Ph Positive ALL: Real World Experience from a Tertiary Care Center in North India
Authors: Sharma Sanjeevan , Yanamandra Uday , Moslem Mir , Kapoor Rajan , Pramanik Suman , Kumar Rajiv , Khurana Harshit , Verma Tarun , Jasjit Singh , Das Satyaranjan , Sharma Ajay , Nair Velu 
Published: October 2019

Abstract
Introduction: The outcomes of Philadelphia positive acute lymphoblastic leukemia(Ph-ALL) have improved significantly after the introduction of tyrosine kinase inhibitors (TKI). The presence of Philadelphia positivity once considered as poor prognosis mandating transplantation, now even can be managed with TKI added to steroids. The data is scarce on Ph-ALL from real-world settings with resource constraints.
Objective: To study the characteristics and outcomes of Ph+ve ALL from real world settings.
Methodology: It is a retrospective observational study wherein the data of all patients of Ph-ALL managed at a tertiary care center in North India over the last 14 years (2004-2018) were analyzed. All case records of the Ph-ALL were perused, digitalized and their survival statistics derived.
Results:Amongst a total of 611 ALL case records, 55 (9%) were Ph-ALL. Ph-ALL cases with complete data (n-51) were analysed for overall survival. The mean age of the patients was 31± 2.41 years (range 3-76) (Fig. 1A). Males constituted 74.5% (n-38) and females, 25.4% (n-13) of our cohort. On risk stratification, 11 (21.5%), 5 (9.8%), and 35 (68.6%) patients were classified as standard, intermediate and high risk. Twenty five percent patients had associated complex karyotype in addition to the Ph positivity.
Of these 24 patients (47.05%) received adult ALL (GMALL protocol), 15 patients (29.4%) received paediatric BFM protocol, and12 patients (23.5%) received Hyper-CVAD. Week 4 Bone marrow evaluation was in CR in 87.2% of patients. L-Asparaginase was given in only 60% of the patients. An interruption in the therapy of more than 2 weeks for various reasons was present in 23.4% of the patients, mainly secondary to infections. Prophylactic cranial irradiation was given in 34.7% of the patients and high dose methotrexate was given in 30.4% of the patients. Relapse was seen in 22% of the patients. CNS disease was present in 17.6% of the patients. Only 19.6% of the patients were subjected to transplant. All patients received TKI, of which 44% received high dose imatinib and 56% patients received dasatinib. A total of 19.6% patients succumbed to the illness at various stages of the therapy.
The cumulative overall survival at 1y (1y-OS) was 95.68% with 3y and 5y OS being 72.09% and 63.07% (Fig. 1B). The survival was not statistically different between patients with and without complex karyotype (p-0.52),based on type of TKI administered (Dasatinib Vs high dose Imatinib) (p-0.76), males and females (p-0.41), risk category (p-0.41) or by the presence of CNS disease (p-0.21) (Fig. 1C-G). The survivals based on the type of protocol was statistically different with the best survival with GMALL protocol and the least survival with Hyper-CVAD therapy (log rank p<0.001)(Fig. 1H).
Conclusion: We have demonstrated in this study the improved outcomes of Ph-ALL who usually present late in resource constraint settings. There was no additional benefit of dasatinib over high dose imatinib in this cohort.
Figure 1. Figure 1.

Disclosures
No relevant conflicts of interest to declare.