ORCID Profile
0000-0002-2819-4041
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Publisher: Wiley
Date: 24-06-2019
DOI: 10.1111/BJH.16064
Abstract: De novo diffuse large B-cell lymphoma (DLBCL) presenting with synchronous central nervous system (CNS) and systemic disease (synDLBCL) is not well described and is excluded from clinical trials. We performed a retrospective analysis of 80 synDLBCL patients treated across 10 Australian and UK centres. Of these patients, 96% had extranodal systemic disease. CNS-directed treatment with combination intravenous cytarabine and high-dose methotrexate ("CNS-intensive") (n = 38) was associated with favourable survival outcomes compared with "CNS-conservative" strategies such as intravenous high-dose methotrexate monotherapy, intrathecal therapy and/or radiotherapy (2-year progression-free survival [PFS] 50% vs. 31%, P = 0·006 2-year overall survival [OS] 54% vs. 44%, P = 0·037). Outcomes were primarily dictated by the ability to control the CNS disease, with 2-year cumulative CNS relapse incidence of 42% and non-CNS relapse 21%. Two-year OS for CNS-relapse patients was 13% vs. 36% for non-CNS relapses (P = 0·02). Autologous stem cell transplantation as consolidation (n = 14) was not observed to improve survival in those patients who received CNS-intensive induction when matched for induction outcomes (2-year PFS 69% vs. 56%, P = 0·99 2-year OS 66% vs. 56%, P = 0·98). Hyperfractionated or infusional systemic treatment did not improve survival compared to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) (2-year OS 49% for both groups). Our study suggests that adequate control of the CNS disease is paramount and is best achieved by intensive CNS-directed induction.
Publisher: Wiley
Date: 20-04-2019
DOI: 10.1111/BJH.15173
Publisher: Informa UK Limited
Date: 06-07-2020
Publisher: Wiley
Date: 23-08-2021
DOI: 10.1111/BJH.17789
Abstract: Richter syndrome (RS), an aggressive lymphoma occurring in the context of chronic lymphocytic leukaemia/small lymphocytic lymphoma, is associated with poor prognosis when treated with conventional immunochemotherapy, therefore, improved treatments are required. Immune checkpoint blockade has shown efficacy in some B-cell malignancies and modest responses in early clinical trials for RS. We investigated the immune checkpoint profile of RS as a basis to inform rational therapeutic investigations in RS. Formalin-fixed, paraffin-embedded biopsies of RS (n = 19), de novo diffuse large B-cell lymphoma (DLBCL n = 58), transformed indolent lymphomas (follicular [tFL], n = 16 marginal zone [tMZL], n = 24) and non-transformed small lymphocytic lymphoma (SLL n = 15) underwent gene expression profiling using the NanoString Human Immunology panel. Copy number assessment was performed using next-generation sequencing. Immunohistochemistry (IHC) for LAG3 and PD-1 was performed. LAG3 gene expression was higher in RS compared to DLBCL (P = 0·0002, log2FC 1·96), tFL (P < 0·0001, log2FC 2·61), tMZL (P = 0·0004, log2FC 1·79) and SLL (P = 0·0057, log2FC 1·45). LAG3 gene expression correlated with the gene expression of human leukocyte antigen Class I and II, and related immune genes and immune checkpoints. IHC revealed LAG3 protein expression on both malignant RS cells and tumour-infiltrating lymphocytes. Our findings support the investigation of LAG3 inhibition to enhance anti-tumour responses in RS.
Publisher: American Society of Hematology
Date: 17-08-2017
DOI: 10.1182/BLOOD-2017-03-737460
Abstract: Central nervous system (CNS) relapses are an uncommon yet devastating complication of non-Hodgkin lymphomas. The identification of patients at high risk of secondary CNS relapse is therefore paramount. Retrospective data indicate prophylactic CNS-directed therapies may reduce the risk of CNS involvement however, no consensus exists about dose, timing, or route of therapy. In addition, prophylaxis is not without risk of treatment-related complications and morbidity. Here, we present a series of case vignettes highlighting our approach to common dilemmas encountered in routine clinical practice. We review the method of assessing CNS relapse risk, factors that increase the likelihood of relapse including histologic subtype, MYC rearrangement, protein expression, and extranodal involvement, and review our clinical practice based on available evidence in administering CNS-directed prophylaxis.
Publisher: Wiley
Date: 16-10-2020
DOI: 10.1111/BJH.17072
Abstract: High‐dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) are used as consolidation in first remission (CR1) in some centres for untreated, transformed indolent B‐cell lymphoma (Tr‐iNHL) but the evidence base is weak. A total of 319 patients with untreated Tr‐iNHL meeting prespecified transplant eligibility criteria [age , LVEF ≥45%, no severe lung disease, CR by positron emission tomography or computed tomography ≥3 months after at least standard cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab (R‐CHOP) intensity front‐line chemotherapy] were retrospectively identified. Non‐diffuse large B‐cell lymphoma transformations were excluded. About 283 (89%) patients had follicular lymphoma, 30 (9%) marginal‐zone lymphoma and six (2%) other subtypes. Forty‐nine patients underwent HDC/ASCT in CR1, and a 1:2 propensity‐score‐matched cohort of 98 patients based on age, stage and high‐grade B‐cell lymphoma with MYC, BCL2 and/or BCL6 rearrangements (HGBL‐DH) was generated. After a median follow‐up of 3·7 (range 0·1–18·3) years, ASCT was associated with significantly superior progression‐free survival [hazard ratio (HR) 0·51, 0·27–0·98 P = 0·043] with a trend towards inferior overall survival (OS HR 2·36 ·87–6·42 P = 0·1) due to more deaths from progressive disease (8% vs. 4%). Forty (41%) patients experienced relapse in the non‐ASCT cohort — 15 underwent HDC/ASCT with seven (47%) ongoing complete remission (CR) 10 chimeric antigen receptor‐modified T‐cell (CAR‐T) therapy with 6 (60%) ongoing CR 3 allogeneic SCT with 2 (67%) ongoing CR. Although ASCT in CR1 improves initial duration of disease control in untreated Tr‐iNHL, the impact on OS is less clear with effective salvage therapies in this era of CAR‐T.
Location: United States of America
No related grants have been discovered for Collin Chin.