Evaluating the Effect of Induction Chemotherapy on Bone Metabolizing Nutrients in Patients of Acute Lymphoblastic Leukemia.

OBJECTIVE: To determine the levels of bone metabolizing nutrients (vitamin D, calcium, magnesium, potassium) in patients with acute lymphoblastic leukemia (ALL) before and after induction chemotherapy, and to correlate the effect of induction chemotherapy on their bone mass (BM). MATERIALS AND METHODS: This quasi-experimental study was carried out at Hayatabad Medical Complex (HMC) and Khyber Medical University (KMU) in Peshawar, Pakistan, in one year. A total of 69 newly diagnosed patients with ALL were enrolled in the study. They were to begin the induction phase of chemotherapy at HMC oncology ward for about four weeks, following standard protocols. Data was collected using a predesigned questionnaire, and blood samples were obtained from all the patients by applying a non-probability consecutive sampling technique. The bone biomarkers levels were measured before therapy and after induction chemotherapy for comparison. Data analysis was performed using Statistical Package for the Social Sciences (SPSS) version 23 (IBM Corp., Armonk, NY, USA), and a p-value of <0.05 was considered significant. RESULTS: The mean age was 13 ± 5.23 years. Out of the 69 patients enrolled in the study, 36 (52%) were male and 33 (48%) were female. After the four-week induction chemotherapy, there was a significant reduction in bone contents levels. Vitamin D, calcium, magnesium and potassium levels were below the levels documented prior to the treatment with a p-value < 0.05. The bone mass remained unchanged after the four weeks of chemotherapy. CONCLUSION: The induction phase of chemotherapy causes a significant reduction in the levels of bone bio contents and results in bone morbidities.

Evaluation of Hematological Parameters in the Genetic Prospective in Epileptic Patients of Khyber Pakhtunkhwa.

BACKGROUND: Epilepsy is a treatable disease, but unfortunately a treatment gap exists in epileptic patients, especially in developing countries, due to adverse effects of antiepileptic drugs and polymorphisms in genes. Carbamazepine is the most commonly used medication in epilepsy, but is related to some serious and rare adverse effects. The aim of the study was to investigate the effect of folate metabolizing genes (MTHFR and DHFR) polymorphisms on different parameters of complete blood count in patients who were treated with carbamazepine and valproic acid. MATERIALS AND METHODS: Blood samples from 267 epileptic patients were collected on consent and surrogate consent forms. The blood was analyzed for changes in different parameters in complete blood count through a blood analyzer. The MTHFR gene was genotyped using the RFLP method. The data were analyzed using GraphPad Prism 6. RESULTS: The homozygous mutant genotype (677CT) of the methylenetetrahydrofolate reductase enzyme (MTHFR C677T) gene significantly affects the level of hemoglobin (P=0.12), hematocrit (P=0.008) and mean corpuscular hemoglobin (P=0.01) compared to the homozygous wild genotype (677CC) and heterozygous mutant genotype (677CT) of the MTHFR (C677T) gene. However, the heterozygous genotype (1298AC) of MTHFR (A1298C) gene affect the total leukocyte count (P=0.037) level significantly. CONCLUSION: Changes in different parameters of complete blood count were statistically significant but clinically insubstantial decreases in different parameters of complete blood count indexes.

Red Cell Alloimmunization In Multitransfused Thalassaemia Major Patients.

BACKGROUND: Lifelong transfusions are life savers for thalassaemia patients but are associated with many complications. Alloimmunization is a major problem for blood banks. Antigens of foreign red blood cells induce the formation of antibodies in patients suffering from thalassaemia. The purpose of this study was to examine the frequency of red cell alloantibodies and to express the type of these antibodies in thalassaemia patients. METHODS: Patients that have received multiple transfusions were included in this study. Those with the positive Coombs test (DAT) results were excluded from the study and remaining patients were screened for antibodies. A panel of known blood group antigens was used for the patients who had a positive antibody screening test because they had alloantibodies in their serum. First, three cell panel was applied. If the screen was positive then eleven cell panels was used to identify the specific antibody. Both the cell panels were applied at room-temperature, liss (low ionic strength saline) and coombs phase. RESULTS: Three hundred & two patients were selected out of which 65.6% (n=198) were males and 34.4% (n=104) females. Patient's age ranged from 1.5 years to 26 years ±5.40 years. All of the patients were given regular red cell transfusion at 2-4 weeks interval. They were given non leukodepleted transfusions. It is not the practice in any thalassaemia Centre in Pakistan to give phenotypically matched blood for Kell, Kidd, Duffy or any other minor group antigens to patients on regular blood transfusion. Alloimmunization was positive in 12 (4.0%) of the 302 patients studied. Male were 66.67% (n=8) and female were 33.33% (n=4). Samples of these positive patients were further tested to determine specificity of alloantibodies. Anti Cw was most common, detected in 4 out of 12 (1.3%) patients. Anti K, k, S and Lua were detected in 2 out of 12 (0.7%) each. CONCLUSIONS: Thalassemia major patients on regular blood transfusions can develop red cell alloantibodies. Detailed pretransfusion screening would add towards better management of these patients.

Mutation Spectrum and Genotype-Phenotype Analyses in a Pakistani Cohort With Hemophilia B.

This study aimed to (1) identify F9 genetic alterations in patients with hemophilia B (HB) of Pakistani origin and (2) determine the genotype-phenotype relationships in these patients. Diagnosed cases of HB were identified through registries at designated tertiary health-care centers across the country. Consenting patients were enrolled into the study. The factor IX (FIX) coagulation activity (FIX:C) and key clinical features were recorded. Direct sequencing of F9 was carried out in all patients. All the variants identified were analyzed for functional consequences employing in silico analysis tools. Accession numbers from National Center of Biotechnology Information ClinVar database were retrieved for the novel variants. Genotype-FIX:C relationships were determined followed by FIX:C clinical phenotype assessment. A total of 52 patients with HB from 36 unrelated families were identified, which mainly comprised patients with moderate HB (n = 35; 67.3%). Among these, 35 patients from 22 unrelated families could be contacted and enrolled into the study. Missense variants were the most frequent (58.8%), followed by nonsense variants (17.6%). A missense, a short insertion, and a nonsense novel variants in exon 2, 6, and 7, respectively, were also identified. The disease manifested FIX:C heterogeneity in relation to the corresponding mutation in a significant number of cases. Clinical phenotype heterogeneity was also observed in relation to FIX:C-based severity assessment. We concluded that the registered FIX-deficient population of Pakistan mainly comprises moderate HB. F9 mutation spectrum in Pakistani patients with HB is heterogeneous. The HB population of Pakistan manifests a significant amount of genotype-FIX:C and FIX:C-clinical phenotype heterogeneities.