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 ...

Vitamin B12 defi ciency and folate defi ciency are common causes of macrocytic anaemia and both are important for many cellular processes. These defi ciencies could be due to inadequate dietary intake, impaired absorption or drug ingestion. We present an interesting case of pancytopenia with microangiopathic haemolytic anaemia (MAHA) and intracranial bleeding (ICB) due to combined vitamin B12 and folate defi ciency, mimicking thrombotic thrombocytopenic purpura (TTP). Case presentationA 47-year-old male was admitted to the haematology ward for fatigue, persistent frontal headache and left upper-quadrant abdominal pain that had lasted one week. He was diagnosed with diffuse large B-cell lymphoma (DLBCL) which was treated with six cycles of dose-adjusted EPOCH-rituximab regimen. An end of treatment positron emission tomography (PET) scan reported no active fl uorodeoxyglucose (FDG) uptake, consistent with disease in remission. He had a history of jejunal resection at the age of 42 for bowel ischaemia with unknown aetiology and defaulted surgical follow-up. He was on treatment for type 2 diabetes mellitus and hypertension.Physical examination revealed scleral icterus, pallor and excess weight. There was an old midline laparotomy scar on the abdomen. Other physical and neurological examination fi ndings were unremarkable. The initial laboratory study (Table 1) showed white blood cell (WBC) count of 3.4 x 109/l, haemoglobin (Hb) of 76g/l platelet count of 67 x 109/l, mean corpuscular volume (MCV) of 91.2fl and reticulocyte count of 10.4%. He had indirect hyperbilirubinemia 62μmol/l and markedly raised lactate dehydrogenase (LDH) 9894U/l. Peripheral blood fi lm (PBF) reported anisopoikilocytosis, polychromasia, ovalocytes, spherocytes, numerous teardrop and fragmented red cells, thrombocytopenia (Figure 1) and hypersegmented neutrophils. His Coomb's test was negative, consistent with non-immune haemolytic anaemia. Coagulation profi le, renal, liver and thyroid function tests Vitamin B12 deficiency and folate deficiency are common causes of macrocytic anaemia and both are important for many cellular processes. These de ciencies 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 de ciency mimicking thrombotic thrombocytopenic purpura (TTP) was made. The patient responded well to vitamin B12 and folate replacement.

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.