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*

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

BACKGROUND: The South Korean criteria for occupational diseases were amended in July 2013. These criteria included formaldehyde as a newly defined occupational carcinogen, based on cases of “leukemia or nasopharyngeal cancer caused by formaldehyde exposure”. This inclusion was based on the Internal Agency for Research on Cancer classification, which classified formaldehyde as definite human carcinogen for nasopharyngeal cancer in 2004 and leukemia in 2012. METHODS: We reviewed reports regarding the causal relationship between occupational exposure to formaldehyde in Korea and the development of these cancers, in order to determine whether these cases were work-related. RESULTS: Previous reports regarding excess mortality from nasopharyngeal cancer caused by formaldehyde exposure seemed to be influenced by excess mortality from a single plant. The recent meta-risk for nasopharyngeal cancer was significantly increased in case-control studies, but was null for cohort studies (excluding unexplained clusters of nasopharyngeal cancers). A recent analysis of the largest industrial cohort revealed elevated risks of both leukemia and Hodgkin lymphoma at the peak formaldehyde exposure, and both cancers exhibited significant dose-response relationships. A nested case-control study of embalmers revealed that mortality from myeloid leukemia increased significantly with increasing numbers of embalms and with increasing formaldehyde exposure. The recent meta-risks for all leukemia and myeloid leukemia increased significantly. In South Korea, a few cases were considered occupational cancers as a result of mixed exposures to various chemicals (e.g., benzene), although no cases were compensated for formaldehyde exposure. The peak formaldehyde exposure levels in Korea were 2.70–14.8 ppm in a small number of specialized studies, which considered anatomy students, endoscopy employees who handled biopsy specimens, and manufacturing workers who were exposed to high temperatures. CONCLUSION: Additional evidence is needed to confirm the relationship between formaldehyde exposure and nasopharyngeal cancer. All lymphohematopoietic malignancies, including leukemia, should be considered in cases with occupational formaldehyde exposure.
Biopsy ; Case-Control Studies ; Classification ; Cohort Studies ; Endoscopy ; Formaldehyde ; Hodgkin Disease ; Humans ; Korea ; Leukemia ; Leukemia, Myeloid ; Mortality ; Nasopharyngeal Neoplasms ; Occupational Diseases ; Occupational Exposure ; Plants ; Workers' Compensation

PURPOSE: This retrospective study was conducted for comparison of survival outcomes and toxicities of autologous stem cell transplantation (ASCT) based on the use of total body irradiation (TBI) as a part of the conditioning regimen in patients with mature T- and natural killer (NK)-cell lymphomas. MATERIALS AND METHODS: Patients who underwent ASCT in the upfront or salvage setting between January 2000 and December 2013 were analyzed. Patients were dichotomized according to the TBI group (n=38) and non-TBI group (n=60) based on the type of conditioning regimen for ASCT. RESULTS: Patients with responsive disease underwent upfront ASCT (TBI, n=16; non-TBI, n=29) whereas patients with refractory disease (TBI, n=9; non-TBI, n=12) or relapsed disease (TBI, n=13; non-TBI, n=19) underwent ASCT after salvage treatment. Hematologic and non-hematologic toxicities were manageable, and the median cumulative toxicity score according to Seattle criteria was estimated as 2 (range, 0 to 7) in both groups. No significant difference in 100-day mortality was observed between the TBI (13%, 5/38) and non-TBI (12%, 12/60) groups, and most deaths were related to disease progression. There was no difference in overall and progression-free survival; however, the TBI group showed a trend of better survival in upfront and salvage ASCT than the non-TBI group. However, patients with refractory disease showed the worst outcome regardless of the use of TBI. Patients who showed complete response before ASCT showed better progression-free survival than thosewho showed partial response. CONCLUSION: TBI could be used as an effective part of conditioning for ASCT in patients with mature T- and NK-cell lymphomas.
Disease Progression ; Disease-Free Survival ; Humans ; Lymphoma ; Lymphoma, Non-Hodgkin* ; Mortality ; Retrospective Studies ; Salvage Therapy ; Stem Cell Transplantation* ; Stem Cells* ; T-Lymphocytes ; Whole-Body Irradiation*

BACKGROUND/AIMS: Recently, large cohort studies regarding associations between autoimmune disease and lymphomas have been reported in a few Western countries. However, Asian data concerning autoimmune-related lymphomas are limited. Therefore, we evaluated the clinical characteristics and prognostic factors of patients with autoimmune disease-related non-Hodgkin lymphoma (NHL) in a single center in Korea. METHODS: We analyzed the data from 11 patients with autoimmune-related NHL. Patients were categorized into two groups, those with rheumatoid arthritis (RA) and those with non-RA-related NHL. Then patients were re-categorized into a group with methotrexate (MTX) usage and a MTX non-usage group. Histological subtype, MTX duration, autoimmune disease duration, treatment modalities, and other data were collected and analyzed. RESULTS: Our study revealed that older RA patients have a greater likelihood of occurrence of NHL (p = 0.042). We confirmed that MTX duration and cumulative dose of MTX have no significant correlation with autoimmune disease and NHL (p = 0.073). In the management of autoimmune disease-related NHL, all patients were directly treated with systemic chemotherapy instead of employing a wait and watch approach. Overall survival (OS) and progression-free survival (PFS) in all autoimmune disease-related NHL were 100% and 87.5%, with no treatment-related mortality during the 2-year follow-up period of our study. CONCLUSIONS: Our study suggests that patients with RA-NHL are characterized by older age at onset compared to those with non-RA-NHL. Also considering of OS and PFS, intensive treatment strategy instead of delayed watchful managements may be required for autoimmune disease-related NHL including of old age group.
Age of Onset ; Arthritis, Rheumatoid ; Asian Continental Ancestry Group ; Autoimmune Diseases ; Clinical Study* ; Cohort Studies ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Korea ; Lymphoma ; Lymphoma, Non-Hodgkin* ; Lymphoproliferative Disorders ; Methotrexate ; Mortality ; Retrospective Studies*

OBJECTIVEThe aim of this study was to investigate the effectiveness of treatment, survival and prognostic factors in Chinese patients with Hodgkin lymphoma.

METHODSA total of previously untreated 415 patients with histologically confirmed Hodgkin lymphoma admitted in the Cancer Hospital, Chinese Academy of Medical Sciences from February 1999 to February 2011 were included in this study. Their short-term and long-term survivals, as well as prognostic factors were analyzed.

RESULTSFor the whole group, 371 cases (89.4%) had complete remission (CR), 33 cases (8.0%) had partial remission (PR) and 11 cases (2.7%) experienced disease progression. The CR rates for stage I, II, III and IV patients were 96.6% (56/58), 92.0% (219/238), 83.6% (51/61) and 77.6% (45/58), respectively (P < 0.001). The 5-year disease-free survival (DFS), progression-free survival (PFS) and overall survival (OS) were 90.6%, 84.1% and 92.5%. The stage I-II patients were significantly better than stage III-IV patients in terms of 5-year DFS rate (94.5% vs. 79.2%, P < 0.001), 5-year PFS rate (91.2% vs. 66.4%, P < 0.001) and 5-year OS rate (97.0% vs. 81.5%, P < 0.001). For stage I-II patients, combined modality therapy was related to better DFS, PFS and OS as compared with radiotherapy alone, and was associated with a better PFS compared with chemotherapy alone. There was a trend that consolidative radiotherapy could improve the long-term survival for stage III-IV patients who achieved disease remission after chemotherapy. What's more, consolidative radiotherapy could significantly improve PFS for those stage II-IV patients who achieved PR after chemotherapy. Multivariate analysis showed that clinical stage and pathological type were independent prognostic factors for the 5-year DFS rate (both P < 0.05), and the stage, elevated serum β2-microglobulin and none-ABVD/BEACOP chemotherapy regimen were independent prognostic factors for 5-year PFS rate and 5-year overall survival rate (P < 0.05 for all).

CONCLUSIONSPatients with HL treated in China have a good prognosis. Combined modality therapy is the preferred treatment for stage I-II patients. Consolidative radiotherapy is recommended to those of stage III-IV patients who experienced PR after chemotherapy. Stage, serum β2-microglobulin and first-line chemotherapy regimen significantly affect the prognosis for patients with Hodgkin lymphoma.

Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Bleomycin ; China ; Combined Modality Therapy ; mortality ; Dacarbazine ; Disease Progression ; Disease-Free Survival ; Doxorubicin ; Hodgkin Disease ; mortality ; pathology ; therapy ; Humans ; Multivariate Analysis ; Prognosis ; Radiotherapy, Adjuvant ; mortality ; Remission Induction ; Survival Rate ; Treatment Outcome ; Vinblastine ; beta 2-Microglobulin ; blood

BACKGROUND/AIMS: In Asia, the incidence of non-Hodgkin lymphoma (NHL) has increased in recent decades. Waldeyer's ring (WR) is the most common site of NHL involving the head and neck. In this study, the pathological distribution of WR-NHL and its clinical features were analyzed retrospectively. METHODS: From January 2000 through December 2010, we analyzed the medical records of 328 patients from nine Korean institutions who were diagnosed with WR-NHL. RESULTS: The study group comprised 197 male and 131 female patients with a median age of 58 years (range, 14 to 89). The rate of localized disease (stage I/II) was 64.9%, and that of low-risk disease (low/low-intermediate, as defined by the International Prognostic Index) was 76.8%. Diffuse large B-cell lymphoma (DLBCL; 240 patients, 73.2%) was the most common pathologic subtype, followed by peripheral T-cell lymphoma (14 patients, 4.3%) and nasal NK/T-cell lymphoma (14 patients, 4.3%). WR-NHL occurred most frequently in the tonsils (199 patients, 60.6%). Extranodal involvement was greater with the T-cell subtype (20 patients, 42.5%) compared with the B-cell subtype (69 patients, 24.5%). Multivariate analyses showed that age > or = 62 years, T-cell subtype, and failure to achieve complete remission were significant risk factors for overall survival. CONCLUSIONS: DLBCL was found to have a higher incidence in Korea than those incidences reported by other WR-NHL studies. T-cell lymphoma occurred more frequently than did follicular lymphoma. T-cell subtype, age > or = 62 years, and complete remission failure after first-line treatment were significant poor prognostic factors for overall survival according to the multivariate analysis.
Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Disease-Free Survival ; Female ; Head and Neck Neoplasms/mortality/*pathology/therapy ; Humans ; Incidence ; Kaplan-Meier Estimate ; Lymphoma, Extranodal NK-T-Cell/pathology ; Lymphoma, Large B-Cell, Diffuse/pathology ; Lymphoma, Non-Hodgkin/mortality/*pathology/therapy ; Lymphoma, T-Cell, Peripheral/pathology ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Proportional Hazards Models ; Recurrence ; Remission Induction ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome ; Young Adult

PURPOSE: High-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) have been used for the treatment of clinically aggressive non-Hodgkin's lymphoma (NHL). However, the superiority of specific conditioning regimens has not yet been established. The present study evaluated the efficacy and toxicity of a conditioning regimen involving fractionated total body irradiation (TBI), and the use of Ara-C and melphalan (TAM) for clinically aggressive NHL. MATERIALS AND METHODS: Between March 2002 and December 2004, 31 patients with aggressive NHL received fractionated TBI with a dose of 12 Gy over 3 days, and were administered 9 g/m2 Ara-C and 100 mg/m2 melphalan followed by autologous peripheral blood stem Cell Transplantation at the Catholic Hematopoietic Stem cell transplantation Center Korea. Patients that responded to first line chemotherapy and achieved complete remission (CR), or were in a first sensitive relapse were defined as having less advanced disease, while the other patients were defined as having more advanced disease. RESULTS: Objective responses were obtained in 24 of 31 patients (77.4%), comprising complete remission in 19 patients (61.3%) and partial remission in 5 (16.1%) patients. The median follow-up time was 28 months (range 1~62 months). At 3 years, the overall survival and event-free survival (EFS) rates were 62.3% and 47.3%, respectively. Patients with less advanced disease and more advanced disease showed 3-year EFS rates of 73.3% and 22.5 %, respectively (p=0.006). Early (within the first 100 days) treatment-related mortality occurred in 3 (9.7%) patients. Of the 31 total patients, 15 (48.4%) developed grade 3 mucositis, 22 (70.9%) developed neutropenic fever, and two (6.5%) developed interstitial pneumonia syndrome >grade 3. CONCLUSION: The modified TAM conditioning regimen and ASCT appear to be a feasible treatment regimen for clinically aggressive NHL, particularly for patients with less advanced disease.
Cytarabine ; Disease-Free Survival ; Drug Therapy ; Fever ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; Humans ; Korea ; Lung Diseases, Interstitial ; Lymphoma, Non-Hodgkin* ; Melphalan ; Mortality ; Mucositis ; Peripheral Blood Stem Cell Transplantation ; Recurrence ; Stem Cell Transplantation* ; Stem Cells* ; Whole-Body Irradiation

BACKGROUND: The ESHAP chemotherapy regimen, that is, the combination of the etoposide, methylprednisolone, high-dose cytarabine and cisplatin, has been shown to be active against relapsing or refractory non-Hodgkin's lymphoma (NHL) in previous therapeutic trials. We attempted to determine whether ESHAP therapy would be effective and well-tolerated in Korean patients. METHODS: Twenty two patients with refractory or relapsed NHLs (all aggressive types) were enrolled in this study. We retrospectively evaluated the treatment response, the survival rate and the time to progression. RESULTS: Six patients (27.3%) attained complete remission and eight patients (36.4%) attained partial remission. The overall response rate was 63.6%. The median survival duration was 15.5 months (95% confidence interval; 10.7 to 20.3 months), and the median duration of the time to progression was 8.3 months (95% confidence interval; 0.3 to 16.3 months). Myelosuppression was the major toxicity, but severe neutropenia or thrombocytopenia was rare, and renal toxicity was also infrequent. CONCLUSIONS: ESHAP regimen is effective in Korean patients suffering with relapsed or refractory NHLs, but a more effective salvage modality is needed because of the short duration of remission and the insignificant impact on long-term survival.
Treatment Failure ; Survival Analysis ; *Salvage Therapy ; Prednisone ; Neoplasm Recurrence, Local/*drug therapy/mortality ; Middle Aged ; Methylprednisolone/administration & dosage ; Male ; Lymphoma, Non-Hodgkin/*drug therapy/mortality/pathology ; Humans ; Female ; Etoposide/administration & dosage ; Disease Progression ; Cytarabine/administration & dosage ; Cisplatin/administration & dosage ; *Antineoplastic Combined Chemotherapy Protocols ; Antineoplastic Agents/administration & dosage ; Aged ; Adult ; Adolescent