominent ability to suppress the proliferation of co-cultured CD8+ T cells than BM-MDSCs from Trem2 knockout mice, and the suppressive ability could be impaired by adding Arg1 inhibitors (CB1158) or supplementing L-arginine. Conclusion In treatment-naïve DLBCL adults, a high surface-TREM2 level on circulating M-MDSCs is a poor prognostic factor for both PFS and OS and warrants further investigation for its potential as a novel target in immunotherapy.

Darinaparsin is a novel organic arsenical compound of dimethylated arsenic conjugated to glutathione, with antitumor activity and a mechanism of action markedly different from other available agents. This phase II, nonrandomized, single-arm, open-label study evaluated the efficacy and safety of intravenous darinaparsin (300 mg/m2 over 1 hour, once daily for five consecutive days, per 21-day cycle) and its pharmacokinetics at multiple doses in 65 Asian patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). The primary endpoint was the overall response rate (ORR). The ORR based on central assessment was 19.3% (90% confidence interval: 11.2-29.9%), which was significantly higher than the predefined threshold of 10% (p = 0.024). The ORR was 16.2% in patients with PTCL-not otherwise specified and 29.4% in patients with angioimmunoblastic T-cell lymphoma. The tumor size decreased in 62.3% of patients. Treatment-emergent adverse events (TEAEs) were observed in 98.5% of patients. Grade ≥3 TEAEs with an incidence rate ≥5% included anemia (15.4%), thrombocytopenia (13.8%), neutropenia (12.3%), leukopenia (9.2%), lymphopenia (9.2%), and hypertension (6.2%). Darinaparsin is effective and well tolerated, with TEAEs that were clinically acceptable and manageable with symptomatic treatment and dose reductions (ClinicalTrials.gov: NCT02653976).

Hemophagocytic lymphohistiocytosis (HLH) is a heterogeneous group of hyperinflammatory statuses that are difficult to diagnose and can be life-threatening. Bone marrow (BM) hemophagocytosis is one of the diagnostic criteria according to HLH 2004 diagnostic criteria and HS score. Limited studies have focused on the prognostic factors of BM hemophagocytosis and its association with hematologic malignancies. We aimed to analyze the clinical significance of BM hemophagocytosis. Patients with BM hemophagocytosis, either by cytology or pathology, were enrolled at Taipei Veterans General Hospital from January 2002 to July 2021. Relevant clinical and laboratory data were extracted from medical records. Of 119 patients with BM hemophagocytosis, 57 were diagnosed with hematologic malignancies. The median age of the patients was 58, ranging from 21 to 90. Splenomegaly (adjusted odds ratio [aOR] 2.96; 95% confidence interval [CI] 1.13-7.79) was a risk factor for hematologic malignancies, while autoimmune disease (aOR 0.07; 95% CI 0.01-0.39) and increased D-dimer (aOR 0.25; 95% CI 0.07-0.92) were protective factors. Risk factors for mortality in patients with BM hemophagocytosis were hematologic malignancies (adjusted hazard ratio [aHR] 2.34; 95% CI 1.24-4.44), Eastern Cooperative Oncology Group score ≥3 (aHR 2.42; 95% CI 1.20-4.89) and thrombocytopenia (aHR 3.09; 95% CI 1.04-9.16). In conclusion, among patients with BM hemophagocytosis, splenomegaly was a predictor of hematologic malignancies. Patients with hematologic malignancies, poor performance status, or thrombocytopenia had a higher mortality risk. Further validation studies are warranted.

Due to increasing use of frontline lenalidomide, effective and safe lenalidomide-free therapies for relapsed/refractory multiple myeloma (RRMM) are needed in Asia. This subgroup analysis of phase 3 CANDOR study evaluated efficacy and safety of KdD vs Kd in Asian patients with RRMM. Self-identified Asian patients with RRMM (KdD = 46; Kd = 20) with 1‒3 prior therapies were included. The primary endpoint of progression-free survival was estimated by stratified Cox regression. Baseline demographics and patient characteristics were balanced in both arms. KdD reduced the risk of progression or death by 25% vs Kd [hazard ratio (HR) = 0.75; 95% CI 0.259, 2.168] in the Asian subgroup, compared with 37% vs Kd (0.63; 0.464, 0.854) in the overall CANDOR population. Percentage of patients who reported grade ≥ 3 treatment-emergent adverse events (TEAEs) in the KdD and Kd arms was 95.7 and 90.0%, respectively. Serious AEs were observed in 58.7 and 40.0% of patients in the KdD and Kd arms, respectively. There were two (4.3%) fatal TEAEs in the KdD arm due to infections. There was a trend toward better efficacy and a favorable benefit-risk profile for KdD vs Kd in Asian patients with RRMM. Cautious interpretation is warranted due to small patient size.

Multiple myeloma (MM), a clonal plasma cell malignancy, composes around 10% of hematologic malignancies. Though recent advances in treatment have dramatically improved MM survival, some aggressive courses of disease and dismal outcomes still exist. Low body weight, undernutrition, and cachexia are noted at MM diagnosis. We aim to evaluate the impact of low body mass index (BMI) and undernutrition in MM patients. We retrospectively analyzed MM patients at Taipei Veterans General Hospital in Taiwan between January 1, 2006 and October 31, 2018. Being underweight is defined as having a BMI of under 18.5 kg/m2. The patient’s baseline characteristics, including BMI, serum albumin level, and comorbidities, etc., were recorded. The primary endpoint of the study was all-cause mortality. A Cox regression model was used to estimate the risk factors of mortality. A total of 378 newly diagnosed MM patients were enrolled in this study. The median age of the patients was 69. Thirty patients (7.9%) were underweight at diagnosis. The median overall survival was 1.3 years (95% CI 0.3–5.7) and 5.0 years (95% CI 3.1–5.9) for patients with low BMI and for patients with normal or higher BMI, respectively. In the multivariate analysis, low BMI (95% CI 1.07–4.44), ECOG ≥2 (95% CI 1.02–2.89), hypoalbuminemia (95% CI 1.21–4.01), high LDH (95% CI 1.22–3.49), and light chain ratio > 100 (95% CI 1.06–2.77) were independent risk factors of mortality. MM patients who were underweight, with hypoalbuminemia, poor performance status, higher LDH, and light chain ratio > 100 were associated with poor overall survival.

Infection is associated with great morbidity and mortality in patients with multiple myeloma (MM), but evidence for invasive fungal infections (IFIs) is lacking. We aimed to investigate risk factors for IFI in MM patients and to determine its impact on patients’ survival. We retrospectively analyzed MM patients at Taipei Veterans General Hospital in Taiwan between January 2002 and October 2018. MM was diagnosed according to the International Myeloma Working Group criteria. IFI was defined according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. All risk factors of IFI in MM patients were estimated using Cox regression models in the univariate and multivariate analyses. Of the 623 patients recruited, 22 (3.5%) were diagnosed with proven or probable IFI. Light chain disease (adjusted hazard ratio [HR] 6.74, 95% confidence interval [CI] 2.10–21.66), hemoglobin less than 8 g/dl (adjusted HR 3.34, 95% CI 1.32–8.42), serum albumin

BACKGROUND Thrombotic microangiopathy (TMA) syndromes are potentially life-threatening complications and are defined as integrated syndromes of microangiopathic hemolytic anemia, thrombocytopenia, and organ injury. Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect various organs, including the hematopoietic system. SLE can complicate with TMA and can be categorized into two distinct groups by chronological association: TMA occurring as the initial presentation and leading to a diagnosis of SLE concurrently (TMA-cSLE) or TMA developing in patients previously diagnosed as having SLE (TMA-pSLE). We examined the differences in clinical characteristics, treatment responses, and clinical outcomes between these groups. METHODS We reviewed data of patients diagnosed as having TMA and SLE at Taipei Veterans General Hospital between 2002 and 2013. We included 29 patients: 8 and 21 in TMA-cSLE and TMA-pSLE groups, respectively. All underwent plasma exchange. Patients' demographic and clinical characteristics, disease activity, and treatment modality were summarized. RESULTS Overall survival (OS) from SLE or TMA diagnosis was poor for the TMA-cSLE group. Median OS from SLE diagnosis was 2.9 months in the TMA-cSLE group and 103.5 months in the TMA-pSLE group (p < 0.001). Median OS from TMA diagnosis was 2.9 months in the TMA-cSLE group and 10.7 months in the TMA-pSLE group (p = 0.58). Time to TMA remission after treatment appeared longer in the TMA-cSLE group (38.00 vs 10.76 days). Multivariate Cox analysis revealed TMA-cSLE and anti-RNP positivity were independent risk factors for mortality in SLE patients with TMA. CONCLUSION The occurrence of TMA with SLE is rare, and its vigorous course results in high mortality and morbidity rates. In patients without a history of autoimmune disease, early suspicion of TMA and working-up for SLE under this condition are vital. Early recognition of TMA-cSLE and prompt plasma exchange with upfront immunosuppressive therapies for TMA-cSLE patients or anti-RNP-positive patients may improve their prognosis.

Introduction: Patients with acute leukemia exposed higher risk for developing invasive fungal infections and the invasive fungal infection is also an important cause of morbidity and mortality during allogeneic hematopoietic stem cell transplantation (allo-HSCT). In addition to candida species, the invasive mold infection (IMI) is most common in invasive fungal infections and the incidence rate is increasing in recent years. Although recent diagnostic approach and treatments for IMI are advanced, the prognosis remains poor. It is essential to understand the risk factors for developing IMI among acute leukemia patients undergoingallo-HSCT. Here, we conducted a retrospective study to demonstrate demographics, microbiology, and risk factors for the development of IMI among 245 adult acute leukemia patients undergoingallo-HSCT at our institution during a 10-year period. Method We reviewed 245 adult acute leukemia patients undergoingallo-HSCT from January 2003 to December 2014. Clinical characteristics including age, sex, underlying disease, type of allogeneic transplant, conditioning regimens, European Group for Blood and Bone marrow Transplantation (EBMT) risk score, and presence of acute graft-versus-host disease (aGVHD) or chronic GVHD (cGVHD) were collected and analyzed. Cox proportional hazard model was adopted to explore the independent risk factors for IMI development. The Kaplan-Meier method was performed to estimate the cumulative incidence and the curve was compared using the log-rank test Results Twenty out of 245 patients developed IMI during study period and the median time to onset after transplantation was 391 days (interquartile range, 220-552 days). The cumulative incidence of IMI in this cohort was 1.9 %, 5.1%, and 12.8% at 6 months, 12 months, and 24 months, respectively. Aspergillus species were the most common and presented in 55% of mold infections. The significant risk factors to predict mold infection after transplantation (Table 1) were smoking (hazard ratio [HR] 4.28, 95% confidence interval [CI] 1.40-13.12; P=0.011), EBMT risk score > 2 (HR 4.37, 95% CI 1.35-14.09; P=0.013), and extensivecGVHD(HR 3.10, 95% CI 1.20-8.00; P=0.019). The cumulative incidence of mold infection in smokers was significantly higher than non-smokers (log-rank P < 0.001) and the Kaplan-Meier curve was shown in Figure 1. Conclusion We identified three risk factors-smoking, EBMT risk score > 2 and extensivecGVHDto predict IMI among acute leukemia patients undergoingallo-HSCT. Smoking may damage respiratory tract epithelium as well as defense-microorganism mechanism and it would lead to IMI easily duringallo-HSCT. This cohort study suggests that early identification of high-risk patients and to provide better prevention strategies would reduce the incidence and severity of IMI in these patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: Overall survival of patients with primary CNS lymphoma (PCNSL) has improved since the introduction of immunochemotherapy. However, up to 10-15% of PCNSL patients still die shortly after diagnosis. In the present study, we aimed to investigate the risk factors of early mortality (death within 60 days after diagnosis) in patients with PCNSL. Methods: We included newly diagnosed PCNSL patients in a tertiary medical center in Taiwan between January 1, 2002 and May 31, 2018. Clinical risk factors were collected and compared between PCNSL patients who had and did not have early mortality. Results: A total of 133 consecutive patients with PCNSL were included in this study. Approximately 9.8% of the PCNSL patients had early mortality. In multivariate analysis, age ≥ 80 (adjusted hazard ratio [HR] 3.34, 95% confidence interval [CI] 1.01-11.04, p = 0.048) and involvement of the basal ganglia (adjusted HR 4.85, 95% CI 1.47-15.95, p = 0.009) were identified as independent risk factors of early mortality. Use of MTX-based chemotherapy served as an independent protective factor for early mortality (adjusted HR 0.19, 95% CI 0.05-0.67, p = 0.010). Infection and tumor-associated mass effect contributed most to early mortality. Conclusion: Early mortality is not uncommon in patients with PCNSL. Identification of patients with higher risk may help clinicians with initiating appropriate surveillance and management.

Due to increasing use of frontline lenalidomide, effective and safe lenalidomide-free therapies for relapsed/refractory multiple myeloma (RRMM) are needed in Asia. This subgroup analysis of phase 3 CANDOR study evaluated efficacy and safety of KdD vs Kd in Asian patients with RRMM.Self-identified Asian patients with RRMM (KdD = 46; Kd = 20) with 1‒3 prior therapies were included. The primary endpoint of progression-free survival was estimated by stratified Cox regression.Baseline demographics and patient characteristics were balanced in both arms. KdD reduced the risk of progression or death by 25% vs Kd [hazard ratio (HR) = 0.75; 95% CI 0.259, 2.168] in the Asian subgroup, compared with 37% vs Kd (0.63; 0.464, 0.854) in the overall CANDOR population. Percentage of patients who reported grade ≥ 3 treatment-emergent adverse events (TEAEs) in the KdD and Kd arms was 95.7 and 90.0%, respectively. Serious AEs were observed in 58.7 and 40.0% of patients in the KdD and Kd arms, respectively. There were two (4.3%) fatal TEAEs in the KdD arm due to infections.There was a trend toward better efficacy and a favorable benefit-risk profile for KdD vs Kd in Asian patients with RRMM. Cautious interpretation is warranted due to small patient size.

Multiple myeloma (MM), a clonal plasma cell malignancy, composes around 10% of hematologic malignancies. Though recent advances in treatment have dramatically improved MM survival, some aggressive courses of disease and dismal outcomes still exist. Low body weight, undernutrition, and cachexia are noted at MM diagnosis. We aim to evaluate the impact of low body mass index (BMI) and undernutrition in MM patients.We retrospectively analyzed MM patients at Taipei Veterans General Hospital in Taiwan between January 1, 2006 and October 31, 2018. Being underweight is defined as having a BMI of under 18.5 kg/mA total of 378 newly diagnosed MM patients were enrolled in this study. The median age of the patients was 69. Thirty patients (7.9%) were underweight at diagnosis. The median overall survival was 1.3 years (95% CI 0.3-5.7) and 5.0 years (95% CI 3.1-5.9) for patients with low BMI and for patients with normal or higher BMI, respectively. In the multivariate analysis, low BMI (95% CI 1.07-4.44), ECOG ≥2 (95% CI 1.02-2.89), hypoalbuminemia (95% CI 1.21-4.01), high LDH (95% CI 1.22-3.49), and light chain ratio 100 (95% CI 1.06-2.77) were independent risk factors of mortality.MM patients who were underweight, with hypoalbuminemia, poor performance status, higher LDH, and light chain ratio 100 were associated with poor overall survival.

Background Extranodal natural killer/T cell lymphoma, nasal type, is one of the more common subtypes of mature T cell lymphoma, especially in the Far East Asian population. This aggressive histologic subtype of peripheral T cell lymphomas is frequently susceptible to exposure of Epstein–Barr virus infection. The optimal treatment is not well elucidated. For stage IV disseminated extranodal natural killer/T cell lymphoma, induction chemotherapy with consolidative autologus or allogeneic hematopoietic stem cell transplantation is recommended as the major first-line treatment. However, there is controversy over which type of chemotherapy is most appropriate and effective as a bridge to autologus or allogeneic hematopoietic stem cell transplantation in patients with newly diagnosed disseminated advanced-stage or relapsed extranodal natural killer/T cell lymphoma because of cancer chemoresistance or associated complications. Pralatrexate is the first US Food and Drug Administration-approved novel agent for the treatment of refractory/recurrent peripheral T cell lymphomas. In our case, pralatrexate was used as a successful bridge to allogeneic hematopoietic stem cell transplantation in a patient with advanced-stage disseminated extranodal natural killer/T cell lymphoma refractory to first-line chemotherapy. Case presentation We presented a case report of a 29-year-old Asian man diagnosed as having stage IV disseminated extranodal natural killer/T cell lymphoma, nasal type, with skin and bone marrow involvement, whose disease was primary refractory to first-line dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide chemotherapy, but obviously responded to treatment with two cycles of single-agent pralatrexate treatment. Monitoring Epstein–Barr virus viremia revealed dramatic downregulation. In addition to complete remission of the involvement of bone marrow and nasal cavity, skin involvement also obtained partial remission. The extranodal natural killer/T cell lymphoma successfully achieved complete remission after a bridge to allogeneic hematopoietic stem cell transplantation. Conclusions This is the first study to present pralatrexate as a successful bridge to allogeneic hematopoietic stem cell transplantation in a 29-year-old Asian male patient with advanced-stage extranodal natural killer/T cell lymphoma refractory to first-line dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide chemotherapy. This case provides a novel treatment opinion for extranodal natural killer/T cell lymphoma, especially for the Far East Asian population.

Infection is associated with great morbidity and mortality in patients with multiple myeloma (MM), but evidence for invasive fungal infections (IFIs) is lacking. We aimed to investigate risk factors for IFI in MM patients and to determine its impact on patients' survival. We retrospectively analyzed MM patients at Taipei Veterans General Hospital in Taiwan between January 2002 and October 2018. MM was diagnosed according to the International Myeloma Working Group criteria. IFI was defined according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. All risk factors of IFI in MM patients were estimated using Cox regression models in the univariate and multivariate analyses. Of the 623 patients recruited, 22 (3.5%) were diagnosed with proven or probable IFI. Light chain disease (adjusted hazard ratio [HR] 6.74, 95% confidence interval [CI] 2.10-21.66), hemoglobin less than 8 g/dl (adjusted HR 3.34, 95% CI 1.32-8.42), serum albumin 3.5 g/dl (adjusted HR 3.24, 95% CI 1.09-9.68), and having received allogeneic stem cell transplantation (allo-SCT) (adjusted HR 5.98, 95% CI 1.62-22.03) were significantly associated with IFI in the multivariate analysis. Contracting IFI was in turn associated with early mortality (adjusted HR 11.60, 95% CI 1.26-106.74). Light chain disease, anemia, hypoalbuminemia, and receiving allo-SCT were independent predictors of IFI in MM patients. The early mortality risk is much higher in those encountering IFI. Physicians must be aware of the rare but potentially lethal infections.

BACKGROUND Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are hematological diseases predominantly occurring in older patients. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the curative therapy for refractory AML or high-risk MDS, old age is often a hurdle to the procedure. We conducted a retrospective study to analyze the prognostic factors predicting outcomes of older patients undergoing allo-HSCT for acute leukemia and MDS. METHODS We collected data from patients diagnosed with acute leukemia or MDS, who underwent allo-HSCT at >50 years of age and reviewed clinical characteristics, including age, sex, underlying disease, European Group for Blood and Bone Marrow Transplantation (EBMT) risk score, and presence of acute graft-versus-host disease (aGVHD) or chronic GVHD (cGVHD). The Cox proportional hazard model was adopted to explore the independent prognostic factors for overall survival (OS), progression-free survival (PFS), and non-relapse mortality (NRM). RESULTS A total of 85 older patients were included, with the median age at allo-HSCT being 55 years. The significant prognostic factors for worse OS or PFS were an EBMT risk score > 3 and grade III-IV aGVHD, while patients with moderate to severe cGVHD would have better OS or PFS. Interestingly, it is not cGVHD but grade III-IV aGVHD that significantly correlated with NRM. CONCLUSION This cohort study suggests that an EBMT risk score >3 and grade III-IV aGVHD predict poor outcomes, and careful management of GVHD may allow better survival for older patients undergoing allo-HSCT.

Introduction Myeloid-derived suppressive cells (MDSCs) represent a collection of myeloid-lineage immature cells owning immunosuppressive ability to facilitate tumor growth and can be phenotyped into two major groups: monocytic MDSC (M-MDSC) and granulocytic MDSC (G-MDSC). Earlier studies demonstrated the association between M-MDSC and prognosis in lymphoma patients. Triggering Receptors Expressed on Myeloid cells 2 (TREM-2) is a transmembrane glycoprotein and well-known to polarize macrophage to M2-like phenotype presenting anti-inflammation properties. Given that both the macrophage and M-MDSC belong to monocytic lineage, we wondered if TREM-2 was also expressed on M-MDSC cell surface and tried to elucidate the clinical impact of surface TREM-2 on M-MDSC derived from patients with newly-diagnosed and treatment-naïve non-Hodgkin lymphoma (NHL). Methods This was a prospective observational study conducted in a tertiary medical center (Taipei Veterans General Hospital) in Taiwan. Adult patients with newly-diagnosed and treatment-naïve NHL were eligible for enrollment from May 15, 2019 to February 28, 2021. Patients with HIV infection or other concurrent malignancies were excluded. The Mann-Whitney U test was used for quantitative data, the Kaplan-Meier estimate and log-rank test for survival data, and Cox regression models for hazard ratios (HRs). Human M-MDSC (defined as CD14 + CD11b + CD33 + HLA-DR - CD15 - cells, Figure A) was obtained from freshly isolated PBMC before initiating any treatment, including steroid. To increase inter-experiment reproducibility, the peripheral blood (PB) from the principal investigator (Hao-yuan Wang) was utilized as an internal control (Healthy Control), and every patient's blood sample was paired to the Healthy Control at the same performance of flow cytometric analysis to calculate the normalized MFI change of TREM-2 as the following: (Patient's TREM2 MFI - Healthy Control's TREM2 MFI) / (Healthy Control's TREM2 MFI) x100 % Results One hundred and one adults with newly-diagnosed and treatment-naïve NHL were prospectively enrolled, with median age of 70 years, DLBCL as the most common pathological subtype (64.4%), 8.9% of patients as the T-cell lymphoma, 18.8% of patients being indolent subtypes, 52.5% of patients having stage IV, 36.6% of patients showing high-risk IPI score, and the median percentage of M-MDSC among peripheral-blood CD45 + cells indicating 0.45%. After a medium follow-up of 14.5 months, we confirmed that patients with higher percentage (>0.82%) of M-MDSC among peripheral-blood CD45 + cells had significantly worse overall survival (non-reach v.s. non-reach, P =0.011) when comparing to those with lower percentage (≦0.82%) of M-MDSC in PB. With regard to the expression of TREM-2 on M-MDSC cell surface, M-MDSC from patients with aggressive lymphoma showed significantly higher normalized MFI change of surface TREM-2 when comparing to M-MDSC from patients with indolent lymphoma (Figure B); the normalized MFI change of surface TREM-2 on M-MDSC derived from patients with higher IPI scores is also significantly higher than those from patients with lower IPI scores (Figure C). Furthermore, patients whose M-MDSCs showed higher normalized MFI change of TREM-2 had significantly worse progression-free and overall survival than those with lower normalized MFI change of surface TREM-2 (Figure D & E). To validate the clinical significance of TREM-2 on M-MDSC cell surface in adults with newly-diagnosed and treatment-naïve NHL, seven factors (age > 70 years, male gender, T-cell subtype, aggressive subtype, high-risk IPI score, percentage of M-MDSC among CD45 + cells in PB >0.82%, and normalized change of surface TREM-2 on M-MDSC >0%) were initially verified by univariate analysis and subsequently put into multivariate analysis if qualified, as shown by Table 1. At last, age (>70 years) and normalized change of TREM-2 on M-MDSC cell surface (>0%) were independent predictors of poor PFS and OS. Conclusion: For adults with newly-diagnosed and treatment-naïve NHL, patients with higher percentage of M-MDSC in PB is associated with worse prognosis; more importantly, high expression of TREM-2 on M-MDSC cell surface is an independent predictor for worse progression and overall survival. The functional role of TREM-2 on M-MDSC warranted further investigation for validating its possibility as an immunotherapeutic novel target. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: Darinaparsin is a novel organic arsenic compound composed of dimethylated arsenic linked to glutathione. In two phase I studies including Japanese and Korean patients with relapsed or refractory peripheral T-cell lymphoma (PTCL), darinaparsin was well tolerated and demonstrated potential efficacy (ASH2015 Abstract #2714 and Jpn J Clin Oncol. 2021, 51:218). The efficacy, safety and pharmacokinetics of darinaparsin in Asian patients with relapsed or refractory PTCL were evaluated in a multinational phase II study. Methods: Eligible patients had histologically confirmed PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL) or anaplastic large cell lymphoma (ALCL), which had relapsed from or were refractory to one or more prior regimen with systemic chemotherapy. Darinaparsin was intravenously administered for 5 consecutive days at 300 mg/m 2/day every 3 weeks. The primary endpoint was the overall response rate (ORR) within 6 cycles of treatment. Tumor response was assessed based on computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (FDG-PET) evaluation by central review according to the Revised Response Criteria for Malignant Lymphoma (J Clin Oncol. 2007, 25:579). Secondary endpoints included progression-free survival (PFS), overall survival (OS), toxicity, and pharmacokinetic parameter. This study was conducted in 25 sites in East Asia (13 in Japan, 6 in Korea, 5 in Taiwan, and 1 in Hong Kong). Results: A total of 65 patients (37, 19, 8 and 1 from Japan, Korea, Taiwan and Hong Kong, respectively) including 43 PTCL-NOS, 17 AITL and 3 ALK-negative ALCL; 45 males and 20 females, with a median age of 68 (range 28-85) years received darinaparsin. The median number of prior systemic chemotherapy regimens was 2 (range 1-11). Approximately 30% of patients did not have evidence of response to the most recent prior systemic therapy. The median number of cycles received darinaparsin was 3 (range 1-39). In 57 evaluable patients, the ORR as assessed by an independent efficacy assessment committee was 19% (11 of 57; 90% Confidence Interval (CI) 11.2-29.9), and the lower limit of the 90% CI exceeded the predefined 10% threshold (p=0.024, binomial test). The ORR was 16.2% (6 of 37) in the subjects with PTCL-NOS and 29.4% (5 of 17) in the subjects with AITL. None of the subjects with ALCL, ALK-negative responded. Of the 11 responders, 5 achieved a Complete Response (CR) (8.8%), and 6 had a Partial Response (PR) (10.5%). Eight of the 11 responders showed response by Cycle 3. The disease control rate defined as the proportion of patients who achieved CR, PR or Stable Disease (SD) was 46% (26 of 57, 90% CI 34.3-57.3), and more than half of the patients achieved tumor shrinkage (Figure 1). Median duration of response (DOR) was 3.8 months (90% CI 2.7-5.7). Four patients who had achieved SD or better continued the treatment with darinaparsin for more than 1 year, and median duration of treatment in these subjects was 28.6 months (range 14-41). Median PFS and OS were 3.3 months (90% CI 1.9-4.2) and 13.7 months (90% CI 9.9-18.6), respectively. Among all 65 treated patients, the incidence of adverse events (AEs) was 97%, and that of drug-related AEs was 68%. AEs with an incidence of ≥ 20% were pyrexia (42%), anemia (25%), thrombocytopenia (20%) and decreased appetite (20%). The incidence of ≥ Grade 3 AEs was 62%, and that of ≥ Grade 3 drug-related AEs was 29%. The common ≥ Grade 3 AEs were anemia (15%), thrombocytopenia (12%), neutropenia (12%), lymphopenia (9%) and leukopenia (9%). While electrocardiogram (ECG) QT prolongation at 3% was reported as drug-related AEs associated with cardiac toxicity, there were no substantial changes from baseline in the descriptive statistics of ECG parameters associated with darinaparsin treatment. There was no apparent ethnic difference in pharmacokinetic profiles of patients studied. Conclusions: Darinaparsin had clinical efficacy and was well tolerated in patients with relapsed or refractory PTCL. AEs were clinically acceptable and manageable. Darinaparsin is a potential option for the treatment of relapsed or refractory PTCL. Updated results of DOR PFS, OS, and long-term safety are being analyzed for presentation at the conference. Figure 1 Figure 1. Disclosures Fukuhara: Ono Pharmaceutical: Honoraria, Research Funding; Novartis: Honoraria; Nippon Shinyaku: Honoraria; Kyowa Kirin: Honoraria; Janssen: Honoraria; Incyte: Research Funding; HUYA Bioscience International: Honoraria; Eisai: Honoraria; Chugai Pharmaceutical: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Bayer: Research Funding; AbbVie: Honoraria; Takeda Pharmaceutical: Honoraria; Zenyaku Kogyo: Honoraria. Kim: Celltrion: Research Funding; Dong-A Pharmaceutical: Research Funding; Eisai: Research Funding; Johnson & Johnson: Research Funding; Kyowa Kirin: Research Funding; Roche: Research Funding; IGM Biosciences: Research Funding; Sanofi: Research Funding. Yamamoto: Nippon Shinyaku: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Sanofi: Honoraria; Solasia Pharma: Research Funding; SymBio: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Yakult: Honoraria, Research Funding; Zenyaku: Honoraria, Research Funding; Micron: Honoraria; IQIVA/Genmab: Research Funding; ADC Therapeutics: Honoraria; Chugai: Honoraria, Research Funding; Daiichi Sankyo: Honoraria; Eisai: Honoraria, Research Funding; IQIVA/Incyte: Research Funding; IQIVA/HUYA: Honoraria; HUYA: Consultancy; Janssen: Honoraria; Kyowa Kirin: Honoraria; Meiji Seika Pharma: Consultancy, Honoraria, Research Funding; MSD: Honoraria; Mundipharma: Research Funding; Bristol-Myers Squibb/Celgene: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding. Izutsu: Novartis: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Pfizer: Research Funding; Symbio: Honoraria, Research Funding; Allergan Japan: Honoraria; FUJI FILM Toyama Chemical: Honoraria; MSD: Research Funding; Janssen: Honoraria, Research Funding; Incyte: Research Funding; Genmab: Honoraria, Research Funding; Chugai: Honoraria, Research Funding; Beigene: Research Funding; Bayer: Research Funding; AstraZeneca: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Yakult: Research Funding; Takeda Pharmaceutical: Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; HUYA Bioscience International: Research Funding; Eisai: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Terui: Ono Pharmaceutical: Speakers Bureau; MSD: Speakers Bureau; Janssen: Speakers Bureau; Esai: Speakers Bureau; Chugai Pharmaceutical: Speakers Bureau; Celgene: Speakers Bureau; AbbVie: Speakers Bureau; Takeda Pharmaceutical: Speakers Bureau. Ando: Astellas Pharma: Honoraria; Celgene: Honoraria; Chugai Pharmaceutical: Research Funding; Kyowa Kirin: Research Funding; Novartis: Honoraria; Takeda Pharmaceutical: Research Funding. Suehiro: Otsuka Pharmaceutical: Research Funding; Ono Pharmaceutical: Research Funding; Novartis: Research Funding; Nippon Shinyaku: Honoraria; Kyowa Kirin: Honoraria, Research Funding; Incyte: Research Funding; Eisai: Honoraria, Research Funding; Chugai Pharmaceutical: Honoraria, Research Funding; Celgene: Research Funding; Bristol-Myers Squibb: Honoraria; Bayer: Research Funding; Amgen BioPharma: Research Funding; Pfizer: Research Funding. Nagahama: Solasia Pharma: Current Employment, Current equity holder in publicly-traded company. Sonehara: Solasia Pharma: Current Employment, Current equity holder in publicly-traded company. Nagai: Ono Pharmaceutical: Honoraria; Sanofi: Honoraria; Sumitomo Dainippon Pharma: Honoraria; SymBio Pharmaceuticals: Honoraria, Research Funding; Takeda Pharmaceutical: Honoraria, Research Funding; Zenyaku Kogyo: Research Funding; Novartis: Honoraria; Nippon Shinyaku: Research Funding; Mundipharma: Honoraria, Research Funding; Kyowa Kirin: Research Funding; Janssen: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Chugai Pharmaceutical: Honoraria, Research Funding; Chordia Therapeutics: Honoraria; Celgene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Bayer: Research Funding; AstraZeneca: Honoraria, Research Funding; AbbVie: Research Funding. Tien: Novartis: Honoraria; Celgene: Honoraria, Research Funding; AbbVie: Honoraria. Tobinai: Ono Pharmaceutical: Consultancy, Honoraria; Solasia Pharma: Honoraria; Mundipharma: Consultancy, Honoraria; Kyowa Kirin: Honoraria; HUYA Bioscience International: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Eisai: Honoraria; Chugai Pharmaceutical: Honoraria; Celgene: Consultancy, Honoraria; Takeda Pharmaceutical: Consultancy, Honoraria; Zenyaku Kogyo: Consultancy, Honoraria; Yakult: Honoraria. OffLabel Disclosure: Darinaparsin is an investigational product that is not approved in any country/region in the world.

This study aimed to examine the prognostic value of anemia for the diagnosis of chronic myeloid leukemia in the chronic phase (CML-CP) receiving imatinib.One hundred and fifty-four CML-CP patients were enrolled. The influences of moderate anemia with hemoglobin (Hb) 10 g/dl, four scoring systems, and the early molecular response at 3 months (BCR-ABL ≤10%; 3M-EMR) on the achievement of a deep molecular response (DMR, MR4.5), progression-free survival (PFS), event-free survival (EFS), and overall survival (OS) were compared.Moderate anemia was identified in 44 (28.6%) patients. These patients had more aggressive baseline features and higher risks, as assessed by scoring systems, and less favorable treatment responses vs those without anemia, including 3M-EMR (50.0% vs 69.1%), a complete cytogenetic response at 6 months (20.5% vs 50.9%), and a major molecular response at 12 months (22.5% vs 45.2%), with a median follow-up of 54.0 months. Furthermore, an Hb of 10 g/dl better distinguished DMR, EFS, PFS, and OS than the EUTOS, Sokal, and Hasford scores, and better predicted the responses and survivals in combination with 3M-EMR than 3M-EMR alone.This finding highlights the significance of anemia in CML-CP, and suggests that patients with anemia at diagnosis should be carefully monitored and might benefit from more potent TKIs if not achieving 3M-EMR.

Bloodstream nontyphoidal salmonella (NTS) infection is rare, but its associated characteristics and microbiological features in immunocompromised patients are worth paying attention to, particularly for those receiving allogeneic hematopoietic stem cell transplantation (SCT). No studies so far have analyzed post-transplant bloodstream NTS infection. Therefore, we reviewed 423 adult patients undergoing allogeneic hematopoietic SCT from 2003 to 2014. Nine out of four hundred twenty-three patients (2.13%) developed post-transplant bloodstream NTS infection, including two patients who had subsequent or combined metastatic infections. The median age at SCT was 35 years (interquartile range, 29-46) among the nine patients with bloodstream NTS infection. Male patients were predominant (78%). The median onset of bloodstream NTS infection was at 315 days after SCT (range, 207-629). Multivariate analysis revealed that extensive chronic graft-versus-host disease (GVHD) (OR 8.054, p = 0.003) and nonmyeloablative transplant conditioning (OR 4.604, p = 0.037) were significant associated characteristics for NTS infection. Currently, there are no published data analyzing and exploring post-transplant bloodstream NTS infections in adult allogeneic hematopoietic SCT. Our study determined the associated characteristics and microbiological features for this infection.

Enhancing the tumour suppressive activity of protein phosphatase 2A (PP2A) has been suggested to be an anti-leukaemic strategy. KIAA1524 (also termed CIP2A), an oncoprotein inhibiting PP2A, is associated with disease progression in chronic myeloid leukaemia and may be prognostic in cytogenetically normal acute myeloid leukaemia. Here we demonstrated that the selective proteasome inhibitor, carfilzomib, induced apoptosis in sensitive primary leukaemia cells and in sensitive leukaemia cell lines, associated with KIAA1524 protein downregulation, increased PP2A activity and decreased p-Akt, but not with the proteasome inhibition effect of carfilzomib. Ectopic expression of KIAA1524, or pretreatment with the PP2A inhibitor, okadaic acid, suppressed carfilzomib-induced apoptosis and KIAA1524 downregulation in sensitive cells, whereas co-treatment with the PP2A agonist, forskolin, enhanced carfilzomib-induced apoptosis in resistant cells. Mechanistically, carfilzomib affected KIAA1524 transcription through disturbing ELK1 (Elk-1) binding to the KIAA1524 promoter. Moreover, the drug sensitivity and mechanism of carfilzomib in xenograft mouse models correlated well with the effects of carfilzomib on KIAA1524 and p-Akt expression, as well as PP2A activity. Our data disclosed a novel drug mechanism of carfilzomib in leukaemia cells and suggests the potential therapeutic implication of KIAA1524 in leukaemia treatment.

Background Survival benefit from chemotherapy in advanced hepatocellular carcinoma (HCC) was limited till now. New chemoregimens with cytotoxicity modulators were explored to improve efficacy. Chemotherapy modulated with valproic acid (VA) as a deacetylation inhibitor of histone and DNA damage response proteins, and hydralazine (HZ) as a DNA hypomethylating agent, hypothetically suppressing DNA repair, were used in phase II trial here for advanced HCC. Methods Between July 2008 and March 2016, patients with chemo-naive advanced HCC, regardless of previous sorafenib treatment, not amenable to local therapy and with Child Pugh score ≤7, were treated with VA (200 mg thrice per day) and HZ (12.5 mg twice per day) in conjunction with gemcitabine and cisplatin (GCGG): gemcitabine (1000 mg/m2 , D1; 800 mg/m2 D8, 15) and cisplatin (70 mg/m2 , D1) every 28 days till disease progression and then with Dox-DTIC: doxorubicin (45 mg/m2 ) and dacarbazine (450 mg/m2 ) every 28 days. The primary endpoint was overall survival (OS); the secondary endpoints were safety, progression-free survival (PFS) and response rate (RR). Results Thirty-seven patients with 16 sorafenib-experienced, underwent GCGG treatment, and 30 of them underwent the following Dox-DTIC treatment. The median OS was 14.6 months (95% confidence interval: 6.0-23.1). The median PFSs for patients treated with VA- and HZ-combined GCGG and Dox-DTIC were 3.7 and 4.2 months, respectively; the RRs were 10/37 (27.0%) and 7/30 (23.3%); and grade 3/4 neutropenia were 54% and 51%. However, there were no chemotherapy-related deaths. Conclusion VA- and HZ-combined sequential chemotherapy was effective in advanced HCC with manageable toxicities.

Post-transplant thoracic air-leak syndrome (ALS) is rare but potentially life-threatening in patients receiving allogeneic haematopoietic stem cell transplantation (HSCT). Nevertheless, papers on thoracic ALS are limited, and this complication remains largely unknown. We reviewed 423 adult patients undergoing allogeneic HSCT from 2003 to 2014. Risk factors, clinical features and survival for thoracic ALS were collected and analysed. Thirteen out of 423 patients (3.1%) developed post-transplant thoracic ALS, including two ALS patients in the early phase. The median age at HSCT was 33 years among 13 patients with thoracic ALS. Male patients were predominant (69%). The median onset time was 253 days (range: 40–2680) after HSCT. Multivariate analysis revealed that grade III–IV acute graft-versus-host disease (GVHD) (p = 0.017), extensive chronic GVHD (cGVHD) (p = 0.019) and prior history of pulmonary invasive fungal infection (p = 0.007) were significant risk factors for thoracic ALS. In patients with cGVHD, those with thoracic ALS had a significantly worse survival than those without thoracic ALS (p = 0.04). Currently, published data analysing and exploring post-transplant thoracic ALS are limited. Our study employed a large patient cohort and determined the risk factors and clinical features for post-transplant thoracic ALS.

Cerebrovascular complications after hematopoietic stem cell transplantation (HSCT) cause serious morbidity and often contribute to mortality. The incidence, risk factors, and outcome of cerebrovascular disease (CVD) after allogeneic HSCT remain poorly defined. We retrospectively evaluated 459 adult patients who underwent allogeneic HSCT at a tertiary medical center between January 2003 and December 2015. A total of 20 patients (4.4%) developed post-transplant CVD. All cerebrovascular accidents occurred in the first two years post-transplant. The two-year incidences of post-transplant CVD, intracranial hemorrhage, and cerebrovascular infarction were 6.1%, 3.2%, and 3.2%, respectively. The incidence rate of CVD within two years after HSCT was 34.7 (95% CI 22.3 to − 53.7) per 1000 person-years, which was about tenfold higher than the general Taiwanese population. The only significant risk factor associated with post-transplant CVD is prior exposure to three or more courses of high-dose cytarabine. Post-transplant CVD is associated with dismal outcome and early mortality. The median overall survival of patients with post-transplant CVD was markedly reduced compared with those without CVD (8.0 vs. 60.6 months). Most patients with post-transplant CVD died within two months after the CVD events. Our study demonstrates that CVD remains a devastating complication after allogeneic HSCT in the modern era.

Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a rare form of cytotoxic T-cell lymphoma. It is believed that SPTL in patients without hemophagocytic syndrome (HPS) follows an indolent course; in contrast, SPTL in patients with HPS has been associated with unfavorable survival. To provide more clinical data on SPTL in Asian populations and to identify optimal therapeutic strategies for SPTL, we assessed the clinicopathological features and long-term follow-up data of 10 Taiwanese SPTL patients diagnosed at a single center. Our study demonstrates a group of patients with high incidence of HPS (50%), rather aggressive courses, and early progression. A total of eight patients underwent hematopoietic stem cell transplant (HSCT), including one autologous HSCT and seven allogeneic HSCT. Seven of eight patients receiving HSCT achieved durable remission and maintained in remission for over 30 months (range 30–132 months). There was no difference in 3-year survival of patients with HPS (80%) compared with patients without HPS (80%). Of long-term survivors in the HPS group, three of four received HSCT (autologous HSCT, n = 1; allogeneic HSCT, n = 2). Our study indicated that HSCT is a curative option for eligible SPTL patients with HPS.

Background: Mycobacterial infections are important and potentially life-threatening complications after organ transplantations. Notably, for the recipients of allogeneic hematopoietic stem cell transplantation (HSCT), there are a few supporting results to explore post-transplant mycobacterial infections. Taiwan is a high endemic area of the infection. We aim to investigate the incidence, risk factors, and survival of post-transplant mycobacterial infections, including mycobacterium tuberculosis (MTB) and non-tuberculous mycobacterium (NTM). Methods: We included 422 adult patients undergoing allogeneic HSCT at an Asian tertiary medical center between January 2003 and December 2014. A total 26 subjects developed post-transplant mycobacterial infections. Risk factors, clinical features, and survival for post-transplant mycobacterial infections were collected and analyzed. Results: Post-transplant mycobacterial infections occurred in 26 (6.2%) of 422 HSCT patients. Two-year cumulative incidences in MTB and NTM were 1.4% and 5.4%. In the multivariate analysis, being age >45 years (adjusted HR 2.21, 95% CI 1.01–4.83) and extensive chronic graft-versus-host disease (cGVHD) (adjusted HR 4.95, 95% CI 2.14–11.46) were identified as independent risk factors of infections. There was a trend as a risk factors in relapsed patients (P = 0.088). For patients with cGVHD, there was a significant difference of post-transplant survival between mycobacterial infections and none (P = 0.036). Pneumonia contributed most to mortality (n = 11, 42.3%). Conclusion: Mycobacterial infections are worth to note in a high endemic area. Once a high-risk group is identified, much effort is required to target new approaches for prevention, early detection and treatment of infections. Keywords: Hematopoietic stem cell transplantation, Mycobacterial infections, Mycobacterium tuberculosis, Non-tuberculous mycobacterium, Graft-versus-host disease

Antibiotics susceptibility of blood stream infections. (DOCX 16Â kb)

Background: For patients with acute myeloid leukemia (AML) who were classified as high risks, failed to achieve complete remission, or relapsed disease after remissions, allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers the chance of durable remission and the potential to cure. In the absence of 8/8 matched donors, an HLA 1-allele mismatched (7/8 1-MM) unrelated donor is an alternative source of hematopoietic stem cell. However, the impact of HLA homozygosity at 1-MM on the outcome and the consensus at desirable donor screening in 7/8 HLA mismatched is not yet clear. A 1-MM in the host-versus-graft (HVG) direction is a 7/8 unidirectional mismatch for a homozygous recipient receiving a graft from a heterozygous donor. A 1-MM in the graft-versus-host (GVH) is for a heterozygous recipient receiving a graft from a homozygous donor. 7/8 bidirectional mismatch is a heterozygous recipient receiving a graft from heterozygous donor. From the biological perceptions, the impact of different histocompatibility transplantations may differ on the prognosis. This study evaluated the outcome of unidirectional and bidirectional 7/8 mismatches in recipients receiving either bone marrow or peripheral blood hematopoietic stem cell for AML patients. Methods: Patients who were at least 12 years of age with AML receiving first hematopoietic stem cell transplantation from a serologically HLA-A, -B, -C, and -DR allele data were included in our study between 2009 and 2014. Data were obtained from Taiwan Society of Blood and Marrow Transplantation (TBMT) Research Database. We excluded those who received HLA-matched sibling grafts, HLA-haploidentical grafts, or unrelated donors who had more than 1-allele mismatch. Those who lacked the clinical information on survival status or survival date were also eliminated. Patients were divided into four histocompatibility groups based on typing at HLA-A, -B, -C, and -DR as unidirectional 7/8 HVG, unidirectional 7/8 GVH, bidirectional 7/8, and 8/8 matched group. Descriptive statistics were used to describe the patients' characteristics, disease status on the time receiving HSCT, intensity of conditioning regimen and treatment features. Associations between four groups and outcomes of overall survival, relapse-free survival, acute GVHD, chronic GVHD, treatment-related mortality (TRM), relapse rate, neutrophil engraftment, engraftment syndrome, and engraftment failures were reviewed. Results: A total of 222 recipients of all-HSCT were included in the analysis. The four comparison groups included nine patients designated as 1-MM HVG, nine as 1-MM GVH, 71 as 1-MM bidirectional, and 133 as 8/8 matched group. Table 1 shows patient and transplant characteristics. Superior overall survival was significantly associated with the higher intensity of induction regimen (myeloablative conditioning, MAC and reduced intensity conditioning, RIC, p Conclusion: Myeloabltive conditioning regimen is associated with more favorable outcomes of overall survival and relapse free survival. 1-MM HVG also tends to have superior overall survival and relapse free survival, although there is no statistical significance due to limited cases. Disclosures No relevant conflicts of interest to declare.

Background Acute myeloid leukemia (AML) is a common hematologic neoplasm in the elderly. The high mortality in elderly AML patients is reported to be associated with old age, poor performance status, and several disease characteristics. Several risk stratification models have been reported. Our aims were to explore risk factors for early mortality in older AML patients and compare the discrimination ability of existing prognostic models. Methods We enrolled newly diagnosed AML patients age 60 and above at Taipei Veterans General Hospital, a national medical center in Taiwan, between July 1, 2008 and May 31, 2017. Our primary endpoint was early mortality, defined as death within two months after initial AML diagnosis. Performance of several existing scoring systems were compared by using the Akaike information criteria (AIC) and Bayesian information criterion (BIC) calculations. Model discrimination ability was also estimated by Harrell's C statistics. Results A total of 478 AML patients were diagnosed during the eight-year follow-up period. After excluding young patients (age < 60) and those without a histopathologic diagnosis, the final cohort included 277 patients. The median age was 74 (range 60-96), and 171 (61.7%) of them were male. One hundred sixteen patients (41.9%) had Eastern Cooperative Oncology Group performance (ECOG) ≥ 2 and 33.9% patients had poor/adverse cytogenetics or molecular abnormalities. The two-month mortality rate was 29.9% (95% confidence interval [CI] 24.8%-35.9%). Age ≥ 80 (adjusted HR 1.95, 95% CI 1.12-3.42), having an antecedent hematologic disorder (adjusted HR 1.86, 95% CI 1.01-3.43), ECOG ≥ 2 (adjusted HR 2.06, 95% CI 1.20-3.54), complex karyotype (adjusted HR 3.13, 95% CI 1.76-5.55), BM blasts ≥ 70% (adjusted HR 1.79, 95% CI 1.02-3.13), WBC ≥ 100 ×109/L (adjusted HR 3.27, 95% CI 1.58-6.75), and creatinine > 1.3 mg/dL (adjusted HR 2.04, 95% CI 1.23-3.39) were identified as independent predictors for early mortality in the multivariate analysis. Furthermore, we systematically reviewed existing prognostic models for elderly AML. We found five scoring models that don't require additional specific examinations beyond clinical practice and later applied them to our elderly AML cohort. The performance of the five models is shown in Table. Kantarjian's prognostic model (Kantarjian H, et. al. Blood 2010) had the highest Harrell's C statistic and the ALMA score (Ramos F, et. al.Leukemia Research 2015) had the lowest AIC and BIC compared with the other prognostic models. Conclusion We identified seven risk factors for early mortality and compared the performance of five prognostic models for elderly AML patients. The finding may help clinicians to stratify patients and initiate appropriate management. Table Disclosures No relevant conflicts of interest to declare.

Omental cake is a term to describe peritoneal thickening caused by different processes. Metastatic malignancy is the most common cause. Plasma cell leukemia is a rare hematological malignancy involving plasma cells and differ from multiple myeloma in its aggressiveness, initial presentation, and dismal prognosis. Herein, we reported a case of primary plasma cell leukemia initially presented with diffuse omental cake and ascites and subsequent systemic capillary leak syndrome.

In the updated 2016 revision of WHO classification, pure erythroid leukemia (PEL) is still viewed as a sole entity without any change of definition. However, erythroleukemia (erythroid/myeloid type) (previously defined as myeloid neoplasms with erythroid predominance [EP] and myeloblasts ≥ 20% or < 20% but ≥ 20% of nonerythroid cells) has been removed. The former is now recognized as acute myeloid leukemia, not otherwise specified (AML-NOS), and the latter as no longer acute erythroid leukemia (AEL) but MDS. Such a change in the updated classification provides us the rationale to conduct this cohort study of patients with AML with EP (AML-EP). We report the impact on survival outcomes and the risk factors for mortality in these patients based on the 2016 WHO classification. A total cohort of 97 consecutive cases of acute myeloid leukemia with erythroid predominance (AML-EP) between 2000 and 2015 was enrolled. Following 2016 WHO classification, AML-EP patients were classified into four groups (Figure 1). Nine PEL patients had more dismal outcomes (median OS: 1 month) as compared with non-PEL patients (Figure 2) and showed more bone marrow fibrosis, worse performance status (PS) and higher serum lactate dehydrogenase (LDH) at diagnosis. In the univariate analysis, risks of death were PEL diagnosis, worse cytogenetic risks, bone marrow fibrosis, leukocytosis, anemia, hypoalbuminemia, high (LDH), and poor PS. In the multivariate analysis, independent predictors of death were PEL diagnosis (adjusted hazards ratio [AHR] 3.00, 95% confidence interval [CI] 1.02¡V8.88, p = 0.029), very poor cytogenetic risk by IPSS-R (AHR 2.73, 95% CI 1.22¡V6.11, p = 0.014), hypoalbuminemia (< 3.7 g/dl) (AHR 2.30, 95% CI 1.09¡V4.83, p = 0.028) and high serum LDH (≥ 250 U/L) (AHR 2.31, 95% CI 1.25¡V4.28, p = 0.008). Based on the karyotype, patients were stratified to different cytogenetic risk groups according to the United Kingdom Medical Research Council (UKMRC) criteria for AML, the revised United Medical Research Council (UKMRC-R) criteria for AML, the International Prognostic Scoring System (IPSS) for MDS, the revised International Prognostic Scoring System (IPSS-R) and the presence or absence of monosomal karyotypes. Cytogenetic risks groups determined by UKMRC-R showed the best ability to predict survival outcomes of AML-EP patients (Figure 3). The outcome of PEL was independently much worse than that of non-PEL. Allogeneic HSCT was administered to 10 patients (one PEL, one AML-MRC, three AML-NOS and five MDS cases), whose disease statuses at transplantation were refractory disease for one and complete remission for nine. As compared to supportive care, the mortality among AML-EP patients did not differ from that of the patients receiving allogenic hematopoietic stem cell transplantation, curative chemotherapy or non-curative chemotherapy. In conclusion, after the 2016 WHO classification was published, only PEL were kept as belonging to neoplasms originated from neoplastic erythroid lineage. This retrospective cohort study reports the clinical features, biological data and survival outcomes of patients with AML-EP and identified PEL diagnosis, very poor cytogenetic risk group of IPSS-R, high serum LDH and low serum albumin as independent predictors for death. Cytogenetic risks groups determined by UKMRC-R showed the best ability to predict survival outcomes of AML-EP patients. The outcome of PEL was independently much worse than that of non-PEL. Figure 1 Patient selection Figure 1. Patient selection Figure 2 Survival curves of patients of pure erythroid leukemia and others PEL, pure erythroid leukemia Figure 2. Survival curves of patients of pure erythroid leukemia and others. / PEL, pure erythroid leukemia Figure 3 Impact of the cytogenetic risk group on mortality HR, hazards ratio; CI, confidence interval; AIC, Akaike information criterion; BIC, Bayesian information criterion (the lowest level represents the best prediction ability) *Adjusted for factors with a p < 0.1 in the Cox univariate analysis. Figure 3. Impact of the cytogenetic risk group on mortality. / HR, hazards ratio; CI, confidence interval; AIC, Akaike information criterion; BIC, Bayesian information criterion (the lowest level represents the best prediction ability). / *Adjusted for factors with a p < 0.1 in the Cox univariate analysis. Disclosures No relevant conflicts of interest to declare.

A 68-year-old woman was admitted to our hospital for the evaluation of right lower quadrant pain and constipation for 4 days. She had cytogenetic remission of acute myeloid leukemia (AML) with initial del 7(q22q32), diagnosed in April 2011 after the induction chemotherapy with idarubicin and Ara-C, and consolidation therapy with high-dose Ara-C and mitoxantrone. However, follow-up of peripheral blood smear and bone marrow cytology showed increased amounts of leukemic blasts, at around 5–7 %, without abnormal cytogenetics in January 2012. We believed that this suggested an early relapse of intramedullary or extramedullary origin. As she was ineligible for bone marrow transplantation and could not tolerate intensive chemotherapy again, low-dose Ara-C therapy was given in March 2012. No more increased leukemic blasts in peripheral blood smear were noted. However, she suffered from progressive abdominal pain and constipation during follow-up in June 2012. Physical examination showed right lower quadrant tenderness at McBurney’s point, with rebounding pain and muscle guarding. A full blood cell count showed a leukocyte count of 1.43 9 10/L with 28.4 % neutrophils, 63.5 % lymphocytes, 7.3 % monocytes, 0.3 % eosinophils, and 0.5 % basophils, a hemoglobin concentration of 87 g/L, and platelet count

Background: Protein phosphatase 2A (PP2A) has been shown to be an important tumor suppressor protein and loss of PP2A function has been identified in several solid cancers and in leukemias. Recent studies have suggested strategies for enhancing PP2A activity as an anti-leukemic approach. Among the potential key players regulating PP2A, a new oncoprotein, called cancerous inhibitor of protein phosphatase 2A (CIP2A), is recently identified as a key factor in the development of malignancies in various human cells. Previously we studied novel drug mechanisms of bortezomib, a proteasome inhibitor, on acute leukemia cells. We discovered that CIP2A plays an indispensable role in mediating bortezomib-induced apoptosis in acute leukemia cells (Hematologica 2013), hepatocellular carcinoma cells (Oncogene 2010) and in breast cancer cells (Breast Cancer Research 2012). Importantly, this mechanism by bortezomib is independent to its proteasome inhibition. Carfilzomib, a more selective proteasome inhibitor than bortezomib, has shown efficacy in multiple myeloma and is being investigated in phase III clinical trials. In this study, we examined the effect of carfilzomib on CIP2A in leukemia cells. Methods: Leukemia cell lines (HL-60, KG-1, THP-1, and K562) were used for in vitro studies. Apoptosis was examined by both flow cytometry and Western blot. Signal transduction pathways in cells were assessed by Western Blot. Quantitative RT-PCR was used for assessing gene transcription. In vivo efficacy of carfilzomib was tested in nude mice with subcutaneous leukemia xenografts. Results: We found carfilzomib induced differential antiproliferative effects and apoptosis. HL-60, KG-1 and THP-1, but not K562 cells, were sensitive to carfilzomib-induced apoptosis. Similarly, carfilzomib-induced apoptosis may be dissociated with its proteasome inhibition. We found CIP2A mediated this apoptotic effect of carfilzomib in leukemia cells. Carfilzomib down-regulated CIP2A in association with p-Akt downregulation. Furthermore, carfilzomib increased PP2A activity and over-expression of CIP2A up-regulated p-Akt and suppressed carfilzomib-induced apoptosis. In addition, carfilzomib downregulated CIP2A mRNA but did not affect the degradation of CIP2A protein. Further dissecting the regulatory mechanism showed that carfilzomib may affect CIP2A transcription though transcriptional factors. Importantly, carfilzomib demonstrated anti-tumor activity in xenografted mice models. Conclusions: CIP2A is a major determinant mediating carfilzomib-induced apoptosis in leukemia cells and may be a therapeutic target in leukemia. This study disclosed a novel drug mechanism of carfilzomib in leukemia cells. (Supported by Taiwan Clinical Oncology Research Foundation, MOST 103-2325-B-075-002, V103C-141; and TVGH-NTUH Joint Research Program VN103-08) Citation Format: Chun-Yu Liu, Wen-Chun Tsai, Man-Hsin Hung, Yuan-Bin Yu, Po-Shen Ko, Cheng-Hwai Tzeng, Chung-Wai Shiau, Kuen-Feng Chen. Carfilzomib transcriptionally regulates CIP2A/PP2A/p-Akt signaling and induces apoptosis in leukemia cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1737. doi:10.1158/1538-7445.AM2015-1737