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2881 Measurable Residual Disease Results & Survival with Augmented Early Intensification Therapy in Intermediate-Risk & High-Risk Group Pediatric Acute Lymphoblastic Leukemia Patients Treated with ALL IC-BFM 2009 Protocol: A Single-Center Study from India

Program: Oral and Poster Abstracts
Session: 614. Acute Lymphoblastic Leukemias: Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II
Hematology Disease Topics & Pathways:
Non-Biological therapies, Chemotherapy, Combination therapy, Therapies, Adverse Events, Minimal Residual Disease
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Prof. Uttam Kumar Nath, MD, DM, Karthik Kumar, MD*, Adamya Gupta, MD*, Reshma Benson, MD* and DR Arjun Kachhwaha, MD, MBBS*

All India Institute of Medical Sciences, Rishikesh, Rishikesh, India


Measurable residual disease (MRD) has proven to be one of the most effective disease monitoring responses in ALL. Multiple treatment groups have demonstrated End-of-Induction (day 33) flow MRD of <0.01% has excellent disease-free survival (DFS). Patients with end-of-consolidation MRD of <0.01% has an overall DFS of 75 % as per COG AALL1131 including the very high-risk B-ALL genotypes. We conducted a study to assess the efficacy & toxicity of augmented early intensification therapy (phase IB) in ALL IC-BFM 2009 protocol for intermediate-risk & high-risk group pediatric ALL patients.


  1. To evaluate efficacy of augmented early intensification therapy (phase IB) in ALL IC-BFM 2009 in terms of achievement of day 78 MRD negative status.
  2. To determine the event-free survival in intermediate-risk & high-risk group patients.
  3. To appraise the adverse events (AEs) of augmented phase IB Induction.


The study enrolled treatment-naïve ALL patients of 1-25 years’ age between April 2021 to February 2023 at AIIMS Rishikesh, India. Patients were risk stratified into Standard (SR), Intermediate (IR) & High risk (HR) groups as per ALL IC BFM 2009 protocol. All patients received Augmented phase IB protocol. The regimen comprised of cyclophosphamide (2 doses), four blocks of cytarabine & 6-mercaptopurine, augmented with vincristine (4 doses), and L-Asparaginase (12 doses). Day 78 bone marrow flowcytometric MRD was performed in all patients irrespective of day 33 marrow morphology & MRD. The study defined complete remission as BM blasts <5% with no extramedullary disease and MRD negativity as <0.01%. The AEs was monitored as per NCI-CTCAE v5.

As per the study protocol, patients of B-ALL with day 33 MRD >0.01%, ph-positive ALL, hypodiploidy and T-ALL with day 78 MRD > 0.01% was considered as HR & treated with High-risk blocks consolidation followed by transplant or delayed intensification & maintenance.


A total of 75 patients enrolled in the study. The M: F ratio was 1.6:1. The median age was 8 years (range 1-25 yrs). B & T-ALL constituted 80% & 20% respectively. ph-positivity accounted 22% of B-ALL. The median Lansky performance was 40 & ECOG was 3 among the participants. The median hb, total white counts, and platelets were 5.9 g/dl, 28 x109/L and 30 x109/L respectively. At diagnosis, 28% of patients had hyperleukocytosis, 15% with bacterial sepsis, 8% with invasive fungal infections, and 8% with CNS leukemia.

At baseline, the distribution of patients in SR, IR & HR was 15%, 68% & 17% respectively. The final risk strata at end-of-induction were 8%, 49% & 43% in SR, IR & HR groups. CNS leukemia accounted for 8% of all patients.

Of the total evaluable patients, 86% achieved day 8 good steroid response (absolute blasts count <1000/cu.mm), 73% & 38% achieved day 15 marrow M1 response (<5%blasts) and MRD < 0.1%, 97% & 77% achieved day 33 M1 marrow response and day 33 MRD <0.01% respectively. Among the study participants who were MRD positive on day 15, three-fourths (75%) of them accomplished MRD negativity at day 33.

Of the 23% patients with day 33 MRD positivity, 80% achieved day 78 MRD negativity of <0.01% with Augmented phase IB with 3 participants being persistent MRD positive.

The median follow-up was 24 months and the overall survival was 74%. The mean survival time was 16.7 months (12.7-20.6) for HR & 21.2 months (18.3-24.1) for IR patients. The subgroup analysis demonstrated an overall survival of 80% for SR, 84% for IR & 64% for HR groups. Nevertheless, the proportion of patients in the SR group (8%) was lower compared to the others.

The commonest hematological adverse events were hypofibrinogenemia (22%), followed by febrile neutropenia (19%), anemia (19%), and thrombocytopenia (18%) respectively. The commonest non-hematological AEs were peripheral neuropathy (5%) and typhlitis (5%).


In our single-center experience, the use of augmented early intensification therapy (phase IB) in ALL IC-BFM 2009 protocol in intermediate-risk & high-risk pediatric ALL patients was associated with achievement of day 78 MRD negative status in 80% patients who had day 33 MRD-positivity without significant treatment-related toxicity, and encouraging event-free survival in this patient population.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH