Acute lymphoblastic leukemia with clonal evolution due to delay in chemotherapy: A report of a case.

Clonal evolution in acute leukemias is one of the most important factors that leads to therapeutic failure and disease relapse. Delay in therapeutic intervention is one of the reasons that leads toward clonal evolution. In this report, we present a case of acute lymphoblastic leukemia in which therapeutic delay resulted in clonal evolution that was detected by conventional karyotyping and was responsible for non-responsiveness of the disease to conventional chemotherapy. A 17-year-old boy presented with generalized body aches, rapidly progressive pallor and lethargy. Bone marrow analysis was consistent with the diagnosis of B-cell ALL. Karyotypic analysis revealed 46, XY male karyotype. The patient left the hospital due to financial reasons and after 40 days came back to the hospital. Repeated bone marrow analysis including cytogenetic studies revealed presence of three different clones of blast cells: one clone showed 46, XY with del(9p) and t (11;14), second clone showed 46, XY with del(7q) and del(9p), and the third clone showed 46, XY normal karyotype. The patient did not respond to chemotherapy and died within 1 week of induction chemotherapy (HyperCVAD-A). Timely diagnosis and institution of chemotherapy in acute leukemias patients is the key to prevent clonal evolution and thus resistance of the disease to therapeutic interventions.

Prevalence, Distribution, and Histopathological Features of Malignant Tumors Reported at Tertiary Level in Afghanistan: A 3-Year Study.

Purpose: Cancer is one of the leading causes of mortality and morbidity, and therefore, tremendous research work is continuously being done around the world with consideration of etiopathogenesis as well as identification of therapeutic targets. Decades of continuous war in Afghanistan has left the medical infrastructure of the country in a miserable situation. There is a serious deficiency in research work in the fields of pathology and oncology at the moment with minimal data available to elaborate about the demographic characteristics of various malignant disorders in the country, which would be indispensable to pave the way for further research and development. Patients and Methods: A descriptive cross-sectional study was conducted to describe the prevalence, distribution, and important histopathological features of malignant tumors reported at tertiary level in Afghanistan. Results: Out of 2328 consecutive cases of solid malignant tumors included in our study, 93.8% were primary and 6.2% were metastatic. Breast was the most common site of origin for primary malignancy (29.5%) in females; however, in males, esophagus was the leading site for primary malignant tumors (16.3%). Invasive ductal carcinoma was the most common histologic type of malignancy in females (87.9%). However, in both genders, squamous cell carcinoma of esophagus and skin, osteosarcoma of bone and soft tissue, and glioblastoma of central nervous system were the most common histologic types of malignancies diagnosed. Small intestine was a frequently involved site affected by extranodal non-Hodgkin lymphomas. Overall, the majority of the cancers were diagnosed in stage-II. Conclusion: Findings in our study were somewhat similar to data presented elsewhere in the world, with some significant differences that could be related to the local factors. Our study revealed that most of the malignant tumors were diagnosed in later stages of the disease, attributable to scarcity of specialized oncology institutions and public awareness.

Acute motor-sensory axonal polyneuropathy variant of Guillain-Barre syndrome complicating the recovery phase of coronavirus disease 2019 infection: a case report.

INTRODUCTION: The novel coronavirus, since its first identification in China, in December 2019, has shown remarkable heterogeneity in its clinical behavior. It has affected humans on every continent. Clinically, it has affected every organ system. The outcome has also been variable, with most of the older patients showing grave outcomes as compared with the younger individuals. Here we present a rare and severe variant of Guillain-Barre syndrome that complicated the disease in recovery phase. CASE PRESENTATION: A 60-year-old Afghan man, who had been recovering from symptoms related to novel coronavirus associated disease, presented with sudden onset of progressive muscle weakness and oxygen desaturation. Electrophysiological workup confirmed the diagnosis of Guillain-Barre syndrome, and early institution of intravenous immunoglobulin resulted in complete resolution. CONCLUSION: Guillain-Barre syndrome has recently been reported in many patients diagnosed with novel coronavirus associated disease. While clinical suspicion is mandatory to guide towards an effective diagnostic workup, early diagnosis of this complication and timely institution of therapeutic interventions are indispensable and lifesaving.

Philadelphia chromosome positive chronic myeloid leukemia with 5q deletion at diagnosis.

BACKGROUND: Although, molecular genetic analyses became more and more important to guide therapy decisions in leukemia, banding cytogenetic analysis has retained its vital role in diagnosis and monitoring of chronic myeloid leukemia (CML), by quick and easy enabling identification of pathognomonic Philadelphia chromosome (Ph). CASE PRESENTATION: A 45 year old female presented with characteristic hematological features of CML in chronic phase; cytogenetic studies revealed the presence of the typical Ph and a deletion of almost entire long arm of a chromosome 5. CONCLUSION: 5q deletions have rarely been reported in CML. Those seen yet were either associated with tyrosine kinase inhibitor therapy or detected post allogeneic stem cell transplantation. To our knowledge, this is the first case of Ph positive CML accompanied by a 5q deletion.

Complex cytogenetic abnormalities in chronic myeloid leukemia resulting in early progression to blast crisis: a case report.

INTRODUCTION: BCR-ABL1, resulting from t(9;22), is the oncogenic driver of chronic myeloid leukemia and the therapeutic target of the disease. Molecular studies have been the gold standard modality for patient assessment since the advent of tyrosine kinase inhibitor therapy. In spite of that, there are cytogenetic abnormalities that can render the disease unresponsive to conventional therapy, thus making cytogenetics an important component of patient management guidelines. CASE PRESENTATION: We present a case of a Tajik, Afghan patient with chronic myeloid leukemia with del(6)(q23.3q27), t(9;22)(q34;q11.2), monosomy 11, monosomy 12, and marker chromosome who, despite having typical clinical and hematological disease with initial response to therapy, progressed to blast crisis very early and thus required special interventions. CONCLUSION: Cytogenetic monitoring is an important pillar in the management of patients with chronic myeloid leukemia that cannot be ignored. It should therefore be a part of patient management not only during diagnosis but also during management. We present an unusual cytogenetic abnormality in a patient with chronic myeloid leukemia that resulted in early disease progression.

Age distribution and types of breast lesions among Afghan women diagnosed by fine needle aspiration cytology (FNAC) at a tertiary care centre in Afghanistan: a descriptive cross-sectional study.

OBJECTIVES: In Afghanistan, breast diseases are a common reason for women to visit hospitals. This is the first study in Afghanistan aimed to describe the age distribution and types of breast diseases among patients diagnosed by fine needle aspiration cytology. DESIGN: Descriptive cross-sectional study. SETTING: French Medical Institute for Mothers and Children, Kabul, Afghanistan. PARTICIPANTS: The study included 650 patients with breast lesions between 1 April 2015 and 1 April 2019. RESULTS: The mean age of diagnosis was 35.38 (SD ±13.11) years, ranging from 15 to 75 years. The most common diagnosis was cancer (24% of all cases). The second most common diagnosed lesion was fibroadenoma, constituting 22.4%, and the third most common lesion was fibrocystic changes, with 15.4% of cases. Inflammatory conditions were diagnosed in 9.7% of cases, granulomatous inflammation in 9.1%, lesions only suspicious for malignancy in 5.5%, lipoma in 2.8% and miscellaneous benign lesions in 11.1%. Cancer was diagnosed at the youngest age of 20 years. Cancer was more common on the left side (62%), and only one case (0.9%) was bilateral. CONCLUSION: Our study showed that cancer was the most commonly diagnosed lesion and was reported at younger ages too. This suggests that physicians should not ignore any breast lump in younger patients and that the possibility of cancer must be considered. Further country-wide studies are suggested to assess breast cancer and associated risk factors.

The BDNF rs6265 variant may interact with overweight and obesity to influence obesity-related physical, metabolic and behavioural traits in Pakistani individuals.

BACKGROUND: The association of the variant rs6265 (G>A) in the brain-derived neurotrophic factor (BDNF) gene with obesity and other obesity-related parameters is not known for the Pakistani population. Moreover, the effects of interaction between BDNF rs6265 and overweight/obesity on obesity-related traits have never been investigated before. AIM: To find the association of the BDNF rs6265 with obesity and related traits and to explore the effect of rs6265 × obesity interaction on obesity-related traits in Pakistanis. SUBJECTS AND METHODS: The study involved a total of 606 subjects, including 306 overweight and obese (OW/OB) cases and 300 normal weight (NW) controls. The genotyping of the BDNF rs6265 was done and obesity-related anthropometric, physical, behavioural and metabolic parameters were determined. Statistical analyses using SPSS software were performed to find the associations. RESULTS: The study revealed a lack of association of the BDNF rs6265 with obesity and obesity-related traits. On the other hand, the interaction between the BDNF rs6265 and overweight/obesity was found to be significantly associated with some of the obesity-related anomalous traits. However, no association between rs6265 and these anomalous traits was seen in either group when the association test was performed in NW and OW/OB groups separately. CONCLUSION: The BDNF rs6265, in the presence of obesity, may be associated with elevated risk of anomalous metabolic, behavioural and physical traits and obesity-related co-morbidities, but it needs to be validated in a significantly larger Pakistani sample population.

MC4R variant rs17782313 and manifestation of obese phenotype in Pakistani females.

MC4R represents a key player involved in melanocortin-mediated control of energy balance. Recently identified near MC4R variant rs17782313 (T > C) can serve as a contributing factor for obese phenotype but its association with obesity has never been sought in a sample of the Pakistani population. The role of genetic variants as causal factors varies across populations. Association studies in a specific population can help us to distinguish global from local gene-gene and gene-environment interactions. This is the first study that investigated the association of rs17782313 with obesity and various obesity-linked anthropometric, metabolic, physical, and behavioural traits in Pakistani subjects including 306 OW/OB (overweight and obese) and 300 NW (normal weight) individuals. The comparison of various aforementioned obesity-linked continuous and categorical variables between OW/OB and NW subjects revealed that almost all variables were found significantly aberrant (p < 0.05) in OW/OB subjects as compared to their age- and gender-matched NW controls indicating greater risk of developing various cardio-metabolic disorders. The genotyping of rs17782313 showed significant association of this variant with obesity and obesity-linked anthropometric traits in females suggesting the gender-specific effect of this variant in our population. The minor allele C increased the risk of obesity by 1.55 times (95% CI = 1.1-2.18, p = 0.01) whereas homozygous CC genotype increased the risk by 2.43 times (95% CI = 1.19-4.96, p = 0.015) in females. However, no association of rs17782313 was observed with any of the obesity-linked metabolic, physical, and behavioural traits except random eating timings. In conclusion, the current study significantly contributes to the knowledge of the genetic proneness to obesity in Pakistani females. This could also be helpful for forthcoming meta-analysis studies elucidating which variants are truly associated with the susceptibility to develop an obese phenotype.