Donor Trait Status Determines Haematological Outcomes Post-Haemopoietic Stem Cell Transplantation in Transfusion Dependent Thalassaemia Independent of HLA Matching and Chimerism Status
Authors: Khan Kinza , O'Boyle Farah , Lund Kirstin , Petterson Toni , Bremathas Sandrine , Hennessy Kelly , Gassas Adam , Karnik Leena , de la Fuente Josu 
Published: December 2024

Introduction: Allogeneic haemopoietic stem cell transplantation (HSCT) is a well-established curative treatment for transfusion dependent thalassaemia (TDT), but the choice has been recently widened recently with the licensing of gene therapy. The intensity of conditioning regimens has been reduced to minimise toxicity, but this has resulted in a higher chance of mixed chimerism. Despite the availability of data on donor-factors affecting outcomes, including HLA-match status and donor age, the impact of donor trait status and chimerism status on haematological outcomes remains underexplored. A better understanding of haematological outcomes will aid in an informed choice for best curative treatment.

Aims: We hypothesised that donor haematological parameters reflect those of the donor provided there are no significant changes in the niche environment.

Methods: Data was collected from 76 consecutive HSCT for TDT at a single institution between 2012 and 2023. reported to the European Bone Marrow Registry was grouped based on donor thalassaemia trait status. All patients had received a first transplant with a median age of 5 years, range 2 and 18. Unrelated donor transplants were excluded due the impossibility of obtaining the data required. 68 patients received a matched related HSCT and 8 a haploidentical HSCT. Red cell indices (Hb, MCV, MCH, MCHC and RDW) were assessed one-year post-transplant and compared to their respective donors at time of stem cell collection. Subgroup analysis was performed stratifying data based on the sex of donor vs patient to identify any disparities or potential influences of sex-mismatch on post-transplant erythropoiesis and myeloid chimerism. Statistical analyses, including Mann-Whitney U and Wilcoxon tests, were performed using IBM-SPSS and values compared between groups.

Results: Recipients of stem cells from thalassaemia trait donors had significantly lower haemoglobin levels than those transplanted from normal donors (p = &lt;0.001) and had red cell indices consistent with thalassaemia trait. Hb, MCH and MCV levels correlated between donor and recipient. The chimerism status had no impact in haematological parameters.

When stratifying the donors based on trait status, normal donors (n=33) demonstrated the following characteristics (median, range): Hb (93.5, 66-119), MCV (79.5, 65.3 -93.7), MCH (26.5, 21.9 - 31.2), MCHC (335, 315- 355) and RDW (13.4, 6.3 - 20.5). Thalassaemia trait donors (n=43): Hb (91, 51- 131), MCV (64, 49.2 - 78.9), MCH (20.1,14.9 - 25.3), MCHC (335, 298 - 343, RDW (15.8, 9.2 - 22.5). The recipient indices at 1-year post-transplant for normal donor recipients (n=33):were as follows (median, range): Hb (122, 96 - 155), MCV (82.6, 22.3 - 35.1), MCH (28.8, 22.3 - 35.1), MCHC (342.5, 316 -373), RDW (13, 10.7 -18.1). Thalassaemia trait donor recipients (n=43): Hb (106, 77- 157), MCV (64.6, 56.3 - 93.2), MCH (21.2, 17.3 - 29.6), MCHC (322, 307 - 351) and RDW (16.5, 12.1 - 19.4).

No significant differences were observed in markers of haemolysis between donor groups (p&gt;0.05) sex mismatch had an effect in reticulocyte production when the recipient of male stem cells was a female with lack of correlation in reticulocyte production (Rs =-0.116, p-value =0.751). The type of transplant had no impact on the outcomes.

Conclusion: Haematological outcomes post-transplantation depend on and correlate with donor red cell indices irrespective of chimerism status and HLA matching, with only impact provided by sex mismatch status when the recipient of male stem cells is female.