Allogeneic stem cell transplantation (allo-SCT) is a salvage treatment option for patients with relapsed or refractory lymphoid malignancies. However, the clinical variables impacting outcomes in these patients remain unclear. We analyzed 58 patients who underwent allo-SCT for lymphoid malignancies, including B-cell lymphoma (BCL, n = 20), Hodgkin’s disease (n = 3), multiple myeloma (n = 9), natural killer/T-cell lymphoma (NK/TCL, n = 4), and TCL (n = 22).The median progression-free survival (PFS) was 27.4 months, while the median overall survival (OS) was 30.6 months.In univariate analysis, human leukocyte antigen (HLA) matching and complete remission status post-transplantation were associated with improved PFS and OS. However, only post-transplant response remained significant for both sur‑ vival outcomes in the multivariate analysis. Moreover, HLA matching was associated with a significantly improved PFS in patients with BCL and NK/TCL, but with better OS only in those with BCL. Complete remission after transplantation was associated with better PFS and OS in patients with BCL, NK/TCL, and TCL. Our results indicate that post-transplant response is an important prognostic indicator in allo-SCT for lymphoid malignancies and may guide clinical decisions and additional treatment.

Allogeneic stem cell transplantation (allo-SCT) is a salvage treatment option for patients with relapsed or refractory lymphoid malignancies. However, the clinical variables impacting outcomes in these patients remain unclear. We analyzed 58 patients who underwent allo-SCT for lymphoid malignancies, including B-cell lymphoma (BCL, n = 20), Hodgkin’s disease (n = 3), multiple myeloma (n = 9), natural killer/T-cell lymphoma (NK/TCL, n = 4), and TCL (n = 22).The median progression-free survival (PFS) was 27.4 months, while the median overall survival (OS) was 30.6 months.In univariate analysis, human leukocyte antigen (HLA) matching and complete remission status post-transplantation were associated with improved PFS and OS. However, only post-transplant response remained significant for both sur‑ vival outcomes in the multivariate analysis. Moreover, HLA matching was associated with a significantly improved PFS in patients with BCL and NK/TCL, but with better OS only in those with BCL. Complete remission after transplantation was associated with better PFS and OS in patients with BCL, NK/TCL, and TCL. Our results indicate that post-transplant response is an important prognostic indicator in allo-SCT for lymphoid malignancies and may guide clinical decisions and additional treatment.

Allogeneic stem cell transplantation (allo-SCT) is a salvage treatment option for patients with relapsed or refractory lymphoid malignancies. However, the clinical variables impacting outcomes in these patients remain unclear. We analyzed 58 patients who underwent allo-SCT for lymphoid malignancies, including B-cell lymphoma (BCL, n = 20), Hodgkin’s disease (n = 3), multiple myeloma (n = 9), natural killer/T-cell lymphoma (NK/TCL, n = 4), and TCL (n = 22).The median progression-free survival (PFS) was 27.4 months, while the median overall survival (OS) was 30.6 months.In univariate analysis, human leukocyte antigen (HLA) matching and complete remission status post-transplantation were associated with improved PFS and OS. However, only post-transplant response remained significant for both sur‑ vival outcomes in the multivariate analysis. Moreover, HLA matching was associated with a significantly improved PFS in patients with BCL and NK/TCL, but with better OS only in those with BCL. Complete remission after transplantation was associated with better PFS and OS in patients with BCL, NK/TCL, and TCL. Our results indicate that post-transplant response is an important prognostic indicator in allo-SCT for lymphoid malignancies and may guide clinical decisions and additional treatment.

Background: AML is a heterogeneous disease, and despite intensive therapy, recurrence is still high in AML patients who achieve the criterion for cytomorphologic remission (residual tumor burden [measurable residual disease, MRD]<5%). This study aimed to develop a targeted next-generation sequencing (NGS) panel to detect MRD in AML patients and validate its performance. Methods: We designed an error-corrected, targeted MRD-NGS panel without using physical molecular barcodes, including 24 genes. Fifty-four bone marrow and peripheral blood samples from 23 AML patients were sequenced using the panel. The panel design was validated using reference material, and accuracy was assessed using droplet digital PCR. Results: Dilution tests showed excellent linearity and a strong correlation between expected and observed clonal frequencies (R>0.99). The test reproducibly detected MRD in three dilution series samples, with a sensitivity of 0.25% for single-nucleotide variants. More than half of samples from patients with morphologic remission after one month of chemotherapy had detectable mutations. NGS-MRD positivity for samples collected after one month of chemotherapy tended to be associated with poor overall survival and progression-free survival. Conclusions Our highly sensitive and accurate NGS-MRD panel can be readily used to monitor most AML patients in clinical practice, including patients without gene rearrangement. In addition, this NGS-MRD panel may allow the detection of newly emerging clones during clinical relapse, leading to more reliable prognoses of AML.

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.

Purpose: Event-free survival at 24 months (EFS24) is known to be a surrogate marker for overall survival (OS) for patients with peripheral T-cell lymphoma (PTCL). We examined the role of EFS24 in PTCL compared to diffuse large B-cell lymphoma (DLBCL), and then assessed the clinical predictive factors of achieving EFS24. Materials and Methods: Patients with newly diagnosed PTCL treated with anthracycline-based chemotherapy were included. Subsequent OS was defined as the time elapsed from 24 months after diagnosis until death from any cause in those who achieved EFS24. Results: Overall, 153 patients were evaluated, and 51 patients (33.3%) achieved EFS24. Patients who achieved EFS24 showed superior OS compared to patients who did not (p < 0.001). EFS24 could stratify the subsequent OS although it did not reach to that of the general population. After matching the PTCL group to the DLBCL group based on the international prognostic index, the subsequent OS in patients who achieved EFS24 was similar between the two groups (p=0.094). Advanced stage was a significant factor to predict the failing EFS24 by multivariable analysis (p < 0.001). Conclusion Patients with PTCL who achieve EFS24 could have a favorable subsequent OS. Since advanced disease stage is a predictor of EFS24 failure, future efforts should focus on developing novel therapeutic strategies for PTCL patients presenting with advanced disease.

Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.

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). Conclusions Initial hyperleukocytosis, extranodal involvement, complex karyotype, del(17) and del(11q) need to be considered in the risk stratification system for CLL.

Background/Aims: Although the use of surveillance 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is discouraged in patients with diffuse large B-cell lymphoma, its usefulness in different subtypes has not been thoroughly investigated. Methods: We retrospectively evaluated 157 patients who showed positive results on surveillance FDG-PET/CT every 6 months following complete response for up to 5 years. All of the patients also underwent biopsies. Results: Seventy-eight (49.6%) of 157 patients had true positive results; the remaining 79 (50.3%), including eight (5.1%) with secondary malignancies, were confirmed to yield false positive results. Among the 78 patients with true positive results, the disease in seven (8.9%) had transformed to a different subtype. The positive predictive value (PPV) of FDG-PET/CT for aggressive B-cell non-Hodgkin’s lymphoma (NHL) was lower than that for indolent B-cell or aggressive T-cell NHL (p = 0.003 and p = 0.018, respectively), especially in patients with a low/low-intermediate international prognostic index (IPI) upon a positive PET/CT finding. On the other hand, indolent B-cell and aggressive T-cell NHL patients showed PPVs of > 60%, including those with low/low-intermediate secondary IPIs. Conclusions The role of FDG-PET/CT surveillance is limited, and differs according to the lymphoma subtype. FDG-PET/CT may be useful in detecting early relapse in patients with aggressive T-cell NHL, including those with low/low-intermediate risk secondary IPI; as already known, FDG-PET/CT has no role in aggressive B-cell NHL. Repeat biopsy should be performed to discriminate relapse or transformation from false positive findings in patients with positive surveillance FDG-PET/CT results.

Purpose: Pharmacological inhibition of mutant isocitrate dehydrogenase (IDH) reduces R-2-hydroxyglutarate (2-HG) levels and restores cellular differentiation in vivo and in vitro. The IDH2 inhibitor enasidenib (AG-221) has been approved by the FDA as a first-in-class inhibitor for the treatment of relapsed or refractory (R/R) IDH2-mutant acute myeloid leukemia (AML). In this study,the effects of a combination of all-trans retinoic acid (ATRA) and AG-221 on AML cell differentiation was explored, along with the mechanisms employed by IDH2-mutant cells in AML. Materials and Methods: We treated the human AML cell line, IDH2-mutant-TF-1, and primary human AML cells carrying IDH2 mutation with 30 μM AG-221 and 100 nM ATRA, alone or in combination. Results: Combined treatment with AG-221 and ATRA inhibited 2-HG production and resulted in synergistic effects on differentiation among IDH2-mutant AML cells and primary AML cells expressing IDH2 mutation. Combined treatment with AG-221 and ATRA altered autophagic activity. AG-221 and ATRA treatment-induced differentiation of IDH2-mutant AML cells was associated with autophagy induction, without suppressing autophagy flux at maturation and degradation stages. A RAF-1/MEK/ERK pathway was founded to be associated with AG-221 and ATRA-induced differentiation in IDH2-mutant AML cells. IDH-associated changes in histone methylation markers decreased after AG-221 and ATRA combination treatment. Conclusion Our preliminary evidence indicates that the addition of ATRA to treatments with IDH2 inhibitor may lead to further improvements or increases in response rates in IDH2-mutant AML patients who do not appear to benefit from treatments with IDH2 inhibitor alone.