Novel strategies for improving hematopoietic reconstruction after allogeneic hematopoietic stem cell transplantation or intensive chemotherapy

ABSTRACT

Introduction: High-dose conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT) as well as intensive poly-chemotherapy for acute myeloid leukemia (AML) induce prolonged periods of neutropenia. The duration of the neutropenia is particularly long following umbilical cord blood transplantation (UCBT).

Areas covered: After briefly reviewing the impact of hematopoietic growth factors administration to hasten hematologic reconstitution after allo-HCT or intensive AML chemotherapy, this article summarizes recent approaches that have been investigated to prompt hematologic reconstruction after UCBT or intensive AML chemotherapy.

Expert opinion: In the allo-HCT setting, administration of G-CSF or GM-CSF shortened the duration of the neutropenia but failed to decrease infection-related mortality or to improve survival. Novel approaches to hasten hematological reconstruction after UCBT such as double UCBT with expansion of one of the 2 UCB units with Notch ligand, mesenchymal stromal cells, nicotinamide, or StemRegenin 1, co-transplanting a single UCB unit with HLA-haploidentical CD34+ cells, or increasing UCB HSC homing to marrow niches via direct intra bone UCB administration, pulse treatment with dmPGE2 or enforced fucosylation are promising and deserve further investigations in prospective phase III studies. In the AML setting, G-CSF or GM-CSF administration after intensive chemotherapy decreased the duration of the neutropenia without improving survival.

KEYWORDS:

• Hematopoietic reconstitution
• AML
• allogeneic hematopoietic stem cell transplantation
• umbilical cord blood
• G-CSF
• GM-CSF
• Notch ligand
• mesenchymal stromal cells
• nicotinamide
• StemRegenin 1

Article highlights

• G-CSF administration significantly prompts neutrophil recovery after allo-HCT or intensive chemotherapy for AML.

• G-CSF administration after allo-HCT or intensive chemotherapy for AML does not improve OS.

• Double UCBT allows patients without a sufficiently rich single UCB unit to benefit from UCBT.

• double UCBT failed to improve engraftment and other transplantation outcomes in patients who had a single UCB unit containing ≥2.5 x 10⁷ TNC/kg recipient.

• double UCBT with expansion of one of the 2 UCB units with Notch ligand, mesenchymal stromal cells, nicotinamide, or StemRegenin 1 results in prompt neutrophil engraftment.

• co-transplanting a single UCB unit with HLA-haploidentical CD34+ cells fastens neutrophil engraftment in comparison to double UCBT.

• increasing UCB HSPC homing to marrow niches via direct intra bone UCB administration, pulse treatment with dmPGE2 or enforced fucosylation also fastens neutrophil engraftment.

This box summarizes key points contained in the article.

Declaration of interest

F Baron is senior research associate of the national fund for scientific research (F.R.S., FNRS), Belgium. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This manuscript has not been funded.