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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

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.

Autologous stem cell transplantation (ASCT) continues to be the standard treatment for transplant-eligible multiple myeloma (MM) patients. A portion of MM patients received ASCT in an isolation room with high-efficiency particulate air (HEPA) filtration. The effectiveness of the HEPA filtration on reducing treatment-related mortality (TRM) is controversial. We enrolled patients with newly diagnosed MM in Taiwan between 2000 and 2017. The primary endpoint of the study was TRM, which was defined as death within 100 days after ASCT. A total of 961 MM patients received ASCT. Of them, 480 patients (49.9%) received ASCT in an isolation room with HEPA filtration (HEPA group). The median overall survival from ASCT was 7.52 years for the HEPA group and 5.88 years for the remaining patients (non-HEPA group) (p = 0.370). The 100-day mortality rate was 1.5% and 1.0% for the HEPA and non-HEPA groups, respectively. In the multivariate analysis, the 100-day mortality had no difference between the HEPA and non-HEPA groups (adjusted hazard ratio 1.65, 95% CI 0.52–5.23). The median cost for ASCT inpatient care was $13,777.6 and $6527.6 for the HEPA and non-HEPA groups, respectively (p

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 Although various prognostic models for primary central nervous system lymphoma (PCNSL) have been developed, there is no consensus regarding the optimal prognostic index. We aimed to evaluate potential prognostic factors and construct a novel predictive model for PCNSL patients. Methods We enrolled newly diagnosed PCNSL patients between 2003 and 2015. The primary endpoint was progression‐free survival (PFS), and the secondary endpoint was overall survival (OS). The prognostic factors identified using multivariate Cox proportional hazards models were used to develop a predictive model. We subsequently validated the prognostic model in an independent cohort. We also evaluated the validity of the existing scores: the International Extranodal Lymphoma Study Group (IELSG), the Nottingham/Barcelona (NB), and the Memorial Sloan‐Kettering Cancer Center models (MSKCC). Results We identified 101 patients with newly diagnosed PCNSL at our center. Multivariate analysis showed that age ≥80, deep brain lesions, and ECOG ≥2 were independent risk factors of PFS. Assigning one point for each factor, we constructed a novel prognostic model, the Taipei Score, with four distinct risk groups (0‐3 points). The performances of the Taipei Score in discriminating both PFS and OS in the training cohort were significant, and the score was validated in the external validation cohort. The IELSG, NB and MSKCC models had insufficient discriminative ability for either PFS or OS in both cohorts. Conclusion The Taipei Score is a simple model that discriminates PFS and OS for PCNSL patients. The score may offer disease risk stratification and facilitate clinical decision‐making., Age, performance status, and deep brain lesions were associated with primary central nervous system lymphoma (PCNSL) survival. The Taipei Score could offer disease risk stratification for PCNSL.

Background Acute myeloid leukemia (AML) is a common hematologic neoplasm with high incidence and mortality in the elderly. Our aims were to explore risk factors for early mortality in elderly AML patients and develop a new prognostic score. Methods We enrolled newly diagnosed AML patients age 60 and above at Taipei Veterans General Hospital between July 2008 and May 2017. The primary endpoint was early mortality, defined as death within two months after AML diagnosis. A multivariate Cox proportional hazards model was used to build a risk‐scoring system incorporating significant risk factors for AML. Results The final cohort included 277 elderly AML patients. The median age was 74 (range 60‐96), and 61.7% were male. The two‐month mortality rate was 29.9%. Age ≥ 80 (adjusted HR 1.88), myocardial infarction (adjusted HR 1.87), ECOG ≥ 2 (adjusted HR 2.10), complex karyotype (adjusted HR 3.21), bone marrow blasts ≥ 70% (adjusted HR 1.88), WBC ≥ 100 × 109/L (adjusted HR 3.31), and estimated glomerular filtration rate (eGFR), Age ≥ 80, myocardial infarction, ECOG ≥ 2, complex karyotype, BM blasts ≥ 70%, WBC ≥ 100 × 109/L, and eGFR

Opening of the cystic fibrosis transmembrane conductance regulator (CFTR) channel is coupled to the motion of its two nucleotide-binding domains: they form a heterodimer sandwiching two functionally distinct ATP-binding sites (sites 1 and 2). While active ATP hydrolysis in site 2 triggers rapid channel closure, the functional role of stable ATP binding in the catalysis-incompetent (or degenerate) site 1, a feature conserved in many other ATP-binding cassette (ABC) transporter proteins, remains elusive. Here, we found that CFTR loses its prompt responsiveness to ATP after the channel is devoid of ATP for tens to hundreds of seconds. Mutants with weakened ATP binding in site 1 and the most prevalent disease-causing mutation, F508del, are more vulnerable to ATP depletion. In contrast, strengthening ligand binding in site 1 with N6 -(2-phenylethyl)-ATP, a high-affinity ATP analogue, or abolishing ATP hydrolysis in site 2 by the mutation D1370N, helps sustain a durable function of the otherwise unstable mutant channels. Thus, tight binding of ATP in the degenerate ATP-binding site is crucial to the functional stability of CFTR. Small molecules targeting site 1 may bear therapeutic potential to overcome the membrane instability of F508del-CFTR. KEY POINTS: During evolution, many ATP-binding cassette transporters - including the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, whose dysfunction causes cystic fibrosis (CF) - lose the ability to hydrolyse ATP in one of the two ATP-binding sites. Here we show that tight ATP binding at this degenerate site in CFTR is central for maintaining the stable, robust function of normal CFTR. We also demonstrate that membrane instability of the most common CF-causing mutant, F508del-CFTR, can be rescued by strengthening ATP binding at CFTR's degenerate site. Our data thus explain an evolutionary puzzle and offer a potential therapeutic strategy for CF.

We investigated the incidence of tuberculosis (TB) in patients with newly diagnosed oral cancer and analyzed the risk factors for TB development and mortality in oral cancer patients. We used Taiwan’s National Health Insurance Database to determine the incidence of TB and to analyze the risk factors for TB in patients newly diagnosed with oral cancer. From 2000 to 2011, we identified 40,327 oral cancer patients and the same number of subjects from the general population matched for sex, age, and comorbidities at a 1:1 ratio. Compared with the matched cohort, oral cancer patients exhibited a higher risk for TB (adjusted hazard ratio (aHR) 2.36, 95% confidence interval (CI) 2.06–2.71). Age ≥ 50 (aHR 1.90, 95% CI 1.57–2.29), being male (aHR 1.98, 95% CI 1.36–2.89), having diabetes mellitus (aHR 1.31, 95% CI 1.05–1.64), alcohol use disorder (aHR 1.42, 95% CI 1.06–1.89), human immunodeficiency virus (HIV) (aHR 8.24, 95% CI 2.05–33.14), chemotherapy (aHR 1.41, 95% CI 1.15–1.72), and radiotherapy for oral cancer (aHR 1.92, 95% CI 1.57–2.36) were identified as independent risk factors for TB in oral cancer patients. Hyperlipidemia was an independent protective factor for TB in oral cancer patients. Old age, male sex, diabetes mellitus, alcohol use disorder, and HIV were independent risk factors for TB in patients with oral cancer. High-risk oral cancer patients should be regularly screened for TB, especially those in endemic areas.

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.

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.

We investigated the risk and impact of mycobacterium tuberculosis (TB) infection in patients with multiple myeloma (MM). We identified 3979 MM patients from Taiwan's National Health Insurance database between 2000 and 2011 and compared the incidence rates of TB infection in these patients with 15,916 randomly selected age-, sex-, and comorbidity-matched subjects without MM. The risk of TB was higher in the myeloma cohort (adjusted hazard ratio [HR] 3.11, 95% confidence interval [CI] 2.41-4.02). Risk factors for MM patients contracting TB were age ≥65 (adjusted HR 1.93, 95% CI 1.19-3.15), alcohol use disorder (adjusted HR 2.86, 95% CI 1.24-6.62), and steroid daily dose equivalent to prednisone 5 mg or more (adjusted HR 2.38, 95% CI 1.50-3.77). MM patients with TB had a higher mortality risk than those without (adjusted HR 2.03, 95% CI 1.54-2.67). The incidence of TB is significantly higher in MM patients.

e16091 Background: Colorectal cancer (CRC) is one of the highest-incident neoplasms in many countries. Although the incidence of CRC is increasing gradually, the mortality rate has not increased due to early detection and multidisciplinary treatment. CRC screening programs, including colonoscopy and fecal occult blood tests, have been reducing CRC-related mortality worldwide. In Taiwan, the CRC screening program uses a biennial fecal immunochemical test (FIT) as the initial screening tool. FIT-positive participants receive a colonoscopy as a CRC confirmation examination. Cancer survivors have a higher incidence of secondary primary malignancies. Methods: We conducted a nationwide population-based study in Taiwan. The cancer survivors with FIT in the Nationwide Colorectal Cancer Screening (NCCS) Program between January 2010 and September 2014 were enrolled as the study group. The patients aged under 50, diagnosed with CRC before the FIT were excluded. The screening participants without a cancer history were served as the comparison group. The primary endpoint was CRC diagnosis within six months after a FIT. The cancer diagnosis was identified by using Taiwan Cancer Registry. The ratios of positive FIT, confirmatory colonoscopy, and CRC diagnosis in the cancer survivors and the comparison cohort were calculated and compared. Analyses were adjusted for participants’ characteristics by using multilevel logistic regression models. Results: We identified 288,919 cancer survivors who participated in the NCCS Program. Of them, 41.1% were male and the median age was 59 (interquartile ranges 54–64). There were 417,907 FITs performed in the study cohort. The FIT positive rates were 11.3% and 7.4% in the study and comparison groups, respectively (OR 1.59 95% CI 1.57–1.60). Of the FIT positive participants, 50.5% and 52.3% received confirmatory colonoscopy or the related examinations within six months, respectively (OR 0.93 95% CI 0.91–0.95). Then 3.0% and 4.4% of those receiving confirmatory colonoscopy were diagnosed with CRC in the study and comparison groups, respectively (OR 0.68 95% CI 0.63–0.74). After adjustment for age, sex, income, a family history of CRC, and comorbidities, the cancer survivors in this screening program had a similar rate of CRC diagnosis compared with those without antecedent malignancies (adjusted OR: 0.97, 95% CI 0.87–1.08). Conclusions: Although the cancer survivors had a higher rate of positive FIT, the CRC diagnosed by the screening did not increase. We further identified the risk factors associated with CRC in the cancer survivors.

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.