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. Myelodysplastic syndromes (MDS) are clonal haematologic disorders characterised by ineffective and dysplastic haematopoiesis that causes cytopenia, leading to the development of acute leukaemia 1,2. Previously, MDS was generally divided into lower-risk (low and intermediate-1) and higher-risk (intermediate-2 and higher) categories on the basis of the International Prognostic Scoring System (IPSS) 3 , and treatment decisions were usually made based on the risk group. The treatment for higher-risk MDS aims to modify the natural course of the disease using hypomethylating agents (HMAs), chemotherapy, or stem cell transplantation, whereas the treatment for lower-risk MDS aims to improve cytopenia, reduce transfusion requirements, and provide the best supportive care 4. However, lower-risk MDS patients with poor prognostic features were known to be associated with progression to acute myeloid leukaemia or severe cytopenia 4. Hence, more active treatments are needed for this group of patients. Currently, two types of HMAs (decitabine or azacitidine) are available for the treatment of MDS 5. Several previous studies reported the efficacy of HMAs in different clinical settings. In higher-risk MDS, a 7-day azacitidine regimen (75 mg/m 2 daily every 4 weeks) was reported to result in higher response rates and better overall survival

Background/AimsBortezomib plus melphalan-prednisone (VMP) is a standard treatment for multiple myeloma, particularly for patients who are ineligible for high-dose therapy. However, early discontinuation or treatment modification is often needed owing to adverse events. The aim of this study was to investigate the clinical outcomes of modifying the dose of melphalan-prednisone (MP) in patients receiving VMP.MethodsWe examined 67 patients who received a modified dose of MP, and 38 patients who received the regularly planned dose of MP. We then analyzed clinical differences between the groups.ResultsAlthough there was no difference in the proportion of discontinuation due to adverse events between dose groups, more patients in the planned-dose group experienced earlier discontinuation in general. The overall response rate (ORR) was 81.0% and complete response (CR) rate was 30.5%. After a median 15.7 months of follow-up, the median progression-free survival (PFS) and overall survival (OS) were 25.0 and 47.8 months, respectively. There was no significant difference in the ORR, CR, PFS, and OS of the two dose groups. A median of four cycles were delivered, and the median cumulative bortezomib dose was 41.6 mg/m2 . The median PFS in patients with doses ≥ 41.6 mg/m2 was longer than that in patients with doses < 41.6 mg/m2 (35.1 months vs. 9.6 months). However, when MP was < 50% of the planned dose, PFS and OS were poor.ConclusionsModifying the dose of MP might be a feasible and effective therapeutic approach for multiple myeloma patients receiving VMP treatment.

Introduction: Hypomethylating agents (HMAs) are used for the treatment of patients with myelodysplastic syndromes (MDS). Two HMAs, decitabine and azacitidine, are currently available for such treatment. Numerous studies have analyzed the clinical efficacy of HMAs in patients with MDS; however, reports directly comparing decitabine and azacitidine in patients with lower-risk (low and intermediate-1) MDS are limited. The clinical efficacy of standard-dose HMA treatment in lower-risk MDS remains controversial. Patients and methods: The Korea University MDS registry is a longitudinal cohort that contains data on 452 patients consecutively diagnosed with MDS from October 2006 to December 2017 in Korea University Medical Center (Korea University Anam, Guro, and Ansan Hospital). In the Korea University MDS registry, 357 patients were classified as having lower-risk MDS. Among them, 115 patients were treated with HMA (decitabine or azacitidine); 111 patients were eligible for the study. We compared treatment responses, survival outcomes, and adverse events between standard-dose decitabine (20 mg/m2 daily for 5 days every 4 weeks) and azacitidine (75 mg/m2 daily for 7 days every 4 weeks) in lower-risk MDS patients. Treatment responses were assessed according to the modified 2006 International Working Group response criteria. Patients who were evaluated received at least one cycle of HMA therapy. The overall response rate (ORR) included complete remission (CR), partial remission, marrow CR, and hematologic improvement. Progression-free survival (PFS) was measured from the time of treatment initiation until disease progression or death from MDS. Results: The CR rates were 16.4% (10/61) in the decitabine group and 6.0% (3/50) in the azacitidine group with borderline significance (P = .090). The ORRs were 67.2% (41/61) and 44.0% (22/50) for decitabine and azacitidine, respectively (P = .014). The erythroid responses for decitabine and azacitidine were 68.3% (41/60) and 44.2% (19/43), respectively (P = .014). In the multivariable analysis, treatment with decitabine (hazard ratio [HR] 2.553; 95% confidence interval [CI] 1.116-5.840; P = .026), hemoglobin (Hb) concentration of <8 g/dL (HR 3.073; 95% CI 1.340-7.048; P = .008), and ≥5% BM blasts (HR 3.739; 95% CI 1.102-12.683; P = .034) were significantly associated with higher ORRs. The median progression-free survival was significantly better in patients treated with decitabine than in those treated with azacitidine (33 vs. 19 months; P = .019). There were no significant differences in the event-free survival and in the overall survival between the two HMAs. In the multivariable analysis, treatment with decitabine (HR 0.496; 95% CI 0.257-0.957; P = .037) and achievement of CR (HR 0.122; 95% CI 0.015-0.993; P = .049) were significant prognostic factors for better survival, whereas ANC below 0.8 × 109/L (HR 1.905; 95% CI 1.032-3.515; P = .039) was a significant prognostic factor for poor prognosis. The poor cytogenetic risk group, as classified by International Prognostic Scoring System (HR 2.136; 95% CI 0.992-4.556; P = .052), also affected the survival unfavorably with borderline significance. There were no significant differences in grade 3 or higher hematologic adverse events between the two HMAs. Conclusions: The standard-dose decitabine therapy showed significantly better ORR, erythroid response, and longer PFS than did standard-dose azacitidine in patients with lower-risk MDS. The frequencies of hematologic adverse events did not differ between the patients who received decitabine and those who received azacitidine. Disclosures No relevant conflicts of interest to declare.

Introduction Immune thrombocytopenic purpura (ITP) is known as an acquired, immune-mediated disease characterized by isolated thrombocytopenia. Many studies have asserted that a diagnosis of ITP does not require a routine bone marrow examination. However, bone marrow examination is necessary in many cases because the diagnosis of ITP requires exclusion of other diseases including bone marrow disease. As both physicians and patients are reluctant to perform an invasive bone marrow examination, other parameters, including the immature platelet fraction (IPF, %), have been incorporated into the differential diagnosis of thrombocytopenia. In this study, we assessed its usefulness of IPF as a diagnostic marker and developed a diagnostic predictive model for ITP. Methods We retrospectively analyzed 330 patients with thrombocytopenia (platelet count < 100 x 109/L) who presented to Korea University Guro hospital between April 2013 and December 2017. We classified patients into 2 groups: those diagnosed with ITP (ITP group) and those without ITP (non-ITP group). ITP was diagnosed on the basis of clinical manifestations and laboratory results according to International Working Group diagnostic criteria. Non-ITP group included thrombocytopenia due to bone marrow disease, infection, drug, liver disease, etc. We used an automated hematologic analyzer (Sysmex XE-2100) to quantify the IPF and estimated other laboratory variables, including hemoglobin, platelet, white blood cell counts, reticulocytes, protein, albumin, bilirubin, pro-thrombin, activated partial thromboplastin time, ferritin, lactate dehydrogenase, blood urea nitrogen, creatinine, and C-reactive protein. All data were statistically analyzed using SPSS version 20. Logistic regression analysis was performed with the laboratory variables to access their diagnostic contribution. We used receiver-operating characteristic (ROC) and the point with the highest sum of sensitivity and specificity on the ROC curve was determined as the cut-off value of each variables. P-values < 0.05 were considered statistically significant. Results A total of 103 and 227 patients were diagnosed as ITP and non-ITP. The median IPF is significantly higher in ITP group, with a value of 10.5% (1.3-48%) vs. 5.9% (0.7-31.5%) in the non-ITP group, and cut-off value for differentiation of ITP was 7.0% with a sensitivity of 64.8% and a specificity of 65.2%. Since ITP remains a diagnosis of exclusion, some patients who did not undergo a bone marrow examination might have been misclassified into the ITP group. To exclude the possibility of misclassification, we conducted a subgroup analysis of only patients who had undergone a bone marrow examination (BM group). A total of 162 patients performed bone marrow examination, 47 and 115 were classified into the ITP and non-ITP group. The median IPF was significantly higher in ITP group, with a value of 13.6% (4.3-38.5%) vs. 4.7% (0.7-31.5%) for the non-ITP group. The cut-off value was 9.25%, with a sensitivity of 78.7% and a specificity of 78.3%. The median IPF was higher in this subgroup and the sensitivity and specificity of the cut-off value were also higher than the former group. (Figure 1) We confirmed that IPF could be a useful parameter for diagnosing ITP, but since IPF alone could not diagnose ITP, we also evaluated other laboratory variables by the logistic regression analysis. Hemoglobin, ferritin showed statistical significance, and the optimal cut-off value was 12 g/dl and 175 mg/ml. To adequately reflect sensitivity and specificity, we divided patients into 3 groups according to IPF; IPF<5, ≥5 and <10, ≥10. We developed simple diagnostic predictive model with these variables. Our model gave point to each of variables; 1 to high hemoglobin level (>12g/dl), low ferritin level (<175ng/ml) and IPF ≥5 and <10, 2 to IPF ≥10. The final score was obtained by summing the points. We demonstrated that ITP could be highly predicted in patients with score 3-4 (80% in all patients group, 89% in BM group) and could be excluded in patients with score 0-1 (95% in all patients group, 97% in BM group). (Table 1) Conclusions The results showed that IPF could be a good diagnostic marker for ITP. We suggested the diagnostic predictive model for ITP using IPF, hemoglobin and ferritin. This model could diagnose ITP with high probability and avoid a bone marrow examination. Further studies would be needed to refine and validate this predictive model. Disclosures No relevant conflicts of interest to declare.

Purpose Autologous stem cell transplantation (ASCT) is widely used as a part of induction treatment for transplantation-eligible patients with multiple myeloma. For successful ASCT, mobilizing hematopoietic stem cells from bone marrow to peripheral blood is essential because collecting a sufficient number of stem cells using apheresis is mandatory. As a method for mobilization, chemomobilization consisting of high-dose chemotherapy plus granulocyte-colony stimulating factor (G-CSF) or G-CSF alone (G-mobilization) has been used. However, the mobilization failure still remains a problematic issue. Given repeated mobilization attempts increase medical costs and the risk of morbidity related with apheresis, the mobilization process should be efficient. Chemomobilization is more effective than G-mobilization, however, chemomobilization has the risk of complication such as febrile neutropenia or chemotherapy-induced second malignancy. Thus, we compared the efficacy and safety of our new chemomobilization regimen, one-day low-dose etoposide with that of two-day low-dose etoposide, one-day high-dose cyclophosphamide, and G-mobilization. Methods We retrospectively analyzed 234 patients who underwent ASCT for MM between 2008 and 2018 in four tertiary hospitals in Korea. One-day low-dose etoposide regimen (E1) was the intravenous (IV) administration of etoposide (375 mg/m2) over 4 hours whereas two-day low-dose etoposide (E2) was the same dose of etoposide on 1st and 2nd day in outpatient clinic. G-CSF administration was started around on 10th day until the end of collection. In G-mobilization regimen (G), the injection of G-CSF was started four days (day -4) before initiation of apheresis (day 0), and G-CSF once a day was maintained untill the end of collection. One-day high-dose cyclophosphamide regimen (C) was the IV administration of cyclophosphamide (3.5 g/m2) on 1st day and the daily injection of G-CSF from 2nd day until the end of stem cell collection. Peripheral blood stem cell collection was started when CD34-positive cells or hematopoietic progenitor cells were more than 5000/μL in peripheral blood, or white blood cell count was more than 5000/μL. In this study, we defined the 'adequate mobilization' as CD34-positive cells more than 4ⅹ106/kg, and 'mobilization failure' as a collected CD34-positive cells less than 2ⅹ106/kg. Neutrophil and platelet engraftment was defined as more than 500/μL and 20,000/μL on consecutive two days, respectively. Results 31 patients received single dose etoposide (E1) between 2016 and 2018 whereas 28 patients received double dose etoposide (E2) between 2011 and 2018. The other two regimens were used in 105 (C, 2008-2015) and 70 patients (G, 2008-2017) according to physicians' decision. The comparison of four regimens showed the median CD34-positive cells of E1 regimen was 5.57ⅹ106/kg that was comparable to that of E2 and C (Table 1). The number of CD34-positive cells on 1st day of apheresis was 4.03ⅹ106/kg in E1 regimen, and it was higher than that of C and G (3.32 and 1.79ⅹ106/kg, respectively). As a result, E1 regimen achieved 'adequate mobilization' in 100% of patients (n=30) like E2 regimen (n=28, 100%). Mobilization failure did not occur in E1 and E2 regimens whereas 4-10% of patients experienced mobilization failure in C and G regimens (Table 1). All patients receiving E1 and E2 regimen but one patient in E1 could collect more than 4ⅹ106/kg of CD34-positive cells within three cycles of apheresis. The occurrence of febrile neutropenia was extremely lower in E1 regimen (7%) than E2 and C regimens (43% and 34%, respectively, p<0.001). Both neutrophil and platelet engraftment were the fastest in E1 (the median 9 days after ASCT, p<0.001). Conclusions One-day low-dose etoposide administration could be effective for chemomobilization in myeloma patients with reduced risk of complication compared to two-day low-dose etoposide, high-dose cyclophosphamide and G-mobilization. Table 1. Table 1. Disclosures No relevant conflicts of interest to declare.