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Venous thromboembolism (VTE), which includes pulmonary embolism and deep vein thrombosis, is a condition characterized by abnormal blood clot formation in the pulmonary arteries and the deep venous vasculature. It is often serious and sometimes even fatal if not promptly and appropriately treated. Moreover, the later consequences of VTE may result in reduced quality of life. The treatment of VTE depends on various factors, including the type, cause, and patient comorbidities. Furthermore, bleeding may occur as a side effect of VTE treatment. Thus, it is necessary to carefully weigh the benefits versus the risks of VTE treatment and to actively monitor patients undergoing treatment. Asian populations are known to have lower VTE incidences than Western populations, but recent studies have shown an increase in the incidence of VTE in Asia. A variety of treatment options are currently available owing to the introduction of direct oral anticoagulants. The current VTE treatment recommendation is based on evidence from previous studies, but it should be applied with careful consideration of the racial, genetic, and social characteristics in the Korean population.

Background Hematopoietic stem cell transplantation (HSCT) patients usually experience mucositis, musculoskeletal pain associated with high-dose chemotherapy, radiation, post-HSCT infection, or graft-versus-host disease. Pain management is important for the patients' quality of life. We evaluated appropriate opioid analgesic use in HSCT patients to propose effective pain management strategies. Methods A retrospective analysis was conducted using electronic medical records of adult patients with HSCT treated with opioids for moderate to severe pain at Seoul National University Bundang Hospital. The numeric rating scale (NRS) was used in pain management. NRS scores of 4‒10 correspond to moderate to severe pain. Appropriate opioid analgesic use was evaluated following published cancer pain management guidelines. Results In total, 119 cases were evaluated, including 369 episodes of moderate to severe pain. Mucositis-related, musculoskeletal, and headache pain occurred in 62.6%, 25.8%, and 6.0% of episodes, respectively. Frequently used opioids were intravenous tramadol (84.9%), fentanyl patch (73.9%), and intravenous morphine sulfate (68.9%). Intravenous and topical administrations were used for mucosal pain. In total, 95.0% of patients received appropriate short-acting opioids for initial pain management, 80.5% received appropriate doses of short-acting opioids, appropriate opioids dose adjustment was done after first assessment in 95.5% of patients, and 85.6% were converted to appropriate long-acting opioids. Conclusion Short-acting opioid analgesic use for initial pain management and dose adjustment after assessment were appropriate. However, initial and conversion dosages recommended by guidelines may be difficult to implement considering the severity of HSCT patients. Pain management guidelines specific for HSCT patients should be developed in the future.

Background Although T-cell-replete hematopoietic cell transplantation (HCT) from haploidentical donors (HIDs) using anti-thymocyte globulin (ATG) has shown promising outcomes, previous studies often adopted heterogenous graft sources and conditioning. Methods We retrospectively compared HCT outcomes from 62 HIDs, 36 partially-matched unrelated donors (PUDs), and 55 matched unrelated donors (MUDs) in patients with acute leukemia or myelodysplastic syndrome using the same graft source of peripheral blood and a reduced intensity conditioning of busulfan, fludarabine, and ATG. Results The estimates of 3-yr disease-free survival (DFS) and overall survival (OS) rates were not significantly different among the MUD, HID, and PUD groups, at 46%, "41%, and 36%" for the DFS rate (P=0.844), and 55%, 45%, and 45% for the OS rate (P=0.802), respectively. Cumulative incidence of relapse and non-relapse mortality at 3 yr was similar among different donor types. Subsequent multivariable analyses showed that the sex of the patient (male) and a high/very high disease risk index were independently associated with poorer DFS and OS, while the donor type was not. Conclusion T-cell replete HCT from HIDs using an ATG-containing reduced intensity conditioning regimen may be a reasonable option in the absence of matched related donors in patients with acute leukemia or myelodysplastic syndrome.

Background Hematopoietic stem cell transplantation (HSCT) patients need parenteral nutrition because of nausea, vomiting, and mucositis caused by conditioning regimens. The demand for glutamine increases during the HSCT period. We evaluated the effects of glutamine-containing parenteral nutrition on the clinical outcomes of HSCT patients. Methods In this retrospective analysis, we reviewed HSCT patients from Seoul National University from August 2013 to July 2017. Depending on their glutamine supplementation status, 91 patients were divided into 2 groups: glutamine group (N=44) and non-glutamine group (N=47). We analyzed the rate of weight change, infection (clinically/microbiologically documented), complications (duration of mucositis and neutropenia, acute graft versus host disease), and 100-days mortality in each group. Results Regarding the clinical characteristics of the patients, there were no significant differences between the 2 groups except that there was a larger proportion of myeloablative conditioning regimen in the glutamine group (P=0.005). In the glutamine group, the average number of days of glutamine use, parenteral nutrition, and mucositis was 7.6±1.4, 14.6±9.9, and 13.3±9.5, respectively. Furthermore, multivariate analysis revealed odds ratios of 0.37 (95% CI, 0.14–0.96; P=0.042) and 0.08 (95% CI, 0.01–0.98; P=0.048) for clinically documented infection and 100-days mortality, respectively, in the glutamine group. Conclusion Results showed that the glutamine group had less clinically documented infection and 100-days mortality than the non-glutamine group, but the other outcomes did not show significant differences. The extended duration of glutamine supplementation according to the period of total parenteral nutrition and mucositis should be considered.

Management options for patients with immune thrombocytopenia (ITP) have evolved substantially over the past decades. The American Society of Hematology published a treatment guideline for clinicians referring to the management of ITP in 2011. This evidence-based practice guideline for ITP enables the appropriate treatment of a larger proportion of patients and the maintenance of normal platelet counts. Korean authority operates a unified mandatory national health insurance system. Even though we have a uniform standard guideline enforced by insurance reimbursement, there are several unsolved issues in real practice in ITP treatment. To optimize the management of Korean ITP patients, the Korean Society of Hematology Aplastic Anemia Working Party (KSHAAWP) reviewed the consensus and the Korean data on the clinical practices of ITP therapy. Here, we report a Korean expert recommendation guide for the management of ITP.

Background Bendamustine may be a potential treatment option for patients with myeloma, but little is known about the utility of bendamustine as a salvage treatment, especially in Asian patients. Methods We performed a multicenter retrospective study of patients with relapsed or refractory myeloma who received bendamustine and prednisone. Results The records of 65 heavily pre-treated patients, who had undergone bortezomib and lenalidomide treatment (median number of previous treatments: 5), were analyzed. The median time from diagnosis to bendamustine treatment was 3.8 years, and the median patient age was 63 years (range, 38‒77 yr). The responses to the last treatment before bendamustine were refractory disease (N=52, 80%) or disease progression from partial response (N=13, 20%). Twenty-three patients responded to the treatment, with an overall response rate of 35% (23/65), and the median number of bendamustine treatment cycles was two (range, 1‒5 cycles). The median overall survival after bendamustine treatment was 5.5 months and the overall survival rate in responders to bendamustine was significantly better than that in non-responders (P=0.036). Conclusion Bendamustine may be a potential salvage treatment to extend survival in a select group of heavily pre-treated patients with relapsed or refractory myeloma.

Multiple myeloma (MM) is the third most common hematologic malignancy in Korea. Historically, the incidence of MM in Korea has been lower than that in Western populations, although there is growing evidence that the incidence of MM in Asian populations, including Korea, is increasing rapidly. Despite advances in the management of MM, patients will ultimately relapse or become refractory to their current treatment, and alternative therapeutic options are required in the relapsed/refractory setting. In Korea, although lenalidomide/dexamethasone is indicated for the treatment of relapsed or refractory MM (RRMM) in patients who have received at least one prior therapy, lenalidomide is reimbursable specifically only in patients with RRMM who have failed bortezomib-based treatment. Based on evidence from pivotal multinational clinical trials as well as recent studies in Asia, including Korea, lenalidomide/dexamethasone is an effective treatment option for patients with RRMM, regardless of age or disease status. Adverse events associated with lenalidomide/dexamethasone, including hematologic toxicity, venous thromboembolism, fatigue, rash, infection, and muscle cramps, are largely predictable and preventable/manageable with appropriate patient monitoring and/or the use of standard supportive medication and dose adjustment/interruption. Lenalidomide/dexamethasone provides an optimal response when used at first relapse, and treatment should be continued long term until disease progression. With appropriate modification of the lenalidomide starting dose, lenalidomide/dexamethasone is effective in patients with renal impairment and/or cytopenia. This review presents updated evidence from the published clinical literature and provides recommendations from an expert panel of Korean physicians regarding the use of lenalidomide/dexamethasone in patients with RRMM.

TO THE EDITOR: Heparin-induced thrombocytopenia (HIT) is a significant complication of heparin therapy. Risk factors for HIT include the type of heparin used, duration of heparin exposure, and clinical setting. Here, we report a 76-year-old man who presented with life-threatening pulmonary thromboembolism and deep-vein thrombosis, preceded by a dramatic decrease in platelet count 1 week after radical cystectomy for transitional cell bladder carcinoma. He was diagnosed with type II HIT caused by a small amount of unfractionated heparin mixed into his total parenteral nutrition (TPN) solution. One thousand units heparin per day were added to his TPN for 1 week. A heparin-platelet factor-4 antibody enzyme-linked immunosorbent assay of his serum was strongly positive. After cessation of TPN infusion, argatroban was started for thrombosis. His platelet count gradually increased to a normal level, and the thrombosis was treated successfully. This case suggests HIT should be suspected in patients with typical clinical manifestations and risk factors, even if the infused heparin dose is small. Heparin is widely used in a variety of medical therapies from the treatment of life-threatening acute thromboembolisms to the maintenance of indwelling vascular catheter patency. However, heparin therapy is often complicated by thrombocytopenia. The incidence of heparin-induced thrombocytopenia (HIT) in patients who receive heparin including unfractionated heparin and low-molecular-weight heparin is 0.1-5% [1]. There are 2 types of HIT. Type I HIT is a relatively common non-immune reaction that causes an asymptomatic, transient, and mild decrease in platelet count. In contrast, type II HIT is an immune complex disorder involving heparin bound to the platelet-specific chemokine, platelet factor-4 (PF4). These heparin-PF4 complexes activate both platelets and endothelial cells, resulting in platelet consumption and endothelial injury with thrombosis and disseminated intravascular coagulation [2]. Heparin use could go unnoticed if it is not applied as a conventional anticoagulant but rather as a supportive agent to maintain vasc,ular patency. However, unrecognized HIT can lead to life-threatening complications. Therefore, it is important to suspect HIT in patients who develop acute thrombosis or thrombotic tendency preceded by a decrease in platelet count during or soon after heparin therapy, even if the infused amount is small. Immediate discontinuation of heparin administration and initiating alternative anticoagulant therapy are critical for avoiding further thrombosis, even before laboratory results are available [3]. To the best of our knowledge, this is the first report on a patient who experienced type II HIT after low-dose heparin added to his total parenteral nutrition (TPN) for 1 week.

Donor Lymphocyte Infusions for Patients with Relapsed Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: a 10-year Experience of Seoul National University Hospital Jin Won Kim, Byung-Su Kim, Dae-Young Kim, Ki Hwan Kim, Ji Young Rhee, Soo-Mee Bang, Inho Kim, Sung-Soo Yoon, Jong-Seok Lee, Seonyang Park and Byoung Kook Kim Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, Department of Internal Medicine, Seoul Municipal Boramae Hospital, Seoul, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

The myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis associated with multilineage cytopenias leading to serious morbidity or mortality, and the additional risk of leukemic transformation. The management of patients with MDS can be very complex and varies according to both the clinical manifestations in individual patients as well as the presence of complicating medical conditions. However, therapeutic dilemmas still exist for MDS due to the multifactorial pathogenetic features of the disease, its heterogeneous stages, and the elderly patient population. For these reasons, proper guidelines for management are necessary. This review describes the proper diagnosis for MDS, decision-making approaches for optimal therapeutic options that are based on a consideration of patient

Multiple myeloma is a hematologic neoplasm with a unique and characteristic manifestation. This con- dition is responsible for 10% of hematologic malignancies, and thus represents 1% of all cases of cancer in the US. In Korea, unlike in Western society, myeloma has classically been relatively rare, due in part to racial differences. However, the incidence of this disease in Korea has increased steadily over the last 25 years. During this period, both the incidence of and mortality due to myeloma increased by up to 30-fold. Currently, incidence rate and mortality rate exceed 1.0/100,000. Possible reasons for this increase include better detection, as well as an actual increase, probably attributable to contributing factors, including pollution, exposure to chemicals, and socioeconomic change, all of which are related to rapid industrialization. Aging is another important factor contributing to this perceived increase. With the advent of targeted therapy, Korean myeloma study group was organized under the auspice of Korean society of hematology. In addition, Korean myeloma registry was established recently. In this study, epide- miological changes in the incidence and mortality of multiple myeloma in Korea are assessed and compared with the situations of the US and Japan. This article also claims the need for multicenter clinical trials as well as activation of basic researches in myeloma. (Korean J Hematol 2006;41:225-234.)

Background: Essential thrombocythemia (ET) has a chronic course, but its main clinical features are thrombosis and hemorrhage. We evaluated the clinical features, including the vascular complications in patients with ET, during the disease courses and we determined the predictable risk factors for major vascular complications. Methods: From 1991 to 2004, the medical records for 69 patients with ET were retrospectively reviewed for evaluating the clinical features, including the vascular complications, and the predictable risk factors for major vascular complications were analyzed. Results: Major vascular thrombotic and hemorrhagic complications were observed in 16 patients (23.2%) and 6 patients (8.7%) at the time of diagnosis, and in 13 (18.8%) and 9 patients (13.0%) during follow-up. The incidence of major vascular thromboses in the older group (age >60 years) was higher than that in the younger group (≤60 years) (34.2% vs 9.7%, respectively, P=0.016) at the time of diagnosis. During follow-up, the major vascular thrombosis risk was increased in patients with a previous thrombosis history (37.5% vs 13.2%, respectively, P=0.029) and in patients with 2 or more combined cardiovascular risk factors (44.4% vs 15.0%, respectively, P=0.035). The probability of 10-year survival in patients with thrombo-hemorrhagic complications during the disease course was lower than that in patients without complication (60.5% vs 93.7%, respectively, P=0.046). Conclusion: Advanced age, a previous thrombosis history and the combined cardiovascular risk factors were the risk factors for major vascular thrombosis in patients with ET. Prevention of thrombo-hemor- rhagic complications is the most important therapeutic goal. Treatment strategies according to risk factors ought to be prospectively investigated.

Background: The aims of this study were to find the incidence and clinical features of Heparin-induced thrombocytopenia (HIT) in acute coronary syndrome patients treated with unfractionated heparin. Methods: The medical records of 554 patients treated with unfractionat ed heparin (UFH) for their coronary artery diseases at the Gachon Medical School Gil Heart Center during 2002~2003. were retrospectively reviewed. The gourp eligible group inclusion in this study was comprised of 338 patients with acute coronary syndrome Results: The median duration of UFH administration was 6 days, ranging from 1 to 22 days. Among the eligible patients, 40 (11.8%) received UFH for >96 hours, and developed thrombocytopenia, which involved a platelet count decrease to less than 100,000 per cubic millimeter or a 50% or greater decrease in the platelet count. Conclusion: Despith the limitations of retrospective analyses, the present study shows that thrombocy- topenia is relatively common in acute coronary syndrome patients treated with UFH, but did not account for HIT associated complication, such as thrombosis. When clinicians recognize the development of HIT without a thrombocytopenia related disease, many will stop the use of heparin for its management.

The Clinical Efficacy of Helicobacter pylori Eradication in Patients with Helicobacter pylori-positive Chronic Thrombocytopenic Purpura Bong-Seog Kim, M.D., Seung-Hyun Nam, M.D., Soo-Mee Bang, M.D., Jae Hoon Lee, M.D., Young Rok Do, M.D. , Ki Young Kwon, M.D., Hong Suk Song, M.D., Hun Mo Ryoo, M.D., Sung Hwa Bae, M.D., Min Kyoung Kim, M.D. , Kyung Hee Lee, M.D., Myung Soo Hyun, M.D., Young Jin Yuh, M.D., Eunkyung Park, M.D., Sang-Jae Lee, M.D., Sung-Soo Yoon, M.D., Seonyang Park, M.D. and Byoung Kook Kim, M.D.