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1097 Donor Trait Status Determines Haematological Outcomes Post-Haemopoietic Stem Cell Transplantation in Transfusion Dependent Thalassaemia Independent of HLA Matching and Chimerism Status

Program: Oral and Poster Abstracts
Session: 112. Thalassemia and Globin Gene Regulation: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical Research, Registries
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Kinza Khan1*, Farah O'Boyle2*, Kirstin Lund, MRCP, BSc3*, Toni Petterson4*, Sandrine Bremathas, RN5*, Kelly Hennessy6*, Adam Gassas, MD7*, Leena Karnik, FRCPath, MRCP8* and Josu de la Fuente, PhD FRCP9,10,11,12

1Imperial College London, Gillingham, ENG, United Kingdom
2St. Marys Hospital, London, United Kingdom
3St Marys Hospital, Imperial College London, London, GBR
4St Marys Hospital, Imperial College NHS Foundation Trust London, London, GBR
5IMPERIAL COLLEGE HEALTHCARE NHS TRUST, London, United Kingdom
6St Marys Hospital, Imperial College London, London, United Kingdom
7St Marys Hospital, Imperial College NHS Foundation Trust, London, United Kingdom
8St Marys Hospital, Imperial College NHS Foundation Trust, London, GBR
9Department of Paediatrics, St Mary’s Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
10Division of Immunology and Inflammation, Imperial College London, London, United Kingdom
11Imperial College Healthcare Trust, St Mary's Hospital, London, United Kingdom
12Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom

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 = <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>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.

Disclosures: de la Fuente: Sanofi: Membership on an entity's Board of Directors or advisory committees; Sangamo: Membership on an entity's Board of Directors or advisory committees; MAAT Pharma: Membership on an entity's Board of Directors or advisory committees; Vertex: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

*signifies non-member of ASH