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Treating relapsed B cell-precursor ALL in children with a setting-adapted mitoxantrone-based intensive chemotherapy protocol (TMH rALL-18 PROTOCOL) — experience from Tata Memorial Hospital, India

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Abstract

The outlook of relapsed ALL in low- and middle-income countries (LMICs) is dismal due to high treatment-related toxicities and inadequate resources. We report our experience of using a locally adapted mitoxantrone-based protocol for non-high risk (HR) relapsed B-ALL (rALL). A retrospective cum prospective study of standard and intermediate risk (SR and IR) rALL patients treated on TMH rALL-18 protocol (adapted from COG/UKALLR3/Int-Re-ALL protocols) between November 2018 and January 2021 was analyzed. The protocol comprising of 7 blocks of multi-agent chemotherapy including mitoxantrone in induction followed by local irradiation and maintenance, underwent serial modifications based on our experience with initial patients. Eighty-two patients (SR rALL, 3; IR rALL, 79) were treated on TMH rALL-18 protocol. Of 321 grade 3/4 reported toxicities, around 43% (138 toxicities) were noted during induction. Induction chemotherapy was outpatient-based; however, 68 patients (82.9%) required supportive care admissions. Twelve out of 19 patients with gram negative bacilli sepsis (included 7 MDRO) died during reinduction. Five remission deaths were seen during block 3 after which cytarabine was dose reduced (3 g to 2 g/m2). Post-reinduction minimal residual disease was negative in 54 (80.6%) out of 67 evaluable patients. At a median follow-up of 24 months (95% CI 22–27), the estimated 2-year event-free and overall survival of the entire cohort was 58% (95% CI 48.1–69.9) and 60.3% (95% CI 50.5–72). Until the time, targeted therapies are freely accessible in LMICs, strengthening supportive care as well as local adaptation of protocols that strike a fine balance between efficacy and tolerability are mandated.

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Data availability

The data supporting the findings of this study are available upon request from the corresponding author. To request access to the data, please contact Dr. Nirmalya Roy Moulik at roymoulik@gmail.com.

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Acknowledgements

We acknowledge Mr. Akash Pawar who helped us in performing statistical analysis in R studio version.

Funding

This research received an intramural grant of 2,57,000 INR (3,116 USD) from TMC-Research Administrative Council (Grant number TRAC/1122/3539/01).

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Author notes

  1. Nirmalya Roy Moulik and Swaminathan Keerthivasagam have contributed equally to the manuscript and should be considered as co-first authors.

Authors and Affiliations

  1. Pediatric Oncology, Tata Memorial Hospital, HBNI, Mumbai, India

    Nirmalya Roy Moulik, Swaminathan Keerthivasagam, Swetha V. Velagala, Venkata Rama Mohan Gollamudi, Jayesh Agiwale, Chetan Dhamne, Akanksha Chichra, Shyam Srinivasan, Gaurav Narula & Shripad Banavali

  2. Cancer Cytogenetics, Tata Memorial Hospital, HBNI, Mumbai, India

    Dhanlaxmi Shetty & Hemani Jain

  3. Hematopathology, Tata Memorial Hospital, HBNI, Mumbai, India

    Papagudi G. Subramanian, Prashant Tembhare, Gaurav Chatterjee & Nikhil Patkar

Authors
  1. Nirmalya Roy Moulik
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  2. Swaminathan Keerthivasagam
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Contributions

NRM and SB designed the chemotherapy protocol and study. SK and NRM wrote the manuscript. SK and SR performed data analysis. JA helped in data collection. GN, CD, VRMG, AC, and SS helped in the patient management. PGS, PT, NP, DS, HJ, and GC contributed from the hematopathology lab. SB gave his valuable inputs for the study design and patient management. All the authors reviewed the manuscript submitted for publication.

Corresponding author

Correspondence to Nirmalya Roy Moulik.

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Ethical approval

The prospective study was approved by the institutional review boards and ethical committee clearance was obtained (ECR/414/Inst/MH/2013/RR-19).

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Informed consent was obtained from the caregivers/parents of the prospectively analyzed patients in our study.

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The authors declare no competing interests.

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Roy Moulik, N., Keerthivasagam, S., Velagala, S.V. et al. Treating relapsed B cell-precursor ALL in children with a setting-adapted mitoxantrone-based intensive chemotherapy protocol (TMH rALL-18 PROTOCOL) — experience from Tata Memorial Hospital, India. Ann Hematol 102, 2835–2844 (2023). https://doi.org/10.1007/s00277-023-05351-x

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