AUTHOR=Tembhare Prashant R. , Narula Gaurav , Khanka Twinkle , Ghogale Sitaram , Chatterjee Gaurav , Patkar Nikhil V. , Prasad Maya , Badrinath Yajamanam , Deshpande Nilesh , Gudapati Pratyusha , Verma Shefali , Sanyal Mahima , Kunjachan Florence , Mangang Gunit , Gujral Sumeet , Banavali Shripad , Subramanian Papagudi G. 

TITLE=Post-induction Measurable Residual Disease Using Multicolor Flow Cytometry Is Strongly Predictive of Inferior Clinical Outcome in the Real-Life Management of Childhood T-Cell Acute Lymphoblastic Leukemia: A Study of 256 Patients

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.00577

DOI=10.3389/fonc.2020.00577

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold> Measurable/minimal residual disease (MRD) status is suggested as a powerful indicator of clinical-outcome in T-cell lymphoblastic leukemia/lymphoma (T-ALL). Contrary to B-cell ALL, reports on T-ALL MRD are limited and mostly based on molecular methods, mainly from developed countries. Multicolor flow cytometry (MFC)-based T-ALL studies are very few. Clinically relevant cut-off levels and ideal time-point for MRD assessment are still inconclusive. In view of lack of T-ALL MRD data from the developing world, we evaluated the prognostic value of MFC-based post-induction (PI)-MRD assessment in T-ALL in the context of standard practice.</p><p><bold>Methods:</bold> We included 256 childhood-T-ALL patients (age &lt; 15 years) treated with a modified-MCP841 protocol, which uses high-dose cytarabine during consolidation, as a part of standard hospital practice. MRD was studied using 10-color 11-antibody MFC with any level of detectable disease being considered positive. Post-induction (PI)-MRD was available in all patients, and post-consolidation (PC) MRD was available mostly in PI-MRD-positive patients (<italic>n</italic> = 88).</p><p><bold>Results:</bold> Three years cumulative-incidence-of-relapse (3years-CIR) in PI-MRD-positive patients was inferior to negative patients (46.3% vs. 18.4%). The median relapse-free-survival (RFS), event-free-survival (EFS) and overall-survival (OS) with hazard ratio (HR) of PI-MRD-positive patients were 21.4 months vs not reached (<italic>p</italic> &lt; 0.0001, HR-4.7), 21.6 months vs. not-reached (<italic>p</italic> = 0.0003, HR-2.01) and 37.3 months vs. not reached (<italic>p</italic> = 0.026, HR-1.64) respectively. RFS, EFS and OS of patients with PI-MRD&lt;0.01% (<italic>n</italic> = 17) were as inferior as PI-MRD ≥ 0.01% in comparison with MRD-negative patients with HR of 4.7 (<italic>p</italic> &lt; 0.0001), 2.45 (<italic>p</italic> = 0.0003), and 2.5 (<italic>p</italic> = 0.029), respectively. Three-years-CIR of patients with hyperleukocytosis (≥100 × 109/L) was also higher (50.5 vs. 27.6%) with inferior RFS, EFS, and OS. Among PI-MRD-positive patients, 3years-CIR, RFS, EFS, and OS of PC-MRD-positive were also inferior to that of negative patients. On multivariate analysis any-level detectable PI-MRD and hyperleukocytosis remained independently associated with inferior RFS, EFS, and OS. A combination of PI-MRD-positive status and hyperleukocytosis identified the patients with the worst clinical outcomes.</p><p><bold>Conclusion:</bold> Detectable PI-MRD using MFC was found to be the strong predictive factor of inferior clinical outcome in T-ALL patients. The combination of PI-MRD status and hyperleukocytosis provides the most influential tool for the management of T-ALL in resource constrained settings from developing world.</p>