INTRODUCTION: Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a curative option for relapse/refractory (R/R) lymphomas that have failed autologous transplantation or for high-risk lymphomas in the upfront setting. We conducted a retrospective analysis on consecutive lymphoma patients who underwent allo-HSCT over a 20-year period (2003- 2022) at Singapore General Hospital and National University Hospital Singapore. METHOD: A total of 121 patients were included in the study. Median age was 41 years. Diagnoses include Hodgkin lymphoma (HL, 15%), B-cell non- Hodgkin lymphoma (B-NHL, 34%), T-cell non-Hodgkin lymphoma (T-NHL, 31%) and natural killer T-cell lymphoma (NKTL, 20%). Moreover, 27% of patients had prior auto-haematopoietic stem cell transplanta-tion (auto-HSCT), and 84% received reduced intensity conditioning (RIC). Donor types were matched sibling donor (45%), matched unrelated donor (29%), haploidentical donor (19%) and cord blood (CB, 7%). RESULTS: After median follow-up of 56 months, estimated 4-year progression-free survival (PFS) and overall survival (OS) for all patients were 38% and 45%, respectively. Non-relapse mortality (NRM) was 15% at day 100 and 24% at 1 year. On univariate analysis, complete remission status at transplant and RIC confers superior OS. On multivariate analysis, HL was associated with superior OS compared to NHL, whereas matched unrelated donor transplant was associated with significantly inferior OS compared to matched sibling donor. CONCLUSION Long-term curative durability was observed with allo-HSCT for patients with relapsed/ refractory lymphomas. This real-world data serves as a valuable historical benchmark for future studies on lymphomas in Singapore and the Asia Pacific region.
Humans ; Singapore/epidemiology* ; Adult ; Male ; Retrospective Studies ; Female ; Hematopoietic Stem Cell Transplantation/methods* ; Middle Aged ; Transplantation, Homologous ; Young Adult ; Transplantation Conditioning/methods* ; Lymphoma/mortality* ; Adolescent ; Hodgkin Disease/mortality* ; Aged ; Lymphoma, B-Cell/mortality*

Acute lymphocytic leukemia (ALL) is one of the most common malignancies, especially in young people. Combination chemotherapy for ALL typically includes corticosteroids (Kantarjian et al., 2000). Hyperglycemia is a well-recognized complication of corticosteroids, and chemotherapy-induced diabetes (CID) is not uncommon (27.5%-37.0%) during the treatment of ALL (Hsu et al., 2002; Weiser et al., 2004; Alves et al., 2007). Besides the effect of corticosteroids, potential factors triggering hyperglycemia in ALL also include direct infiltration of the pancreas by leukemia cells and β cell dysfunction induced by chemotherapeutic agents such as L-asparagine (Mohn et al., 2004).
Adolescent ; Adult ; Age Factors ; Aged ; Antineoplastic Agents/adverse effects* ; Diabetes Mellitus/chemically induced* ; Female ; Humans ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality* ; Young Adult

Lung cancer remains a leading cause of cancer mortality worldwide, including in Korea. Systemic therapy including platinum-based chemotherapy and targeted therapy should be provided to patients with stage IV non-small cell lung cancer (NSCLC). Applications of targeted therapy, such as an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and anaplastic lymphoma kinase (ALK) inhibitors, in patients with NSCLC and an EGFR mutation or ALK gene rearrangement has enabled dramatic improvements in efficacy and tolerability. Despite advances in research and a better understanding of the molecular pathways of NSCLC, few effective therapeutic options are available for most patients with NSCLC without druggable targets, especially for patients with squamous cell NSCLC. Immune checkpoint inhibitors such as anti-cytotoxic T lymphocyte antigen-4 or anti-programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) have demonstrated durable response rates across a broad range of solid tumors, including NSCLC, which has revolutionized the treatment of solid tumors. Here, we review the current status and future approaches of immune checkpoint inhibitors that are being investigated for NSCLC with a focus on pembrolizumab, nivolumab, atezolizumab, durvalumab, and ipilimumab.
Carcinoma, Non-Small-Cell Lung* ; Drug Therapy ; Epithelial Cells ; Gene Rearrangement ; Humans ; Immunotherapy ; Korea ; Lung Neoplasms ; Lymphocytes ; Lymphoma ; Mortality ; Phosphotransferases ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor

Adolescent ; Busulfan ; therapeutic use ; Child ; Child, Preschool ; Cyclophosphamide ; therapeutic use ; Cyclosporine ; therapeutic use ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Infant ; Leukemia ; drug therapy ; mortality ; therapy ; Leukemia, Myeloid, Acute ; drug therapy ; mortality ; therapy ; Male ; Mycophenolic Acid ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; mortality ; therapy ; Retrospective Studies ; Treatment Outcome

BACKGROUND: Non-Hodgkin T/NK cell lymphoma is a rare and widely variable type of lymphoma with the most dismal prognosis. This study aimed to investigate varied impact of the clinical indicators to the overall survival (OS). METHODS: We conducted a retrospective study to identify the non-invasive clinical features of T cell lymphoma that can predict prognosis with an innovative analysis method using quantile regression. A total of 183 patients who visited a top-tier hospital in Beijing, China, were enrolled from January 2006 to December 2015. Demographic information and main clinical indicators were collected including age, erythrocyte sedimentation rate (ESR), survival status, and international prognostic index (IPI) score. RESULTS: The median age of the patients at diagnosis was 45 years. Approximately 80% of patients were at an advanced stage, and the median survival time after diagnosis was 5.1 months. Multivariable analysis of the prognostic factors for inferior OS associated with advanced clinical staging [HR=3.16, 95%CI (1.39-7.2)], lower platelet count [HR = 2.57, 95%CI (1.57-4.19), P < 0.001] and higher IPI score [HR = 1.29, 95%CI (1.01-1.66), P = 0.043]. Meanwhile, T cell lymphoblastic lymphoma [HR = 0.40, 95%CI (0.20-0.80), P = 0.010], higher white blood cell counts [HR = 0.57, 95%CI (0.34-0.96), P = 0.033], higher serum albumin level [HR = 0.6, 95%CI (0.37-0.97), P = 0.039], and higher ESR [HR = 0.53, 95%CI (0.33-0.87), P = 0.011] were protective factors for OS when stratified by hemophagocytic lymphohistiocytosis (HLH). Multivariable quantile regression between the OS rate and each predictor at quartiles 0.25, 0.5, 0.75, and 0.95 showed that the coefficients of serum β2-microglobulin level and serum ESR were statistically significant in the middle of the coefficient curve (quartile 0.25-0.75). The coefficient of IPI was negatively associated with OS. The coefficients of hematopoietic stem cell transplantation (HSCT) and no clinical symptoms were higher at the middle of the quartile level curve but were not statistically significant. CONCLUSIONS The IPI score is a comparatively robust indicator of prognosis at 3 quartiles, and serum ESR is stable at the middle 2 quartiles section when adjusted for HLH. Quantile regression can be used to observe detailed impacts of the predictors on OS.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Disease-Free Survival ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, Large B-Cell, Diffuse ; mortality ; pathology ; Lymphoma, Non-Hodgkin ; mortality ; pathology ; Lymphoma, T-Cell ; mortality ; pathology ; Male ; Middle Aged ; Prognosis ; Regression Analysis ; Retrospective Studies ; Survival Rate ; Young Adult

BACKGROUND: Bendamustine is an attractive option for the management of both de novo and relapsed lymphomas. It is being increasingly used in the conditioning regimen for autologous stem cell transplantation (SCT) and can be an alternative to the traditionally-used carmustine. In this study, we aimed to determine the safety and efficacy of bendamustine in the conditioning regimen for autologous SCT in refractory/relapsed lymphomas. METHODS: We designed a descriptive study to evaluate bendamustine in combination with etoposide, cytarabine, and melphalan (BeEAM) in the conditioning regimen for autologous SCT. RESULTS: Fourteen patients (median age, 28 yr) with Hodgkin's lymphoma (HL) (N=8), non-Hodgkin's lymphomas (NHL) (N=5), or peripheral T-cell lymphoma, not otherwise specified (PTCL NOS) (N=1) were included in the study. A median number of 5.95×10⁶ CD34+ cells/kg were transfused. Median times to absolute neutrophil count and platelet engraftment were 17 days and 24 days, respectively. The 100-day transplantation mortality rate was 28% (4 patients). Eight patients (57.14%) had GII-III acute kidney injury, four patients (28.5%) had GIII-IV hyperbilirubinemia, and twelve patients (85%) had GII-III diarrhea. After 3 months, 37% (5 patients) and 21.4% (3 patients) demonstrated complete response and partial response, respectively. The median follow-up was 5.5 months (15 days–19 mo). At the final follow-up, 7 patients (50%) were alive and in CR. CONCLUSION: Our study showed that bendamustine is a potentially toxic agent in the conditioning regimen for autologous SCT, resulting in significant liver, kidney, and gastrointestinal toxicity. Further studies are required to assess its safety and efficacy at reduced doses.
Acute Kidney Injury ; Bendamustine Hydrochloride ; Blood Platelets ; Carmustine ; Cytarabine ; Diarrhea ; Etoposide ; Follow-Up Studies ; Hodgkin Disease ; Humans ; Hyperbilirubinemia ; Kidney ; Liver ; Lymphoma ; Lymphoma, Non-Hodgkin ; Lymphoma, T-Cell, Peripheral ; Melphalan ; Mortality ; Neutrophils ; Stem Cell Transplantation ; Stem Cells

Autoimmune diseases (ADs) increase the risk of non-Hodgkin's lymphoma and contribute to poor prognosis of patients. However, the association between immunologic markers and clinical outcome has rarely been investigated. This study aims to analyze the prognostic value of pretreatment immunologic markers in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively reviewed the data on 502 patients with DLBCL treated in our institution from January 2013 to March 2018. Survival functions were estimated using Kaplan-Meier method and Cox regression model. The 3-year progression free survival (PFS) and overall survival (OS) rates were 70.2% and 80.9%, respectively, and the complete remission (CR) rate was 78.1%. Among the patients, those with multiple ( ⩾ 3) abnormal immunologic markers had significantly shorter 3-year PFS (52.7% vs. 77.3%, P < 0.001) and OS (68.5% vs. 85.8%, P = 0.001) than those without multiple abnormal immunologic markers. Multivariate analysis revealed that the presence of multiple abnormal immunologic markers and the elevated serum levels of lactate dehydrogenase were the independent adverse prognostic factors for PFS (P = 0.008, P < 0.001) and OS (P = 0.003, P < 0.001). Meanwhile, advanced Ann Arbor stage was an independent adverse prognostic factor for PFS (P = 0.001) and age > 60 years for OS (P = 0.014). In conclusion, the immunologic status was closely related to lymphoma progression, and this study provides new insights into the risk stratification of patients with DLBCL.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers ; China ; Disease Progression ; Female ; Humans ; Immunotherapy ; methods ; Lymphoma, Large B-Cell, Diffuse ; mortality ; therapy ; Male ; Middle Aged ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; Survival Analysis ; Survival Rate ; Young Adult

OBJECTIVETo study the effects of minimal residual disease (MRD) level on day 33 of remission induction and IKZF1 genotype on the survival of children with B-lineage acute lymphoblastic leukemia (B-ALL).

METHODSA total of 152 children with newly-diagnosed B-ALL who had complete remission after the first cycle of the chemotherapy and had complete follow-up information were enrolled in this study. According to the MRD detection by flow cytometry on day 33 of remission induction, they were divided into three groups: standard-risk (SR) group (MRD <10; n=60), intermediate-risk (IR) group (10≤ MRD <10; n=55), and high-risk (HR) group (MRD ≥10; n=37). Nested RT-PCR was used to determine the IKZF1 genotype of all children before chemotherapy. The effects of MRD level on day 33 of remission induction and IKZF1 genotype on the recurrence-free survival (RFS) of children with B-ALL were analyzed.

RESULTSThere were 7 common IKZF1 subtypes in all the 152 children with B-ALL: IK1, IK2/3, IK4, IK6, IK8, IK9, and IK10. Of the 152 children, 130 had functional subtypes of IKZF1 and 22 had non-functional subtypes of IKZF1. During the follow-up period, relapse occurred in 26 (17%) children, and the recurrence rate was highest in the HR group (P<0.05). However, there was no significant difference in the recurrence rate between the SR group and the IR group (P>0.05). The cumulative recurrence rate of the children with non-functional subtypes of IKZF1 was significantly higher than that of those with functional types of IKZF1 (P<0.01). The predicted 5-year RFS rates in the SR, IR, and HR groups were (94.2±2.9)%, (86.7±3.8)%, and (56.2±4.5)% respectively (P<0.05). The 5-year RFS rate of the children with functional subtypes of IKZF1 was significantly higher than that of those with non-functional subtypes of IKZF1 (P<0.01). There was no significant difference in the predicted 5-year RFS rate between the children with functional subtypes of IKZF1 and those with non-functional subtypes of IKZF1 in the SR group (P>0.05). However, the predicted 5-year RFS rate of the children with functional subtypes of IKZF1 was significantly higher than that of those with non-functional subtypes of IKZF1 in the IR group and the HR group (P<0.05).

CONCLUSIONSB-ALL children with non-functional subtypes of IKZF1 have a high recurrence rate, and the recurrence rate will be even higher in B-ALL children with non-functional subtypes of IKZF1 and MRD ≥10 on day 33 of chemotherapy.

Antineoplastic Combined Chemotherapy Protocols ; Child ; Child, Preschool ; Female ; Genotype ; Humans ; Ikaros Transcription Factor ; genetics ; Male ; Neoplasm, Residual ; genetics ; mortality ; therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; mortality ; therapy ; Prognosis ; Recurrence ; Remission Induction ; Survival

OBJECTIVETo study the clinical features and treatment outcome of children with mature B-cell non-Hodgkin's lymphoma (B-NHL).

METHODSA total of 28 previously untreated children with mature B-NHL were enrolled and given the chemotherapy regimen of CCCG-B-NHL-2010. Among them, 20 were given rituximab in addition to chemotherapy. The children were followed up for 31 months (ranged 4-70 months). A retrospective analysis was performed for the clinical features of these children. The Kaplan-Meier method was used for survival analysis. A univariate analysis was performed to investigate the prognostic factors.

RESULTSAmong the 28 children, 17 (61%) had Burkitt lymphoma, 8 (29%) had diffuse large B-cell lymphoma (DLBCL), and 3 (11%) had unclassifiable B-cell lymphoma. As for the initial symptom, 13 (46%) had cervical mass, 10 (36%) had maxillofacial mass, 9 (32%) had hepatosplenomegaly, 5 (18%) had abdominal mass, and 5 (18%) had exophthalmos. Of all children, 14 had a lactate dehydrogenase (LDH) level of <500 IU/L, 3 had a level of 500-1 000 IU/L, and 11 had a level of ≥ 1 000 IU/L. After two courses of chemotherapy, 21 children achieved complete remission and 7 achieved partial remission. At the end of follow-up, 24 achieved continuous complete remission and 4 experienced recurrence. The 2-year event-free survival rate was (85.7± 6.6)%. The children with bone marrow infiltration suggested by bone marrow biopsy, serum LDH ≥500 IU/L, and bone marrow tumor cells >25% had a low 2-year cumulative survival rate.

CONCLUSIONSThe CCCG-B-NHL 2010 chemotherapy regimen combined with rituximab has a satisfactory effect in the treatment of children with B-NHL. Bone marrow infiltration on bone marrow biopsy is associated with poor prognosis.

Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Bone Marrow ; pathology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Lymphoma, B-Cell ; diagnosis ; drug therapy ; mortality ; pathology ; Male ; Prognosis ; Progression-Free Survival ; Retrospective Studies ; Rituximab ; administration & dosage ; Treatment Outcome

BACKGROUND: The incidence of lymphoplasmacytic lymphoma (LPL) is lower in Asian than in Western populations. Few studies have described the clinical features and treatment outcomes of patients with LPL, including non-IgM LPL, in East Asia. METHODS: We retrospectively analyzed patients diagnosed with LPL at Asan Medical Center between January 2001 and March 2016. We evaluated the clinical features and survival outcomes of patients with LPL and non-IgM LPL and compared these data with those of patients with LPL/Waldenström's macroglobulinemia (WM). RESULTS: The median age at diagnosis of patients with LPL was 61.5 years (range, 34–77 yr); most patients were male (91%). Approximately three-quarters of the 22 patients with LPL were in the low or intermediate risk groups according to the International Prognostic Scoring System for Waldenström's Macroglobulinemia classification. The median follow-up duration was 75 months [95% confidence interval (CI), 48–102 mo], and the median overall survival (OS) was 81 months (95% CI, 0–167 mo). The number of patients in the non-IgM LPL group who exhibited extramedullary involvement was higher than in the LPL/WM group. OS of the LPL/WM group was improved compared with that of the non-IgM LPL group [median not reached vs. 10.0 mo (95% CI, 0–36.7); P=0.05]. CONCLUSION: We present a single-center experience of 22 patients with LPL, including a non-IgM cohort, in Korea. The treatment of non-IgM LPL was heterogeneous, and patients with non-IgM LPL showed a higher 5-year mortality rate and more adverse prognostic factors than those with LPL/WM.
Asian Continental Ancestry Group ; Chungcheongnam-do ; Classification ; Cohort Studies ; Diagnosis ; Far East ; Follow-Up Studies ; Humans ; Incidence ; Korea* ; Lymphoma* ; Male ; Mortality ; Retrospective Studies ; Waldenstrom Macroglobulinemia