title: Assessment of hematologic progenitor engraftment by complete reticulocyte maturation parameters after autologous and allogeneic hematopoietic stem cell transplantation.
abstract: OBJECTIVE
  Hematopoietic restoration after marrow ablation is initiated by the erythroid compartment. However, the absolute microscope counts or corrected percentage of reticulocytes have proven to be poor markers of hematopoietic engraftment. Some reports have highlighted the usefulness of automatic flow cytometry methods to determine highly fluorescent reticulocytes, or mean fluorescence index. In this series of 60 hematopoietic stem cell transplants, we sought the normal kinetics throughout the post-transplant period of the following reticulocyte maturing parameters: highly fluorescent reticulocytes (RETH), immature reticulocyte fraction (IRF), mean fluorescence index (MFI) and also mean reticulocyte volume (MRV).
  
  
  METHODS
  Sixty consecutive patients undergoing allogeneic bone marrow (30 cases) and autologous mobilized stem cell transplantation (30 cases) were studied. Parameters of reticulocyte maturation were measured every other day from the beginning of the conditioning regimen until myeloid engraftment.
  
  
  RESULTS
  Nadir values for the analyzed reticulocyte parameters were found between days +4 and +7 and thereafter, increases in these reticulocyte parameters appeared earlier than the rise in neutrophils. We considered erythroid engraftment to have occurred on the day when RETH reached 3%, IRF 10%, MFI 10 and MRV 110 fL. These cut-offs were assigned considering the 25% quartile for each parameter on the day that the myeloid engraftment occurred. The median engraftment days for RETH were +9 and +16, for IRF +9 and +13, for MFI +9 and +13 and for MRV +11 and +13 in autologous and allogeneic procedures, respectively. When compared to standard neutrophil engraftment, IRF and MFI engraftment occurred significantly earlier in all patients. Remarkably, we found a statistical correlation between the day a reticulocyte parameter reached its cut-off and the subsequent day of absolute neutrophil count (ANC) recovery for MFI after allogeneic transplants and for MRV after autologous procedures (p < 0.001 and p= 0.02, respectively). Of all the clinical parameters tested, only the number of infused CD34 cells showed a statistical influence on erythroid engraftment in autologous transplant.
  
  
  CONCLUSIONS
  Early reticulocytes appear sooner than neutrophils after both autologous and allogeneic transplants, and any determined reticulocyte parameter can reliably measure this fraction. Nevertheless, our results show that MRV and MFI cut-offs are useful for determining subsequent myeloid engraftment. These findings could be relevant to decision-making in those patients with primary graft failure heralded by an absence of increasing values of MFI and MRV, indicating very low production of reticulocytes from the graft, who could, therefore, benefit from earlier rescue therapy.
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Reina Sofia University Hospital, Avda. Menedez Pidal s/n, 14004 Córdoba, Spain. md1togoa@uco.es
authors.forename: A
authors.initials: A
authors.lastname: Torres
authors.forename: J
authors.initials: J
authors.lastname: Sánchez
authors.forename: D
authors.initials: D
authors.lastname: Lakomsky
authors.forename: J
authors.initials: J
authors.lastname: Serrano
authors.forename: M A
authors.initials: MA
authors.lastname: Alvarez
authors.forename: C
authors.initials: C
authors.lastname: Martín
authors.forename: C
authors.initials: C
authors.lastname: Valls
authors.forename: L
authors.initials: L
authors.lastname: Nevado
authors.forename: A
authors.initials: A
authors.lastname: Rodriguez
authors.forename: J
authors.initials: J
authors.lastname: Casaño
authors.forename: F
authors.initials: F
authors.lastname: Martínez
authors.forename: P
authors.initials: P
authors.lastname: Gómez
mesh_terms: D000293:Adolescent; D000328:Adult; D048429:Cell Size; D002648:Child; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000592:standards*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy; D017701:Reticulocyte Count; D012156:Reticulocytes / Q000166:cytology; D013997:Time Factors; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous