A ten-year follow-up study of children with thalassemia major post transplantation using treosulfan, thiotepa, and fludarabine-based conditioning regimen and its impact on growth and puberty.

Background: We present a uniform cohort of children with thalassemia major who underwent treosulfan-based conditioning for hematopoietic stem cell transplantation (HSCT) and its impact on growth and puberty.

Patients and methods: The study included retrospective analysis of children up to 18 years of age who underwent allogeneic HSCT for transfusion-dependent thalassemia major between 2010 to 2020 with a minimum follow-up period of two years.

Results: Of 202 children in the study, 59% were males and 41% were females and 110/202 (54%) had a matched family donor (MFD), 62/202 (31%) haploidentical and 30/202 (15%) matched unrelated donor (MUD). Seventy-three (36%) were <5 years of age at HSCT, 90 (45%) between 5 to 10 years, and 39 (19%) were over 10 years of age. The mean height SDS at HSCT was -0.574 and at the current assessment, the mean height SDS was -0.669 (p=0.391). There was no significant reduction in growth potential. Twenty-nine (14.4%) were short at the time of HSCT (height SDS <-2) and at the current assessment, six (20.7%) continued to remain short, while 23 (79.3%) had catch-up growth and moved to height SDS ≥-2. The mean height SDS during HSCT in Class 1 thalassemia was -0.216, -0.478 in Class 2, and -0.898 in Class 3 respectively (p=0.026). The current height SDS in these classes are -0.115, -0.710, and -0.929 respectively, confirming that children in Class 1 and 2 were able to catch up on their growth; however, Class 3 patients failed to catch up growth after HSCT (p=0.010). In the children currently above 10 years of age, 17 (43.6%) were in Tanner stage 5. Of the 83 female children, 45 (54.2%) attained spontaneous menarche. Fourteen (6.9%) children required growth hormone supplementation.

Conclusion: Our study demonstrates the impact of treosulfan-based conditioning on growth and puberty in children with thalassemia major. Despite the higher cost of treosulphan, growth potential was maintained and pubertal growth was per age for majority of the children in the cohort.