T315I - a gatekeeper point mutation and its impact on the prognosis of chronic myeloid leukemia.

Objectives: kinase domain mutations are an important cause of resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukaemia (CML) of which T315I is the most treatment-resilient. This study aimed to observe the frequency of T315I and its impact on disease prognosis in terms of progression and survival.

Methods: Patients with a response which categorized them into warning zone/or who failed to respond to their TKI treatment completely as per the European LeukemiaNet (ELN) were labeled as non-responders.

Cytogenetic culture failure and its causes in hematological disorders; a single centre perspective.

Objective: To highlight the reasons of culture failure in bone marrow aspirate samples sent for Cytogenetic analysis and to identify the associated parameters causing this impact.

Methodology: This is a retrospective cross-sectional study conducted in the Clinical and Molecular Cytogenetics Laboratory of NIBD Hospital, Karachi, Pakistan. The rates of culture failure are assessed from the year 2017-2020 along with their reasons.

Fludarabine/Cyclophosphamide Conditioning Regimen in Aplastic Anemia Patients Receiving Matched-Sibling Donor Transplant Is Non-inferior to ATG/Cyclophosphamide: A Single-Center Experience from Pakistan.

The successful outcome of allogeneic hematopoietic stem cell transplant (HSCT) in aplastic anemia patients is driven by suitable donor selection, appropriate conditioning regimen, early intervention, and optimal supportive care after transplant. Pakistan, being a developing country, faces grave economic challenges due to meager health care budget; therefore, cost constraints remain the foremost impediment in optimizing transplant facilities for socioeconomically deprived patients. We conducted a single-center retrospective analysis of aplastic anemia patients ( = 130), who received matched sibling donor transplants from 2011 to 2019, treated with either fludarabine/cyclophosphamide (Flu/Cy) or antithymocyte globulin/cyclophosphamide (ATG/CY) conditioning regimen.

CLINICAL RELEVANCE OF EXTENDED PLATELET INDICES IN THE DIAGNOSIS OF IMMUNE THROMBOCYTOPENIA.

Immune thrombocytopenia (ITP) is an autoimmune disorder. Besides platelet count, immature platelet fraction (IPF) can be used as a tool to predict megakaryocytic activity in ITP patients. The aim of the study was to evaluate the utility of extended platelet indices in ITP diagnosis and their association with disease persistence and severity.

P-Loop mutations-Negative prognosticators in tyrosine kinase inhibitors resistant chronic myeloid leukemia patients.

Introduction: P-Loop mutations in CML patients prevent the conformational change in BCR-ABL1 necessary for drug binding. The present study aimed to evaluate the impact of mutations in this domain on the prognosis of the disease and also to associate the baseline Sokal relative risk score with the overall survival in non-responding CML patients.

Methods: Blood samples were analyzed using ARMS-PCR and then an association was assessed between presence/absence of mutations, hematological and molecular response, disease progression, overall survival, and Sokal score.

Beyond the In-Practice CBC: The Research CBC Parameters-Driven Machine Learning Predictive Modeling for Early Differentiation among Leukemias.

A targeted and timely treatment can be a beneficial tool for patients with hematological emergencies (particularly acute leukemias). The key challenges in the early diagnosis of leukemias and related hematological disorders are their symptom-sharing nature and prolonged turnaround time as well as the expertise needed in reporting confirmatory tests. The present study made use of the potential morphological and immature fraction-related parameters (research items or cell population data) generated during complete blood cell count (CBC), through artificial intelligence (AI)/machine learning (ML) predictive modeling for early (at the pre-microscopic level) differentiation of various types of leukemias: acute from chronic as well as myeloid from lymphoid.

Diagnosis and Management of Diffuse Large B-Cell Lymphoma: Society of Medical Oncology, Pakistan Society of Hematology, and Pakistan Society of Clinical Oncology Joint Clinical Practice Guideline.

Diffuse large B-cell lymphoma (DLBCL) is the commonest non-Hodgkin lymphoma encountered by hematopathologists and oncologists. Management guidelines for DLBCL are developed and published by countries with high income and do not cater for practical challenges faced in resource-constrained settings. This report by a multidisciplinary panel of experts from Pakistan is on behalf of three major national cancer societies: Society of Medical Oncology Pakistan, Pakistan Society of Hematology, and Pakistan Society of Clinical Oncology.

Sequencing of SARS-CoV-2 in local transmission cases through Oxford Nanopore MinION platform from Karachi Pakistan.

Introduction: The first case of severe acute respiratory syndrome 2 (SARS-CoV-2) was imported to Pakistan in February 2020, since then 8,260 deaths have been witnessed. The virus has been constantly mutating and local transmission cases from different countries vary due to host dependent viral adaptation. Many distinct clusters of variant SARS-CoV-2 have been defined globally.

Usefulness of convalescent plasma transfusion for the treatment of severely ill COVID-19 patients in Pakistan.

Background: Convalescent plasma(CP) was utilized as potential therapy during COVID-19 pandemic in Pakistan. The study aimed at appraisal of CP transfusion safety and usefulness in COVID pneumonia.

Methods: Single arm, MEURI study design of non-randomized open label trial was conducted in five centers.

Mature and Immature/Activated Cells Fractionation: Time for a Paradigm Shift in Differential Leucocyte Count Reporting?

Leucocytes, especially neutrophils featuring pro- and anti-cancerous characteristics, are involved in nearly every stage of tumorigenesis. Phenotypic and functional differences among mature and immature neutrophil fractions are well reported, and their correlation with tumor progression and therapy has emerging implications in modern oncology practices. Technological advancements enabled modern hematology analyzers to generate extended information (research parameters) during complete blood cell count (CBC) analysis.

A Pragmatic Scoring Tool to Predict Hydroxyurea Response Among β-Thalassemia Major Patients in Pakistan.

Despite high prevalence and incidence of β-thalassemia in Pakistan, there is very limited work on the use of hydroxyurea (HU) in thalassemia patients in the country. This is the first insight regarding genetic profiling of BCL11A and HU responses in Pakistani β-thalassemia. It correlates single-nucleotide polymorphisms on BCL11A (rs4671393, rs766432) and HBG2 (XmnI), age at first transfusion, and β-globin mutations with HU response in β-thalassemia major (BTM).

Incorporating a clinical oncology pharmacist into an ambulatory care pharmacy in pediatric hematology-oncology and transplant clinic: Assessment and significance.

Background: Beta thalassemia patients, post-bone marrow transplant, and leukemia patients require long term therapy with an intense care follow-up especially for pediatric hematology-oncology origin. Emergence of side effects and noncompliance to therapy lead to reduced efficacy of medicines resulting in relapse of diseases. There is an increasing fact to support the incorporation of a pharmacist into clinical team due to their distinctive skills.

Peripheral Blood Stem Cell Harvest HPC Count Is an Effective Surrogate Marker for CD34+ Cell Count in Allogeneic Stem Cell Transplant Setting.

Objective: We assessed the predictive potential of XN-HPC for CD34+ cell count as obtained through Sysmex automated hematology analyzers (XN-1000).

Methods: This study was conducted at the National Institute of Blood Diseases and Bone Marrow Transplantation in 84 donors between December 2012 and December 2017 in the first phase and later validated in 112 donors between December 2017 and December 2018. Sysmex XN-1000 and BD FACS Calibur estimated XN-HPC and CD34+ cells of peripheral blood apheresis product, respectively.

A distinct molecular mutational profile and its clinical impact in essential thrombocythemia and primary myelofibrosis patients.

Background: Classical MPNs including ET and PMF have a chronic course and potential for leukaemic transformation. Timely diagnosis is obligatory to ensure appropriate management and positive outcomes. The aim of this study was to determine the mutational profile, clinical characteristics and outcome of ET and PMF patients in Pakistani population.

Case report of one month and 15 days old baby with type V hyperlipoproteinemia (HLP).

Background: Most of the patients with type 1 and V hyperlipoproteinemia (HLP) present with symptoms and signs of acute pancreatitis due to marked elevation of triglycerides, but this baby presented with a chest infection, which was later diagnosed as type V HLP on laboratory workup.

Case Presentation: We report a case of a 1 month and 15 days old baby boy, product of 2-nd degree consanguinity admitted to a nearby hospital with complaints of refusal to feed, cough and excessive crying. On examination his heart rate was 102 beats/min, respiratory rate was 55 breaths/min and temperature was within the normal range, provisional diagnosis of Pneumonia was made.

Cell Population Data-Driven Acute Promyelocytic Leukemia Flagging Through Artificial Neural Network Predictive Modeling.

A targeted and timely offered treatment can be a benefitting tool for patients with acute promyelocytic leukemia (APML). Current round of study made use of potential morphological and immature fraction-related parameters (cell population data) generated during complete blood cell count (CBC), through artificial neural network (ANN) predictive modeling for early flagging of APML cases. We collected classical CBC items along with cell population data (CPD) from hematology analyzer at diagnosis of 1067 study subjects with hematological neoplasms.

Characterization of the mutation spectrum in a Pakistani cohort of type 3 von Willebrand disease.

Introduction: Type 3 von Willebrand disease (VWD), a severe autosomal recessive hereditary bleeding disorder, is described by the virtual absence of von Willebrand factor (VWF). In consanguineous populations, for example Pakistan, the disease is reported with a higher incidence rate than the worldwide prevalence.

Aims: This study aims to characterize molecular pathology and clinical profile of type 3 VWD cohort of Pakistani origin.

Correction to: Identification of novel mutations in congenital afibrinogenemia patients and molecular modeling of missense mutations in Pakistani population.

[This corrects the article DOI: 10.1186/s12959-017-0143-3.].

Hydroxyurea (hydroxycarbamide) for transfusion-dependent β-thalassaemia.

Background: Hydroxyurea (hydroxycarbamide) promotes the production of foetal haemoglobin (HbF) by reactivating gamma-genes. Evidence has shown clinical benefits of hydroxyurea in people with sickle cell anemia; however, only a few studies have assessed this treatment in people with beta (β)-thalassaemia.

Objectives: The primary objective is to review the efficacy of hydroxyurea in reducing or ameliorating the requirement of blood transfusions in people with transfusion-dependent β-thalassaemia.

Early and sustained deep molecular response achieved with nilotinib in high Sokal risk chronic myeloid leukemia patients.

Background: Nilotinib (Tasigna®) is a second-generation tyrosine kinase inhibitor that shows faster and deeper molecular responses (MR) in comparison to Imatinib as initial therapy in chronic phase chronic myeloid leukemia (CML). Efficacy and safety data for nilotinib in the Asian population is scarce, particularly in Pakistan. We aimed to determine the MR to nilotinib and its safety profile in patients with chronic phase CML.

Lung resistance-related protein (LRP) predicts favorable therapeutic outcome in Acute Myeloid Leukemia.

There is conflicting evidence that MDR1, MRP2 and LRP expression is responsible for chemotherapy resistance. We conducted this study to explore their role in AML therapy outcomes. Bone marrow and peripheral blood samples of 90 AML patients, receiving chemotherapy, were analyzed by real time PCR.

Gene expression of , , , and topoisomerase IIα as an indicator of chemotherapy response in AML treated with cytarabine and daunorubicin.

Purpose: Acute myeloid leukemia patients are commonly treated with cytarabine (Ara-C) and anthracyclines but the sustained remission rate is not very promising. We explored the role of drug-metabolizing enzymes and transporters in the therapeutic response.

Patients And Methods: Bone marrow and peripheral blood samples of 90 newly diagnosed acute myeloid leukemia patients treated with standard 3+7 regimen were analyzed through real-time PCR for expression of human equilibrative nucleoside transporter 1, deoxycytidine kinase, cytidine deaminase (), deoxycytidine monophosphate deaminase () and topoisomerase IIα ().