Infused CD34+ cell dose predicts response to stem cell boost in children with poor graft function following allogeneic hematopoietic stem cell transplantation: a multicenter study from the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC).

BACKGROUND

Poor graft function (PGF) is a severe and potentially life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT), characterized by persistent cytopenias despite adequate donor chimerism. Although CD34+ selected stem cell boost (CD34+SCB) has emerged as a promising treatment, evidence in pediatric patients remains limited, and the optimal CD34+ cell dose required to achieve complete hematologic recovery has not been established.

OBJECTIVES

To evaluate outcomes of CD34+SCB in children with PGF, identify factors associated with hematologic recovery and survival, and determine the CD34+ cell dose required to achieve complete hematologic recovery with external validation.

METHODS

We conducted a national multicenter retrospective study. Pediatric patients (≤18 years) with severe PGF involving at least two hematopoietic lineages who received CD34+SCB from the original donor were included in the training cohort (n=42). Primary endpoint was complete response (CR). Secondary endpoints included overall response rate (ORR), overall survival (OS) and factors associated with CR and OS. The optimal CD34+ cell dose threshold predicting CR was identified using maximally selected rank statistics and externally validated with an independent cohort.

RESULTS

Median time from HSCT to PGF diagnosis was 89 days, and 88% of patients presented with trilineage cytopenia. The median infused CD34+ cell dose was 7.3 × 106/kg. ORR and CR were 83.3% and 61.9%, respectively, with median time to CR of 43 days. With a median follow-up of 19.9 months, 2-year OS was 59.5%. Most deaths were due to infections and occurred in non-responders. In multivariable analysis, infused CD34+ cell dose was the only independent factor predictor of CR (HR 1.14, 95% CI 1.02-1.26; p=0.019). A threshold of 4.65 × 10⁶ CD34+ cells/kg significantly discriminated the probability of achieving CR in the training cohort (p=0.016) and was independently validated in the external cohort (p=0.013). Previous chronic graft-versus-host disease (GVHD) and haploidentical transplantation were independently associated with inferior OS. CD34+SCB demonstrated a favorable safety profile, with low incidences of de novo acute and chronic GVHD

CONCLUSION

CD34+SCB is an effective and safe therapeutic strategy for pediatric PGF following HSCT, achieving high hematologic recovery rates with acceptable long-term survival. Infused CD34+ cell dose is the main determinant of complete hematologic recovery, and a minimum threshold may help optimize treatment outcomes. Further studies are warranted to refine risk-adapted approaches in this high-risk population.