Purpose: Chronic myeloid leukemia (CML) in children, adolescents, and young adults is rare and differs from older adults. This study evaluated the outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in young Korean CML patients during the tyrosine kinase inhibitor (TKI) era. Materials and Methods: A retrospective analysis of 35 CML patients aged < 40 years who underwent allogeneic HSCT from 2009 to 2019 was conducted using Korean Blood and Marrow Transplantation Registry data. Patients were grouped by age < 20 years at HSCT (group 1, n=15) and 20-40 years at HSCT (group 2, n=20). Survival outcomes including overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) were analyzed using the Kaplan-Meier method. Results: The median time between diagnosis and HSCT was 8.9 months. All the patients achieved engraftment but platelet recovery was significantly slower in group 1 (p=0.034). Acute and chronic graft-versus-host disease occurred in 54.3% and 34.3%, respectively. Five-year OS, RFS, and EFS rates of total patients were 66.8%, 50.8%, and 47.6%, with better OS was observed in group 1 by multivariable analysis (p=0.048). Disease status at HSCT was a significant predictor of OS (p=0.028), RFS (p=0.003), and EFS (p=0.004). Disease progression occurred in 13 out of 35 patients (37.1%); treatment-related mortality accounted for 63.6% of deaths (7 out of 11). Conclusion When performed at a younger age, allogeneic HSCT result in superior outcome in CML. Achieving remission before HSCT is critical for improved outcomes, highlighting the importance of pretransplant remission via optimal TKI strategies and minimal residual disease monitoring.

Purpose: Stem cell transplantation (SCT) has historically played a major role in the long-term remission of mantle cell lymphoma (MCL), an incurable hematological malignancy. Using data from the Korean Society of Bone and Marrow Transplantation registry, we retrospectively analyzed the role of autologous (auto) and allogeneic (allo) SCT in longterm MCL survival. Methods: This study analyzed data from 188 patients (age ≥ 19 years at the time of transplantation) who underwent a transplant for MCL from 2011 to 2020. Progression-free survival (PFS) was defined as the time from transplantation to disease progression, relapse, or death from any cause. Overall survival (OS) was defined as the time from transplan‑ tation to death from any cause or the last follow-up. Results: In total, 109 patients underwent consolidative SCT after first-line chemotherapy. The 3-year PFS and OS rates were 65.4% and 78.5%, respectively, in the auto-SCT group, and 66.7% and 71.4%, respectively, in the allo-SCT group. The PFS and OS did not differ significantly between the auto- and allo-SCT groups. As part of salvage treatment, 52 patients with relapsed or refractory disease underwent auto- or allo-SCT. Patients who underwent auto-SCT with complete remis‑ sion/partial remission status reported better outcomes. In patients with refractory status, allogeneic transplantation using human leukocyte antigen (HLA) fully matched donors was a significantly favorable factor for PFS and OS. Conclusion The long-term survival of patients who underwent consolidative transplantation was similar to that reported in previous studies. Auto-SCT may be beneficial in patients who respond to salvage therapy, whereas allo-SCT with HLA-matched donors may be an alternative for patients with refractory disease. 

Multiple myeloma (MM), a hematological malignancy, is characterized by malignant plasma cell proliferation in the bone marrow. Recent treatment advances have significantly improved patient outcomes associated with MM.In this study, we aimed to develop comprehensive, evidence-based guidelines for the diagnosis, prognosis, and treat‑ ment of MM. We identified 12 key clinical questions essential for MM management, guiding the extensive literature review and meta-analysis of the study. Our guidelines provide evidence-based recommendations by integrating patient preferences with survey data. These recommendations include current and emerging diagnostic tools, thera‑ peutic agents, and treatment strategies. By prioritizing a patient-centered approach and rigorous data analysis, these guidelines were developed to enhance MM management, both in Korea and globally.

Purpose: The role of allogeneic stem cell transplantation (alloSCT) in multiple myeloma (MM) treatment remains controversial. We conducted a retrospective, multicenter, nationwide study in Korea to evaluate the outcomes of alloSCT in Asian patients with MM. Materials and Methods: Overall, 109 patients with MM who underwent alloSCT between 2003 and 2020 were included in this study. Data were collected from the Korean Multiple Myeloma Working Party Registry. Results: The overall response rate and stringent complete response plus complete response (CR) rates were 67.0 and 46.8%, respectively, after alloSCT. At a median follow-up of 32.5 months, the 3-year probability of progression-free survival (PFS) and overall survival (OS) rates were 69.3% and 71.8%, respectively. The 3-year probabilities of OS rates in the upfront alloSCT, tandem auto-alloSCT, and later alloSCT groups were 75.0%, 88.9%, and 61.1%, respectively. Patients who achieved CR before or after alloSCT had significantly longer OS (89.8 vs. 18 months and 89.8 vs. 15.2 months, respectively). Even though patients who did not achieve CR prior to alloSCT, those who achieve CR after alloSCT had improved PFS and OS compared to those who had no achievement of CR both prior and after alloSCT. Patients who underwent alloSCT with 1-2 prior treatment lines had improved PFS (22.4 vs. 4.5 months) and OS (45.6 vs. 15.3 months) compared to those with three or more prior treatment lines. Conclusion AlloSCT may be a promising therapeutic option especially for younger, chemosensitive patients with earlier implementation from relapse.

Purpose: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard management for relapsed or high-risk non-Hodgkin’s lymphoma (NHL). We reported the busulfan, melphalan, and etoposide (BuME) conditioning regimen was effective in patients with relapsed or high-risk NHL. Moreover, the busulfan, cyclophosphamide, and etoposide (BuCE) conditioning regimen has been used widely in ASCT for NHL. Therefore, based on these encouraging results, this randomized phase II multicenter trial compared the outcomes of BuME and BuCE as conditioning therapies for ASCT in patients with NHL. Materials and Methods: Patients were randomly assigned to receive either BuME (n=36) or BuCE (n=39). The BuME regimen was comprised of busulfan (3.2 mg/kg/day, intravenously) administered on days –7, –6, and –5, etoposide (400 mg/m2 intravenously) on days –5 and –4, and melphalan (50 mg/m2/day intravenously) on days –3 and –2. The BuCE regimen was comprised of busulfan (3.2 mg/kg/day intravenously) on days –7, –6, and –5, etoposide (400 mg/m2/day intravenously) on days –5 and –4, and cyclophosphamide (50 mg/kg/day intravenously) on days –3 and –2. The primary endpoint was 2-year progression-free survival (PFS). Results: Seventy-five patients were enrolled. Eleven patients (30.5%) in the BuME group and 13 patients (33.3%) in the BuCE group had disease progression or died. The 2-year PFS rate was 65.4% in the BuME group and 60.6% in the BuCE group (p=0.746). There were no non-relapse mortalities within 100 days after transplantation. Conclusion There were no significant differences in PFS between the two groups. Therefore, busulfan-based conditioning regimens, BuME and BuCE, may be important treatment substitutes for the BCNU-containing regimens.

Purpose: This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL). Materials and Methods: Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy. Results: Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016). Conclusion Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by uncontrolled terminal complement activation. Eculizumab, a monoclonal antibody C5 inhibitor was introduced in Korea in 2009 and has been the standard treatment option for PNH. Methods: This study assessed the long-term efficacy/safety of eculizumab in PNH using real-world data from the Korean Health Insurance Review and Assessment Service. Eighty patients who initiated eculizumab from 2009–2020 were enrolled. Results: At eculizumab initiation, the median age was 51.5 years, lactate dehydrogenase (LDH) 6.8 × upper limit of normal, and granulocyte clone size 93.0%. All patients had at least one PNH-related complication before eculizumab initiation, including renal failure (n = 36), smooth muscle spasm (n = 24), thromboembolism (n = 20), and pulmonary hypertension (n = 15). The median (range) duration of eculizumab treatment was 52.7 (1.0, 127.3) months (338.6 total treated patient-years). Despite high disease activity in the study population before treatment initiation, overall survival was 96.2% and LDH levels were stabilized in most patients during treatment. PNH-related complications at treatment initiation were resolved in 44.4% of patients with renal failure, 95.8% with smooth muscle spasm, 70.0% with thromboembolism, and 26.7% with pulmonary hypertension. Extravascular hemolysis occurred in 28.8% of patients (n = 23; 0.09 per patient-year) and breakthrough hemolysis in 18.8% (n = 15; 0.06 per patient-year). No treatment discontinuation cases related to eculizumab were observed. Conclusion These data provided evidence for the long-term efficacy and safety of eculizumab in Korean PNH patients with high disease burdens.

Despite the availability of therapies to treat patients with immune thrombocytopenia (ITP), there is currently little data from randomized trials to assist clinicians in managing patients. The evidence-based guidelines of the Korean Society of Hematology Aplastic Anemia Working Party (KSHAAWP) are intended to support patients and physicians in the management of ITP. Experts from the KSHAAWP discussed and described this guideline according to the current treatment situation for ITP in Korea and finalized the guidelines. The expert panel recommended the management of ITP in adult and pediatric patients with newly diagnosed, persistent, and chronic disease refractory to first-line therapy with minor bleeding. Management approaches include observation and administration of corticosteroids, intravenous immunoglobulin, anti-D immunoglobulin, and thrombopoietin receptor agonists. Currently, evidence supporting strong recommendations for various management approaches is lacking. Therefore, a large focus was placed on shared decision-making, especially regarding second-line treatment.

Purpose: Analysis of circulating tumor DNA (ctDNA) in blood could allow noninvasive genetic analysis of primary tumors. Although there have been unmet needs for noninvasive methods in patients with primary central nervous system lymphoma (PCNSL), it is still not determined whether plasma ctDNA analysis could be useful for patients with PCNSL. Materials and Methods: Targeted deep sequencing of 54 genes was performed in cell-free DNA isolated from plasma samples collected pretreatment, during treatment, and at the end of treatment in 42 consecutively diagnosed PCNSL patients between January 2017 and December 2018. Results: Targeted sequencing of plasma cell-free DNA detected somatic mutations representing ctDNA in 11 cases (11/41, 27%). The detection of ctDNA was not related to the concentration of cell-free DNA or tumor volume. The mutation profiles of these 11 cases varied between patients. The most frequently mutated gene was PIM1 (4/11, 36.4%), whereas KMT2D, PIK3CA, and MYD88 were each observed in three patients (3/11, 27%). The mutations of 13 genes were concordantly found in primary tumor tissue and plasma ctDNA, giving a detection sensitivity of 45%. During the serial tracking of seven patients with complete response, the disappearance of ctDNA mutations was found in four patients, whereas three patients had detected ctDNA mutation at the end of treatment. Conclusion The plasma ctDNA mutation analysis still has limited value for surveillance and predicting treatment outcomes of PCNSL because the detection efficiency was lower than other systemic lymphomas. Thus, analytical platforms should be improved to overcome anatomical hurdles associated with PCNSL.

Background/Aims: We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). Methods: We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. Results: The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. Conclusions Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.