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Relapsed Chronic Lymphocytic Leukaemia with Concomitant Extensive Chronic Graft versus Host Disease after Allogeneic Haematopoietic Stem Cell Transplantation Successfully Treated with Oral Venetoclax

Teoh CS, Goh AS

Case Rep Transplant, 2021;2021:8831125.
PMID: 33552611 DOI: 10.1155/2021/8831125

A middle-aged gentleman who was diagnosed with high-risk chronic lymphocytic leukaemia (CLL), Rai stage IV, Binet C with del(17p) and del(13q) underwent allogeneic haematopoeitic stem cell transplantation (allo-HSCT) from a human leukocyte antigen (HLA) identical sister. The patient developed extensive skin, oral, and liver chronic graft versus host disease (GVHD) required tacrolimus, mycophenolate mofetil (MMF), and prednisolone. At seventh month after allo-HSCT, the patient presented with systemic symptoms, right cervical lymphadenopathy, splenomegaly, marked pancytopaenia, and elevated lactate dehydrogenase (LDH). Bone marrow study, immunophenotyping (IP), chromosome analysis, and PET-CT scan confirmed relapsed CLL with no evidence of Richter's transformation or posttransplant lymphoproliferative disease (PTLD). Withdrawal of immunosuppressant (IS) worsened cutaneous and liver GVHD. Chemotherapy was not a suitable treatment option in view of immunodeficiency. The patient underwent extracorporeal photopheresis (ECP) therapy eventually for extensive chronic GVHD, and the IS were gradually tapered to the minimal effective dose. The relapsed CLL was treated successfully with oral venetoclax accessible via a compassionate drug program. This case highlights challenges in managing relapsed CLL and loss of graft-versus-leukaemia (GVL) effect despite extensive chronic GVHD. Venetoclax is an effective and well-tolerated oral novel agent for relapsed CLL after allo-HSCT.
Microangiopathic haemolytic anaemia and thrombocytopenia due to combined vitamin B12 and folate deficiency masquerading as thrombotic thrombocytopenic purpura

Lee KT, Teoh CS, Chew TK, Goh AS

J R Coll Physicians Edinb, 2020 Jun;50(2):144-147.
PMID: 32568285 DOI: 10.4997/JRCPE.2020.213

Vitamin B12 deficiency and folate deficiency are common causes of macrocytic anaemia and both are important for many cellular processes. These deficiencies could be due to inadequate dietary intake, impaired absorption or drug ingestion. We present a case of a 47-year-old male with a history of diffuse large B-cell lymphoma (DLBCL) who was admitted for fatigue, persistent frontal headache and left upper-quadrant abdominal pain. Further investigation showed that he had pancytopenia with microangiopathic haemolytic anaemia (MAHA) and intracranial bleeding (ICB). Serum vitamin B12 and folate were later found to be low and a diagnosis of combined vitamin B12 and folate deficiency mimicking thrombotic thrombocytopenic purpura (TTP) was made. The patient responded well to vitamin B12 and folate replacement.
The Pattern of Uveitis among Chinese, Malays, and Indians in Singapore

Siak J, Jansen A, Waduthantri S, Teoh CS, Jap A, Chee SP

Ocul Immunol Inflamm, 2017;25(sup1):S81-S93.
PMID: 27419535 DOI: 10.1080/09273948.2016.1188968

PURPOSE: To describe the pattern of uveitis among Chinese, Malays, and Indians at a tertiary referral institution in Singapore.
METHODS: Charts between January 1997 and December 2010 were retrospectively reviewed. Charts between January 2014 and December 2014 were prospectively reviewed.
RESULTS: A total of 1249 and 148 charts were retrospectively and prospectively reviewed, respectively. The top causes of anterior uveitis (AU) were HLA-B27, idiopathic, and CMV AU. The top known causes of intermediate uveitis were tuberculosis, primary intraocular lymphoma, and sarcoidosis. The top causes of posterior uveitis were CMV retinitis, toxoplasmosis, and dengue maculopathy. The top causes of panuveitis were VKH, idiopathic panuveitis, tuberculosis, and Behçet disease. HLA-B27 and CMV AU were more frequent among Chinese (21% vs 9% (non-Chinese); p<0.001; 10% vs 5% (non-Chinese); p<0.001, respectively). Tuberculous uveitis was more frequent among Malays and Indians (12% (non-Chinese) vs 5% (Chinese), p<0.001).
CONCLUSIONS: Different uveitis patterns were encountered among patients of different races.
Impact of Double Expression of C-MYC/BCL2 Protein and Cell of Origin Subtypes on the Outcome among Patients with Diffuse Large B-Cell Lymphoma: a Single Asian Center Experience

Teoh CS, Lee SY, Chiang SK, Chew TK, Goh AS

Asian Pac J Cancer Prev, 2018 May 26;19(5):1229-1236.
PMID: 29801406

Background: Diffuse large B-cell lymphoma (DLBCL) with double expression of c-MYC and BCL2 protein is
associated with dismal outcome after treatment with R-CHOP. Local data on disease burden and survival outcome in
DLBCL is limited. We investigated the prognostic values of c-MYC/BCL2 protein co-expression and cell of origin
subtypes using immunohistochemistry (IHC) and to determine their associations with multiethnic groups under
resource limited setting. Methods: This was a retrospective study which recruited 104 patients in between June 2012
and December 2015 for IHC review and analysis. Result: We demonstrated that patients with high International
Prognostic Index (IPI) (score 3-5) and co-expression of c-MYC/BCL2 protein had significant inferior overall survival
(OS) and event free survival (EFS) respectively (P<0.05). c-MYC/BCL2 protein co-expression was more common in
non-germinal center B-cell (non-GCB) (P=0.048) and contributed to adverse prognosis in this group of patients (OS,
P=0.004; EFS, P=0.005). In multivariate analysis, double-protein co-expression was a significant independent predictor
of inferior outcome after adjusted for IPI and cell of origin subtypes (OS hazard ratio [HR], 2.11; 95% CI, 1.01 to 4.04;
P=0.048; EFS HR, 2.31; 95% CI, 1.05 to 5.04; P=0.036). In addition, non-GCB subtype was more common than GCB
in Malays (60% vs 40%, P=0.106) and Chinese (81.2% vs 18.8%, P=0.042). Indians had more DLBCL without c-MYC/
BCL2 protein co-expression compared to double-protein positive cases (66.7% vs 33.3%, P=0.414). Otherwise, the
prognostic impact of ethnicity on survival outcome was insignificant (P=0.961). Conclusion: c-MYC/BCL2 protein
co-expression in non-GCB subtype constituted a unique group with extremely inferior outcome regardless of ethnicity.
Gene expression profile (GEP) may possibly provide insights into the cause of discrepancies in DLBCL subtypes and
protein expression among the multiethnic groups.
Fulltext Herbal Ingestion During Pregnancy and Post-Partum Period is A Cause For Concern

Teoh CS, Aizul MHI, Wan Fatimah Suriyani WM, Ang SH, Nurul Huda MZ, Nor Azlini MI, et al.

Med J Malaysia, 2013 Apr;68(2):157-60.
PMID: 23629564 MyJurnal

The potential harms of herbs to the pregnant mothers and their foetuses as well as the effect of herbs taken by nursing mothers on their babies remain largely unknown. Common perception is that herbal medicines ingestion during pregnancy and confinement period is a common practice among multi-racial Malaysian mothers. The purpose of this study was to explore the usage of herbal medicines during pregnancy and post-partum period among mothers who gave birth at a tertiary hospital in a metropolitan city of Malaysia. This cross sectional study was conducted between October and December 2010. The subjects were interviewed twice after giving birth: before hospital discharge and 6 to 8 weeks later. A total of 323 mothers were recruited for this study. The prevalence of herbs ingestion during pregnancy was 13.9%, with half of the users consuming it during the first trimester. A total of 163 (52.9%) mothers ingested herbs during the post-partum period. Significantly more Chinese (p=0.01) and Malay (p=0.04) mothers ingested herbs during pregnancy and post-partum period, respectively. Infants of mothers who ingested herbs had a higher rate of neonatal jaundice compared to infants of mothers who did not ingest herbs during the post-partum period (P=0.001).
Fulltext Clinical Significance of BCL2, C-MYC, and BCL6 Genetic Abnormalities, Epstein-Barr Virus Infection, CD5 Protein Expression, Germinal Center B Cell/Non-Germinal Center B-Cell Subtypes, Co-expression of MYC/BCL2 Proteins and Co-expression of MYC/BCL2/BCL6 Proteins in Diffuse Large B-Cell Lymphoma: A Clinical and Pathological Correlation Study of 120 Patients

Ting CY, Chang KM, Kuan JW, Sathar J, Chew LP, Wong OJ, et al.

Int J Med Sci, 2019;16(4):556-566.
PMID: 31171907 DOI: 10.7150/ijms.27610

Background: Clinical significance of germinal center B-cell (GCB) and non-GCB sub-categorization, expression of MYC, BCL2, BCL6, CD5 proteins and Epstein Barr virus encoded RNA (EBER) positivity in diffuse large B-cell lymphoma (DLBCL) remain controversial. Could these biomarkers accurately identify high risk DLBCL patients? Are MYC, BCL2 and BCL6 proteins expression feasible as baseline testing to predict c-Myc, BCL2 or BCL6 gene rearrangements? Aims: To investigate prognostic values of GCB/non-GCB sub-categorization, Double Protein Expression Lymphoma (DPL), Triple Protein Expression Lymphoma (TPL), positivity of CD5 protein and EBER in patients with DLBCL disease. To evaluate correlation between BCL2 , c-Myc and BCL6 gene rearrangements with BCL2, MYC and BCL6 proteins expression. Methods: Diagnostic tissue samples of 120 DLBCL patients between January 2012 to December 2013 from four major hospitals in Malaysia were selected. Samples were subjected to immunohistochemical staining, fluorescent in-situ hybridization (FISH) testing, and central pathological review. Pathological data were correlated with clinical characteristics and treatment outcome. Results: A total of 120 cases were analysed. Mean age of diagnosis was 54.1 years ± 14.6, 64 were males, 56 were females, mean follow up period was 25 months (ranged from 1 to 36 months). Of the 120 cases, 74.2% were non-GCB whereas 25.8% were GCB, 6.7% were EBER positive, 6.7% expressed CD5 protein, 13.3% were DPL and 40% were TPL. The prevalence of c-Myc, BCL2, BCL6 gene rearrangements were 5.8%, 5.8%, and 14.2%, respectively; and 1.6% were Double Hit Lymphoma (DHL). EBER positivity, DPL, TPL, c-Myc gene rearrangement, BCL2 gene rearrangement, extra copies of BCL2 gene and BCL6 gene rearrangement were associated with shorter median overall survival (P<0.05). IPI score was the significant determinants of median overall survival in DPL and TPL (P<0.05). CD5 protein expression and GCB/non-GCB sub-categorization did not affect treatment outcome (P>0.05). Overall, c-Myc, BCL2 and BCL6 gene rearrangements showed weak correlation with expression of MYC, BCL2 and BCL6 proteins (P>0.05). Fluorescent in situ hybridization is the preferred technique for prediction of treatment outcome in DLBCL patients. Conclusion:c-Myc, BCL2, and BCL6 gene rearrangements, EBER expression, DHL, TPL and IPI score are reliable risk stratification tools. MYC, BCL2 and BCL6 proteins expression are not applicable as baseline biomarkers to predict c-Myc, BCL2, and BCL6 gene rearrangements.