Day 45 Lymphocyte Recovery Is Independently Associated with Transplant-Related Mortality after Adult Myeloablative Double-Unit Cord Blood Transplantation (dCBT)

Abstract Background: Our center has reported that the infused viable CD34+ cell dose of the dominant unit determines the speed & success of neutrophil recovery after dCBT (Purtill et al, Blood 2014). However, how unit characteristics affect lymphocyte recovery has not been determined, & the effect of both delayed neutrophil & lymphocyte recoveries on transplant-related mortality (TRM) requires investigation. Methods: The association between 1) dominant unit characteristics (TNC, CD34+, CD3+ cell doses & 8-allele HLA-match) & lymphocyte recovery, & 2) the effect of both neutrophil & lymphocyte recoveries on TRM were analyzed in 98 adult myeloablative dCBT recipients (median age 42 years, range 16-69) transplanted for hematologic malignancies. The analysis was restricted to adults given the significant differences in patients (pts), grafts, & neutrophil recovery in children. Results: The cumulative incidence of day 45 neutrophil engraftment ≥ 0.5 x 109/L was 96% (95%CI:89-99) with a median recovery of 25 days (range 12-43). The day 45 cumulative incidence of lymphocyte engraftment ≥ 0.2 x 109/L was also 96% (95%CI:89-99, median 25 days, range 12-59). Dominant unit infused viable CD34+ cell dose determined both neutrophil (as previously reported) & also lymphocyte recovery. To analyze if the speed & success of neutrophil & lymphocyte recovery are important in determining subsequent TRM in engrafting pts, we performed a day 45 landmark analysis of the 93 patient subset who achieved neutrophil engraftment & were alive 45 days post-dCBT (5 pts with graft failure or early death were excluded). In univariate analysis, a trend toward increased day 45-180 TRM was observed among the 51 pts with delayed neutrophil engraftment > 25 days [HR 2.71 (95%CI 0.88-8.42), p = 0.084], but there was no association between the absolute neutrophil count on day 45 & subsequent TRM. Conversely, while the time to lymphocyte recovery ≥ 0.2 x 109/L was not significant, the day 45 lymphocyte count correlated significantly with day 45-180 TRM. A lymphocyte cut-point of 0.3 x 109/L was identified below which TRM risk was markedly increased: 17 dCBT recipients with a day 45 lymphocyte count 40 years & recipient CMV seropositivity were also associated with a trend toward increased day 45-180 TRM in univariate analysis whereas regimen intensity, disease status, & dominant unit HLA-match were not. Patient demographics (age, weight, disease stage, CMV serostatus, & conditioning intensity) & dominant unit characteristics (infused TNC, viable CD34+, CD3+ cell doses) were similar in pts with day 45 lymphocyte counts > or 40 years & CMV serostatus were not significant (p = 0.196 & p = 0.418, respectively). The relationship between lymphocyte recovery & TRM was maintained when the 20 pts on therapy for acute GVHD by day 45 were excluded. Conclusion: Both early neutrophil & lymphocyte recovery are critically important factors in the success of adult myeloablative dCBT. While it is well appreciated that early failure of neutrophil recovery is associated with a very high mortality rate, this analysis of pts engrafting with neutrophils suggests a low lymphocyte count ( Table . Variable n HR (95%CI) p Speed of ANC recovery 42 Reference 0.069 ≥ 25 days 51 2.94 (0.92-9.39) Lymphocyte count at day 45 > 0.2 x 109/L 76 Reference 17 12.10 (4.21-34.81) * Recipient age and CMV serostatus were included in the initial model but removed using a backward conditional method. Download : Download high-res image (84KB) Download : Download full-size image Figure 1 . Disclosures No relevant conflicts of interest to declare.