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.

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.

View largeDownload slide

Figure

View largeDownload slide

Figure

Close modal

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.