title: Novel strategies for improving hematopoietic reconstruction after allogeneic hematopoietic stem cell transplantation or intensive chemotherapy.
abstract: 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.
authors.affiliation: a Department of Medicine, Division of Hematology , University and CHU of Liège , Liège , Belgium.|b Giga-I3, Section of Hematology , University of Liège , Liège , Belgium.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Baron
authors.affiliation: c Division of Hematology and Bone Marrow Transplantation , The Chaim Sheba Medical Center , Ramat-Gan , Israel.|d EBMT Paris Office , Hospital Saint Antoine , Paris , France.|e Department of Bone Marrow Transplantation , Tel Aviv University (TAU) , Tel Aviv , Israel.
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D006410:Hematopoiesis / Q000187:drug effects* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000639:trends; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy*; D009503:Neutropenia / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control; D011446:Prospective Studies; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods / Q000639:trends; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000379:methods / Q000639:trends
chemical_list: D000970:Antineoplastic Agents
keywords: AML; G-CSF; GM-CSF; Hematopoietic reconstitution; Notch ligand; StemRegenin 1; allogeneic hematopoietic stem cell transplantation; mesenchymal stromal cells; nicotinamide; umbilical cord blood