Clinical Research in Chronic Lymphocytic Leukemia in Pakistan; A Systematic Review

Background: Significant advances have been made in the treatment of chronic lymphocytic leukemia (CLL) since the turn of the new millennium. However, most clinical trials were done in developed countries where minority ethnicities were underrepresented. Materials and Methods: To gauge the quality of research in CLL being done in Pakistan, we conducted a comprehensive literature search using PubMed, Clinicaltrials.gov, and Google Scholar on 14 January 2022 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Results: A total of 16 studies met the inclusion criteria. The most common study design was cross-sectional. Eight studies evaluated the clinicohematological profile of CLL patients and the effect of various cytogenic abnormalities through fluorescence in situ hybridization (FISH) technique on disease progression and prognosis. Five studies discussed the prevalence of abnormalities such as autoimmune cytopenias and other serum chemistry derangements. Only two studies evaluated treatment outcomes, among which one study reported a 2-year overall survival of 65% among patients with 17p deletion. None of the studies had patients on novel targeted agents. No pharmaceutical sponsored or funded clinical trials were found. Conclusions: Our review suggests that although small clinical studies continue to be performed across the country, multiple financial and logistical barriers need to be addressed for larger, more impactful clinical trials to be conducted that will help answer demographic-specific questions and decrease reliance on foreign studies.

[1]  A. Ramsey,et al.  Subcutaneous immunoglobulin replacement for treatment of humoral immune dysfunction in patients with chronic lymphocytic leukemia , 2021, PloS one.

[2]  Fengling Li,et al.  The global burden and attributable risk factors of chronic lymphocytic leukemia in 204 countries and territories from 1990 to 2019: analysis based on the global burden of disease study 2019 , 2021, Biomedical engineering online.

[3]  Harsh P Patel,et al.  The Impact of Atrial Fibrillation on hospitalization Outcomes for Patients With Chronic Lymphocytic Leukemia Using the National Inpatient Sample Database. , 2021, Clinical lymphoma, myeloma & leukemia.

[4]  M. Ammad Ud Din,et al.  Ibrutinib does not add to the humoral dysfunction in patients with chronic lymphocytic leukemia: A single-center experience. , 2021, Hematology/oncology and stem cell therapy.

[5]  A. Mato,et al.  COVID-19 vaccine efficacy in patients with chronic lymphocytic leukemia , 2021, Leukemia.

[6]  Khadija,et al.  CORRELATION OF TRISOMY 12 WITH CLINICAL FEATURES AND OTHER LABORTARY PARAMETERS IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKAEMIA , 2021 .

[7]  G. Shefer,et al.  Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia , 2021, Blood.

[8]  E. Mayo-Wilson,et al.  The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. , 2021, Journal of clinical epidemiology.

[9]  A. Neri,et al.  Time to first treatment and P53 dysfunction in chronic lymphocytic leukaemia: results of the O-CLL1 study in early stage patients , 2020, Scientific Reports.

[10]  S. Adil,et al.  Frequency Of TP53 Gene Mutation In Patients With Chronic Lymphocytic Leukaemia. , 2020, Journal of Ayub Medical College.

[11]  I. Haq,et al.  Pancreaticoduodenectomy: Outcomes of a complex surgical procedure from a developing country. , 2020, Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.].

[12]  D. Lad,et al.  Quality of life in patients of chronic lymphocytic leukemia using the EORTC QLQ‐C30 and QLQ‐CLL17 questionnaire , 2020, European journal of haematology.

[13]  J. Burger Treatment of Chronic Lymphocytic Leukemia. , 2020, The New England journal of medicine.

[14]  A. Khurshid,et al.  CLINICO-PATHOLOGICAL FEATURES IN PATIENTS OF CHRONIC LYMPHOCYTIC LEUKEMIA WITH DEL 11q22 , 2020 .

[15]  T. Kipps,et al.  Targeted Therapy in Chronic Lymphocytic Leukemia , 2019, Cancer journal.

[16]  M. Hallek Chronic lymphocytic leukemia: 2020 update on diagnosis, risk stratification and treatment , 2019, American journal of hematology.

[17]  Farah Asif Clinical Trials in Pakistan, missing opportunity. , 2019, JPMA. The Journal of the Pakistan Medical Association.

[18]  Nasiruddin,et al.  Autoimmune cytopenias in chronic lymphocytic leukemia , 2019, Pakistan journal of medical sciences.

[19]  T. Shamsi,et al.  Frequency of Zap-70 and CD38 in Newly Diagnosed Cases of B-Cell Chronic Lymphocytic Leukemia , 2019, National Journal of Health Sciences.

[20]  E. Fadul,et al.  Clinical presentation and hematological profile among young and old chronic lymphocytic leukemia patients in Sudan , 2019, BMC Research Notes.

[21]  Shujaat Ahmad,et al.  Prevalence of Acute and Chronic Forms of Leukemia in Various Regions of Khyber Pakhtunkhwa, Pakistan: Needs Much More to be done! , 2019, Bangladesh Journal of Medical Science.

[22]  L. Kumar,et al.  Chronic lymphocytic leukemia with deletion 17p: An Indian scenario , 2019, South Asian Journal of Cancer.

[23]  S. Khan,et al.  Clinicohematological parameters and outcomes in a cohort of chronic lymphocytic leukemia patients with Deletion 17p from Pakistan , 2018, Blood research.

[24]  D. Lad,et al.  Reduced Dose Ibrutinib Due to Financial Toxicity in CLL , 2018, Indian Journal of Hematology and Blood Transfusion.

[25]  S. O'brien,et al.  Evolution of CLL treatment — from chemoimmunotherapy to targeted and individualized therapy , 2018, Nature Reviews Clinical Oncology.

[26]  Fawad,et al.  Outcomes of first line chemotherapy in patients with chronic lymphocytic leukemia , 2016, Pakistan journal of medical sciences.

[27]  M. Iqbal What ails medical research in Pakistan? Role of institutions , 2015, Pakistan journal of medical sciences.

[28]  S. Sultan,et al.  Serum 25-hydroxyvitamin D Insufficiency in B-Chronic Lymphoid Leukemia at the Time of Disease Presentation in Pakistan. , 2015, Asian Pacific journal of cancer prevention : APJCP.

[29]  S. Sultan,et al.  Direct Coombs Test Positivity in B-Chronic Lymphoid Leukemia: a Marker of Advanced Clinical Disease. , 2015, Asian Pacific journal of cancer prevention : APJCP.

[30]  S. Sultan,et al.  ZAP-70 protein expression in B-cell chronic lymphoid leukemia: a single center experience from Pakistan. , 2015, Asian Pacific journal of cancer prevention : APJCP.

[31]  S. Irfan,et al.  Clinico-hematological profile of patients with B-chronic lymphoid leukemia in Pakistan. , 2015, Asian Pacific journal of cancer prevention : APJCP.

[32]  S. Murad,et al.  Efficacy and safety of sorafenib-gemcitabine combination therapy in advanced hepatocellular carcinoma: an open-label Phase II feasibility study. , 2014, Hematology/oncology and stem cell therapy.

[33]  A. Polliack,et al.  Geography, ethnicity and “roots” in chronic lymphocytic leukemia , 2013, Leukemia & lymphoma.

[34]  S. Vishnubhatla,et al.  Assessment of 285 cases of chronic lymphocytic leukemia seen at single large tertiary center in Northern India , 2012, Leukemia & lymphoma.

[35]  N. Akinola,et al.  Management of Chronic Lymphocytic Leukemia in Less-Resourced Countries. , 2021, Cancer journal.

[36]  N. Rafiq,et al.  Hematological and Biochemical Parameters in Pakistani Chronic Lymphoblastic Leukemia Patients , 2014 .

[37]  A. Lone,et al.  AUTOIMMUNE COMPLICATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA: A SINGLE CENTER EXPERIENCE , 2013 .