Risk stratification for early mortality in newly diagnosed acute promyelocytic leukemia: a multicenter, non-selected, retrospective cohort study.

Introduction: Despite the current effective treatments for acute promyelocytic leukemia (APL), early mortality (EM), defined as death within 30 days of presentation, is a major hurdle to long-term survival. Methods: We performed a multicenter retrospective study to evaluate the incidence and clinical characteristics of EM in patients with newly diagnosed APL and to develop a risk stratification model to predict EM. Results: We identified 313 eligible patients diagnosed between 2000 and 2021 from five academic hospitals. The median age was 50 years (range 19-94), and 250 (79.9%) patients were <65 years. Most patients (n=274, 87.5%) received their first dose of all-trans retinoic acid (ATRA) within 24 hours of presentation. EM occurred in 41 patients, with a cumulative incidence of 13.1%. The most common cause of EM was intracranial hemorrhage (n=22, 53.6%), and most EMs (31/41, 75.6%) occurred within the first seven days of APL presentation. In a multivariable analysis, we identified three independent factors predicting EM: age ≥65 years (HR, 2.56), white blood cell count ≥8.0 x 109/L (HR, 3.30), and ATRA administration >24 hours of presentation (HR, 2.95). Based on these factors, patients were stratified into three categories with a significantly increasing risk of EM: 4.1% for low risk (54.3%; no risk factors; HR 1), 18.5% for intermediate risk (34.5%; 1 factor; HR 4.81), and 40.5% for high risk (11.2%; 2-3 factors; HR 13.16). Discussion: The risk of EM is still not negligible in this era of ATRA-based therapies. Our risk model serves as a clinically useful tool to identify high-risk patients for EM who may be candidates for novel treatments and aggressive supportive strategies.

Mediating Effect of Stress Recognition on the Effect of Generalized Anxiety Disorder on Smartphone Dependence.

The widespread adoption of the smartphone has led to both positive and negative consequences for adolescents' mental health. This study examines the interplay between smartphone dependence (SPD), generalized anxiety disorder (GAD), and various mental health outcomes among Korean adolescents. Data from the 16th Adolescence Health Behavior Survey (2020), including 54,948 middle and high school students, were analyzed. Adolescents were categorized into three groups based on SPD severity. The GAD-7 scale assessed anxiety, and other factors such as subjective health recognition, happiness, weight control efforts, and body mass index (BMI) were considered. Adolescents with higher SPD exhibited lower academic performance, decreased happiness, and increased perception of stress. GAD levels were positively correlated with SPD, with higher SPD linked to more severe GAD symptoms. Additionally, higher SPD was associated with increased loneliness, sadness, and suicidal thoughts, plans, and attempts as well as a greater likelihood of habitual drug use. Gender differences revealed that females were more prone to sadness, hopelessness, and suicidal thoughts, while males exhibited higher rates of drug use. This study highlights the complex relationship between SPD, GAD, and mental health outcomes among Korean adolescents. Stress recognition was found to mediate the association between GAD and SPD. The process-macro result of the total effect between SPD on GAD and the direct effect of the SPD pathway on GAD was significant; thus, the stress recognition was mediated. Effective interventions should target stress management, especially among adolescents with high smartphone dependence, to mitigate the risk of mental health issues. These findings underscore the importance of addressing smartphone dependence and its impact on the mental well-being of adolescents.

Cytomegalovirus reactivation under pre-emptive therapy following allogeneic hematopoietic stem cell transplant: Pattern, survival, and risk factors in the Republic of Korea.

INTRODUCTION: Pre-emptive therapy for cytomegalovirus (CMV) reactivation has been used in allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is unclear if this strategy has poorer clinical outcomes in CMV-endemic areas and if more aggressive prophylaxis is required. METHODS: We retrospectively analyzed the patterns and survival after CMV reactivation in patients undergoing pre-emptive therapy following allo-HSCT and assessed high-risk patients who could benefit from aggressive CMV prophylaxis in endemic areas. RESULTS: Of the 292 patients who underwent allo-HSCT, 70.5% (donor+ or recipient+) were CMV seropositive. CMV reactivation occurred in 139 patients (47.6%), with a median of 31.5 days from day 0 of allo-HSCT. The overall survival of patients with CMV reactivation who received pre-emptive therapy did not differ from those without reactivation. Of the 139 patients with CMV reactivation, 78 (56.1%) underwent ≥2 rounds of pre-emptive therapy. In multivariate analysis, the risk of CMV reactivation was higher in patients with multiple myeloma, with CMV seropositivity of the recipient and donor, administered with a higher dose of anti-thymocyte globulin (ATG), and with acute graft-versus-host disease (aGVHD) ≥ grade 2. CONCLUSION: Although half of the patients with allo-HSCT were administered with pre-emptive therapy for CMV, CMV reactivation did not affect their survival, indicating the advantages of pre-emptive therapy, even in CMV-endemic areas. The cost-effectiveness of more aggressive CMV prophylaxis should be re-evaluated in patients at a high risk for CMV reactivation.

Rituximab plus multiagent chemotherapy for newly diagnosed CD20-positive acute lymphoblastic leukemia: a prospective phase II study.

BACKGROUND/AIMS: We performed a prospective study to determine the efficacy and safety of rituximab including chemotherapy in CD20-positive acute lymphoblastic leukemia (ALL). METHODS: Patients with newly diagnosed ALL, aged ≥ 15 years, were eligible for the study if their leukemic blast cells in bone marrow expressed CD20 ≥ 20% at the time of diagnosis. Patients received multiagent chemotherapy with rituximab. After achieving complete remission (CR), patients received five cycles of consolidation with concomitant rituximab. Rituximab was administered monthly from day 90 of transplantation for patients who received allogeneic hematopoietic cell transplantation. RESULTS: In patients with Philadelphia (Ph)-negative ALL, 39 of 41 achieved CR (95.1%), the 2- and 4-year relapse-free survival (RFS) rates were 50.4% and 35.7%, and the 2- and 4-year overall survival (OS) rates were 51.5% and 43.2%, respectively. In the group with Ph-positive ALL, all 32 patients achieved CR, the 2- and 4-year RFS rates were 60.7% and 52.1%, and the 2- and 4-year OS rates were 73.3% and 52.3%, respectively. In the Ph-negative ALL group, patients with higher CD20 positivity experienced more favorable RFS (p < 0.001) and OS (p = 0.06) than those with lower CD20 positivity. Patients who received ≥ 2 cycles of rituximab after transplantation had significantly improved RFS (hazard ratio [HR], 0.31; p = 0.049) and OS (HR, 0.29; p = 0.021) compared with those who received < 2 cycles. CONCLUSION: The addition of rituximab to conventional chemotherapy for CD20-positive ALL is effective and tolerable (Clinicaltrials. gov NCT01429610).

Prognostic outcomes of cytomegalovirus reactivation after autologous stem cell transplantation.

Background: Cytomegalovirus (CMV) reactivation is a common complication in patients undergoing allogeneic stem cell transplantation. However, the incidence of CMV reactivation is low after autologous stem cell transplantation (auto-SCT), and the prognostic value of CMV reactivation remains controversial. Moreover, reports on late CMV reactivation after auto-SCT are limited. We aimed to analyze the association between CMV reactivation and survival outcomes and develop a predictive model for late CMV reactivation in patients undergoing auto-SCT. Methods: Data of 201 patients who underwent SCT at the Korea University Medical Center from 2007 to 2018 were collected. We analyzed prognostic factors for survival outcomes after auto-SCT and risk factors for late CMV reactivation using a receiver operating characteristic curve. Then, we developed a predictive risk model for late CMV reactivation based on results of the risk factor analysis. Results: Early CMV reactivation was significantly associated with better overall survival (OS) (hazard ratio [HR], 0.329; P = 0.045) in patients with multiple myeloma; however, no significant differences were observed in patients with lymphoma. For late CMV reactivation, a serum lactate dehydrogenase level greater than the upper limit of normal (HR, 2.251; P = 0.027) and late CMV reactivation (HR, 2.964; P = 0.047) were independent risk factors for poor OS, while lymphoma diagnosis (vs. multiple myeloma; HR, 0.389; P = 0.016) was an independent risk factor for good OS. In risk factor analysis for late CMV reactivation, T-cell lymphoma diagnosis (odds ratio [OR], 8.499; P = 0.029), ≥ two prior chemotherapies (OR, 8.995; P = 0.027), failure to achieve complete response (CR) after transplantation (OR, 7.124; P = 0.031), and early CMV reactivation (OR, 12.853; P = 0.007) were significantly associated with late CMV reactivation. To develop the predictive risk model for late CMV reactivation, a score (1 to 1.5) was assigned for each of the above-mentioned variables. The optimal cutoff value (1.75 points) was calculated using the receiver operating characteristic curve. The predictive risk model showed good discrimination, with an area under the curve of 0.872 (standard error, 0.062; P < 0.001). Conclusions: Late CMV reactivation was an independent risk factor for inferior OS, whereas early CMV reactivation was associated with better survival in patients with multiple myeloma. This risk prediction model could be helpful in identifying high-risk patients who require monitoring for late CMV reactivation and potentially benefit from prophylactic or preemptive therapy.

Perception and safety analysis of COVID-19 vaccination in cancer patients: A multicenter, real-world study.

BACKGROUND: Although various coronavirus disease 2019 (COVID-19) vaccines have been delivered to the public worldwide, data on cancer populations are limited. Vaccine hesitancy related to safety concerns is observed among cancer patients. We report the perception of COVID-19 vaccines and their safety profile after vaccination among cancer patients. MATERIALS AND METHODS: Between April and November 2021, a multicenter survey was conducted on 318 patients treated in any hemato-oncology outpatient clinic among three hospitals under the Korea University Medical Center. The medical records of the patients were reviewed to obtain detailed clinical and hematological toxicity data. RESULTS: A perception survey was conducted among 293 patients. Among them, 53.9% were concerned about developing vaccine-related adverse events (VRAEs) and 23.5%, about negative effects on cancer treatment. During the study period, 255 and 186 patients participated in a safety survey after the first and second doses, respectively. After the first dose, 62% of patients reported VRAEs (2.4%, grade 3), whereas 48.9% reported VRAEs (2.7%, grade 3) after the second dose. For both doses, injection-site pain and sore arm pain were the most common VRAEs, followed by myalgia, fatigue, and headache. No grade 4/5 VRAEs were observed, and there were no differences in complete blood count after vaccination. Multivariate analysis revealed female sex, active cancer treatment, and mRNA vaccines as independent risk factors for VRAE development in cancer patients. CONCLUSION: Despite high levels of concern, COVID-19 vaccines were well tolerated by cancer patients, with a safety profile consistent with that of the general population.

PVR (CD155) Expression as a Potential Prognostic Marker in Multiple Myeloma.

Poliovirus receptor (PVR, CD155) is upregulated during tumor progression, and PVR expression is associated with poor prognosis in cancer patients; however, prognostic implications for PVR in multiple myeloma (MM) have not been investigated. PVR plays an immunomodulatory role by interacting with CD226, CD96, and TIGIT. TIGIT is a checkpoint inhibitory receptor that can limit adaptive and innate immunity, and it binds to PVR with the highest affinity. We used immunohistochemistry, ELISA, qPCR, and flow cytometry to investigate the role of PVR in MM. PVR was highly expressed in patients with MM, and membrane PVR expression showed a significant correlation with soluble PVR levels. PVR expression was significantly associated with the Revised-International Staging System stage, presence of extramedullary plasmacytoma and bone lesion, percentage of bone marrow plasma cells (BMPCs), and ß2-microglobulin levels, suggesting a possible role in advanced stages and metastasis. Furthermore, TIGIT expression was significantly correlated with the percentage of BMPCs. Patients with high PVR expression had significantly shorter overall and progression-free survival, and PVR expression was identified as an independent prognostic factor for poor MM survival. These findings indicate that PVR expression is associated with MM stage and poor prognosis, and is a potential prognostic marker for MM.

Postoperative Thromboembolism According to the Type of Surgery: A Nationwide Study in the Republic of Korea.

Postoperative thromboembolism (TE) is a serious, but preventable, complication in surgical patients. Orthopedic surgery, neurosurgery, and vascular surgery are considered high risk for TE, and current guidelines recommend TE prophylaxis. However, insufficient data exist regarding TE risk in other general surgeries. This study identified the actual incidence and relative risk of postoperative TE in the real world, according to surgery type. Twenty-six surgeries between 1 December 2017 and 31 August 2019 were selected from the Health Insurance Review and Assessment Service database and analyzed for postoperative TE events. Among all patients, 2.17% had a TE event within 6 months of surgery and 0.75% had a TE event owing to anticoagulant treatment. The incidence of total TE events was the highest in total knee replacement (12.77%), hip replacement (11.46%), and spine surgery (5.98%). The incidence of TE with anticoagulant treatment was the highest in total knee replacement (7.40%), hip replacement (7.20%), and coronary artery bypass graft (CABG) surgery (3.81%). Hip replacement, total knee replacement, CABG surgery, spine surgery, and cardiac surgery except CABG surgery, showed relatively higher risks for total claimed venous TE. The relative risk of venous TE with anticoagulant treatment was the highest for hysterectomy, partial hepatectomy, hip replacement, cardiac surgery except CABG surgery, and total knee replacement. The relative risk of arterial TE was the highest for cardiac surgery, total knee replacement, and hip replacement. In the real world, the incidence of postoperative TE events from total knee replacement and those from hip replacement remain high, and some surgeries could have a relatively higher risk of TE than other surgeries. For patients undergoing these surgeries, studies to reduce the incidence of postoperative TE in clinical practice should be conducted.

The effect of the response to the coronavirus disease pandemic on treatment outcomes in patients with lymphoma and multiple myeloma.

BACKGROUND/AIMS: Relatively little data are available on how the response to the coronavirus disease 2019 (COVID-19) pandemic has affected treatment outcomes in patients receiving chemotherapy for lymphoma or multiple myeloma. We aimed to determine the effect of COVID-19 countermeasures on treatment outcomes in this patient population. METHODS: We retrospectively analyzed data on patients treated for lymphoma or multiple myeloma in two tertiary hospitals in Seoul. Patients were divided into two groups: group 1 included patients who received chemotherapy between September and December 2019 (the control period), and group 2 included patients who received chemotherapy between September and December 2020 (the study period). Countermeasures to COVID-19 were applied to the patients in group 2. The countermeasures implemented included mask wearing and regular handwashing at home and in hospital; COVID-19 risk assessments on all hospital visitors; and pre-emptive COVID-19 screening for all newly hospitalized patients and their resident guardians. RESULTS: No differences in treatment outcomes, including treatment response, incidence and duration of neutropenia or neutropenic fever, delays in chemotherapy, or number of deaths during chemotherapy, were observed between the g roups. None of the patients in group 2 tested positive for COVID-19, and there were no COVID-19-related deaths during the study period. CONCLUSION: Countermeasures to COVID-19 did not affect treatment outcomes in patients receiving chemotherapy for lymphoma or multiple myeloma. Data on the effect of countermeasures to COVID-19 on treatment outcomes should continue to be analyzed to ensure that treatment outcomes are not adversely affected.

A nationwide study of patients with monoclonal gammopathy of undetermined significance with a 10-year follow-up in South Korea.

In clinical practice, most patients with monoclonal gammopathy of undetermined significance (MGUS) undergo long-term follow-up without disease progression. There is insufficient real-world data about how closely and whether anything other than disease progression should be monitored. Herein, we performed a nationwide study of 470 patients with MGUS with a 10-year follow-up to determine the patterns of disease progression and other comorbidities. During the follow-up period, 158 of 470 patients with MGUS (33.62%) progressed to symptomatic monoclonal gammopathies. Most of these were multiple myeloma (134/470 patients, 28.51%), and those diagnosed within 2 years after diagnosis of MGUS was high. Approximately 30-50% of patients with MGUS had hypertension, diabetes, hyperlipidemia, and osteoarthritis at the time of diagnosis, and these comorbidities were newly developed during the follow-up period in approximately 50% of the remaining patients with MGUS. Approximately 20-40% of patients with MGUS have acute or chronic kidney failure, thyroid disorders, disc disorders, peripheral neuropathy, myocardial infarction, stroke, and heart failure during the follow-up period. Altogether, when MGUS is diagnosed, close follow-up of the possibility of progression to multiple myeloma is required, especially within 2 years after diagnosis; simultaneously, various comorbidities should be considered and monitored during the follow-up of patients with MGUS. Continuous research is needed to establish appropriate follow-up guidelines.

Prediction Model for Cereblon Expression in Bone Marrow Plasma Cells Based on Blood Markers in Multiple Myeloma Patients.

BACKGROUND: Cereblon (CRBN) is a direct target of immunomodulatory drugs (IMiDs) and is known to be sensitive and responsive to IMiD therapy. We evaluated CRBN expression in bone marrow plasma cells and analyzed whether CRBN expression was associated with multiple myeloma prognosis. Lastly, we developed a nomogram model for predicting high CRBN expression based on clinically significant blood markers. METHODS: We evaluated 143 multiple myeloma patients (internal dataset) who underwent bone marrow examinations. For evaluating the prognostic ability of the nomogram model, two external cohorts (235 patients in external dataset 1 and 156 patients in external dataset 2) were analyzed. The expression of CRBN in bone marrow aspirate samples was evaluated using immunohistochemistry. High CRBN expression was defined as the study-defined H-score ≥6. RESULTS: In the high CRBN group, the median progression-free survival (PFS) and overall survival (OS) of patients receiving the IMiD-based therapy and non-IMiD therapy were 29 and 10 months for PFS, and NR (not reached) and 54 months for OS, respectively. IMiD-based therapy was significantly associated with better PFS and OS outcomes. High CRBN expression was independently predicted by female sex, high serum free-light chain (FLC) ratio, higher serum M-protein level, and higher ß2-microglobulin level. Based on these results, we constructed a new nomogram model to predict high CRBN expression and the effectiveness of IMiD therapy in multiple myeloma. CONCLUSION: This nomogram could improve the prognostic evaluation of myeloma patients exhibiting high CRBN expression treated with IMiD therapy and might help provide personalized treatment strategies to clinicians.

Efficacy and safety of two pegfilgrastim biosimilars: Tripegfilgrastim and pegteograstim.

Our aim was to compare the efficacy and safety of two recently developed biosimilars of pegfilgrastim, a pegylated form of the recombinant human granulocyte-colony stimulating factor (G-CSF) analog filgrastim with those of the reference pegfilgrastim. We retrospectively analyzed data from patients diagnosed with diffuse large B-cell lymphoma (DLBCL) who were treated with first-line R-CHOP chemotherapy and received pegylated G-CSF for primary prophylaxis. The following pegylated G-CSFs were analyzed in this study: reference pegfilgrastim (Neulasta® ) and two of its biosimilars (tripegfilgrastim; Dulastin® and pegteograstim; Neulapeg® ). In total, 296 patients were enrolled. The number of patients with at least one episode of neutropenia during R-CHOP chemotherapy was the lowest in the reference cohort (pegfilgrastim: 127 of 193 patients, 65.8%; tripegfilgrastim: 64 of 69 patients, 92.8%; pegteograstim: 28 of 34 patients, 82.4%, P < .001). The number of patients with at least one episode of febrile neutropenia was also lowest in the reference cohort (pegfilgrastim: 67 of 193 patients, 34.7%; tripegfilgrastim: 38 of 69 patients, 55.1%; pegteograstim: 16 of 34 patients, 47.1%, P = .009). There were no differences in the duration of neutropenia and febrile neutropenia or treatment outcomes (rate of complete response or relapse and survival). There were no reports of grade 3 or higher adverse events requiring discontinuation of prophylactic pegylated G-CSF in any group. The safety of the pegfilgrastim biosimilars for prophylactic purposes was comparable to that of the reference pegfilgrastim; however, in terms of their efficacy, the incidence of neutropenia and febrile neutropenia tended to be higher than that when using pegfilgrastim. The clinical relevance of these results in the biosimilar cohorts should be explored.

Nationwide study of paroxysmal nocturnal hemoglobinuria in South Korea: paradox of eculizumab.

Eculizumab is effective in managing patients with paroxysmal nocturnal hemoglobinuria (PNH). In South Korea, the financial support for eculizumab therapy is extended by the National Health Insurance Services (NHIS) only to patients with high-risk PNH for approximately 10 years. In this study, we performed a nationwide analysis of the real-world efficacy of eculizumab therapy in patients diagnosed with PNH between January 1, 2002, and December 31, 2016, by using the NHIS database. Patients treated with eculizumab (the eculizumab-treated group) exhibited a significantly higher survival rate than patients not treated with eculizumab (the eculizumab-untreated group), with 4-year survival rates after propensity score matching of 98.31% and 79.67%, respectively (p = 0.0489). The mean red blood cell (RBC) transfusion units per 12 months after eculizumab therapy were significantly lower than that before eculizumab therapy (5.75 units vs. 12.28 units, p < 0.0001). The median time for the first transfusion in the eculizumab-treated group was significantly longer than that in the eculizumab-untreated group. The 4-year transfusion-independence rate for the eculizumab-treated group was significantly higher than that for the eculizumab-untreated group (20.81% vs. 10.24%, p = 0.078). There was no significant difference between the two groups in the incidence of new documented complications related to PNH. In conclusion, eculizumab therapy for patients with high-risk PNH may effectively improve the survival rate and reduce the transfusion requirement. Paradoxically, eculizumab-treated patients with severe PNH exhibit a higher survival rate than eculizumab-untreated patients with less severe PNH.

Impact of subsequent chemotherapy on the survival of elderly patients with extensive stage small cell lung cancer.

BACKGROUND/AIMS: The prognosis of small cell lung cancer (SCLC) is still poor because of rapid recurrence, despite good response to initial chemotherapy. Additionally, patients' old ages and comorbidities are often obstacles that make it difficult to apply subsequent treatment after initial treatment. This retrospective study analyzed the correlation of post-progression survival (PPS) with overall survival (OS), and prognostic factors including comorbidities to figure out impact of subsequent chemotherapy on OS in elderly extensive disease SCLC. METHODS: We analyzed 101 patients of age 65 years or older who were recently diagnosed with extensive disease SCLC (ED-SCLC) in Korea University Medical Center between January 1995 and December 2015. The degree of comorbidity was scored using simplified comorbidity score (SCS). Correlation between PPS, progression-free survival (PFS) and OS was analyzed using a Pearson correlation coefficient. Cox proportional hazards regression was employed to examine the influence of clinical variables on survival. RESULTS: Median age of patients was 71 years old (range, 65 to 83). Median OS was 8.7 months (range, 0.3 to 42.7). PPS was a reliable factor on OS than PFS (R2 = 0.852, p < 0.001). Prognostic factors associated with improved survival were SCS < 9, administration > 4 cycles of first line chemotherapy and subsequent second line chemotherapy. CONCLUSION: PPS was more correlated with OS than PFS in elderly patients with ED-SCLC. The most important prognostic factors for PPS and OS included SCS and second line chemotherapy. Patients receiving subsequent treatment had increased OS regardless of degree of comorbidity.

Immature platelet fraction based diagnostic predictive scoring model for immune thrombocytopenia.

BACKGROUND/AIMS: The diagnosis of immune thrombocytopenia (ITP) is based on clinical manifestations and there is no gold standard. Thus, even hematologic malignancy is sometimes misdiagnosed as ITP and adequate treatment is delayed. Therefore, novel diagnostic parameters are needed to distinguish ITP from other causes of thrombocytopenia. Immature platelet fraction (IPF) has been proposed as one of new parameters. In this study, we assessed the usefulness of IPF and developed a diagnostic predictive scoring model for ITP. METHODS: We retrospectively studied 568 patients with thrombocytopenia. Blood samples were collected and IPF quantified using a fully-automated hematology analyzer. We also estimated other variables that could affect thrombocytopenia by logistic regression analysis. RESULTS: The median IPF was significantly higher in the ITP group than in the non-ITP group (8.7% vs. 5.1%). The optimal cut-off value of IPF for differentiating ITP was 7.0%. We evaluated other laboratory variables via logistic regression analysis. IPF, hemoglobin, lactate dehydrogenase (LDH), and ferritin were statistically significant and comprised a diagnostic predictive scoring model. Our model gave points to each of variables: 1 to high hemoglobin (> 12 g/dL), low ferritin (≤ 177 ng/ mL), normal LDH (≤ upper limit of normal) and IPF ≥ 7 and < 10, 2 to IPF ≥ 10. The final score was obtained by summing the points. We defined that ITP could be predicted in patients with more than 3 points. CONCLUSION: IPF could be a useful parameter to distinguish ITP from other causes of thrombocytopenia. We developed the predictive scoring model. This model could predict ITP with high probability.

Analysis of bone marrow supernatant neutrophil gelatinase-associated lipocalin and hematological parameters in hematological malignancy.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a urine biomarker related to acute renal injury. Whereas several studies have evaluated NGAL levels in hematological malignancy, using peripheral blood (PB). Recently, bone marrow (BM) NGAL level was reported to be higher than PB NGAL level in individuals with hematological malignancy, suggesting that BM NGAL would reflect BM microenvironment better than PB NGAL. We measured BM NGAL levels in patients with hematological malignancy, comparing those with NGAL levels in normal BM. We evaluated the association of BM NGAL with hematological parameters including neutrophil counts. METHODS: BM samples were collected from 107 patients who underwent BM examination. Immunoassays were used to assess NGAL levels. Data on hematological parameters were collected from medical records. Intergroup comparisons were performed using the Kruskal-Wallis H test and Pearson chi-square test. Single and multiple regression analyses were performed to analyze the relationships. RESULTS: The independent factors that affected the BM NGAL level were neutrophil counts and BM band neutrophil%, while neutrophil count was the main influencing factor. The acute myeloid leukemia (n = 18) and myelodysplastic syndrome (n = 25) groups showed statistically lower BM NGAL levels than patients with normal BM. The myeloproliferative neoplasm group (n = 34) showed higher BM NGAL levels than patients with normal BM, but this difference was not statistically significant. Neutrophil counts and BM band neutrophil% showed intergroup patterns similar to those of BM NGAL levels. CONCLUSION: BM NGAL was related to neutrophil count and BM band neutrophil%, showing different levels according to hematological malignant disease entities.

The role of platelet function analyzer-200 in predicting perioperative bleeding risk.

BACKGROUND/AIMS: Various preoperative screening tests, such as platelet count, prothrombin time, activated partial thromboplastin time, and bleeding time, have been widely used to evaluate the risk of bleeding during surgery. Use of platelet function analyzer (PFA)-100/200 for assessing platelet function instead of bleeding time is increasing. However, its role in predicting the perioperative risk of bleeding remains controversial. METHODS: Data of 703 patients who underwent surgery under general anesthesia were retrospectively analyzed. Preoperative platelet function was measured using PFA-200 system and the association with intraoperative bleeding was assessed. Additionally, other variables that could affect PFA-200 results were assessed by logistic regression analysis. RESULTS: Collagen/epinephrine (COL/EPI) test was prolonged in 199/703 (28.3%) patients (EPI group), while 99/212 (46.7%) patients showed COL/adenosine diphosphate test abnormalities. Bleeding over 300 mL during surgery occurred in 14.3% and 20.1% of patients in the normal and EPI groups, respectively (p = 0.058). In addition, red blood cell transfusion within 72 hours after surgery rate was significantly higher in the EPI group than in the normal group (31.7% vs. 23.4%, p = 0.024). In multivariate logistic analysis, prolongation closure time with COL/EPI (p = 0.068) was marginally associated with risk of bleeding during surgery. Furthermore, PFA-200 results were influenced by various factors, such as nonsteroidal anti-inflammatory drug use, blood group, hematocrit, and time of blood collection. CONCLUSION: Preoperative PFA-200 test may be helpful in predicting the risk of perioperative bleeding. However, its results should be carefully interpreted because they are affected by several factors.

Comparison between 5-day decitabine and 7-day azacitidine for lower-risk myelodysplastic syndromes with poor prognostic features: a retrospective multicentre cohort study.

Numerous studies have analysed the clinical efficacies of hypomethylating agents (HMAs) in patients with myelodysplastic syndromes (MDS). However, reports that compare the two HMAs, decitabine and azacitidine, in patients with lower-risk (low and intermediate-1) MDS are limited. We compared 5-day decitabine and 7-day azacitidine regimens in terms of treatment responses, survival outcomes, and adverse events in patients with lower-risk MDS with poor prognostic features. The overall response rates (ORRs) were 67.2% and 44.0% in the patients treated with decitabine and azacitidine, respectively (P = 0.014). While the median progression-free survival (PFS) was significantly better in the patients treated with decitabine than in those treated with azacitidine (P = 0.019), no significant differences in event-free and overall survival rates were observed between the two groups. Multivariate analysis revealed that compared with azacitidine treatment, decitabine treatment is significantly associated with a higher ORR (P = 0.026) and longer PFS (P = 0.037). No significant differences were observed in the incidence of grade 3 or higher haematologic adverse events in response to the two HMAs. In conclusion, in lower-risk MDS, especially with poor prognostic features, ORR and PFS were significantly better with 5-day decitabine treatment than with 7-day azacitidine treatment, with comparable safety.

Efficacy of posaconazole prophylaxis in acute myeloid leukemia and myelodysplastic syndrome patients treated with hypomethylating agents.

BACKGROUND: Although many acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients have been treated with hypomethylating agents (HMAs) as a substitute for intensive chemotherapy in recent years, the incidence of invasive fungal infections (IFIs) and the efficacy of posaconazole as antifungal prophylaxis in these patients are not well known to date. METHODS: We retrospectively analyzed 280 AML and MDS patients treated with HMAs to identify IFI incidence and posaconazole efficacy as antifungal prophylaxis in these patients. RESULTS: The overall incidence of probable or proven IFIs was 7.9% (22/280 patients): 11.5% in the no-use group (17/148 patients) and 3.8% in the posaconazole group (5/132 patients). Most IFIs occurred during the early cycles of the HMAs (median: 3 cycles; range: 1-8 cycles), especially in patients who had neutropenia or did not respond to HMAs. Posaconazole significantly lowered IFI incidence compared with that in the no-use group in univariate and multivariate analyses. Moreover, patients who had reduced liver function at HMA initiation, were treated with decitabine therapy, and did not respond to HMA chemotherapy were independently associated with a higher IFI risk. In subgroup analysis, posaconazole appeared to be more beneficial for patients with good Eastern Cooperative Oncology Group performance score or liver function at HMA initiation. CONCLUSION: Thus, in AML and MDS patients receiving HMAs, IFI risk may be high during the early cycles, especially when the underlying disease is not controlled. Posaconazole could represent antifungal prophylaxis in these patients; further studies are needed for its appropriate indications.