Hematopoietic Stem Cell Transplant for Acute Myeloid Leukaemia in Children and Adolescents: Multicentric Experience from India
Authors: Bhat Sunil , Jain Sandeep , Yadav Satya P , Nirmal Garima , Katewa Satyendra , Kalra Manas , Daruvala Rhea , Dayalan Deena , Nair Velu , Rastogi Neha , Badiger Shobha , Mallya Pooja , Joshi Ravi , Malhotra Payal , Thakkar Dhwanee , Sharma Rahul , Chadha Vaibhav , Sachdeva Anupam , Kapoor Gauri , Kharya Gaurav 
Published: December 2024

Introduction: Hematopoietic stem cell transplantation (HSCT) is a curative approach in patients with high-risk Acute Myeloid Leukaemia (AML)/MDS. This multicentric retrospective analysis aimed to investigate outcomes and risk factors associated with HSCT in children (&lt;21 years) with AML at various tertiary care centres across India.

Methods: Retrospective data was collected and analysis was carried out on all patients with high-risk AML (based on cytogenetics or remission status post induction I/II)/MDS aged ≤21 years undergoing HSCT between 2012 and 2024 at 8 participating tertiary care centres across the country.

Results: In our multicentre retrospective study, we evaluated the outcomes of 154 patients undergoing HSCT for high-risk AML(n=82) and relapsed AML (n= 72). Sixty-eight (44%) underwent HLA identical HSCT and 86 (66%) underwent haploidentical family donor (HFD) HSCT {16 underwent T cell depleted (TCD) HSCT, rest received T cell replete (TCR) HSCT}. Median age of cohort was 10 years (range 10 month- 21 years). Majority of patients underwent transplants in CR 2 (n=72; 46.8%) or CR1 (n=71; 46.1%) and 11 (7.1%) had refractory disease while undergoing HSCT. One hundred ten (71.4 %) patients were MRD negative at time of HSCT. Majority of patients 142 (92.2%) received myeloablative/ reduced toxicity condition regime. Fifty-three (35.4%) received one or other serotherapy. In TCR HFD HSCT, PTCY along with CNI/ mTOR inhibitors were used as GVHD prophylaxis whereas for TCD HFD HSCT, short course CNI was given. In HLA identical HSCT, CNI + methotrexate was the most common GVHD prophylaxis barring few patients at one centre where PTCY/mTOR inhibitors was used as GVHD prophylaxis. Median CD 34 infused was 7.3 x 10 6/ Kg recipient body weight. Median time to neutrophil and platelet engraftment were 14 days (range, 9- 26 days) and 15 days (range, 9-35 days), respectively. Twenty-eight (18.2%) patients had disease relapse. The incidences of acute GVHD Grade II-IV was 37 (24%), Grade III- IV 8 (5 %) and 12.3% (n=19) had chronic GvHD, 6 extensive. With a median follow up of 353 days (8- 4155 days), the probability of event free survival (EFS) and overall survival (OS) was 57.9% and 59.6%. Median chimerism's at day +30 and day+100 was 100% and 99.2%. For patients in CR1, CR2 and refractory disease, the OS was 70.8%, 55.9% and 18.2% respectively (p- value=0.003). There was no difference in survival of patients, who underwent HLA Identical HSCT (60.9%) or HFD HSCT (58.3%) (p- value= 0.01). On univariate logistic regression analysis, disease not in remission {HR 95%CI= 2.59 (1.25-5.35) and MRD positive status HR 95 % CI= 2.25 (1.2-4.213)} prior to HSCT were associated with inferior outcomes and on multivariate logistic regression analysis, disease not in remission {HR (95%CI= 2.269 (1.05-4.89)} prior to transplant was the only significant predictor of poor survival.

Conclusions: Our retrospective analysis suggests comparable outcomes of HSCT for AML as reported by previous investigators. Remission status prior to HSCT is the most important predictor of the outcome. The outcomes are best when HSCT is offered in CR1 and the outcomes of HFD HSCT are comparable with HLA identical donor HSCT.