Absolute lymphocyte count on day 30 is a surrogate for robust hematopoietic recovery and strongly predicts outcome after T cell-depleted allogeneic stem cell transplantation

Abstract

Several studies have shown that a higher lymphocyte count 3-4 weeks after allogeneic stem cell transplantation (SCT) is associated with better transplant outcome. However, the factors determining early lymphocyte recovery are not defined. To further explore the relationship between lymphocyte recovery and outcome we analyzed lymphocyte counts and other engraftment parameters in 157 patients with leukemia (48 acute myelogenous leukemia, 80 chronic myelogenous leukemia, and 29 acute lymphoblastic leukemia [ALL]) receiving T cell-depleted myeloablative SCT from an HLA-identical sibling. In multivariate analysis the day 30 absolute lymphocyte count (LC30) above the median of 450/muL was associated with improved survival (71% +/- 5% versus 38% +/- 6%, P < .0001), less relapse (21% +/- 5% versus 44% +/- 7%, P = .009), less nonrelapse mortality (NRM; 9 +/- 3 versus 36% +/- 6%, P < .0001) and less acute graft-versus-host disease (aGVHD) (34% +/- 5% versus 51% +/- 6%, P = .025). The beneficial effect of a higher LC30 influenced outcome in patients with both standard and high-risk disease but did not affect survival and relapse in ALL. We found that a higher LC30 correlated with higher lymphocyte counts at all time points between 30 and 90 days post-SCT and also with more rapid neutrophil and platelet engraftment. These results indicate that LC30 is a surrogate for robust engraftment and identifies an "at-risk" population of patients after T cell-depleted SCT.

Figure 1

A. LC30 distribution in AML, ALL and CML; B. comparison LC30, day 60 lymphocyte (LC60) and day 90 lymphocyte (LC90) counts post-transplantation between group with LC30 < and > 450/µl.

Figure 2

Time to A. neutrophil and B. platelet engraftment in patients with LC30 < vs >450/µl

Figure 3

Cumulative incidence of A. acute GVHD and B. chronic GVHD and incidence in patients with LC30 above and below 450/µl

Figure 4

A. cumulative incidence of non-relapse mortality; B. LC30, disease risk (HR- high risk; SR- standard risk) and NRM

Figure 5

A. cumulative incidence of relapse; B. LC30, disease risk (HR- high risk; SR- standard risk) and relapse; C. LC30 and relapse in acute lymphoblastic leukemia (ALL)

Figure 6

A. Overall survival; B. LC30, disease risk (HR- high risk; SR- standard risk) and survival; C. LC30 and survival in acute lymphoblastic leukemia (ALL)