Recent advances in diagnosis of acute myeloid leukaemia : a review.

Acute Myeloid Leukaemia is one of the commonest blood cancer in Malaysia. Recent advancements in molecular genetics have led to better understanding of AML pathogenesis which is crucial for patient stratification and therapeutic options. The advent of next generation sequencing (NGS) is now the vogue to interrogate acute myeloid leukaemia (AML) genome at single base pair resolution. In this review, we will discuss current approaches in the diagnosis of AML and the role of NGS in elucidation of genomic aberrations. Although NGS is anticipated to impact the new era of AML diagnosis, there are challenges in understanding mutations found in an AML genome and how this technology will be implemented in a diagnostic setting. NGS will pave the way for perso nalized medicine approach, with the hope of better response to tailored treatment regimen

Antigen expression pattern of acute promyelocytic leukaemia cases in Malaysia

Introduction: Acute Promyelocytic Leukaemia (APL) is associated with devastating coagulopathy and life threatening condition which requires immediate medical attention. It is crucial to establish an expedited diagnosis as early therapeutic intervention has led to optimal patient management. In this study, we assessed the type and frequency of antigen expressions in APL and correlated these findings with genetic studies. Methods: Multiparametric immunophenotyping was performed on 30 samples and findings were correlated with karyotypes, FISH for t(15;17) translocation and RT-PCR for PML-RARα for detection of breakpoint cluster regions (bcr1,bcr2 and bcr3). Results: On SSC/CD45, APL cells displayed high to moderate SSC, with the expression of CD33 (100%), CD13 (96.8%), cMPO (71%) but lacked CD34 (3.2%) and HLA-DR (9.7%). Aberrant expression of CD4 was seen in 12.9% and CD56 in 6.5% of the cases. A significant association between cumulative aberrant antigen expression and bcr1 were observed bcr1 (X2(2) =6.833,p.05) and (X2(2)=4.599,p>.05) respectively. Conclusions: Flow cytometry is a rapid and effective tool in detecting APL. It is interesting to note that there is significant association between cumulative aberrant antigen expression and genotype analysis. Further validation is required to corroborate this relationship

Immature reticulocyte fraction in guiding stem cell harvest in autologous peripheral blood stem cell transplant

Peripheral blood (PB) CD34+ cells enumeration is currently the most reliable method to guide the timing of stem cell harvest. However, its usage is restricted by being technically challenging, costly, and time-consuming. Immature reticulocyte fraction (IRF) determination, which is simpler and cheaper and has a faster turn-around time, has been proposed for a similar purpose. The purpose of this study is to evaluate the value of IRF in guiding stem cell harvest and examine the correlation between IRF and PB CD34+ cells count. Daily pre-harvest tests, i.e. PB CD34+ cells and IRF from 21patients scheduled for autologous PBSC transplant were assessed. Stem cells harvests were commenced when the PB CD34+ cell count were more than 10 cell/ul. A total of 205 pre-harvest tests were analysed. Following stem cell mobilisations, both the IRF and PB CD 34+ cell counts rose with a variable pattern. In this study, we observed that the IRF peaks preceded the PB CD34+ count by 2 days. On the day of stem cell harvest, all the peak IRF values were >0.3. The PB CD34+ cell counts correlated with the harvested stem cell yield, whereby r2 = 0.77, p 0.3 may be used as a cut-off value for the initiation of PB CD34+ quantification prior to stem cell harvest

Aggressive variant large granular lymphocytic leukaemia: a case report

Clonal disorders of LGL may either be CD3+ CD56- or CD3- CD56+ phenotype and these have been designated as T-cell leukaemia (T-LGL) or natural killer cell (NK)-LGL leukaemia respectively. Clonality is usually demonstrated by clonal rearrangement of T-cell receptor gene rearrangement or identified by flowcytometry analysis. Most patients with T-LGL will have an indolent course. In this report we described an aggressiveness of disease in a patient with clonal CD3+ LGL leukaemia whose cells also co-expressed CD56 diagnosed by flowcytometry. The patient responded well to interrupt all standard risk protocol however succumbed to her disease while waiting for upfront stem cell transplant. This case highlights on both the classical laboratory findings of rare entity of disease as well as a review of the literature pertaining particularly on its management

Qualitative flow cytometric analysis of Malaysian myelodysplastic syndromes (MDS) patients.

Myelodysplastic syndromes (MDS) are a group of haematological malignancies categorized by ineffective hematopoiesis that result in dysplasia. Although morphological diagnosis is a traditional and standard technique that is used for the diagnosis of MDS, the heterogeneous blood and bone marrow characteristics of MDS patients can potentially obscure the right diagnosis. Thus, we have utilized flow cytometric immunophenotyping as a supportive mechanism to obtain a more accurate and faster method for detection of abnormal markers in MDS. Flow cytometry was used for analyzing bone marrow samples from newly diagnosed MDS patients to investigate the abnormal antigen expression patterns in granulocytic, monocytic, erythroid, lymphoid lineages and myeloid precursors. The results were compared with those obtained from cases that had Idiopathic Thrombocytopenic Purpura (ITP) as a control. The most common abnormality found in the granulocytic lineage was the decrease of CD10. Low expressions of CD13 were the most frequent abnormality in the monocytic lineage. The erythroid lineage was found to have low expression of CD235A+/CD71+, reduce of CD71 and decreased CD235a. In conclusion, this method is useful for confirming cases in which it is difficult to make a diagnosis by morphology

Trend Analysis of Tides Level and Projection Sea Level Rise On the West Coast of Peninsular Malaysia

Globally, sea levels are rising due to climate change caused by humans. Current and future sea level rise will have a variety of effects, particularly on coastal infrastructure. This study analysed the tidal level trend and projected sea level rise along the western coast of peninsular Malaysia using tide level records collected between 1986 and 2012. The seasonal Mann-Kendall test and linear trend were used to determine the tide level trend over time and to predict sea level rise for 2050 and 2100. Based on a confidence interval of 95%, the results of the analysis indicated a rising trend at all stations. Tau values for the Mann-Kendall test range between 0.16 and 0.33, while seasonal Mann-Kendall values range between 0.18 and 0.41. Based on the sea level projection analysis, the mean sea level will rise between 8.77 cm and 14.29 cm in 2050, and between 20.44 cm and 33.20 cm in 2100. In conclusion, the sea level trend at all stations on the west coasts of peninsular Malaysia exhibits an upward trend

Thrombosis at unusual sites in reproductive age group-a case series

Thrombosis is one of the causes of morbidity and mortality in women of reproductive age group. Thrombosis at unusual sites may pose diagnostic and management dilemma for health care personnel. Teamwork and good communication provide the best modalities for maximum benefits to patients. Here with, we presented case a series of thrombosis at unusual sites seen and managed in our clinic. A 35 year-old Malay lady presented with left hemiparesis while she was on oestrogen based combined contraception pills (C-OCP). Imaging studies showed extensive venous thrombosis with bilateral acute cortical infarct. Thrombophilia screening of antiphospholipid syndrome were negative. She was put on anticoagulant and stopped 2 years after the incident. A 40 year-old Malay lady presented with abdominal discomfort, lethargy and massive splenomegaly. Bone marrow and trephine examination revealed primary myelofibrosis with positive JAK2617F. Imaging study showed chronic portal vein thrombosis with portal vein hypertension, complicated by gastro-oesophageal varices. She was put on hydroxyurea and later started on ruxolitinib with banding done over her gastro-oesophageal varices. A 26 year-old Malay lady presented with serositis, mouth ulcer and anaemia symptoms. Laboratory studies were positive for systemic lupus erythematosus and negative for antiphospholipid study. Imaging study showed long segment thrombosis of right internal jugular vein with surrounding subcutaneous oedema. She is currently stable on anticoagulants and steroid. Teamwork and holistic approach is practiced in the investigation and management to provide maximum benefits for patients

Trend Analysis of Tides Level and Projection Sea Level Rise On the West Coast of Peninsular Malaysia

Globally, sea levels are rising due to climate change caused by humans. Current and future sea level rise will have a variety of effects, particularly on coastal infrastructure. This study analysed the tidal level trend and projected sea level rise along the western coast of peninsular Malaysia using tide level records collected between 1986 and 2012. The seasonal Mann-Kendall test and linear trend were used to determine the tide level trend over time and to predict sea level rise for 2050 and 2100. Based on a confidence interval of 95%, the results of the analysis indicated a rising trend at all stations. Tau values for the Mann-Kendall test range between 0.16 and 0.33, while seasonal Mann-Kendall values range between 0.18 and 0.41. Based on the sea level projection analysis, the mean sea level will rise between 8.77 cm and 14.29 cm in 2050, and between 20.44 cm and 33.20 cm in 2100. In conclusion, the sea level trend at all stations on the west coasts of peninsular Malaysia exhibits an upward trend

MTHFR C677T polymorphism, homocysteine and B vitamins status in a sample of Chinese and Malay subjects in Universiti Putra Malaysia.

INTRODUCTION: Methylenetetrahydrofolate reductase (MTHFR) C677T is involved in folate and homocysteine metabolism. Disruption in the activity of this enzyme will alter their levels in the body. METHODOLOGY: This study assessed MTHFR C677T polymorphism and its relationship with serum homocysteine and B-vitamins levels in a sample of Chinese and Malays subjects in UPM, Serdang. One hundred subjects were randomly selected from among the university population. Folate, vitamin B12, B6, and homocysteine levels were determined using MBA, ECLIA, and HPLC, respectively. PCR coupled with HinfI digestion was used for detection of MTHFR C677T polymorphism. RESULTS: The frequency of T allele was higher in the Chinese subjects (0.40) compared to the Malay (0.14). Folate, vitamin B12 and B6 levels were highest in the wild genotype in both ethnic groups. Subjects with heterozygous and homozygous genotype showed the highest homocysteine levels. The serum folate and homocysteine were mainly affected by homozygous genotype. CONCLUSION: MTHFR C677T polymorphism plays an important role in influencing the folate and homocysteine metabolism

Childhood idiopathic myelofibrosis : a case report and review of literature.

Idiopathic myelofibrosis occurs predominantly in older adults. It is very rarely seen in children. We describe a 3-year-old girl with Down's syndrome who presented with recurrent chest infections associated with anaemia and easy bruising. There was mild hepatosplenomegaly. Full blood picture revealed pancytopaenia with leucoerythroblastosis with absence of circulating blast cells. Repeated attempts at bone marrow aspiration and trephine biopsy were unsuccessful. A trephine biopsy from the tibia showed depressed myelopoiesis and erythropoiesis, megakaryocytes with atypical morphology and increased bone marrow reticulin fibres, findings compatible with idiopathic myelofibrosis. She was treated symptomatically as she was clinically stable. Review of the English literature online yielded 46 reported cases of childhood idiopathic myelofibrosis with variable outcome from spontaneous remission to an indolent course with shortened survival. 6 cases evolved to another malignancy. 5 cases were associated with Down's syndrome