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

  • Soumya Surath Panda
  • Venkatraman RadhakrishnanEmail author
  • Prasanth Ganesan
  • Rejiv Rajendranath
  • Trivadi S. Ganesan
  • Kamalalayan Raghavan Rajalekshmy
  • Rajesh Kumar Bhola
  • Hemlata Das
  • Tenali Gnana Sagar
Original Article


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.


Acute lymphoblastic leukemia Flow cytometry Minimal residual disease 



The project was funded through an Educational Grant from Dell Inc, USA.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Human and Animals Rights

All procedures performed in the study were in accordance with the ethical standards of the institution and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed Consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Indian Society of Hematology and Blood Transfusion 2019

Authors and Affiliations

  • Soumya Surath Panda
    • 2
  • Venkatraman Radhakrishnan
    • 1
    Email author
  • Prasanth Ganesan
    • 1
  • Rejiv Rajendranath
    • 1
  • Trivadi S. Ganesan
    • 1
  • Kamalalayan Raghavan Rajalekshmy
    • 1
  • Rajesh Kumar Bhola
    • 2
  • Hemlata Das
    • 2
  • Tenali Gnana Sagar
    • 1
  1. 1.Departments of Medical OncologyCancer Institute (WIA)Adyar, ChennaiIndia
  2. 2.Department of Medical OncologyIMS and SUM Hospital, Siksha O Anusandhan UniversityBhubaneswarIndia

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