Real-World Challenges of Managing Diffuse Large B-Cell Lymphoma in a Developing Country.

PURPOSE: To highlight challenges and cancer care disparities in patients of diffuse large B-cell lymphoma management in resource-constrained settings. MATERIALS AND METHODS: This multicenter retrospective study included 738 patients from 12 public and private sector hematology-oncology centers across Pakistan. Patients were divided into limited-resource and enhanced-resource settings as per national diffuse large B-cell lymphoma (DLBCL) guidelines. RESULTS: The median age at diagnosis was 47 years (range, 14-89). Male:female ratio was 2.5:1. Majority of the patients (69.3%) were treated in limited-resource settings. Computed tomography was used as a staging modality in 442 (60%) patients. Limited-stage DLBCL was present in 13.5% of patients, while 86.3% had advanced-stage disease at diagnosis. First-line regimens included rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in 56% and cyclophosphamide, doxorubicin, vincristine, prednisone in 34% of patients, while 10% of patients received palliative regimens upfront. Of evaluable data, complete remission was documented in 299 (74.4%) patients, 39 (9.8%) had partial response and 63 (13.5%) had progressive disease. Disease-free survival (DFS) and overall survival (OS) status were not available for 345 (46.8%) patients at the time of data collection. Overall study cohort had a median follow-up of 2.2 years with a median OS of 3.6 years (95% CI, 3.1 to 4.1), median DFS of 3.1 years (95% CI, 2.6 to 3.6), and a 5-year OS of 40% and DFS of 36%. CONCLUSION: Patients from low- and middle-income countries present at an earlier age and have more advanced disease. Patients were frequently lost to follow-up, and record keeping was inadequate more so in patients treated in limited-resource settings. There is a need to establish a national lymphoma registry, improve record keeping, and standardize treatments to ensure improvement in treatment outcomes.

Brief cognitive behavior therapy for stigmatization, depression, quality of life, social support and adherence to treatment among patients with HIV/AIDS: a randomized control trial.

OBJECTIVE: Individuals living with HIV/AIDs are at a high risk of many problems like depression, stigma, quality of life, decreased adherence to treatment, and lack of social support. The present study aimed to investigate the impact of brief-cognitive behavior therapy (B-CBT) on reducing depression and stigma and improving treatment adherence, quality of life, and social support among patients with HIV/AIDS attending antiretroviral therapy (ART). MATERIALS AND METHODS: This randomized clinical trial was conducted at ART Clinic in the Tehsil Headquarters Hospital Shahkot Nankana Sahib from July 2021 to October 2021. After baseline screening, 126 patients met the eligibility criteria and 63 were allocated to the experimental group (EXPg = 63) and 63 to waitlist-control group (WLCg = 63). Participants' age range was from 20 to 55 years. Participants who were taking ART treatment were enrolled for the CBT treatment. Before this, all the participants completed a baseline assessment to ensure a level of severity and diagnosis. A total of eight CBT based therapeutic sessions were conducted individually with EXPg. To assess the outcomes among patients receiving ART, we used Demographic form, Patient health questionnaire, HIV stigma scale, General medication adherence scale, Multidimensional scale of perceived social support, and WHOQOL BREF scale. RESULTS: Findings suggest that B-CBT significantly reduced the level of depression (i.e. F (1, 78) = 101.38, p < .000, η2 = .599), and social stigma (i.e. F (1, 78) = 208.47, p < .000, η2 = .787) among patients with HIV/AIDS. Furthermore, CBT substantially improved the level of adherence to treatment (i.e. F(1,78) = 24.75, p < .000, η2 = .503), social support (i.e. F (1, 78) = 128.33, p < .000, η2 = .606), and quality of life (i.e. F (1, 78) = 373.39, p < .000, η2 = .837) among patients with HIV/AIDS. Significant mean difference M(SD) on PHQ at post-analysis in the EXPg vs. WLCg was seen 1.22(0.47) vs. 2.30(0.68) and similarly, on MPSS at a post-analysis in the EXPg vs. WLCg 2.85(0.36) vs. 1.70(0.51) which indicates sound therapeutic outcomes. CONCLUSIONS: Cognitive behavioral therapy effectively decreases the level of depression and stigma and enhances the level of social support, quality of life, and adherence to treatment among HIV/AIDS patients. It is concluded that cognitive behavior therapy is an effective treatment approach for patients with HIV/AIDS. TRIAL REGISTRATION: Thai clinical trial registry (i.e. TCTR = TCTR20210702002 ).

Assessment of Hepatic Profile in Acquired Aplastic Anemia: An Experience From Pakistan.

INTRODUCTION:  Aplastic anemia (AA) is characterized by pancytopenia and hypocellular marrow in the absence of an abnormal infiltrate or increase in reticulin fibrosis. The diagnosis of AA is challenging at times due to decreased cellularity and overlapping morphological features with other bone marrow failure syndromes. Hepatitis-associated aplastic anemia (HAAA) is a rare variant in which patients typically present with jaundice and hepatitis followed by pancytopenia almost within 6 months. Post-hepatitis AA accounts for approximately 1-5% of cases, and invariably such cases are negative for the known hepatitis virus as well. There is limited literature available to understand the correlation of AA with hepatitis with none reported at the national level in our region. As AA is relatively more prevalent in Southeast Asia as compared to the western world and hepatitis is a prevalent disease in our population, the main purpose of this study was to assess the hepatic profile and determine the association of hepatitis in AA at the time of diagnosis. MATERIALS AND METHODS:  A cross-sectional study was carried out at the National Institute of Blood Disease and Bone Marrow Transplantation, Karachi, from November 2019 to December 2020 after the informed consent from patients. The study included all treatment-naïve patients of acquired AA with no prior history of taking steroids, immunosuppressive treatment, or chemoradiation therapy. Liver function tests, complete blood count, prothrombin time (PT), and activated partial thromboplastin time were performed, along with viral profiles (HAV, Hep B, Hep C, and HIV). SPSS version 23 (IBM Corp., Armonk, NY) was used for statistical analysis. Mean and standard deviations were computed for quantitative variables while percentages and frequencies were reported for qualitative variables. T-test was used to observe the main difference between groups and a p-value <0.05 was considered to be significant. RESULTS:  Out of a total of 351 patients, 29 (8.2%) patients with AA tested positive for viral hepatitis. Hepatitis A was the most prevalent hepatitis (4.0%), followed by hepatitis C (3.7%). The comparison of platelet counts in patients with and without hepatitis was reported to be of statistical significance (p-value < 0.05). A significant statistical difference (p-value < 0.0001) was found in platelet count and PT in patients of AA with and without hepatitis. CONCLUSION:  Overall, this study revealed that <10% of patients of AA had a positive screening for hepatitis A, B, and C and low platelet count, and PT was statistically significant when compared between the patients with and without hepatitis. Hepatitis being prevalent in our part of the world might have an important causal association with AA. Patients with AA should be screened for liver functions and viral hepatitis at the time of diagnosis. In addition to hepatitis A, B, and C and HIV, other causes of hepatitis should also be screened such as parvovirus B19, human herpes virus 16, and adenovirus which are not included in routine diagnostic viral testing panel.

Coagulation Abnormalities and Risk Assessment in Acute Promyelocytic Leukemia: An Experience From a Resource-Constraint Country.

Introduction The objective of the study was to assess the impact of coagulopathy in risk-stratified acute promyelocytic leukemia (APML) patients irrespective of bleeding manifestation. Patients and methods This was a cross-sectional study design conducted at the National Institute of Blood Diseases and Bone Marrow Transplantation (NIBD & BMT) from November 2019 to December 2021. A total of 62 patients between three years to 74 years of age of either gender and treatment-naive cases of APML were included in the study. Morphological diagnosis was made on bone marrow samples, and confirmation was done by karyotyping/fluorescence in situ hybridization (FISH) and/or polymerase chain reaction (PCR). Complete blood count (CBC), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, and fibrinogen levels were done for bleeding risk assessment. Cases other than APML and cases on treatment were excluded from the study. Results A total of 85 APML patients were registered at our institute. Among them, 62 (73%) were included in the analysis as per the inclusion criteria of the study. The median age was 32 (3-74) years, with a male predominance of 34 (55%). According to the Sanz score, 18 (29%) patients were noted to have low risk; however, 22 (35.4%) patients were found to have an intermediate-risk disease and 22 (35.4%) patients had high-risk disease. There was positive bleeding history among 44 (71%) patients, followed by fever in 28 (45%) patients. Raised PT, APTT, and D-dimer were found in 46 (74%), 38 (61%), and 52(83.8%) patients, respectively. Low fibrinogen levels were observed among 16 (26%) patients. The association of risk stratification and bleeding history with CBC and coagulation parameters was observed. Platelet count and total leucocyte count were noted to be significantly associated with risk stratification. However, there was no association observed between the rest of the parameters with risk stratification and bleeding. Conclusion The results of our study suggest that regardless of bleeding symptoms, coagulation parameters must be investigated at the time of diagnosis in patients with suspected APML, and in addition to all-trans-retinoic acid (ATRA), transfusion of fresh frozen plasma should be done. It has clinical value, and adding it to the algorithm of treatment would be beneficial to the patients in the developing world, where resources are already meager.

Environmental and occupational determinants of myelodysplastic syndrome: A case-control study from Pakistan.

BACKGROUND: Myelodysplastic syndromes (MDS) are heterogeneous group of haematopoietic stem cell disorders and have variable reduction in the production of red cells, platelets and mature granulocytes. AIM: We conducted a case-control study evaluating the environmental and occupational determinants as risk factors of MDS. METHODS: A case-control study was conducted including 150 de novo MDS cases and 450 age and gender-matched controls. Disease characteristics, sociodemographics and exposure to environmental and occupational determinants were collected through a questionnaire. Chi-square test was applied to observe association, and binary logistic regression was applied to predict the odds of having MDS. RESULTS: A total of 600 participants were analysed. Those who were exposed to arsenic (OR 31.81, CI: 19.0-53.0, P-value: .000), benzene (OR 1.564, CI: 1.07-2.27, P-value: .01) using natural source of water (OR 3.563, CI: 2.29-5.53, P-value: .000) and smokers (OR 3.1, P-value: .000) were more likely to have MDS. Unmarried were less likely to acquire MDS than married (OR 0.239, CI: 0.15-0.36, P-value: .000), Sindhi speaking were 1.419 times more likely to have MDS than participants speaking other languages. Uneducated participants were more likely to have MDS than educated and powder milk users were more likely to have MDS than dairy milk users. CONCLUSION: Our results revealed that arsenic, use of natural source of water and benzene exposure might lead to higher risk of acquiring MDS. This study would be helpful to understand the aetiology of disease in Pakistani population.

The Dawn of next generation DNA sequencing in myelodysplastic syndromes- experience from Pakistan.

BACKGROUND: Myelodysplastic syndromes (MDS) are clonal disorders of hematopoietic stem cells exhibiting ineffective hematopoiesis and tendency for transformation into acute myeloid leukemia (AML). The available karyotyping and fluorescent in situ hybridization provide limited information on molecular abnormalities for diagnosis/prognosis of MDS. Next generation DNA sequencing (NGS), providing deep insights into molecular mechanisms being involved in pathophysiology, was employed to study MDS in Pakistani cohort. PATIENTS AND METHODS: It was a descriptive cross-sectional study carried out at National institute of blood diseases and bone marrow transplant from 2016 to 2019. Total of 22 cases of MDS were included. Complete blood counts, bone marrow assessment and cytogenetic analysis was done. Patients were classified according to revised WHO classification 2016 and IPSS score was applied for risk stratification. Baseline blood samples were subjected to analysis by NGS using a panel of 54 genes associated with myeloid malignancies. RESULTS: The median age of patients was 48.5 ± 9.19 years. The most common presenting complaint was weakness 10(45.45%). Cytogenetics analysis revealed abnormal karyotype in 10 (45.45%) patients. On NGS, 54 non-silent rare frequency somatic mutational events in 29 genes were observed (average of 3.82 (SD ± 2.08) mutations per patient), including mutations previously not observed in MDS or AML. Notably, two genes of cohesin complex, RAD21 and STAG2, and two tumor suppressor genes, CDKN2A and TP53, contained highest number of recurrent non-silent somatic mutations in the MDS. Strikingly, a missense somatic mutation p.M272Rof Rad21 was observed in 13 cases. Overall, non-silent somatic mutations in these four genes were observed in 21 of the 22 cases. The filtration with PharmGKB database highlighted a non-synonymous genetic variant rs1042522 [G > C] located in the TP53. Genotype GG and GC of this variant are associated with decreased response to cisplatin and paclitaxel chemotherapy. These two genotypes were found in 13 cases. CONCLUSION: Sequencing studies suggest that numerous genetic variants are involved in the initiation of MDS and in the development of AML. In countries like Pakistan where financial reservation of patients makes the use of such analysis even more difficult when the availability of advanced techniques is already a prevailing issue, our study could be an initiating effort in adding important information to the local data. Further studies and large sample size are needed in future to enlighten molecular profiling and ultimately would be helpful to compare and contrast the molecular characteristics of Asian versus global population.

Additional cytogenetic abnormalities in chronic myeloid leukaemia; an experience from Pakistan.

OBJECTIVE: To evaluate the presence and characteristics of additional karyotype abnormalities in chronic myeloid leukaemia cases. METHODS: The cross-sectional study was conducted at the Department of Cytogenetics and Molecular Pathology, National Institute of Blood Diseases and Bone Marrow Transplant, Karachi, from May 2010 to September 2016 and comprised diagnosed chronic myeloid leukaemia patients regardless of age and gender. Baseline cytogenetic evaluation was done on overnight, 24-hrs un-stimulated and 72-hrs stimulated bone marrow cultures, and karyotypes were defined according to the International System for Human Cytogenetic Nomenclature2013. Data was analysed using SPSS 23. RESULTS: There were 222 cases with a median age of 38 years (range: 12-84 years). The male-to-female ratio was 1.8:1. Chronic myeloid leukaemia was detected in 18(8.1%) patients having additional cytogenetic abnormalities. Among the patients found positive, cytogenetic type was minor in 10(55.55%), major 3(16.66%), complex 3(16.66%), and variant 2(11.11%). CONCLUSION: Additional cytogenetic abnormalities were found in 8% of the sample.

Utilisation of blood products at a centre in Pakistan. Is donating better than wasting?

The study was designed to investigate the quantity and reasons of wastage of blood products. This was an observational study conducted from February 2018 to February 2019 at the National Institute of Blood Disease and Bone Marrow Transplantation (NIBD and BMT), PECHS campus. The study was approved by the institutional review board. Wastage and reasons of wastage for all the blood products were evaluated. Frequencies were calculated by using SPSS version 23.0. A total of 2,880 bags of blood products were available, including 960 each of platelets, packed red cells and fresh frozen plasma. The overall wastage rate was 3.5%. Packed red cells and platelets were fully consumed, yet shortage of supply was observed. However, highest wastage was observed in fresh frozen plasma i.e. 102 bags. Expiry of unused products 60 (59%) followed by broken bags 30 (29%) were two common modes of wastage. Wastage of blood products is a genuine issue in a hospital setup, strategies and plan of action should be discussed and implemented to ensure that they are available when and where they are needed most.

Seasonal variations in hematological disorders: A 10-year single-center experience.

AIMS: To assess the seasonal variations in hematological disorders among patients diagnosed on the basis of bone marrow biopsy, who attended National Institute of Blood Diseases (NIBD) clinics during 2006 to 2015. METHODS: We retrospectively reviewed the 10-year records of hematological disorders among patients' NIBD clinics from year 2006 to 2015. All cases of aplastic anemia (AA), acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), immune thrombocytopenic purpura (ITP), and acute promyelocytic leukemia (APML) were categorized on the basis of the seasons in which they were diagnosed such as winter (December-February), spring (March-May), southwest monsoon periods (June-September), and retreating monsoon period (October and November). Statistical analysis was performed by using SPSS and STATA. Inferential statistics were explored using the chi-square test for heterogeneity to evaluate seasonal variations. P-value <0.05 was taken as significant. RESULTS: A total of 1982 cases were reviewed. Men were predominantly higher (n = 1190, 60%) as compared to women (n = 792, 40%). Frequency of ALL was found to be higher (513, 25.9%), followed by ITP (504, 25.4%), AML (490, 24.7%), AA (396, 20%), while APML was observed in only 79 (4%) patients. Seasonal variations in the diagnosis of hematological disorders were observed (P-value < .001), except in APML diagnosis (P-value = .445). Significant seasonal variations were also detected in both genders in stratified analysis. CONCLUSION: The finding of this study has reported an increase in the hematological disorder during 2006 to 2015. Particularly, majority of the cases were reported in southwest monsoon period, whereas least cases were reported in retreating period. Significant seasonal and yearly variations were detected in all diagnosis except the APML.

Emerging Anti-Microbial Resistance in Febrile Neutropenia: Is it high time to evaluate quality control measures?

OBJECTIVE: We performed a prospective analysis at our center to find out the most common organisms causing bacterial infections to establish pattern of antibiotic resistance, in order to combat febrile neutropenia effectively in the terms of outcome as well as cost. METHODS: A hospital based observational study was conducted at National Institute of Blood Diseases and bone marrow transplantation from January 2017 to December 2017. Patients presented with absolute neutrophil count (ANC) of less than 500/ml were enrolled. Data were analyzed by SPSS version 21.0. P value of <0.05 was considered statistically significant. RESULTS: In this study, a total of 242 patients from various hematological disorders were enrolled and 403 bacterial isolates were obtained. The most frequent isolated gram-negative organisms were Escherichia coli, followed by Klebsiella pneumoniae and the most prevalent gram-positive organisms were staphylococcus aureus and Enterococcus species. The antimicrobial susceptibility testing revealed that most of the Staphylococcus aureus isolates were highly resistant to methicillin (p=0.002), whereas Enterococcus species were resistant to vancomycin (p=0.000). CONCLUSION: The choice of empirical antibiotic regimen should be based on local spectrum of bacteria and their regional susceptibility pattern to improve the survival and minimize hospital stay of patients.

Clinicohematological and cytogenetic profile of myelodysplastic syndromes in Pakistan-compare and contrast.

BACKGROUND: Myelodysplastic syndromes (MDS) are clonal stem cell disorders exhibiting cytopenias, ineffective hematopoiesis and morphological dysplasia. Bone marrow cytogenetics, inspite of being incorporated as mandatory tool in diagnosis are done less frequently due to limited availability of this technique in Pakistan. The aim of the study was to study baseline clinicohematological and cytogenetic characteristics of patients presenting with de novo MDS. RESULTS: A retrospective cross sectional study was done at National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, Pakistan from 2010 to 2016. Total of 177 patients were included in the study having median age 51 years and male to female ratio of 3:1. Pancytopenia was observed in 80 (45%) patients and bicytopenia in 74 (42%). Mean Hb% was 7.8 ± 2.18 g/dl, total leukocyte count (TLC) 8.8 ± 13.6 × 109/l, platelet count was 82 ± 95.7 × 109/l. Of total 170 (96%) were transfusion dependent. Refractory cytopenias with multilineage dysplasia (RCMD) was the most common world health organization (WHO) category. Karyotype was done in 98 (55%) patients out of which 44 (45%) had abnormal karyotype, complex karyotype (CK) was most commonly observed in 12 (12.2%) followed by monosomy 7 in 7 (7.1%). CONCLUSIONS: We found younger median age at diagnosis, higher mean TLC and no significant history of recurrent infections. CK and monosomy 7 carry bad prognostic implications and early disease transformation to acute myeloid leukemia (AML). Monosomy 7 being associated with bad overall survival, such patients must be identified early with close clinical follow up and offered stem cell transplant. This is the largest cohort of patients of MDS evaluated for baseline clinical and cytogenetic characteristics in our country.

Prevalence of transfusion transmissible infections in blood donors of Pakistan.

BACKGROUND: Transfusion-transmitted infections threaten the safety of patients requiring blood transfusion, which in turn imposes serious challenges for the availability of safe blood products that are still affordable in health care systems with limited resources. The aim of the study was to determine the prevalence of transfusion-transmitted infections in blood donors and to evaluate the demographic characteristics of reactive and non-reactive blood donors. METHODS: A prospective cohort study was conducted at our institute in Karachi, Pakistan. Donors were required to fill a detailed questionnaire and were screened for Hepatitis B, Hepatitis C, Human immunodeficiency viruses, Syphilis and Malaria by ELISA and thick film (malaria). RESULTS: Of the 16,602 blood donors, 16,557 were males and 45 females (mean age 28.6 ± 2). Nine hundred and seventy three (5.8%) donations were reactive in any screening assay, with 58 (0.35%) donations reacting in more than one assay. The prevalence of Hepatitis B, Hepatitis C, Human immunodeficiency viruses, Syphilis and Malaria was found to be 1.84, 1.7, 0.04, 2.1 and 0.07% respectively. Characteristics among the infections were evaluated and it was found that unmarried donors had a higher chance to be infected by Hepatitis B virus and Syphilis as compared to the other infections. On the other hand, construction workers and married donors were at more risk to be infected by Syphilis rather than the other infections. In case of co-infections, personnel with different occupations and marital status were infected by more than one pathogen. CONCLUSION: A substantial percentage of the blood donor's harbored transfusion-transmitted infections. Prevention of TTIs should be the main goal right now. There is a need for stringent selection of blood donors with the emphasis on getting voluntary donations and comprehensive screening of donor's blood for TTIs using standard methods to ensure the safety of blood recipient.