Use of Droplet Digital Polymerase Chain Reaction for Detecting Minimal Residual Disease: A Prospective Multi-Institutional Study

BACKGROUND/AIM: Droplet digital polymerase chain reaction (ddPCR) is an exact method of measuring nucleic acids. The aim of this prospective study was to evaluate minimal residual disease (MRD) using ddPCR in chronic myeloid leukemia (CML) patients. PATIENTS AND METHODS: Between May 2013 and November 2014, CML patients treated with nilotinib were enrolled in our study. BCR/ABL1 transcripts levels were evaluated using ddPCR at the first time of complete molecular response (CMR). We enrolled 15 patients from 7 Institutions. The treatment period and median follow-up period were 45 months and 47 months, respectively. RESULTS: Patients with a high level of BCR/ABL1 transcript had a greater tendency to lose the CMR during the follow-up period (p=0.095). In addition, patients with a low level of BCR/ABL1 transcript showed a longer duration of CMR compared to those with a high level (p=0.032). CONCLUSION: We found that ddPCR is a sensitive method for detecting MRD and that MRD could affect the duration of the treatment response.ope

항체동정검사상 범응집반응을 보인 환자에서 최소반응강도 적혈구제제의 수혈 효과

Background:In patients who had serum autoantibody that reacted with all screening red blood cells (panagglutination), waiting for compatible blood is likely to delay a needed transfusion. In some cases of severely diminished hemoglobin counts, the least incompatible blood may be transfused. However, the least incompatible transfusion therapy is challenged by the presence of unexpected antibody in patient's serum, which may cause a transfusion reaction. The aim of this study was to evaluate the effect of the least incompatible transfusion on clinical outcomes in patients with panagglutination. Methods:We conducted a retrospective study of 49 patients with panagglutination on an unexpected antibody screening test between January 2006 and July 2010. In 36 patients having the least incompatible blood transfusion, changes in hemoglobin and lactate dehydrogenase (LD) values before and after transfusion were analyzed. One year mortality after initial need for transfusion was documented. Results:In all 36 patients who underwent transfusion, hemoglobin values showed an increase of 1.2 (0.0∼3.0) g/dL per unit without occurrence of acute transfusion reactions indicated by an increase in the LD level. The least incompatible transfusion did not show an association with increased all-cause mortality. Conclusion:As an alternative to the time consuming process of alloantibody detection, patients with severe anemia can be effectively transfused with "least incompatible units" in an emergency clinical setting without experiencing acute transfusion reactions.ope

Treatment outcome and prognostic factors of Korean patients with chronic lymphocytic leukemia: a multicenter retrospective study

Background/aims: Compared with Western countries, chronic lymphocytic leukemia (CLL) rarely occurs in Asia and has different clinical characteristics. Thus, we aimed to evaluate the clinical characteristics, treatment outcomes, and prognostic significance of Korean patients with CLL. Methods: We retrospectively analyzed 90 patients with CLL who had received chemotherapy at 6 centers in Korea between 2000 and 2012. Results: Compared with Western patients with CLL, Korean patients with CLL express lambda (42.0%) and atypical markers such as CD22 and FMC7 (76.7% and 40.0%, respectively) more frequently. First-line chemotherapy regimens included chlorambucil (n = 43), fludarabine and cyclophosphamide (FC) (n = 20), fludarabine (n = 13), rituximab-FC (n = 4). The remaining patients were treated with other various regimens (n = 10). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 79.3% and 28.1%, respectively. Multivariate analyses showed that hyperleukocytosis (≥ 100 × 103/μL), extranodal involvement, and the Binet C stage were significant negative prognostic factors for OS (hazard ratio [HR] 4.75, p = 0.039; HR 21.6, p = 0.002; and HR 4.35, p = 0.034, respectively). Cytogenetic abnormalities including complex karyotypes (≥ 3), del(11q), and del(17) had a significantly adverse impact on both OS and PFS (p < 0.001 and p = 0.010, respectively). Conclusion: Initial hyperleukocytosis, extranodal involvement, complex karyotype, del(17) and del(11q) need to be considered in the risk stratification system for CLL.ope

Changing the strategic paradigm for the treatment of adult acute myeloid leukemia

Background: Acute myeloid leukemia (AML) is a representative blood cancer, accounting for most adult leukemia cases in Korea. Until recently, intensive chemotherapy and hematopoietic stem cell transplantation were the only curative treatment options for AML. However, the recent introduction of new drugs is bringing about changes in the strategic paradigm for the treatment of AML. Current Concepts: Along with the clinical eligibility for receiving intensive treatment and hematopoietic stem cell transplantation, the most critical determinants in treating AML are precise classification and risk stratification based on cytogenetic and molecular information. The recently revised World Health Organization classification, newly proposed International Consensus Classification, and the latest version of the European LeukemiaNet risk stratification reflect the importance of cytogenetic and molecular information. Although there have been no significant changes for a long time in the landscape of AML, especially in the field of treatment, the treatment paradigm has started to evolve with the introduction of new drugs. This evolution is led by FLT3 inhibitors, Bcl-2 inhibitors, isocitrate dehydrogenase inhibitors, target agents against CD33 antigens, and liposomal formulations of chemotherapeutics. Discussion and Conclusion: Successful initial treatment to induce complete remission followed by post-remission treatment to remove residual disease can lead to the achievement of long-term survival and cure goals in AML. We hope that new drugs will markedly improve the treatment outcomes for patients with AML. © Korean Medical Association.ope

Therapeutic Comparison of Chemotherapy and Surgery for Early Stage Diffuse Large B-cell Gastric Lymphoma

PURPOSE: The use of surgery versus stomach-preserving treatment for primary gastric lymphoma has caused controversy among doctors. This retrospective, single center study aims to evaluate the efficacy and benefit of stomach-preserving treatment against surgery for early stage diffuse large B-cell lymphoma of stomach. MATERIALS AND METHODS: From August 1991 to January 2006, 43 cases of early-stage diffuse large B-cell gastric lymphoma were reviewed. RESULTS: Eleven cases were treated with chemotherapy or chemotherapy plus radiation (CT +/- RT), 17 were treated with surgery alone (OP), and 15 were treated with surgery plus adjuvant chemotherapy (OP + CT). The complete remission and response rates were 63.6% and 90.9% in those treated with CT +/- RT (7 complete responders, 3 partial responders, 1 non-responder), 100% and 100% in those treated with OP, and 100% and 100% in those treated with OP + CT, respectively. Five-year overall survival rates were 85.7%, 87.5%, and 100% in those treated by CT +/- RT, OP, and OP + CT, respectively (p=0.76). The five-year disease free survival rates were 100%, 87.5% and 100% in those treated by CT +/- RT, OP, and OP + CT, respectively (p=0.99). There was no significant difference in overall survival and disease free survival between modalities. Even though there are no definite differences in the number of complications between those treated by CT +/- RT or OP, these facts reflect little concern on complications after surgery. CONCLUSION: In preventing morbidity arising from early or late complications from surgery and promoting quality of life, chemotherapy should be a primary consideration for early stage diffuse large B-cell lymphoma of the stomach.ope

Exercise Perception duringHematopoietic Transplantation forHematological Cancer Patients

The purpose of this study is to understand exercise perception during hematopoietic transplantation for hematological cancer patients. In-depth interview along with observation and field-note were used to collect data from nine hematological cancer patients undergoing recovery of hematopoietic transplantation. Phenomenological research method were used to gain a deep understanding of their experience. Eleven themes and five categorizes emerged from the data: ‘Pain of fighting with cancer’, ‘Desolate space’, ‘Exercise; another hope’, ‘Lack of exercise information’, and ‘Difficulty in practice.’ The results highlight the significant impact that cancer treatment has on hematological cancer patients. Hematological cancer patients undergoing high-dose treatment in desolate aseptic room, shared their perception of exercise barrier during treatment period. Although the patients perceived exercise to be beneficial and they wanted exercise to be part of the treatment programs, they were obscured and emphasized the difficulty of exercise in practice.ope

Can we consider discontinuation of hypomethylating agents in patients with myelodysplastic syndrome : a retrospective study from The Korean Society of Hematology AML/MDS Working Party

It is often difficult to continue treatment with hypomethylating agent(HMA) in clinical practice because of problems such as toxicities, poor economics, etc. We compared clinical outcomes of those patients who continued HMA and those who discontinued HMA because of other causes, and evaluated factors associated with survival in those patients who discontinued HMA. Patients were divided into two groups: treatment failure, those who stopped treatment due to disease progression; and discontinuation, those who discontinued treatment because of other causes. The median progression free survival(PFS) was 9.2 months (range 7.7 - 10.7 months) vs 28.9 months (range 22.6 - 35.2) in the treatment failure and discontinuation groups, respectively (P < 0.001). In a multivariate analysis, a lower risk by WPSS was an independent predictive factor for a longer PFS, and a lower risk by WPSS and median number of HMA cycles greater than seven were independent predictive factors for longer overall survival(OS) only in the discontinuation group. Patients who discontinued HMA without disease progression showed a prolonged survival than those who failed HMA treatment. Especially, a lower risk by WPSS and longer duration of HMA treatment may be predictive factors for a longer PFS and OS in patients who discontinued HMA.ope

Results of Multicenter Phase II Study With Imatinib Mesylate in Allogeneic Recipients With Steroid-Refractory Chronic GVHD

In this multicenter phase II study, we evaluated the safety and efficacy of imatinib in patients with steroid-resistant chronic graft-versus-host disease (cGVHD) and evaluated the quality of life (QOL) of the enrolled patients using the Short Form 36 (SF-36) health survey questionnaire. Thirty-six patients who were diagnosed with steroid-refractory cGVHD and treated with imatinib between March 2013 and February 2019 received 100 mg/day of imatinib for 2 weeks. Depending on the patient's condition and investigator's decision, the imatinib dose was allowed to be increased by 100 mg every 2 weeks up to 400 mg/day. Patients who achieved stable disease (SD), partial remission (PR), and complete remission (CR) at 3-month response evaluations continued imatinib for up to 6 months. The majority of the patients had multi-organ cGVHD, with skin (63.9%), lungs (44.4%), mouth (38.9%), and eyes (38.9%) as the most common sites. The overall response rate was 58.3%, including 3 and 18 patients with CR and PR, respectively, and an overall decline in National Institutes of Health (NIH) severity scores was observed at study completion in the absence of significant adverse effects. The overall response rates were 70.5%, 66.7%, 34.8%, and 25% in patients with gastrointestinal, liver, skin, and lung cGVHD, respectively. Factors representing emotional well-being were significantly improved based on the patient-reported QOL evaluation using SF-36. The effect of imatinib on steroid tapering, which was notable in responders, was also present in 50% of those who achieved SD without worsening cGVHD. Imatinib exhibited therapeutic efficacy in steroid-refractory and steroid-dependent cGVHD with tolerable toxicity.Clinical Trial Registration: KCT0006785.ope

Exercise barriers and facilitators during hematopoietic stem cell transplantation: a qualitative study

Objective: Although exercise is beneficial in patients undergoing hematopoietic stem cell transplantation (HSCT), motivating patients to exercise is challenging. We aimed to understand exercise barriers and facilitators during HSCT treatment while participating in a daily unsupervised exercise programme. Participants: Patients scheduled to have HSCT. Study design: 6 participants were included in this descriptive qualitative study during HSCT treatment while participating in an exercise programme to identify perceived barriers and facilitators of the exercise. An average of three semi-structured interviews were conducted per patient. Setting: Exercise during HSCT treatment in an isolated immune room. Intervention: Daily unsupervised exercise. Results: A total of six patients completed a 6-week exercise programme as well as all scheduled interviews, whose compliance to the exercise programme ranged from 12% to 79%. Based on interview results, three themes were identified as barriers to exercise and four themes were identified as facilitators to exercise. Patients experienced physical and psychological barriers such as nausea, vomiting, sore throat, reduced appetite, decreased willpower and anxiety due to feelings of isolation. Environmental factors included negative opinions about exercise programmes and lack of encouragement from the haematologist. Facilitators of exercise included willpower, easy and simple exercise, convincing explanations from haematologists and supervised support from exercise specialists. Conclusion: Our study has identified potential barriers and facilitators associated with exercise participation during HSCT. Supervised exercise recommended by a haematologist, convincing explanation on the benefit of exercise by medical personnel, positive feedback from other HSCT survivors and supervision by exercise specialists may increase compliance to the exercise programme during HSCT. Trial registration number: ISRCTN61498391.ope

Pevonedistat in East Asian patients with acute myeloid leukemia or myelodysplastic syndromes: a phase 1/1b study to evaluate safety, pharmacokinetics and activity as a single agent and in combination with azacitidine

Pevonedistat, the first small-molecule inhibitor of NEDD8-activating enzyme, has demonstrated clinical activity in Western patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). We report findings from a phase 1/1b study in East Asian patients with AML or MDS, conducted to evaluate the safety/tolerability and characterize the pharmacokinetics of pevonedistat, alone or in combination with azacitidine, in this population, and determine the recommended phase 2/3 dose for pevonedistat plus azacitidine. Twenty-three adult patients with very high/high/intermediate-risk AML or MDS were enrolled in Japan, South Korea and Taiwan. All 23 patients experienced at least one grade ≥ 3 treatment-emergent adverse event. One patient in the combination cohort reported a dose-limiting toxicity. Eighteen patients discontinued treatment; in nine patients, discontinuation was due to progressive disease. Three patients died on study of causes considered unrelated to study drugs. Pevonedistat exhibited linear pharmacokinetics over the dose range of 10-44 mg/m2, with minimal accumulation following multiple-dose administration. An objective response was achieved by 5/11 (45%) response-evaluable patients in the pevonedistat plus azacitidine arm (all with AML), and 0 in the single-agent pevonedistat arm. This study showed that the pharmacokinetic and safety profiles of pevonedistat plus azacitidine in East Asian patients were similar to those observed in Western patients as previously reported. The recommended Phase 2/3 dose (RP2/3D) of pevonedistat was determined to be 20 mg/m2 for co-administration with azacitidine 75 mg/m2 in Phase 2/3 studies, which was identical to the RP2/3D established in Western patients.ope