CD34⁺ selected stem cell boosts can improve poor graft function after paediatric allogeneic stem cell transplantation

Abstract

SummaryPoor graft function (PGF) is a severe complication of haematopoietic stem cell transplantation (HSCT) and administration of donor stem cell boosts (SCBs) represents a therapeutic option. We report 50 paediatric patients with PGF who received 61 boosts with CD34 + selected peripheral blood stem cells (PBSC) after transplantation from matched unrelated (n = 25) or mismatched related (n = 25) donors. Within 8 weeks, a significant increase in median neutrophil counts (0Á6 vs. 1Á516 9 10 9 /l, P < 0Á05) and a decrease in red blood cell and platelet transfusion requirement (median frequencies 1 and 7 vs. 0, P < 0Á0001 and <0Á001), were observed, and 78Á8% of patients resolved one or two of their cytopenias. 36Á5% had a complete haematological response. Median lymphocyte counts for CD3 + , CD3 + CD4 + , CD19 + and CD56 + increased 8Á3-, 14Á2-, 22.-and 1Á6-fold.The rate of de novo acute graft-versus-host disease (GvHD) grade I-III was only 6% and resolved completely. No GvHD grade IV or chronic GvHD occurred. Patients who responded to SCB displayed a trend toward better overall survival (OS) (P = 0Á07). Thus, administration of CD34 + selectedSCBs from alternative donors is safe and effective. Further studies are warranted to clarify the impact on immune reconstitution and survival.Keywords: stem cell boost, poor graft function, haematopoietic stem cell transplantation, haematopoietic recovery.The therapeutic use of haematopoietic stem cell transplantation (HSCT) from matched unrelated or full haplotype mismatched related donors has been extended in recent years to a wide range of malignant and non-malignant diseases. Poor graft function (PGF) after HSCT is a relevant complication and is defined as at least bilinear severe cytopenia, and/or transfusion requirement, which occurs in a situation of full donor chimerism (thus differentiating from graft rejection)

Incidence, Risk Factors, and Outcomes of Primary Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation

“…In the patients with PGF who had a hematopoietic response, the median CD34 + dose was higher than that in the patients who did not show a response. In a recent study, a CD34 + cell dose >3.25 £ 6 /kg was related to a better improvement in neutrophil count [12]; however, no multivariate analysis found a cutoff value of CD34 + cells correlated with hematopoietic recovery. We suspected that two aspects may affect the result.…”

Advances in the understanding of poor graft function following allogeneic hematopoietic stem-cell transplantation

“…Another study focused mainly on pediatric patients ( n = 50) also identified good tolerance and efficacy. 70 To generate SCB, donors traditionally must undergo an additional peripheral blood stem-cell (PBSC) collection. However, realistically, many patients might not be able to receive fresh SCB if their donors are unwilling or unable to accept another PBSC collection.…”

G‐CSF administration prior to donor lymphocyte apheresis promotes anti‐leukaemic effects in allogeneic HCT patients

“…One of the most significant parameters for improved OS was the increased number of CD34 + stem and progenitor cells produced by G‐CSF administration prior to donor lymphocyte collection. It is an established procedure to administer purified CD34 + cells after allo‐HCT in case of mixed chimerism or poor graft function (Chandra et al , ; Mainardi et al , ). Moreover, CD34 + stem cell dose is one of the most important parameters to evaluate graft quality and predict haematopoietic recovery in autologous‐ and allo‐HCT settings (Weaver et al , ; Allan et al , ; Torlen et al , ; Rezvani et al , ).…”