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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.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.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.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.

Epstein-Barr virus-infected B cells are found at high frequency in peripheral T cell lymphoma. Herein, we report a case involving excessive EBV-positive B cells accompanying peripheral T cell lymphoma, not otherwise specified in the nasopharynx masquerading as nasopharyngeal extranodal NK/T cell lymphoma. A large number of Epstein-Barr virus-infected B cells infiltrate in between CD3-positive cytotoxic tumor T cells, as if EBV was infecting tumor T cells. After chemotherapy, the T cell lymphoma population decreased, but the B cell population expanded to form EBV-positive diffuse large B cell lymphoma in the tonsils and nasopharynx. At the follow-up, bone marrow biopsy exhibited infiltration of composite peripheral T cell lymphoma, not otherwise specified, and EBV-positive diffuse large B cell lymphoma. Although this condition is rare, the cell lineage of EBV-infected cells must be confirmed when diagnosing extranodal NK/T cell lymphoma to exclude the possibility of misdiagnosis by Epstein-Barr virus-infected B cells.

Composite lymphoma is very rare and a combination of Hodgkin lymphoma and non-Hodgkin lymphoma and even histiocytic tumors can occur. Because of the unfamiliarity, not only can this cause diagnostic problems, but can also affect treatment plan. We report a case of composite lymphoma in a 40-year-old male. Initial biopsy showed a composite lymphoma of follicular lymphoma grade 1 and classic Hodgkin lymphoma. After chemotherapy, another lymph node was taken because of disease progression, which revealed follicular lymphoma, grade 3a without Hodgkin lymphoma component.

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.Conclusions: 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.

Background/aims Nilotinib is used for treating patients with imatinib-sensitive or -resistant chronic myeloid leukemia (CML); however, nilotinib-resistant cases have been observed in recent years. In addition, a considerable number of patients receiving nilotinib developed diabetes. Metformin is a front-line drug for the treatment of type 2 diabetes, and several studies have shown that diabetes patients treated with metformin have reduced incidence of cancer. This study aimed to define the effect of metformin on CML cells to determine whether metformin overcomes nilotinib resistance, and to identify novel targets for the treatment of nilotinib resistance. Methods We observed the effects of metformin and nilotinib on K562 and KU812 human CML cell lines. Nilotinib-resistant CML cell lines were generated by exposing cells to gradually increasing doses of nilotinib. Then, we investigated the driving force that makes resistance to nilotinib and the effect of metformin on the driving force. Results Sub-toxic doses of metformin enhanced nilotinib efficacy by reducing Bcl-xL expression, which induces apoptosis in CML cells. Next, we generated nilotinib-resistant K562 and KU812 cell lines that overexpressed the c-Jun N-terminal kinase (JNK) gene. JNK silencing by a JNK inhibitor restored sensitivity to nilotinib. Furthermore, metformin was effective in decreasing phosphorylated JNK levels, restoring nilotinib sensitivity. Combined treatment with nilotinib and metformin was more effective than combined treatment with nilotinib and a JNK inhibitor in terms of cell proliferation inhibition. Conclusion This study suggested that combination therapy with metformin and nilotinib may have clinical benefits of enhancing antileukemia efficacy and overcoming resistance to nilotinib.

Three new selenophene-based conjugated copolymers having different ratios of the monomeric units were designed, synthesized and thoroughly characterized. The introduction of an electron-poor and surfaced building moiety like selenathiazole was highly efficient in tuning the bandgap and polymer properties. The chalcogenophene-based medium-bandgap polymers demonstrated low-lying HOMO energy levels (∼5.87 eV), which is benign for use in multi-junction polymer solar cell applications. The representative polymers with heavy atoms revealed the change in electronegativity and atomic size that highly affected the molecular property, its topological features, and photovoltaic properties in polymer solar cells. The selenium-substituted (0.5:0.5) polymer donors showed power conversion efficiencies above 3% when combined with [6,6]-phenyl-C71-butyric acid methyl ester (PC70BM) acceptors in a quintessential bulk-heterojunction solar cell.

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, 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.

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 de layed. Therefore, novel diagnostic parameters are needed to distinguish ITP from other causes of thrombocytopenia. Immature platelet fraction (IPF) has been pro posed 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 anal ysis. 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. Conclusions: IPF could be a useful parameter to distinguish ITP from other caus es of thrombocytopenia. We developed the predictive scoring model. This model could predict ITP with high probability.

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.

BackgroundCereblon (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.MethodsWe 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.ResultsIn 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 β2-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.ConclusionThis 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.

BACKGROUND Single-dose etoposide was used an outpatient-based protocol for mobilization in patients with multiple myeloma (MM) for autologous stem cell transplantation (ASCT). Thus, we retrospectively analyzed the efficacy and safety of our one-day protocol in comparison with that of previous methods. METHODS We retrospectively analyzed 168 patients with MM who underwent peripheral blood stem cell collection for upfront ASCT between 2008 and 2018. The mobilization protocols included G-CSF alone (G-mobilization), one-day 375 mg/m2 of etoposide (E375), two-days of 375 mg/m2 of etoposide (E750), or one-day high-dose (3.5 g/m2 ) cyclophosphamide (HD CY). For comparison of efficacy of each protocol, collected CD34+ cells over 4 × 106 /kg and under 2 × 106 /kg were defined as "adequate harvest" and "harvest failure," respectively. RESULTS The median number of collected CD34+ cells was 5.58 × 106 /kg in patients receiving single-dose etoposide, and the percentage of uncomplicated optimal harvest of E375 (65.6%, 21/32) was significantly higher than that of E750 (41.9%, 13/31) and HD CY (31.3%, 15/48). The E375 showed the highest rate of adequate harvest (96.9%, 31/32) compared to that of E750 (87.1%), HD CY (75.0%), and G-mobilization (59.6%). Most E375 patients achieved adequate harvest without complication (29/32, 90.6%), the CD34+ cell collection yield on apheresis days one and two of E375 was not significantly different from that of E750, and no harvest failures occurred for E375. Neutrophil and platelet engraftments were significantly faster in E375 than other groups (P

목적: 비호지킨림프종 환자를 위한 병기 설정 검사는 골수흡인 검사와 골수 조직 검사의 방법으로 시행하게 된다. 두 가지 검사 결과가 일치하면 골수 침범 여부가 명백하나골수흡인 검사에서만 양성이 나온 경우는 가이드라인이 없으며 임상적으로 논란의 여지가 있다. 따라서 본 연구에서는 이러한 환자군에 대하여 임상 적용에 필요한 생존율을 형태학적인 방법으로 비교 분석함으로써 임상적으로 고려해야 할 사안을 검토하는 것으로 하였다. 방법: 본 연구는 고려대학교의료원의 림프종 레지스트리에 1991년부터 2016년까지 등록된 환자를 대상으로 하여 대상군은 골수비침습군(BMA-/BMBx-), 흡인 검사에서만 양성이고 조직 검사에서는 음성이 나온 군(BMA+/BMBx-), 조직검사에서 골수 침범이 확인된 군(BMBx+)으로 구분하였으며 카플란-마이어 생존분석과 다변량 분석을 사용하였다. 결과: 환자군은 총 1,735명 중에서 불충분한 결과를 가진 409명을 제외하고 1,326명을 대상으로 하였다. 카플란-마이어 생존분석에서 BMBx+군은 BMA-/BMBx-군과 비교하여 유의하게 좋지 않은 생존율을 보였으나(p < 0.001) BMA+/BMBx-와 다른 군 간의 전체 생존율에 대한 유의한 차이는 없었다 (vs. BMA-/BMBx-, p = 0.163; BMBx+, p = 0.292). 그러나 다른 생존율과 관련된 인자들을 보정한 다변량 분석에서 BMA+/BMBx-는 BMA-/BMBx-에 비하여 경계선 상의 유의성을 보여주었으며(p = 0.081) 이는 특히 지연성 비호지킨림프종 환자의 서브그룹 분석에서는 유의한 차이를 나타냈다 (p = 0.003). 결론: 비호지킨림프종 환자에서 골수흡인 검사에서만 양성이 나오더라도 불량한 예후를 시사하고 있음을 인지하고 주의를 기울이는 것이 중요하다 하겠다.

AimGene expression analysis facilitates the detection of diagnostic and prognostic biomarkers for myeloid haematological malignancies. The Oncomine Myeloid Research Assay (OMA; Thermo Fisher Scientific, Massachusetts, USA) provides a comprehensive analysis of gene expression of five target genes, along with gene alteration and fusion. Here, we present the performance of the OMA for gene expression analysis.MethodsIn total, 53 RNA samples from patients diagnosed with acute myeloid leukaemia (AML) or myelodysplastic syndrome were included. Of these 53 samples, 3 were evaluated for reproducibility and 50 were evaluated for comparison with RNA-sequencing (RNA-seq). The prognostic impact of the gene expression profile produced by both OMA and RNA-seq in AML was investigated using follow-up data from 33 patients with AML.ResultsThe OMA showed good intrarun and interrun reproducibility. Compared with the RNA-seq results, high correlations were found in BAALC, MECOM and WT1 (all r>0.9), with moderate correlations in MYC (r=0.75, pSMC1A (r=0.42, p=0.002). The agreement between OMA and RNA-seq in classifying the dysregulated expression group was almost perfect, except for SMC1A (κ=0.175). Among these five genes, only BAALC showed a significant clinical impact in patients with AML. Patients with high BAALC expression showed significantly shorter overall survival based on both OMA (p=0.037) and RNA-seq (p=0.003).ConclusionsOMA gene expression analysis offers reproducible and accurate gene expression data for most targeted genes and demonstrates the utility of BAALC expression as a prognostic marker in AML.

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.

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.

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.

Background/aim Exosomes, derived from chronic myelogenous leukaemia (CML) cells, can be used as biomarkers and new targets for the detection of the BCR-ABL transcript. This study aimed to identify these possibilities. Materials and methods Human CML cell line-derived exosomes and CML-patients-derived exosomes were isolated with a size-exclusion chromatography column and ExoQuick™ exosome precipitation solution, respectively. Isolated exosomes were analysed by nested PCR to detect the BCR-ABL transcript. Results Exosomes derived from the two human CML cell lines yielded a 250-bp band. RNA sequence analysis revealed 99% sequence homology with the partial mRNA for the human BCR-ABL chimeric protein. This ~250-bp band was also observed in the exosomes derived from patients with CML. However, only patients at the blast and accelerated phases showed the exosomal BCR-ABL transcript. Conclusion CML-derived exosomes could act as novel targets for the detection of the BCR-ABL transcript.

Surveillance computed tomography (CT) is usual practice for patients with aggressive non-Hodgkin lymphoma (aNHL) in complete remission (CR). However, evidence to support this strategy is lacking. We retrospectively analyzed our institutional lymphoma registry, including patients with lymphoma consecutively enrolled from June 1995 to October 2016. Of 1,385 patients with aNHL, 664 achieved CR and were followed up with or without surveillance CT. Surveillance CT was performed for 609 patients every 3 or 6 months for the first 2 years, then every 6 or 12 months thereafter. Relapse was detected in 171 patients, of whom 152 underwent surveillance CT during follow-up. Of these 152 patients, asymptomatic relapse was detected in 67 (44%) using surveillance CT, and symptomatic relapse outside the surveillance interval was detected in the remaining 85 (56%). Detection of asymptomatic relapse using surveillance CT did not improve the overall or post-relapse survival in patients with relapsed aNHL. Surveillance CT interval (3 or 6 months) did not affect survival. No subgroups were identified that favored the use of surveillance CT to detect relapse. The results of this study suggest that routine surveillance CT in patients with aNHL to detect asymptomatic relapse might have a limited role in improving survival. CT is recommended when a relapse is clinically suspected.

728 Copyrightc 2015 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Received: 2014. 8. 14 Revised: 2014. 10. 2 Accepted: 2015. 7. 30

Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis associated with a high mortality rate. Bacterial peritonitis (BP), a complication of EPS treatment, is uncommon, and treatments for BP are not well known. We report two patients who had undergone steroid treatment who developed BP after hemodialysis transfer. In the first case, we treated the BP with antibiotics and performed several surgical drainage procedures; however, the fluid became too thick to drain. This patient died of malnutrition and sepsis. In the second case, antibiotics and surgical enterolysis with peritonectomy were used to treat the BP. Solid food was accepted on day 7 postoperatively, and the patient was stable after 20 months. Thus, surgical enterolysis with peritonectomy may be a good treatment modality for patients with EPS and BP. (Korean J Med 2015;89:346-352)

Background: Despite the advances in acute myeloid leukemia (AML) treatment, the prognosis of elderly patients remains poor and no definitive treatment guideline has been established. In the present study, we aimed to evaluate the effectiveness of intensive chemotherapy in elderly AML patients and to determine which subgroup of patients would be most responsive to the therapy. Methods: We retrospectively analyzed 84 elderly patients: 35, 19, and 30 patients were administered intensive chemotherapy, low-dose chemotherapy, and supportive care, respectively. Results: Among those who received intensive chemotherapy, there were 17 cases of remission after induction chemotherapy; treatment-related mortality was 22.9%. The median overall survival was 7.9 months. Multivariate analysis indicated that the significant prognostic factors for overall survival were performance status, fever before treatment, platelet count, blast count, cytogenetic risk category, and intensive chemotherapy. Subgroup analysis showed that intensive chemotherapy was markedly effective in the relatively younger patients (65-70 years) and those with de novo AML, better-to-intermediate cytogenetic risk, no fever before treatment, high albumin levels, and high lactate dehydrogenase levels. Conclusions: Elderly AML patients had better outcomes with intensive chemotherapy than with low-intensity chemotherapy. Thus, appropriate subgroup selection for intensive chemotherapy is likely to improve therapeutic outcome. © 2014 S. Karger AG, Basel

Purpose Eculizumab is reported to be highly effective in managing patients with paroxysmal nocturnal hemoglobinuria (PNH). However, eculizumab therapy is associated with high cost and thus is inaccessible to all patients with PNH. Additionally, there are some restrictions in the coverage of PNH therapy from the health insurance, which varies depending on each country. In South Korea, majority of the cost involved in eculizumab therapy is supported by the National Health Insurance Service (NHIS) with very limited indication. The patients with PNH must satisfy all of the following criteria to be eligible for financial support from NIHS: (1) PNH granulocyte count ≥ 10%; (2) lactate dehydrogenase ≥ 1.5 times the upper limit of normal; (3) at least 4 units of red blood cells must have be transfused in the past 12 months (transfusion-dependent anemia (TDA)); and (4) exhibit at least more than one of the PNH-related complications (except TDA), which include thrombosis, renal insufficiency, pulmonary insufficiency, or recurrent smooth muscle spasm. These criteria are the narrowest indication for eculizumab therapy compared with those used by other countries. Hence, we performed a nation-wide study including all the patients with PNH in South Korea using the NHIS database to investigate the real-world efficacy of eculizumab. Methods The National Health Insurance Database of the NHIS in South Korea was used to collect the data of patients diagnosed with PNH between January 1, 2002 and December 31, 2016. Propensity score (PS) method was used to evaluate the real-world effects of eculizumab on patient survival. For PS method, the patients with PNH were divided into the following two groups: (1) patients treated with eculizumab; and (2) patients not treated with eculizumab. Additionally, the patients used for the analysis were limited to those who are surviving from the time of introduction of eculizumab in South Korea (October 1, 2012). In total, 11 variables were selected for PS matching according to the indications for using eculizumab in South Korea: age, sex, TDA, venous thrombosis, arterial thrombosis, AA, MDS, acute renal failure (ARF), chronic renal failure (CRF), prescription of opioid analgesic drug (≥ 2 times), and pulmonary hypertension. The patients diagnosed with acute leukemia were excluded. The time point of the matching was designated as the date on which the eculizumab was first administered. All survival or complication analyses were performed using the Cox proportional hazard regression model. The duration of PNH was used as the explanatory variable to estimate the proper treatment effect. Results Eculizumab-treated patients exhibited significantly higher survival rate than the eculizumab-untreated patients (4-year survival after propensity score matching, 98.31% vs. 79.67%, p = 0.0489). The mean RBC transfusion units per 12 months after eculizumab therapy was 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 (p = 0.0078). The 4-year transfusion-independence rate for the eculizumab-treated group was significantly higher than that for the eculizumab-untreated group (20.81%; 95% CI, 10.71-33.20%, vs. 10.24%; 95% CI, 4.17-19.50%). There was no significant difference in the incidence of new documented complications related to PNH between the two groups. These complications include venous thrombosis (p = 0.886), arterial thrombosis (p = 0.112), acute renal failure (p = 0.745), chronic renal failure (p = 0.827), use of opioid analgesics (p = 0.142), and pulmonary hypertension (p = 0.396). Conclusions Eculizumab therapy for high-risk PNH patients may effectively improve the survival rate and reduce the transfusion requirement. Paradoxically, the eculizumab-treated patients with severe PNH exhibit higher survival rate than the eculizumab-untreated patients with less severe PNH. Disclosures No relevant conflicts of interest to declare.

BACKGROUND/AIMS The aims of this study were to identify the value of inflammatory markers as pretreatment prognostic factors for patients with multiple myeloma (MM) and to estimate the value of a prognostic index including these markers at diagnosis. METHODS A total of 273 newly diagnosed MM patients undergoing active treatment were analyzed in this study. The prognostic values for survival of the pretreatment inflammatory markers were investigated. A myeloma prognostic index (MPI) was derived using prognostic factors determined to be independently significant on multivariate analysis. RESULTS A high pretreatment neutrophil-lymphocyte ratio (NLR), low platelet count, and high C-reactive protein (CRP) level had independently unfavorable significance for overall survival (OS). The MPI was derived based on these factors. Per the MPI, 1 point each was assigned to high NLR, low platelet count, and high CRP. Risk categories were stratified into low- (score 0), intermediate- (score 1), and high-risk (score 2 or 3) groups. The MPI demonstrated independent statistical significance for OS on multivariate analysis ([intermediate: hazard ratio (HR), 1.91; 95% confidence interval (CI), 1.12 to 3.24] and [high: HR, 3.37; 95% CI, 2.00 to 5.69]; p < 0.001). Moreover, this significance could be observed regardless of age, renal function, and exposure to novel agents. In addition, the International Staging System risk group could be further significantly stratified using the MPI. CONCLUSIONS The MPI, consisting of pretreatment inflammatory markers, NLR, platelet count, and CRP, might be effective in predicting the survival of newly diagnosed MM patients undergoing active treatment.

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 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.