1.Long-term survival and clinical implications of allogeneic stem cell transplantation in relapse/refractory lymphoma: A 20-year Singapore experience.
Wei Sheng Joshua LOKE ; Jean Rachel CATAPIA ; Chay Lee LOW ; Francesca LIM ; Jeffrey QUEK ; Hein THAN ; Yeow Tee GOH ; Yeh Ching LINN ; Colin Phipps DIONG ; Aloysius HO ; William HWANG ; Chung Cheng Jordan HWANG ; Aditi GHOSH ; Liang Pui KOH ; Lip Koon TAN ; Joanne LEE ; Li Mei Michelle POON ; Cheng Kiat Lawrence NG
Annals of the Academy of Medicine, Singapore 2024;54(1):5-16
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*
2.Innovative analysis of predictors for overall survival from systemic non-Hodgkin T cell lymphoma using quantile regression analysis.
Da-Yong HUANG ; Yi-Fei HU ; Na WEI ; Li FU ; Lin WU ; Jing SHEN ; Jing-Shi WANG ; Zhao WANG
Chinese Medical Journal 2019;132(3):294-301
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
3.Presence of multiple abnormal immunologic markers is an independent prognostic factor of diffuse large B-cell lymphoma.
Yiwen CAO ; Zhenhua LIU ; Wen WU ; Ying QIAN ; Qin SHI ; Rong SHEN ; Binshen OUYANG ; Pengpeng XU ; Shu CHENG ; Jin YE ; Yiming LU ; Chaofu WANG ; Chengde YANG ; Li WANG ; Weili ZHAO
Frontiers of Medicine 2019;13(1):94-103
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
4.Clinical features and prognosis of children with mature B-cell non-Hodgkin's lymphoma: an analysis of 28 cases.
Zai-Sheng CHEN ; Yong-Zhi ZHENG ; Yi-Qiao CHEN ; Qin-Li GAO ; Jian LI ; Jian-Zhen SHEN
Chinese Journal of Contemporary Pediatrics 2018;20(6):470-474
<b>OBJECTIVEb>To study the clinical features and treatment outcome of children with mature B-cell non-Hodgkin's lymphoma (B-NHL).
<b>METHODSb>A 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.
<b>RESULTSb>Among 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.
<b>CONCLUSIONSb>The 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
5.NAPD regimen for patients with recurrent refractory diffuse large B-cell lymphoma.
Chenghui HUANG ; Hui WU ; Haihua ZHU ; Lan LIU ; Ruifang TIAN ; Cong XU ; Xiaofei LI ; Lihui WANG ; Ke CAO ; Peiguo CAO
Journal of Central South University(Medical Sciences) 2018;43(7):754-759
To investigate the clinical efficacy and toxicities for the NAPD regimen (vinorelbine, cytarabine, cisplatin, and dexamethasone) in the treatment of recurrent refractory diffuse large B-cell lymphoma.
Methods: A total of 30 patients identified with recurrent refractory diffuse large B-cell lymphoma were enrolled in this retrospective study. The curative efficacy of NAPD regimen was evaluated after 2 consecutive cycles. The toxicities and adverse reaction were evaluated after 1 cycle. The objective response rate (ORR), overall survival (OS), progress free survival (PFS), and the rates of 1, 2, and 4-year OS and PFS were analyzed. The prognosis was evaluated with univariate analysis.
Results: The ORR was 56.7% and clinical benefit rate (CBR) was 83.3% after 2 cycles. Five patients achieved complete remission, 12 achieved partial remission, and 8 achieved stable disease. The median OS was 22 (1.5-140) months. The 1, 2, and 4-year OS rates were 59.1%, 48.2%, and 40.2%, respectively. The median PFS was 14 (1.5-140) months. The 1, 2 and 4-year PFS rates were 56.3%, 42.2%, and 31.7%, respectively. The main adverse reaction was myelosuppression. Three patients suffered from grade III-IV leukopenia and 1 thrombocytopenia. Grade I-II gastrointestinal toxicity was 20%. No heart, liver, and kidney damages at grade III-IV were observed.
Conclusion: The NAPD regimen is effective and its toxicity is well tolerated for the treatment of recurrent refractory diffuse large B-cell lymphoma. It is a salvage chemotherapy regimen worth to be verified.
Antineoplastic Combined Chemotherapy Protocols
;
adverse effects
;
therapeutic use
;
Cisplatin
;
administration & dosage
;
Cytarabine
;
administration & dosage
;
Dexamethasone
;
administration & dosage
;
Humans
;
Induction Chemotherapy
;
Lymphoma, Large B-Cell, Diffuse
;
drug therapy
;
mortality
;
Neoplasm Recurrence, Local
;
drug therapy
;
mortality
;
Retrospective Studies
;
Salvage Therapy
;
methods
;
Treatment Outcome
;
Vinblastine
;
administration & dosage
;
analogs & derivatives
;
Vinorelbine
6.Gastric Adenocarcinoma Secondary to Primary Gastric Diffuse Large B-cell Lymphoma.
Riwa SAKR ; Marcel MASSOUD ; Georges AFTIMOS ; Georges CHAHINE
Journal of Gastric Cancer 2017;17(2):180-185
Despite the decreasing incidence and mortality from gastric cancer, it remains a major health problem worldwide. Ninety percent of cases are adenocarcinomas. Here, we report a case of gastric adenocarcinoma developed after successful treatment of prior primary gastric diffuse large B-cell lymphoma (DLBCL). Our patient was an elderly man with primary gastric DLBCL in whom complete remission was achieved after R-CHOP (cyclophosphamide, adriamycin, vincristine, prednisolone plus rituximab) chemotherapy. Helicobacter pylori infection persisted despite adequate treatment leading to sustained chronic gastritis. The mean time to diagnose metachronous gastric carcinoma was seven years. We believe that a combination of many risk factors, of which chronic H. pylori infection the most important, led to the development of gastric carcinoma following primary gastric lymphoma. In summary, patients who have been successfully treated for primary gastric lymphoma should be followed up at regular short intervals. H. pylori infection should be diagnosed promptly and treated aggressively.
Adenocarcinoma*
;
Aged
;
B-Lymphocytes*
;
Doxorubicin
;
Drug Therapy
;
Gastritis
;
Helicobacter pylori
;
Humans
;
Incidence
;
Lymphoma
;
Lymphoma, B-Cell*
;
Mortality
;
Neoplasms, Second Primary
;
Prednisolone
;
Risk Factors
;
Stomach Neoplasms
;
Vincristine
7.Reduced Dose Intensities of Doxorubicin in Elderly Patients with DLBCL in Rituximab Era.
Hyerim HA ; Bhumsuk KEAM ; Tae Min KIM ; Yoon Kyung JEON ; Se Hoon LEE ; Dong Wan KIM ; Chul Woo KIM ; Dae Seog HEO
Cancer Research and Treatment 2016;48(1):304-311
PURPOSE: The dose intensity of doxorubicin (DID) is important to the survival of diffuse large B cell lymphoma (DLBCL) patients. However, due to expected toxicities, most elderly patients cannot receive full doses of anthracyclines. The purpose of this study was to evaluate the effect of DID on the survival of elderly DLBCL patients (age > or = 70 years) in the rituximab era. MATERIALS AND METHODS: We analyzed 433 DLBCL patients who were treated with R-CHOP between December 2003 and October 2011 at the Seoul National University Hospital. Of these patients, 19.2% were aged > or = 70 years. We analyzed the survival outcomes according to DID. RESULTS: Significantly poorer overall survival (OS) was observed for patients aged > or = 70 years (2-year OS rate: 59.9% vs. 84.2%; p < 0.001). DID < or = 10 mg/m2/wk had a significant effect on the OS and progression-free survival (PFS) in elderly patients (2-year OS rate: 40.0% in DID < or = 10 mg/m2/wk vs. 62.6% in DID > 10 mg/m2/wk; p=0.031; 2-year PFS: 35.0% vs. 65.7%; p=0.036). The OS on each 1.7 mg/m2/wk doxorubicin increment above 10 mg/m2/wk in elderly patients was not significant among the groups (2-year OS rate: 75.0% in DID 10.0-11.7 mg/m2/wk vs. 66.7% in DID 15.0-16.7 mg/m2/wk; p=0.859). Treatment related mortality was not related to DID. CONCLUSION: DID can be reduced up to 10 mg/m2/wk in elderly DLBCL patients in the rituximab era. Maintenance of DID > 10 mg/m2/wk and judicious selection of elderly patients who are tolerant to DID is necessary.
Aged*
;
Anthracyclines
;
Disease-Free Survival
;
Doxorubicin*
;
Humans
;
Lymphoma, B-Cell
;
Mortality
;
Seoul
8.Usefulness of Flow Cytometric Analysis for Detecting Leptomeningeal Diseases in Non-Hodgkin Lymphoma.
Sang Yong SHIN ; Seung Tae LEE ; Hee Jin KIM ; Young Lyun OH ; Seok Jin KIM ; Won Seog KIM ; Sun Hee KIM
Annals of Laboratory Medicine 2016;36(3):209-214
BACKGROUND: The clinical usefulness of flow cytometry (FCM) for the diagnosis of leptomeningeal diseases (LMD) in non-Hodgkin lymphomas has been suggested in previous studies but needs to be further validated. With this regards, we evaluated the use of FCM for LMD in a series of Korean patients with non-Hodgkin lymphoma. METHODS: FCM and cytomorphology were conducted using samples obtained from clinically suspected LMD patients, follow-up LMD patients, and those with high risk of developing tumorigenic diseases. We then compared results of FCM and cytomorphology. In total, 55 and 47 CSF samples were analyzed by FCM and cytomorphology, respectively. RESULTS: Of the samples analyzed, 25.5% (14/55) and 12.8% (6/47) were positive by FCM and cytomorphology, respectively. No samples were determined as negative by FCM but positive by cytomorphology. Seven patients were positive only by FCM and negative by cytomorphology, and six among them were clinically confirmed to have LMD either by follow-up cytomorphology or imaging study. CONCLUSIONS: We observed a high detection rate of tumor cells by FCM compared with cytomorphology. FCM study can be useful in early sensitive detection of LMD.
Adult
;
Aged
;
Female
;
Flow Cytometry
;
Glucose/cerebrospinal fluid
;
Humans
;
Leukocytes/cytology
;
Lymphoma, Large B-Cell, Diffuse/diagnosis/mortality
;
Lymphoma, Non-Hodgkin/*complications
;
Male
;
Meningeal Neoplasms/cerebrospinal fluid/complications/*diagnosis
;
Middle Aged
;
Prognosis
;
Retrospective Studies
;
Survival Rate
9.Prognostic value of bone marrow hematogones in childhood B-lineage acute lymphoblastic leukemia.
Yue-Fan WANG ; Yong-Mei JIANG ; Ju GAO ; Ping ZHOU ; Ge ZHANG
Chinese Journal of Contemporary Pediatrics 2016;18(4):292-296
<b>OBJECTIVEb>To study the prognostic value of hematogones (HGs) for childhood B-lineage acute lymphoblastic leukemia (B-ALL) during consolidation chemotherapy.
<b>METHODSb>A retrospective analysis was conducted for 196 children with newly-diagnosed B-ALL. They were divided into high-risk group (n=55), intermediate-risk group (n=69), and low-risk group (n=72) by risk stratification, and into complete remission group (n=165) and relapse group (n=31) by clinical outcome. The European BIOMED-1 standard flow cytometry for minimal residual disease (MRD) was used to determine the number of HGs during consolidation chemotherapy. The Kaplan-Meier survival curve was used to assess event-free survival (EFS).
<b>RESULTSb>The high-risk group had a significantly lower number of HGs than the intermediate-risk and low-risk groups (P<0.05). The number of HGs in the complete remission group was significantly higher than in the relapse group (P<0.05). The children with HGs ≤1.0% had a significantly lower EFS than those with HGs <1.0% (P<0.05).
<b>CONCLUSIONSb>HGs can be used to assess the treatment outcome and prognosis in children with B-ALL, and proliferation of HGs reflects the good effect of chemotherapy in such children.
Adolescent ; Bone Marrow ; pathology ; Child ; Child, Preschool ; Female ; Flow Cytometry ; Humans ; Infant ; Male ; Neoplasm, Residual ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; mortality ; pathology ; Prognosis ; Retrospective Studies
10.Significance of PAX5 deletion in childhood B-lineage acute lymphoblastic leukemia without reproducible chromosomal abnormalities.
Xiao-Ming LIU ; Li ZHANG ; Min RUAN ; Tian-Feng LIU ; Jia-Yuan ZHANG ; Fang LIU ; Ben-Quan QI ; Xiao-Juan CHEN ; Shu-Chun WANG ; Wen-Yu YANG ; Ye GUO ; Yao ZOU ; Yu-Mei CHEN ; Xiao-Fan ZHU
Chinese Journal of Contemporary Pediatrics 2016;18(4):287-291
<b>OBJECTIVEb>To identify the incidence of PAX5 deletion in childhood B-lineage acute lymphoblastic leukemia (B-ALL) without reproducible chromosomal abnormalities and to investigate the association between PAX5 abnormalities and prognosis of ALL.
<b>METHODSb>Multiplex ligation-dependent probe amplification was used to determine the copy numbers of PAX5 gene in children newly diagnosed with B-ALL without reproducible chromosomal abnormalities between April 2008 and April 2013 and controls (children with non-hematologic diseases or tumors). The patients were classifiied into deletion group and non-deletion group based on the presence of PAX5 deletion.
<b>RESULTSb>Eighteen (21%) out of 86 children with B-ALL had PAX5 deletion. The deletion group had a significantly higher total white blood cell count at diagnosis than the non-deletion group (P=0.001). The Kaplan-Meier analysis demonstrated that the deletion group had a significantly lower disease-free survival (DFS) rate than the non-deletion group (0.69±0.12 vs 0.90±0.04; P=0.017), but there was no significant difference in the overall survival rate between the two groups (P=0.128). The Cox analysis showed that PAX5 deletion was a risk factor for DFS (P=0.03).
<b>CONCLUSIONSb>PAX5 deletion is an independent risk factor for DFS in B-ALL children without reproducible chromosomal abnormalities.
Acute Disease ; Adolescent ; Cell Lineage ; Child ; Child, Preschool ; Chromosome Aberrations ; Disease-Free Survival ; Female ; Gene Deletion ; Humans ; Infant ; Male ; PAX5 Transcription Factor ; genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; mortality

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