Risk factors of early disease progression and decreased survival for multiple myeloma patients after upfront autologous stem cell transplantation.

Multiple myeloma (MM) stands as the second most prevalent hematological malignancy, constituting approximately 10% of all hematological malignancies. Current guidelines recommend upfront autologous stem cell transplantation (ASCT) for transplant-eligible MM patients. This study seeks to delineate factors influencing post-ASCT outcomes in MM patients. Our cohort comprised 150 MM patients from Taipei Veterans General Hospital, with progression-free survival (PFS) as the primary endpoint and overall survival (OS) as the secondary endpoint. A Cox proportional hazards model was employed to discern potential predictive factors for survival. ASCT age ≥ 65 (hazard ratio [HR] 1.94, 95% confidence interval [CI] 1.08-3.47) and the presence of extramedullary disease (HR 2.53, 95% CI 1.53-4.19) negatively impacted PFS. Conversely, treatment response ≥ VGPR before ASCT (HR 0.52, 95% CI 0.31-0.87) and total CD34+ cells collected ≥ 4 × 106 cells/kg on the first stem cell harvesting (HR 0.52, 95% CI 0.32-0.87) were positively associated with PFS. For OS, patients with ISS stage III (HR 2.06, 95% CI 1.05-4.04), the presence of extramedullary disease (HR 3.92, 95% CI 2.03-7.58), light chain ratio ≥ 100 before ASCT (HR 7.08, 95% CI 1.45-34.59), post-ASCT cytomegalovirus infection (HR 9.43, 95% CI 3.09-28.84), and a lower conditioning melphalan dose (< 140 mg/m2; HR 2.75, 95% CI 1.23-6.17) experienced shorter OS. In contrast, post-ASCT day + 15 absolute monocyte counts (D15 AMC) > 500/µl (HR 0.36, 95% CI 0.17-0.79) and post-ASCT day + 15 platelet counts (D15 PLT) > 80,000/µl (HR 0.48, 95% CI 0.24-0.94) were correlated with improved OS. Significantly, early PLT and AMC recovery on day + 15 predicting longer OS represents a novel finding not previously reported. Other factors also align with previous studies. Our study provides real-world insights for post-ASCT outcome prediction beyond clinical trials.

Challenges and Considerations in Identifying the Origin of Peritoneal Carcinomatosis: A Case Report.

Invasive lobular cancer (ILC) of the breast is the second most common type of invasive breast cancer. Clinical determination of the growth pattern of ILC of the breast is difficult. Furthermore, the ILC of the breast has a unique metastatic pattern that involves gastrointestinal and peritoneal sites. Our patient was initially misdiagnosed with left ovarian cancer based on the findings of positron emission tomography and computed tomography. Herein, we report a case of ILC of the breast presenting as peritoneal carcinomatosis. The ESMO Clinical Practice Guidelines for cancers of unknown primary sites were used in the diagnosis of the carcinoma of unknown primary origin. Image-guided biopsy and immunohistochemical staining are also useful in the diagnosis of these cancer types.

Risk Factors and Outcomes of Stem Cell Mobilization Failure in Multiple Myeloma Patients.

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 <1 × 106 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 <500/µL (adjusted OR 10.75, 95% CI: 1.82-63.57, p = 0.009), platelet count <150,000/µL (adjusted OR 12.49, 95% CI: 2.65-58.89, 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 <500/µL, platelet count <150,000/µL, and treatment duration more than 180 days before stem cell mobilization are risk factors for unsuccessful stem cell collection. Our prediction models have high sensitivity and specificity for mobilization failure prediction and allow for early interventions for possible PMs.

Long-term outcomes of frontline intensification in primary CNS lymphoma: A real-world single-center experience.

BACKGROUND: Frontline intensification (including consolidative whole-brain radiotherapy or high-dose chemotherapy with autologous stem-cell transplantation after induction therapy) has been proposed to treat primary central nervous system lymphoma (PCNSL). However, no prospective randomized trials have answered whether frontline intensification can offer a survival benefit to PCNSL patients. We aim to clarify the outcomes and survival influence of frontline intensification on real-world patients with different risk-stratified PCNSLs. METHODS: Between January 2003 and December 2016, 110 PCNSL adults were retrospectively included, and 76 patients achieved at least PR after induction therapy, including 38 patients who received frontline intensification. The median follow-up with the 31 survivors was 7.52 years. RESULTS: Of the 38 induction-completed patients who had not received frontline intensification, 95% achieved post-induction therapy CR/CRu; however, all inevitably recurred. In the 38 who received frontline intensification, CR/CRu improved from 45% (pre-frontline intensification) to 84% (post-frontline intensification), and they achieved significantly better PFS (non-reach vs. 522 days, p < 0.001) and OS (non-reach vs. 899 days, p < 0.001). Additionally, patients had similar PFS and OS rates when receiving HDC-ASCT and/or WBRT as frontline intensification. Frontline intensification significantly improved PFS and OS survival in higher-risk patients (intermediate/high IELSG risk, MSKCC group 2/3, or Nottingham/Barcelona score ≥ 2 points) but did not improve OS in lower-risk patients. Among the 38 patients who received frontline intensification, two had treatment-related mortality; 14 recurred after frontline intensification. MTX-based chemotherapy was the main salvage modality, and the median OS was 295 days after recurrence. Progressive disease and infection (especially pneumonia) are two major causes of mortality in patients who receive frontline intensification. CONCLUSIONS: When achieving CR/CRu/PR after induction chemotherapy, frontline intensification should be adopted to improve PFS and OS in real-world PCNSL patients, especially higher-risk patients.

Demethylation and Up-Regulation of an Oncogene after Hypomethylating Therapy.

BACKGROUND: Although hypomethylating agents are currently used to treat patients with cancer, whether they can also reactivate and up-regulate oncogenes is not well elucidated. METHODS: We examined the effect of hypomethylating agents on SALL4, a known oncogene that plays an important role in myelodysplastic syndrome and other cancers. Paired bone marrow samples that were obtained from two cohorts of patients with myelodysplastic syndrome before and after treatment with a hypomethylating agent were used to explore the relationships among changes in SALL4 expression, treatment response, and clinical outcome. Leukemic cell lines with low or undetectable SALL4 expression were used to study the relationship between SALL4 methylation and expression. A locus-specific demethylation technology, CRISPR-DNMT1-interacting RNA (CRISPR-DiR), was used to identify the CpG island that is critical for SALL4 expression. RESULTS: SALL4 up-regulation after treatment with hypomethylating agents was observed in 10 of 25 patients (40%) in cohort 1 and in 13 of 43 patients (30%) in cohort 2 and was associated with a worse outcome. Using CRISPR-DiR, we discovered that demethylation of a CpG island within the 5' untranslated region was critical for SALL4 expression. In cell lines and patients, we confirmed that treatment with a hypomethylating agent led to demethylation of the same CpG region and up-regulation of SALL4 expression. CONCLUSIONS: By combining analysis of patient samples with CRISPR-DiR technology, we found that demethylation and up-regulation of an oncogene after treatment with a hypomethylating agent can indeed occur and should be further studied. (Funded by Associazione Italiana per la Ricerca sul Cancro and others.).

A clinical trial with valproic acid and hydralazine in combination with gemcitabine and cisplatin followed by doxorubicin and dacarbazine for advanced hepatocellular carcinoma.

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.

The influence of high-efficiency particulate air filtration on mortality among multiple myeloma patients receiving autologous stem cell transplantation.

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 < 0.001). Although half of MM patients in Taiwan received ASCT in HEPA room, it didn't affect 100-day mortality.

Underweight as a risk factor of mortality in patients with newly diagnosed multiple myeloma.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: MM patients who were underweight, with hypoalbuminemia, poor performance status, higher LDH, and light chain ratio > 100 were associated with poor overall survival.

Risk and impact of invasive fungal infections in patients with multiple myeloma.

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.

Difference in thrombotic microangiopathy between concurrently and previously diagnosed systemic lupus erythematosus.

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.

A new prognostic score for disease progression and mortality in patients with newly diagnosed primary CNS lymphoma.

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.

The risk of early mortality in elderly patients with newly diagnosed acute myeloid leukemia.

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) < 45 (adjusted HR 2.60) were identified as independent predictors for early mortality in the multivariate analysis. A simplified score incorporating the seven factors was developed with good predictive ability measured by Harrell's C statistic [0.72 (95% CI 0.66-0.78)]. CONCLUSIONS: We identified seven potential risk factors for early mortality and built up a new prognostic score for elderly AML patients. The new score may help clinicians stratify patients and initiate appropriate management. Further validation of our findings on other cohorts is warranted.

Mycobacterial infections in adult recipients of allogeneic hematopoietic stem cell transplantation: A cohort study in a high endemic area.

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.

Risk Prediction for Early Mortality in Patients with Newly Diagnosed Primary CNS Lymphoma.

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.

Risk factors and clinical features for post-transplant thoracic air-leak syndrome in adult patients receiving allogeneic haematopoietic stem cell transplantation.

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 disease after allogeneic hematopoietic stem cell transplantation: incidence, risk, and clinical outcome.

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.

Increased risk of tuberculosis in oral cancer patients in an endemic area: a nationwide population-based study.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: Old age, male sex, diabetes mellitus, alcohol use disorder, and HIV were independent risk factors for TB in patients with oral cancer. CLINICAL RELEVANCE: High-risk oral cancer patients should be regularly screened for TB, especially those in endemic areas.

Invasive mold infections in acute leukemia patients undergoing allogeneic hematopoietic stem cell transplantation.

BACKGROUND/PURPOSE: Patients with acute leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are exposed to high risk of developing invasive fungal infections, and the invasive mold infections (IMIs) are becoming more and more common after transplantation. Here, we conducted a retrospective study to analyze demographics, microbiology, and risk factors for IMIs development in adult acute leukemia patients undergoing allo-HSCT. METHODS: We reviewed 245 adult acute leukemia patients undergoing allo-HSCT from January 2003 to December 2014. Clinical characteristics including age, sex, 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 IMIs developments. RESULTS: Seventeen of 245 patients developed IMIs during the study period. The cumulative incidence of IMIs in this cohort was 8.7% and 16.8% at 6 and 12 months, respectively, with Aspergillus species being the most common pathogen. The significant risk factors predicting IMIs were unrelated donor transplantation (hazard ratio [HR] 5.11), smoking (HR 3.55), EBMT risk score > 2 (HR 4.22), and moderate to severe cGVHD (HR 3.76). CONCLUSIONS: We identified four risk factors-unrelated donor transplantation, smoking, EBMT risk score >2 and moderate to severe cGVHD to predict IMIs among acute leukemia patients undergoing allo-HSCT. This cohort study suggests early identification of high-risk patients and to provide better prevention strategies would reduce the incidence and severity of IMIs in these patients.

Hematopoietic stem cell transplantation for subcutaneous panniculitis-like T-cell lymphoma: single center experience in an Asian population.

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.

Primary bone marrow lymphoma: A hematological emergency in adults with fever of unknown origin.

Primary bone marrow lymphoma (PBML) represents non-Hodgkin lymphoma (NHL) that primarily arises in the bone marrow (BM) without lymphadenopathy. This condition has various definitions and can be masked by prolonged fever, leading to delayed diagnosis. We aimed to identify clinical features and risk indicators of PBML. We enrolled 269 adults with fever of unknown origin (FUO) who underwent a BM study for potential PBML. Thirty patients were diagnosed with PBML (26 and 4 patients in the training and validation cohort, respectively), and 20 patients (67%) showed initial manifestation of hemophagocytic lymphohistiocytosis (HLH). Among PBML patients in the training cohort, their median overall survival is short (8 days), with pneumonia being the most common direct cause of early mortality, followed by life-threatening HLH. Despite extremely poor prognoses, some B-cell PBML patients who survived 30 days after BM studies achieved long-term survival with rituximab-based treatment. To assist general practitioners in early PBML diagnosis when approaching adults with naïve FUO, we identified several risk indicators, including elevated serum alkaline-phosphate levels, lowered serum immunoglobulin-G levels, cytopenia in ≥2 lineages, and peripheral blood leukoerythroblastosis. Our recently published scoring system, which can predict hematological BM disease in FUO adults, showed excellent ability in recognizing PBML early, with high sensitivity and specificity. We conclude that PBML is a specific "clinical" phenotype of NHL; moreover, we have identified diagnostic clues for early identification of FUO adults with underlying PBML, which should be considered a hematological emergency once suspected in any adult with FUO.