Risk factors associated with allogeneic haematopoietic stem cell graft failure in paediatric acute leukaemias

April 2021 Clinical practice Tobias Rawson

Although uncommon, graft failure is a severe complication following allogeneic haematopoietic stem cell transplantation (aHSCT) in paediatric patients. Currently, there are no known risk factors to identify paediatric patients who may be at a greater risk of this complication when patients are treated with an ex vivo T-cell depletion protocol beforehand. Investigating this, a Spanish research group retrospectively analysed risk factors and outcomes in 148 T-cell deprived haploidentical transplantations. All patients received a T-cell depletion protocol consisting of fludarabine, busulfan and thiotepa. Total body irradiation was not used, and the median total number of CD34+ cells infused was 7.85 x 106/kg.

Age below 9 years associated with increased risk of graft failure

The median age of patients in this analysis was 9, with an AML and ALL split of 47% and 53%, respectively. In total, 22 patients experienced graft failure, 13 being primary and the remaining 9 being secondary. At a median follow-up of 48 months, 64% of these 22 patients were still alive and disease-free. Subsequently, the disease-free survival (DFS) rate in these graft failure patients was 53% (+/- 12%). Conversely, the DFS in the overall study population was 57%.

Multivariate analysis revealed age younger than 9 years was associated with an increase in graft failure (HR [95%-CI]: 5.0 [1.1-23.2], p<0.037). An even higher increase in the chance of graft failure was observed in patients with pre-transplant CD8+ concentration ≥150 μL (HR [95%-CI]: 12.0 [1.6-95.3], p<0.016). Additionally, the cumulative incidence of graft failure at 70 days in patients with both risk factors was 24% (+/- 6%), whilst patients with CD8+ ≥ 150 μL was 6% (+/- 4%) and patients younger than 9 years was 3% (+/- 2%).

CONCLUSION

In this retrospective analysis, paediatric AML/ALL patients who were treated with an ex vivo T-cell depleting protocol and were subsequently treated with aHSCT, being under the age of 9 and having a CD8+ concentration ≥150 μL was associated with a higher risk of graft failure. Although further prospective research is required to validate these findings, these results highlight the significance of pre-existing cellular immunity and support the use of T-cell population analysis in the pre-transplant patient workup.

Reference

Torija I et al., Risk factors and survival of graft failure in pediatric patients with hematological malignancies treated with allogeneic hematopoietic stem-cell transplantation from haploidentical donors using exviv T-cell-depletion. Presented at EBMT 2021; Abstract P185.

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