In-Suk Kim
Blood Res 2020; 55(S1): S19-S26Abstract : Minimal residual disease (MRD) monitoring has proven to be one of the fundamental independent prognostic factors for patients with acute lymphoblastic leukemia (ALL). Sequential monitoring of MRD using sensitive and specific methods, such as real-time quantitative polymerase chain reaction (qPCR) or flow cytometry (FCM), has improved the assessment of treatment response and is currently used for therapeutic stratification and early detection. Although both FCM and qPCR yield highly consistent results with sensitivities of 10‒4, each method has several limitations. For example, qPCR is time-consuming and laborious: designing primers that correspond to the immunoglobulin (IG) and T-cell receptor (TCR) gene rearrangements at diagnosis can take 3‒4 weeks. In addition, the evolution of additional clones beyond the first or index clone during therapy cannot be detected, which might lead to false-negative results. FCM requires experienced technicians and sometimes does not achieve a sensitivity of 10‒4. Accordingly, a next generation sequencing (NGS)-based method has been developed in an attempt to overcome these limitations. With the advent of high-throughput NGS technologies, a more in-depth analysis of IG and/or TCR gene rearrangements is now within reach, which impacts all applications of IG/TR analysis. However, standardization, quality control, and validation of this new technology are warranted prior to its incorporation into routine practice.
Junshik Hong, Seo-Yeon Ahn, Yoo Jin Lee, Ji Hyun Lee, Jung Woo Han, Kyoung Ha Kim, Ho-Young Yhim, Seung-Hyun Nam, Hee-Jin Kim, Jaewoo Song, Sung-Hyun Kim, Soo-Mee Bang, Jin Seok Kim, Yeung-Chul Mun, Sung Hwa Bae, Hyun Kyung Kim, Seongsoo Jang, Rojin Park, Hyoung Soo Choi, Inho Kim, Doyeun Oh; on behalf of the Korean Society of Hematology Thrombosis and Hemostasis Working Party
Blood Res 2021; 56(1): 6-16Abstract : 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.
Sung-Eun Lee
Blood Res 2021; 56(S1): S26-S33Abstract : The identification of driver mutations in Janus kinase (JAK) 2, calreticulin (CALR), and myeloproliferative leukemia (MPL) has contributed to a better understanding of disease pathogenesis by highlighting the importance of JAK signal transducer and activator of transcription (STAT) signaling in classical myeloproliferative neoplasms (MPNs). This has led to the therapeutic use of novel targeted treatments, such as JAK2 inhibitors. More recently, with the development of next-generation sequencing, additional somatic mutations, which are not restricted to MPNs, have been elucidated. Treatment decisions for MPN patients are influenced by the MPN subtype, symptom burden, and risk classification. Although prevention of vascular events is the main objective of therapy for essential thrombocythemia (ET) and polycythemia vera (PV) patients, disease-modifying drugs are needed to eradicate clonal hematopoiesis and prevent progression to more aggressive myeloid neoplasms. JAK inhibitors are a valuable therapeutic strategy for patients with myelofibrosis (MF) who have splenomegaly and/or disease-related symptoms, but intolerance, refractory, resistance, and disease progression still present challenges. Currently, allogeneic stem cell transplantation remains the only curative treatment for MF, but it is typically limited by age-related comorbidities and high treatment-related mortality. Therefore, a better understanding of the molecular pathogenesis and potential new therapies with the aim of modifying the natural history of the disease is important. In this article, I review the current understanding of the molecular basis of MPNs and clinical studies on potential disease-modifying agents.
Zahra Nekoukar, Minoo Moghimi, Ebrahim Salehifar
Blood Res 2021; 56(4): 229-242Abstract : Chronic myeloid leukemia (CML), a myeloproliferative disorder caused by the over activity of BCR-ABL1 (breakpoint cluster region-Abelson), has been successfully treated by Tyrosine kinase inhibitors (TKIs). While imatinib is known as the first-line treatment of CML, in some cases other TKIs including dasatinib, nilotinib, bosutinib, and ponatinib may be preferred. Dasatinib, a second-generation TKI, inhibits multiple family kinases including BCR-ABL, SRC family kinases, receptor kinases, and TEC family kinases. It is effective against most imatinib-resistant cases except T315I mutation. Despite the superiority of dasatinib in its hematologic and cytogenetic responses in CML compared to imatinib, its potentially harmful pulmonary complications including pleural effusion (PE) and pulmonary arterial hypertension (PAH) may limit its use. Appropriate management of these serious adverse reactions is critical in both improving the quality of life and the outcome of the patient. In this narrative review, we will scrutinize the pulmonary complications of dasatinib and focus on the management of these toxicities.
Hebat-Allah Hassan Nashaat, Maha Anani, Fadia M. Attia
Blood Res 2022; 57(1): 6-12Abstract : Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic that has strained health care systems worldwide and resulted in high mortality. The current COVID-19 treatment is based on supportive and symptomatic care. Therefore, convalescent plasma (CP), which provides passive immunization against many infectious diseases, has been studied for COVID-19 management. To date, a large number of randomized and non-randomized clinical trials as well as many systematic reviews have revealed conflicting results. This article summarizes the basic principles of passive immunization, particularly addressing CP in COVID-19. It also evaluates the effectiveness of CP as a therapy in patients with COVID-19, clinical trial reports and systematic reviews, regulatory considerations and different protocols that are authorized in different countries to use it safely and effectively. An advanced search was carried out in major databases (PubMed, Cochrane Library, and MEDLINE) and Google Scholar using the following key words: SARS-CoV-2, COVID-19, convalescent plasma, and the applied query was “convalescent plasma” AND “COVID-19 OR SARS-CoV-2”. The results were filtered and duplicate data were removed. Collective evidence indicates that two cardinal players determine the effectiveness of CP use, time of infusion, and quality of CP. Early administration of CP with high neutralizing anti-spike IgG titer is hypothesized to be effective in improving clinical outcome, prevent progression, decrease the length of hospital stay, and reduce mortality. However, more reliable, high quality, well-controlled, double-blinded, randomized, international and multicenter collaborative trials are still needed.
Hyungwoo Cho
Blood Res 2022; 57(S1): S20-S26Abstract : The term “monoclonal gammopathy of clinical significance” (MGCS) refers to any plasma cell or B-cell clonal disorder that does not meet the current criteria for malignant disorders but produces a monoclonal protein that directly or indirectly results in organ damage. The most commonly affected organs are the kidneys, nerves, and skin. This review summarizes the current classification of MGCS and its diagnostic and treatment approaches.
Ashwag Saleh Alsharidah
Blood Res 2022; 57(2): 101-105Abstract : Vascular complications lead to morbidity and mortality in patients with diabetes. Diabetic nephropathy (DN) is one of the main life-threatening problems for these patients, as it is the main cause of end-stage renal disease. This study aimed to measure the clinical effects of diabetes in patients with diabetes and in patients with diabetic nephropathy. Improved hypoglycemic control in patients with diabetes could impressively reduce platelet hyperreactivity, and oxidative stress alters the levels of many coagulation and thrombosis factors, resulting in an abnormal hemostasis and impaired levels of numerous serum markers. Most studies have revealed that coagulation factor levels are high in patients with diabetes and nephrodiabetes. Serum inflammatory factors, and coagulation and endothelial functions are good predictors of diabetic nephropathy. This literature review was conducted with access to scholarly databases and Google Scholar through Qassim University, and it analyzes studies from early 2010 until November 2020. Many studies have inferred that diabetes severely affects hemostasis and increases the risk of cardiovascular disease.
Abstract : Myelofibrosis (MF) includes primary MF, post-essential thrombocythemia MF, and post-polycythemia vera MF. MF is a progressive myeloid neoplasm characterized by ineffective clonal hematopoiesis, extramedullary hematopoiesis, a reactive bone marrow environment resulting in reticulin deposition and fibrosis, and a propensity for leukemia transformation. The identification of driver mutations in JAK2, CALR, and MPL has contributed to a better understanding of disease pathogenesis and has led to the development of MF-specific therapies, such as JAK2 inhibitors. Despite the fact that ruxolitinib and fedratinib have been clinically developed and approved, their use is limited due to adverse effects such as anemia and thrombocytopenia. Recently, pacritinib has been approved for a group of thrombocytopenic patients with significant unmet clinical needs. In symptomatic and anemic patients with prior JAK inhibitor exposure, momelotinib was superior to danazol in preventing exacerbation of anemia and in controlling MF-associated signs and symptoms, such as spleen size. Although the development of JAK inhibitors is remarkable, modifying the natural course of the disease remains a priority. Therefore, many novel treatments are currently under clinical development. Agents targeting bromodomain and extra-terminal protein, anti-apoptotic protein Bcl-xL, and phosphatidylinositol-3-kinase delta have been studied in combination with JAK inhibitors. These combinations have been employed in both the frontline and “add-on” approaches. In addition, several agents are being studied as monotherapies for ruxolitinib-resistant or -ineligible patients. We reviewed several new MF treatments in the advanced stages of clinical development and treatment options for cytopenic patients.
Silvia Park, Byung Sik Cho, Hee-Je Kim
Blood Res 2020; 55(S1): S14-S18Abstract : Despite expanding knowledge in the molecular landscape of acute myeloid leukemia (AML) and an increasing understanding of leukemogenic pathways, little has changed in the treatment of AML in the last 40 years. Since introduction in the 1970s, combination chemotherapy consisting of anthracycline and cytarabine has been the mainstay of treatment, with major therapeutic advances based on improving supportive care rather than the introduction of novel therapeutics. Over the last decades, there have been extensive efforts to identify specific target mutations or pathways with the aim of improving clinical outcomes. Finally, after a prolonged wait, we are witnessing the next wave of AML treatment, characterized by a more “precise” and “personalized” understanding of the unique molecular or genetic mapping of individual patients. This new trend has since been further facilitated, with four new FDA approvals granted in 2017 in AML therapeutics. Currently, a total of eight targeted agents have been approved since 2017 (as of Jan. 2020). In this review, we will briefly discuss these newer agents in the context of their indication and the basis of their approval.
Yu Ri Kim, Dae-Young Kim
Blood Res 2021; 56(S1): S17-S25Abstract : Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of defective apoptosis, a disruption of the regulatory pathway that terminates immune and inflammatory responses. Fever, cytopenia, splenomegaly, and/or hemophagocytosis are typical findings of this syndrome. HLH can be induced by genetic disorders (familial) or secondary causes. Familial HLH is rare, while secondary causes in adults include infection, autoimmunity, and malignancy. HLH in adults tends to be confused with or misdiagnosed as sepsis, mainly due to similar clinical manifestations and laboratory findings, which make it difficult to diagnose HLH rapidly and adopt immunosuppressive agents and/or chemotherapy adequately. Treatment of pediatric HLH using HLH-2004 or multi-agent chemotherapy can be applied in adult patients, although the dose and type of drug need to be adjusted. It is highly recommended that allogenic hematopoietic stem cell transplantation should be used in patients who become reactivated or are refractory to the initial treatment as soon as possible to improve survival. Future clinical trials are warranted to determine more suitable treatments for adult patients with HLH.
Young Hoon Park, Dae-Young Kim, Seongkoo Kim, Young Bae Choi, Dong-Yeop Shin, Jin Seok Kim, Won Sik Lee, Yeung-Chul Mun, Jun Ho Jang, Jong Wook Lee, Hoon Kook, on behalf of Korean Aplastic Anemia Working Party
Blood Res 2022;57: 20-28Young Hoon Park
Blood Res 2022;57: S79-S85Jae-Sook Ahn, Hyeoung-Joon Kim
Blood Res 2022;57: S32-S36Junhun Cho
Blood Res 2022;57: S55-S61+82-2-516-6582