Chromosomal Breakage in Fanconi Anemia and Consanguineous Marriages: A Social Dilemma for Developing Countries.

Introduction A clear picture of the prevalence of Fanconi anemia is not known due to limited studies and research of the subject. This study will detect the frequency of positive chromosomal breakage in pediatric aplastic patients and provide the evidence-based guidelines which help in consideration of appropriate treatment and awareness to the society. Methods A total of 104 aplastic anemia patients were recruited of age <18 years whose samples were tested for chromosomal breakage with mitomycin C (MMC). History of consanguinity between parents were documented for all the patients referred to us. Result Out of 104 diagnosed aplastic anemia patients, 35 (33.7%) patients were found to be Fanconi positive. Mean age of all hypoplastic patients for aplastic anemia and Fanconi anemia was 10.7 ± 4.5 and 10.6 ± 3.5, respectively. Male preponderance was found to be higher (64, 61.5%) as compared to females (40, 38.5%) in aplastic patients. The male to female ratio was observed as 2.5:1 in Fanconi patients while 1.3:1 in non-Fanconi aplastic patients. Parental consanguinity was observed in 33 (94.2%) with Fanconi anemia. Conclusion Fanconi anemia accounts for significant number of patients with hypoplastic bone marrow, therefore consanguineous marriages should be avoided through mass education in Pakistan.

Environmental determinants of aplastic anemia in Pakistan: a case-control study.

AIM: Aplastic anemia (AA) affects the Asian population two to three fold more than people in other regions. Besides the host genetics and socioeconomic status, several other environmental exposures have been linked with an AA etiology. We aimed to examine the association of various environmental exposures with AA occurrence among Pakistani individuals. SUBJECTS AND METHODS: A case-control study was conducted in Karachi, Pakistan, where cases (diagnosed AA patients) were selected from the National Institute of Blood Disease and Bone Marrow Transplantation (NIBD), while for each case, a single control (who was free of AA and visited the outpatient department of the same hospital for the treatment of minor ailments) was selected matched by age and sex. A total of 428 participants were included in this study with equal proportions of cases and controls. Information related to disease characteristics, sociodemographics and exposure to chemicals was collected through a survey questionnaire, laboratory investigations and medical records. Descriptive results were reported as frequencies and proportions, adjusted odds ratios with 95 % confidence intervals and population attributable risk (PAR) as percentage. RESULTS: Among study participants (n = 428), AA was significantly associated with various environmental exposures. Participants residing in rural settings (OR = 2.29, 95 % CI 1.12-4.67, p-value < 0.01) and those who reported exposure to pesticides (OR = 3.58, 95 % CI 1.27-10.10, p-value 0.01; PAR = 18.16 %) were significantly more likely to report AA. Participants with a formal education were significantly less likely to have AA (OR = 0.27, 95 % CI 0.10-0.71, p-value < 0.01). CONCLUSIONS: This study observed a significant association of aplastic anemia with a lower socioeconomic profile, and certain environmental exposures among the Pakistani population. The evidence may be helpful in understanding the pathophysiology of aplastic anemia in the context of environmental exposures.

Outcome of Inversion 16 in TKD Positive and Negative Acute Myeloid Leukemia Patients.

abstract.

Epidemiologic and HLA antigen profile in patients with aplastic anemia.

OBJECTIVE: To analyze patients suffering from aplastic anemia (AA, peripheral pancytopenia and hypocellular bone marrow in the absence of dysplasia, infiltration and fibrosis) for documenting patient's baseline characteristics and association with various human leucocyte antigens. STUDY DESIGN: An observational, cross-sectional study. PLACE AND DURATION OF STUDY: The National Institute of Blood Disease (NIBD), Karachi, from March 2003 to August 2008. METHODOLOGY: All consecutive patients with confirmed diagnosis of AA were evaluated. Data included the baseline characteristics, complete blood counts (CBC), bone marrow biopsy findings, severity of disease, exposure to drugs or chemicals, viral serology and their HLA expression. The data was analyzed on SPSS programme and frequencies were documented. RESULTS: Among 318 patients, there were 236 (74.21%) males and 82 (25.78%) females. Median age was 16 and 70% belonged to urban population. Drug exposure could be established in 23 (7.23%) of cases, while 4 (1.25%) were HBV surface antigen positive and 7 (2.2%) were HCV antibodies positive. In all, 73 (22.9%) had very severe AA, 195 (61.32%) had severe AA while 50 (15.7%) cases had non-severe AA. HLA B5 (52) showed high expression in 83 patients (26%) in comparison to 5.9% reported in healthy population. CONCLUSION: AA was found to affect young adult males living in urban areas. HLA B5 (52) showed higher expression in patients with aplastic anemia.

JAK2V617F mutation in chronic myeloid leukemia predicts early disease progression.

OBJECTIVE: To determine the association of JAK2V617F mutation along with BCR-ABL translocation or Philadelphia chromosome in chronic myeloid leukemia with early disease progression to advanced stages (accelerated phase or blast crisis) and poor outcome. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, from February 2008 to August 2009. METHODOLOGY: All the newly diagnosed cases of BCR-ABL or Philadelphia positive CML were tested for JAK2V617F mutation by Nested PCR. Demographic data, spleen size, hemoglobin levels, white blood cell and platelet counts were recorded. Independent sample t-test was used for age, haemoglobin level and spleen size. Fisher's exact test was applied to compare disease progression in JAK2V617F mutation positive and negative cases. RESULTS: Out of 45 newly diagnosed cases of CML, 40 were in chronic phase, 01 in accelerated phase and 04 in blast crisis. JAK2V617F mutation was detected in 12 (26.7%) patients; 09 (22.5%) in chronic phase, none in accelerated phase and 03 (75%) in blast crisis. During a mean follow-up of 8 months, 03 patients in chronic phase transformed in blast crisis and 02 into accelerated phase. Overall 08 out 0f 11 (73%) JAK2V617F positive patients either had advanced disease or showed disease progression. Only 2 of 20 (10%) available patients, negative for the mutation, showed disease progression by transforming into blast crisis (p < 0.001). No statistically significant difference was seen in the age, spleen size, haemoglobin levels, white blood cells and platelets counts in JAK2V617F positive patients. CONCLUSION: JAK2V617F mutation was detected in 26.7% cases of chronic myeloid leukemia. A significant proportion of them showed early disease progression.