Unraveling clinical and biological predictors of successful treatment free remission in Chronic Myeloid Leukemia and its impact on the healthcare system in a low- and middle-income country

Abstract

Objectives: Tyrosine Kinase Inhibitors (TKIs) have revolutionized the management of Chronic Myeloid Leukemia (CML), making treatment free remission (TFR) possible in eligible patients. However, TFR data in Pakistan remains scarce. This study aimed to evaluate relapse-free survival (RFS) outcomes and identify clinical predictors of successful TFR in CML patients.

Methodology: Adult CML (chronic phase) patients > 18 years, eligible for TFR were included. It was an observational (cohort based study) and was conducted between 2022 and 2025 at Armed Forces Bone Marrow Transplant Center (AFBMTC), Rawalpindi. Minimum required duration of TKI was > 3 years and duration of DMR was > 2 years. Data was collected from bone marrow transplant center.

Results: Thirty patients (16 males and 14 females) attempting TFR were analyzed. Median age at diagnosis was 34.5 years (range 19 – 60) and the median age at discontinuation was 38.5 years (range 24-63). Most patients had an intermediate SOKAL risk score (56.7%, n=17), while 30% (n=9) were low risk and 13.3% (n=4) had high risk. Imatinib was the most frequently used first-line TKI (83.3%, n=25), followed by nilotinib (16.7%, n=5). The median treatment duration of TKI was 40 months (range 36-60), and the median duration of sustained deep molecular response before attempting TFR was 30.5 months (range 24-49). RFS was 80% at six months and 66.7% at 12 months. Depth and duration of DMR and SOKAL scores positively defined the success of TFR with depth of DMR achieving significance levels. Relapsed patients (9 out of 10) had high or intermediate SOKAL risk scores.

Conclusion: Despite limited data available for Pakistan, TFR remains a viable and safe option in carefully selected patients.