Flow Cytometry Based MRD and Its Impact on Survival Outcome in Children and Young Adults with ALL: A Prospective Study from a Tertiary Cancer Centre in Southern India

Abstract

Presence of minimal residual disease (MRD) following induction chemotherapy is a well-recognized risk factor to predict relapse in acute lymphoblastic leukemia (ALL). There is paucity of data on MRD and outcome in ALL from India. We share our experience in establishing a flow cytometry-based MRD assay for ALL with emphasis on determination of the number of patients who had MRD on day 35 of induction therapy and its correlation with outcome and other prognostic factors. We prospectively studied MRD in patients with ALL less than 25 years who achieved morphological complete remission with induction therapy. The initial series consisted of 104 patients with ALL. Ninety-two patients had bone marrow samples collected on day 35 of remission induction chemotherapy that was adequate for MRD. Strategy of monitoring MRD was based on flow cytometry using six color staining according the leukemia associated immunophenotype found at diagnosis. Data analysis was done using Fisher exact test. The median age was 8.5 years (range 0.9-22 years). Thirty-seven out of ninety-two patients (40.2%) had MRD at end of induction. MRD on day 35 was between 0.01 and 0.1% in 18.9% of patients, between 0.1 and 1% in 59.5% and more than 1% in 21.6% patients. Among the patients who had MRD, 16.7% had favourable cytogenetics, 60% had intermediate and 13.3% had high-risk cytogenetics. The presence or absence of residual leukemia by flow cytometry at day 35 was not significantly related to age (p = 1.0), male gender (p = 0.08) hyperleukocytosis (p = 0.25) or day 8 blast clearance (p = 0.21). However, T cell phenotype (p \ 0.001) was significantly associated with MRD. The 5-year event free survival (EFS) for patients who had MRD versus those who did not was 69% and 61.1% respectively (p = 0.41). The 5-year overall survival (OS) for patients who had MRD versus those who did not was 72.5% and 61.1% respectively (p = 0.33). Flow cytometric techniques can be applied to monitor MRD in patients of ALL undergoing induction therapy. Our results suggest MRD correlates with certain known prognostic factors. Though the EFS and OS was lower in MRD positive patients, the results were not statistically significant probably because of the small sample size.

Minimal Residual Disease in the Management of B-Cell Acute Lymphoblastic Leukemia: A Systematic Review of Studies from Indian Settings

“…[ 31 ] 10 Flow cytometry-based MRD assay for BCP-ALL with emphasis on assay standardization and cost A cost-effective MRD panel is applicable to over 90% of patients Panda et al . [ 17 ] 104 Flow cytometry-based MRD assay for ALL with emphasis on the determination of the number of patients who had MRD on day 35 of induction therapy and its correlation with the outcome and other prognostic factors MRD correlates with certain known prognostic factors Though EFS and OS were lower in MRD-positive patients, the results were not statistically significant, probably because of the small sample size Chatterjee et al . [ 32 ] 214 Expression of CD304/neuropilin-1 in adult B-cell ALL patients and evaluation of its practical utility in MFC-based MRD analysis CD304 is commonly expressed in adult B-cell ALL It distinguishes B-cell ALL blasts from normal precursor B cells A stable MRD marker is distinctly useful in the detection of MFC-based MRD monitoring Das et al .…”

“…There is a paucity of data on MRD from an Indian context, and a complete understanding of MRD assessments and their correlation with outcomes among B-cell ALL patients is also lacking [ 17 ]. The primary objective of this review was to survey the available literature that discusses different aspects of MRD testing in the Indian context, specifically focusing on adolescent and young adults (AYA) and adult B-cell ALL patients.…”