Clinical Profile, Molecular Characterization and Outcomes in Patients of Acute Lymphoblastic Leukemia

Abstract

Introduction-Leukaemia comprises 3% of global cancer cases. ALL, constituting 25% of haematological cancer diagnoses, is aggressive. Annual global incidence of adult ALL is approximately 1 in 100,000. It affects bone marrow, blood, and other sites. Attempts have been made to classify it based on various criteria like FAB and WHO classification. Pathogenesis involves complex interactions between exposures, heredity, and chance. Treatment includes remission induction, consolidation, maintenance, and prophylaxis. New therapies like targeted treatments, immunotherapy, and stem cell transplantation show promise. Our study aims to explore clinical presentation and outcomes of adult ALL patients. Cytogenetic profiles will be assessed through karyotyping and PCR. Hematologic and molecular parameters will be correlated with overall outcomes, including disease-free and overall survival. The study's hypothesis is to describe clinical profile, molecular characterization, and outcomes in Acute Lymphoblastic Leukaemia patients.

Aims -The aims of our research is to study the clinical profile, the cytogenetic profile by conventional karyotyping and PCR  and to study the overall outcome in the form of disease-free survival and overall survival in patients of Acute Lymphoblastic Leukemia.

Objective- To study the correlation of various hematologic and molecular parameters with overall outcome in patients of Acute Lymphoblastic Leukemia.

Materials and Methods- It was a Retrospective and Prospective observational study conducted at Army Hospital (Research & Referral) from January 2013 to May 2019. A total of 200 patients aged more than 15 years diagnosed as acute lymphoblastic leukemia were enrolled as part of study.

Results- A total of 200 Patients with ALL were included in this study. Data was entered in Excel sheet and following findings were observed. Our study has Male preponderance with Male patient twice the number of Female patients. The mean age at presentation was 26.34 years with SD 6.36. It was found that 52.55 % (103) patients have normal cytogenetics while 25.51 % (50) patients have abnormal cytogenetics. Cytogenetics was not available in 3% (6) patients while in 18. 87% (37) patients it was unknown. Bone marrow was evaluated at 4 weeks after the therapy. It has been observed that 88.32% (174) patients achieved complete morphological remission while 7.1% (14) patients did not achieve complete remission. Bone marrow of 4.56 % (9) patients was not evaluable. 17 patients received bone marrow transplantation during the course of the treatment. Majority of the patients with ALL expressed CD10 antigen (63%) and CD 19 (68%) antigen. The various chromosomal abnormalities observed includes PCR (1; 19), PCR (4;11), PCR (bcr-abl), Abnormal karyotype, Philadelphia chromosome and Hyperdiploidy. Overall survival at the end of 1 yr, 2 yr, 3 yr and 4 yr was 95%, 77%, 58% and 52% respectively. Survival rate among male female patients was almost similar. Patients with abnormal cytogenetics were having lower survival rates (56 % Vs 60 %)as compared to that of normal cytogenetics (log rank p =0.482). Patients receiving adult type treatment protocol, the patients who were not given CRRT and the patients who do notreceive HDMTx therapy were having lower survival rates. In our study we have found that CNS involvement reduces overall survivalof the ALL patients.

Conclusion- In our study ALL patients were distributed over the age range of 15-39 years of age. Overall survival rates were lower in patients of age group 30-60 years.(3 yr OS (CI) 0.49 vs. 0.62)  Male predominance(67 %) was noted in our study. Overall survival was not significantly associated with gender.  Majority of the patients with ALL expressed CD10 antigen (63%) and CD 19 (68%) antigen.  It was observed that 52.55 % (103) patients have normal cytogenetics while 25.51 % (50) patients had abnormal cytogenetics. Overall survival rates were lower (56% vs 60%) in patients with abnormal cytogenetics.  Only 9 % of the patient received Bone marrow transplantation.88.32% of patients achieved bone marrow remission at the end of 4 week while only 7 % patients had not achieved bone marrow remission.  52% of the patients were treated with Hyper CVAD regime. The remaining patients were treated with Pediatric like and adult protocol (¼ th patients in each group) which had lower Overall survival rates. (3 yr OS (CI) 0.72 vs 0.61 vs 0.29)