Predictive Value for Engraftment and Survival of Total Nucleated Cell Dose (TNC) as Compared to CD34+ Cell Dose after Autologous and Allogeneic Bone Marrow Transplant (BMT) for Hematologic Malignancies.
Authors: Kassim Adetola A. , Mineishi Shin , Jagasia Madan , Vurisikala Madhuri , Goodman Stacey , Greer John P. , Chinratanalab Wichai , Ruffner Katherine , Morgan David S. , Stein Richard S. , Brandt Stephen , Schuening Friedrich G. 
Published: April 2020

INTRODUCTION: An adequate dose of CD34+ cells is necessary for autologous or allogeneic transplants of peripheral blood stem cells (PBSC), to ensure early and sustained hematopoietic engraftment and favorable clinical outcome. CD34+ cell dose was predictive of survival, posttransplant morbidity and rate of hematologic recovery following allogeneic T-cell-depleted BMT [Mavroudis et al. Blood, 1996]. High TNC doses have been found to influence the outcome of autologous and allogeneic BMT favorably. A low CD34+ cell dose results in higher mortality and poorer survival after blood and marrow stem cell transplantation from an HLA-identical sibling, and 2 x 106 CD34+ cells/kg has been suggested as minimum cell dose [S Singhal et al, BMT 2000]. There are no comparative data on the relationship of TNC dose and CD34+cell dose of unmanipulated marrow on transplant outcome.

METHODS: Fifty-four patients received BMT from HLA-identical sibling donors between January 1999 and June 2004. Twenty-nine (51%) patients had Chronic Myeloid Leukemia, thirteen (24%) Acute Myeloid leukemia, five (9%) Non-Hodgkin’s Lymphoma (NHL), four (7%) Myelodysplastic syndrome, three (5%) Acute Lymphocytic Leukemia, one (2%) Chronic Lymphocytic Leukemia, one (2%) Myelofibrosis, one (2%) Multiple Myeloma (MM), one (2%) Hodgkin’s disease (HD) and one (2%) Aplastic Anemia. Nine patients received autologous, G-CSF mobilized marrow, after failing PBSC collection (7 NHL, 1 HD and 1 MM). These reflect the two populations of BMT patients now commonly seen. TNC and CD34+ cell doses of each graft were analyzed.

RESULT: There was no correlation (r = 0.361) between the TNC and the CD34+ cell content of the grafts in either allogeneic (allo) (figure 1 below) or autologous (auto) BMT. The median TNC and CD34+ cell doses were 3.16x 108/kg and 3.67 x 106/kg respectively for allo patients and 3.62 x 108/kg and 1.61 x 106/kg for auto patients. In allo patients, TNC dose above 3.16x 108/kg correlated with better neutrophil (p=0.0130) and platelet engraftment (p=0.0002), while CD34+ cell dose above 3.67 x 106/kg correlated with better platelet engraftment (p= 0.0221), but not neutrophil engraftment (p=0.6106). Both TNC and CD34+ cell doses were not predictive of overall survival (p=0.1265, p=0.3216 respectively) in allo patients. Both TNC and CD34+ cell doses in auto patients did not correlate with neutrophil (p= 0.481 and 0.1122 respectively) engraftment, but CD34+ cell dose correlated with platelet engraftment (p= p= 0.0448). Average neutrophil recovery time was 20 days in both auto and allo patients, while platelet recovery time was 29 days for allo and 48 days for auto.

Figure Figure

bold]CONCLUSION: For patients undergoing allogeneic BMT, CD34+ count in the allograft may not add valuable information, while in patients who failed autologous PBSC mobilization and undergoing BMT, CD34+ counts may add useful information, particularly for platelet engraftment.