Ten-year epidemiology and risk factors of cytomegalovirus infection in hematopoietic stem cell transplantation patients in Taiwan.

BACKGROUND: Cytomegalovirus (CMV) can cause infection and critical diseases in hematopoietic stem cell transplantation (HSCT) recipients. This study aimed to explore the cumulative incidence and risk factors for CMV infection and disease among HSCT recipients in Taiwan. METHODS: This retrospective cohort study using the Taiwan Blood and Marrow Transplantation Registry (TBMTR) included HSCT recipients between 2009 and 2018 in Taiwan. The primary outcome was cumulative incidence of CMV infection or disease at day 100 after HSCT. Secondary outcomes included day 180 cumulative incidence of CMV infection or disease, infection sites, risk factors for CMV infection or disease, survival analysis, and overall survival after CMV infection and disease. RESULTS: There were 4394 HSCT recipients included in the study (2044 auto-HSCT and 2350 allo-HSCT). The cumulative incidence of CMV infection and disease was significantly higher in allo-HSCT than in auto-HSCT patients at day 100 (53.7% vs. 6.0%, P < 0.0001 and 6.1% vs. 0.9%, P < 0.0001). Use of ATG (HR 1.819, p < 0.0001), recipient CMV serostatus positive (HR 2.631, p < 0.0001) and acute GVHD grades ≥ II (HR 1.563, p < 0.0001) were risk factors for CMV infection, while matched donor (HR 0.856, p = 0.0180) and myeloablative conditioning (MAC) (HR 0.674, p < 0.0001) were protective factors. CONCLUSION: The study revealed a significant disparity in terms of the incidence, risk factors, and clinical outcomes of CMV infection and disease between auto and allo-HSCT patients. These findings underscore the importance of considering these factors in the management of HSCT recipients to improve outcomes related to CMV infections.

Efficacy, safety and cost of emicizumab prophylaxis in haemophilia A patients with inhibitors: A nationwide observational study in Taiwan.

INTRODUCTION: Emicizumab mimicking the cofactor function of activated factor VIII (FVIII) restores haemostasis. METHODS: This nationwide observational study aimed to retrospectively investigate efficacy, safety, and cost in 1 year before and up to 3 years after emicizumab prophylaxis for haemophilia A (HA) patients with FVIII inhibitors. RESULTS AND DISCUSSION: A total of 39 severe HA patients with a median age of 23.0 years were enrolled. The median historical peak FVIII inhibitor titre was 174.2 BU/mL with an interquartile range of 56.5-578.8 BU/mL. The median annualized bleeding rate reduced from 24 to 0 events in the first year after emicizumab prophylaxis (p < .01) and sustained in the second and third years. The median annualized joint bleeding rate reduced to 0 and maintained up to 3 years (p < .01). Twenty-seven patients (69.2%) had target joints before emicizumab prophylaxis and only seven patients (17.9%) of them had target joints after prophylaxis. Medical costs, including cost of haemostatic therapy, frequency of outpatient department visits, emergency room visits and hospital admission, were significantly reduced after emicizumab prophylaxis (p < .01). FVIII inhibitor titre decreased after emicizumab prophylaxis. Overall, three (7.7%) patients experienced 202 grade 1 drug-related adverse events after emicizumab prophylaxis. No serious adverse events were reported during emicizumab prophylaxis period. The adherence to emicizumab prophylaxis was 100% up to 3 years. CONCLUSIONS: HA patients with FVIII inhibitors treated with emicizumab prophylaxis resulted in a significant reduction in treated bleeds and associated costs. No new safety events were observed.

Prognostic factors in patients with bone marrow hemophagocytosis and its association with hematologic malignancies.

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.

A nonparametric method for classification trees using grouped covariates.

A group of variables are commonly seen in diagnostic medicine when multiple prognostic factors are aggregated into a composite score to represent the risk profile. A model selection method considers these covariates as all-in or all-out types. Model selection procedures for grouped covariates and their applications have thrived in recent years, in part because of the development of genetic research in which gene-gene or gene-environment interactions and regulatory network pathways are considered groups of individual variables. However, little has been discussed on how to utilize grouped covariates to grow a classification tree. In this paper, we propose a nonparametric method to address the selection of split variables for grouped covariates and their following selection of split points. Comprehensive simulations were implemented to show the superiority of our procedures compared to a commonly used recursive partition algorithm. The practical use of our method is demonstrated through a real data analysis that uses a group of prognostic factors to classify the successful mobilization of peripheral blood stem cells.

Distinct Immunogenetic Profiles of Chronic Lymphocytic Leukemia in Asia: A Taiwan Cooperative Oncology Group Registry Study.

Asian patientswith chronic lymphocytic leukemia (CLL) exhibit immunoglobulin heavy variable (IGHV) gene repertoires that are distinct from those observed in Western populations, and a higher proportion of Asian CLL patients carry heavy loads of somatic hypermutations (SHM) within the B-cell receptor immunoglobulins (BcR IG). Due to the low regional incidence of CLL in Asia, only a limited number of studies had attempted to probe the phenomenon of BcR IG stereotypy in Asian populations. In this study, we analyzed the IGHV-IGHD-IGHJ gene rearrangements from a series of 255 CLL patients recruited in a nationwide, multicenter study in Taiwan. Our analysis revealed that the IGHV gene repertoire was characterized by evident biases, with IGHV3-7, IGHV4-34, and IGHV3-23 being the most frequent rearranged IGHV genes, and a higher proportion of cases carrying mutated IGHV. In terms of BcR stereotypy, the incidence of major subsets was less frequent in this cohort, with subsets #77 and #28A being the most common, while the incidence of minor subsets was approximately equivalent to that reported in the Western cohorts. With this study, we provide evidence that CLL in Asia is indeed associated with distinct immunogenetic characteristics regarding IGHV gene usage, SHM status, and BcR IG stereotypy.

The abrogated role of premedication in the prevention of transfusion-associated adverse reactions in outpatients receiving leukocyte-reduced blood components.

BACKGROUND AND OBJECTIVES: Although it remains controversial, premedication before transfusion is a common clinical practice to prevent transfusion-associated adverse reactions (TAARs) in Taiwan. Thus, we aimed to investigate whether premedication prevented outpatients from developing TAARs and whether an educational programme could improve the understanding of physicians related to the unnecessary use of premedication, and this could elicit changes in their prescribing activities without affecting the occurrence of TAARs. MATERIALS AND METHODS: Clinical data from outpatients receiving transfusion therapy, including predisposing diseases, histories of transfusion and TAARs, premedication and the occurrence of TAARs in the period April 2017 to October 2018, were retrospectively obtained. The evidence-based transfusion programme implemented to educate physicians was started in January 2018. RESULTS: A total of 5018 blood units were transfused to 803 outpatients, with 2493 transfusion events reported in the study interval. The most frequently transfused component was leukocyte-reduced packed red cells (n = 4338), followed by leukocyte-reduced apheresis platelets (n = 540) and other blood components. The overall premedication rate significantly decreased from 92.4% to 76.7% after the educational programme (p < 0.001). There was no remarkable change in the occurrence of TAARs per patient event between the periods before and after the educational programme (1.11% vs. 1.14%, p = 0.964). Besides, it was shown that the occurrence of TAARs was associated with the history of TAARs and inversely related to multiple transfusions, but not premedication. CONCLUSION: Decreased premedication was not associated with increased incidence of TAARs in outpatients; these findings provide important evidence to support the need to revise clinical practices in the era of leukocyte-reduced blood products.

Total knee replacement for patients with severe hemophilic arthropathy in Taiwan: A nationwide population-based retrospective study.

BACKGROUND: Total knee replacement (TKR) surgery is a treatment option for advanced hemophilic arthropathy. Due to its rarity and complexity, previous reports could only demonstrate the results of single-site studies including few cases. This population-based study aimed to investigate the major epidemiological characteristics, mean consumption of coagulation factors, length of hospital stays, complications, and failure rate of primary TKR for severe hemophilia patients in Taiwan. METHODS: A cohort of 996 hemophilia patients registered between 1995 and 2011 was included, and 103 primary TKRs were performed on 75 patients. Unilateral TKR was performed on 47 patients and bilateral TKRs on the remaining 28 patients, including 12 simultaneous and 16 staged surgeries. The mean age at surgery was 32.3 years (range, 17.3-55.7), and the mean follow-up duration was 77.9 months (range, 2.3-176.8). RESULTS: Failure was noted in 8 patients (8.5%) at mean 32.8 months (range, 2.3-95) after surgery. Four patients revealed aseptic loosening, whereas infection in 4. The 10-year prosthesis survivorship was 88.6%. For patients receiving unilateral TKR, the mean length of hospital stay was 15 days (range, 7-32). The mean cost of factor supplement was United States Dollar (USD) 43 543 with a mean 4-unit packed red blood cells transfusion (range, 0-38). The total admission cost was USD 48 326 (range, USD 4165-262 619). CONCLUSION: The prevalence of TKA for hemophilia patients was 7.5% in Taiwan. The mean hospital stay was 14 days, and the 10-year prosthesis survivorship was 88.6%. The mean daily factor usage was decreased from 235.7 units preoperatively to 202.1 units postoperatively. In comparison with the staged-bilateral TKRs, the simultaneous procedures significantly reduced the mean total cost from USD 101 923 to USD 61 587 (p = 0.023). Therefore, in terms of cost-effectiveness, bilateral simultaneous TKR is more preferable than staged procedures.

Detection of the HLA-DQB1*06:02:43 allele in a Taiwanese leukemic patient.

One nucleotide substitution in codon 57 of HLA-DQB1*06:02:01:01 results in a novel allele, HLA-DQB1*06:02:43.

Tumor lysis syndrome as a risk factor for very early mortality in HIV-associated non-Hodgkin's lymphoma: A 10-year single-center experience.

BACKGROUND: Despite the effectiveness of combination antiretroviral therapy, persons living with human immunodeficiency virus (PLWHIV) remain at a high risk of developing non-Hodgkin lymphoma (NHL). We aimed to analyze the demographics and outcomes of the HIV-associated NHLs. METHODS: Between 2005 and 2014, PLWHIV with NHLs were retrospectively enrolled at a tertiary referral center. Characteristics and survival were reviewed and analyzed. RESULTS: Twenty-two HIV-associated NHLs were identified, with a median follow-up of 14 months (range, 0.1-139.7), including eight diffuse large B-cell lymphomas (DLBCLs), eight primary central nervous system lymphomas (PCNSLs), and six Burkitt's lymphomas (BLs). Nine patients (40.9%) were diagnosed with NHLs and HIV infection concurrently. The prognosis of DLBCL patients tended to be better prognosis than that of BL and PCNSL patients (median overall survival: not reached vs. 3.5 months, p = 0.056). Very early mortality (death within 14 days after NHL diagnosis) was noted in five patients (22.7%), and tumor lysis syndrome (TLS) is a predictive factor for very early mortality among PLWHIV (hazard ratio:11.3, 95% confidence interval: 1.1-114.4, p = 0.04). CONCLUSION: Management of the early treatment phase of HIV-associated NHLs remains a major challenge. Careful intervention to patients with TLS might be the key to improve treatment outcomes.

Simultaneous integrated boost with helical arc radiotherapy of total skin (HEARTS) to treat cutaneous manifestations of advanced, therapy-refractory cutaneous lymphoma and leukemia - dosimetry comparison of different regimens and clinical application.

BACKGROUND: Helical irradiation of the total skin (HITS) was modified as simultaneous integrated boost (SIB)-helical arc radiotherapy of total skin (HEARTS) technique and applied to an acute myeloid leukemia (AML) patient with disseminated leukemia cutis. METHODS: The original HITS plan was revised for different regimens, i.e. HEARTS, low-dose HEARTS and SIB-HEARTS. The uniformity index (UI), conformity index (CI), and dose of organs at risk (OARs) were used to evaluate the plans. Additionally, the SIB-HEART (21/15 Gy) was delivered to the total skin and chloromas. RESULTS: No significant differences were observed for the CI and UI between HITS and HEARTS regimens. Compared with HITS, the reduced mean doses to various bone marrows ranged from 17 to 88%. The mean OARs doses for the head, chest and abdomen of a patient with AML treated with SIB-HEARTS (21/15 Gy) were 2.1 to 21.9 Gy, 1.8 to 7.8 Gy and 1.7 to 3.3 Gy, respectively. No severe adverse effects were noted except for grade 4 leukocytopenia and thrombocytopenia. CONCLUSION: HEARTS and different regimens reduced the dose to OARs and bone marrow while maintaining the uniformity and conformity. SIB-HEARTS deliveries different doses to the total skin and enlarged tumors simultaneously. TRIAL REGISTRATION: Retrospectively registered and approved by the Institutional Review Board of our hospital ( FEMH-106151-C ).

Correction: Characteristics and risk of chronic graft-versus-host disease of liver in allogeneic hematopoietic stem cell transplant recipients.

[This corrects the article DOI: 10.1371/journal.pone.0185210.].

Characteristics and risk of chronic graft-versus-host disease of liver in allogeneic hematopoietic stem cell transplant recipients.

Chronic graft-versus-host-disease (cGvHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Among various organ-specific cGvHD, the cGvHD of liver is less well-characterized. In this study, we applied the National Institutes of Health 2014 scoring criteria of cGvHD to analyze a retrospective cohort of 362 allo-HSCT recipients focusing on cGvHD of liver. The overall incidence of liver cGvHD with a score of 3 by 1.5 years post-transplant was 5.8% (21/362). Poor outcome, in terms of overall survival (OS), were observed in patients with scores of 3 liver cGvHD, comparing to those with scores less than 3 (hazard ratio [HR] 2.037, 95% confidence interval [CI] 1.123-3.696, P = 0.019). In multivariate analysis, male gender (HR 4.004, P = 0.042) and chronic hepatitis C virus (HCV) infection status (HR 19.087, P < 0.001) were statistically significant risk factors for scores of 3 liver cGvHD. Our results indicate that liver cGvHD with scores of 3 has a grave prognosis following allo-HSCT, and that HCV carrier status and male are risk factors. Early recognition of this devastating complication might help in prompt immunosuppressive therapy and reducing late poor outcome.

Moderate anemia at diagnosis is an independent prognostic marker of the EUTOS, Sokal, and Hasford scores for survival and treatment response in chronic-phase, chronic myeloid leukemia patients with frontline imatinib.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Clinical-associated characteristics and microbiological features of bloodstream nontyphoidal salmonella infection in adult patients receiving allogeneic hematopoietic stem cell transplantation.

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.

Carfilzomib induces leukaemia cell apoptosis via inhibiting ELK1/KIAA1524 (Elk-1/CIP2A) and activating PP2A not related to proteasome inhibition.

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.

The uniqueness of morphological features of pure erythroid leukemia in myeloid neoplasm with erythroid predominance: A reassessment using criteria revised in the 2016 World Health Organization classification.

We reviewed 97 consecutive cases of myeloid neoplasm with erythroid predominance (MN-EP) between 2000 and 2015. Following 2016 WHO classification, MN-EP patients were classified into four groups. Eight pure erythroid leukemia (PEL) (including t-MN and AML-MRC morphologically fulfilled criteria for PEL) patients had dismal outcomes (median OS: 1 month) and showed more bone marrow fibrosis, worse performance status (PS) and higher serum lactate dehydrogenase (LDH) at diagnosis than the other groups. In the univariate analysis, risks of death in MN-EP patients included the morphologic features of PEL, very poor cytogenetic risk by IPSS-R, bone marrow fibrosis, leukocytosis, anemia, hypoalbuminemia, high LDH, and poor PS. In the multivariate analysis, independent predictors of death were morphologic features of PEL (adjusted hazards ratio [HR] 3.48, 95% confidence interval [CI] 1.24-9.74, p = 0.018), very poor cytogenetic risk by IPSS-R (adjusted HR 2.73, 95% CI 1.22-6.10, p = 0.015), hypoalbuminemia (< 3.7 g/dl) (adjusted HR 2.33, 95% CI 1.10-4.91, p = 0.026) and high serum LDH (≥ 250 U/L) (adjusted HR 2.36, 95% CI 1.28-4.36, p = 0.006). Poor or unfavorable risk in different cytogenetic risk systems independently predicted death and UKMRC-R was the best model.

Risk factors and characteristics of blood stream infections in patients with newly diagnosed multiple myeloma.

BACKGROUND: Patients with multiple myeloma are generally immune-compromised either due to pronounced depression in primary antibody responses or because of anti-myeloma therapy. Infection is a major risk factor for early deaths among these patients. The impact of blood stream infections (BSI) on newly diagnosed myeloma patients has been less studied. We aimed to study the incidence and risk factors of BSI within 3 months after diagnosis of multiple myeloma in a tertiary referral center. METHODS: Between November 2002 and December 2008, consecutive patients with multiple myeloma in Taipei Veterans General Hospital were retrospectively enrolled. Characteristics of patients with or without BSI were collected. Possible factors associated with development of BSI were analyzed by Cox regression. RESULTS: There were a total of 222 patients. The incidence of BSI within 3 months after diagnosis is 11.7%. The patients with BSI had poorer survival outcomes than those without (mortality rate: 50% vs. 20.9%, p < 0.001). Moreover, advanced International Staging System stage (stage III vs. I/II: odds ratio [OR] 2.69, p = 0.049) and poor Eastern Cooperative Oncology Group (ECOG) performance status (ECOG > 2 vs. ≤ 2: OR 3.58, p = 0.005) were the independent risk factors of BSI, whereas immunoglobulin deficiency and low absolute lymphocyte count were not associated with risk of BSI development. CONCLUSIONS: Our study highlights the characteristic of myeloma patients with BSI and the importance of disease and host factors on risk of BSI. Myeloma patients with risks of BSI should be properly managed to reduce early mortality.

Risk of hemophagocytic lymphohistiocytosis in adults with fevers of unknown origin: the clinical utility of a new scoring system on early detection.

The diagnosis of hemophagocytic lymphohistiocytosis (HLH) is delayed by most physicians. This study aimed to identify early parameters and suitable scoring systems for the risk of HLH. Clinical and laboratory data collected ≤3 days after admission were defined as early parameters and used to calculate the number of HLH-2004 criteria met and bone marrow (BM) score. Between January 2006 and February 2016, 233 immunocompetent adults with naïve fever of unknown origin who underwent a BM study were enrolled to mimic patients at risk of HLH and randomly assigned into the developmental or validation cohort. Hemophagocytic lymphohistiocytosis was finally diagnosed in 47 patients, with non-Hodgkin lymphoma as the major etiology (51.1%). Upon admission, four-fifths of patients who developed subsequent HLH fulfilled ≤3 of 8 HLH-2004 criteria, and 6 early parameters were independent predictors of HLH: anemia (hemoglobin < 10 g/dL), thrombocytopenia (platelet count < 100 × 103 /µL), leukoerythroblastosis, hyperbilirubinemia (total bilirubin > 2 × upper normal limit), hyperferritinemia (ferritin > 1000 ng/mL), and splenomegaly. Compared with the HLH criteria met upon admission, the BM score was an independent predictor (odds ratio = 1.621; 95% confidence interval, 1.355-1.940) with excellent discrimination (area under the receiver operating characteristic curve = 0.920; 95% confidence interval, 0.883-0.958). The sensitivity and specificity for a BM score cutoff of 10 points were 95% and 75%, respectively. When approaching immunocompetent adults with a continuously high fever, the BM score at initial admission assists with early identification of patients at risk of HLH.

Risk of stroke in patients with newly diagnosed multiple myeloma: a retrospective cohort study.

Cerebrovascular events are a common complication among patients with cancer, increasing morbidity and mortality. However, the association between multiple myeloma and cerebrovascular events remains unclear. We therefore investigated multiple myeloma patients' risk factors for stroke to devise a better stroke-prevention strategy. This study includes consecutive patients 20 years and older who were newly diagnosed with symptomatic multiple myeloma at Taipei Veterans General Hospital, a tertiary medical center, between January 1, 2002 and December 31, 2014. The primary outcome was stroke development. Patients with head injuries, brain tumors, brain parenchymal invasions, or antecedent malignancies were excluded. Hazard ratios (HRs) of stroke risk factors for multiple myeloma patients were estimated by Cox proportional regression analysis. Overall, 395 patients with a median age of 70 years were investigated. In the median follow-up period of 18 months, cerebrovascular events occurred in 16 patients, including 10 ischemic strokes and 6 hemorrhagic strokes. The 5-year estimated cumulative incidence rate was 7.45%. In the multivariate analysis, the κ light chain isotype (adjusted HR, 8.37; 95% confidence interval [CI], 1.91-39.8), previous cerebrovascular accidents (adjusted HR, 5.16; 95% CI, 1.48-17.9), and serum creatinine > 2 mg/dL (adjusted HR, 4.21; 95% CI, 1.10-16.0) were identified as independent risk factors for stroke. Subgroup analysis showed that atrial fibrillation (adjusted HR, 8.07) and previous cerebrovascular accident (adjusted HR, 4.89) are significant risk factors for ischemic stroke. Serum creatinine > 2 mg/dL (adjusted HR, 30.6) and previous cerebrovascular accident (adjusted HR, 13.9) are significant for hemorrhagic stroke. Moreover, therapeutic strategies for multiple myeloma were not associated with stroke in our study. This study demonstrates that risk of stroke increases in myeloma patients with a κ light chain isotype, previous cerebrovascular events, and renal impairment. Further prospective clinical studies to clarify the relationship between multiple myeloma and stroke are warranted.