Impact of White Blood Cell Count Recovery On Clinical Outcomes After Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Kim Haesook T , Frederick David G , Andler Emily , Armand Philippe , Kao Grace , Cutler Corey , Koreth John , Alyea Edwin , Antin Joseph H , Soiffer Robert J , Ritz Jerome , Ho Vincent T. 
Published: October 2019

Abstract
Abstract 4136

Background:
Studies have shown that absolute lymphocyte count (ALC) early after allogeneic hematopoietic stem cell transplantation (HSCT) affects clinical outcomes. We hypothesize that the white blood cell (WBC) count at 1 month after HSCT may also predict transplant outcomes.

Methods:
1115 adult patients undergoing allogeneic HSCT from 2003 through 2009 at Dana-Farber/Brigham and Women's Hospital were analyzed. The median age was 51 yrs (range 18–74); median follow up time among survivors was 4.3 years (range 1.1–9.2); 596 patients received reduced intensity conditioning (RIC) and 519 received myeloablative conditioning (MAC). Using the restricted cubic spline estimates on the log relative hazard over WBC at 1 month post HSCT, WBC was categorized as: low (0-<2), normal (2–10), and high (>10×109 cells/L).

Results:
The outcomes are summarized in the table and figure below. One-year OS was 52%, 71%, 48% for low, normal, high WBC at 1 month post HSCT, respectively, (p<0.0001) and 1-year PFS was 39%, 56%, and 44% for low, normal, high WBC, respectively (p<=0.0001). One year cumulative incidence of NRM was 15%, 5.2%, 9.1% for low, normal, high WBC (p=0.008 for low vs normal, p=0.33 for high vs normal) in RIC and 23%, 15%, 28% for low, normal, high WBC (p=0.28 for low vs normal, p=0.001 for high vs normal) in MAC. One year cumulative incidence of relapse was 51%, 44%, 58% for low, normal, high WBC (p=0.49 for low vs normal, p=0.04 for high vs normal) in RIC but 27%, 22%%, 23% for low, normal, high WBC (p=n.s.) in MAC. In multivariable multinomial logistic regression analysis, age (OR=0.94, p=0.004) and sirolimus containing GVHD prophylaxis (OR=3.3, p=0.044) in MAC, and mismatched donor type (OR=3.0, p=0.03) in RIC were the risk factors for low WBC; AML/CML (OR=8.2, p=0.009), CLL (OR=13.9, p=0.0036) in RIC and high disease-relapse index (ref. Armand et al, Blood, 2012) (OR=3.26, p=0.04) were risk factors for high WBC. In multivariable Cox model adjusting for other prognostic factors, both low and high WBC at 1 month were associated with poor OS (Low WBC: HR 1.59, p=0.01; High WBC: HR 1.85, p=0.007) and PFS (low WBC: HR 1.59, p=0.008; high WBC: HR 1.68, p=0.017) in RIC and high WBC at 1 month was associated with both poor OS (HR 1.93, p<0.0001) and PFS (HR 1.7, p=0.0006) in MAC. Furthermore, low or high WBC was associated with viral or fungal infection within 100 days of HSCT (viral: 27%, 9%, 9%,p=0.019 in MAC; 9%, 4%, 15%, p=0.01 in RIC; fungal: 27%, 6%, 9%,p=0.0006 in MAC; 2%, 2%, 9%, p=0.046 in RIC). In the MAC cohort, high WBC at 1 month was associated with development of subsequent grade II-IV acute GVHD: 41%, 39%, 51% for low, normal, (p<0.001). In the RIC cohort, only 48% in low (p<0.001) and 54% in high WBC (p=0.02) achieved ≥90% donor chimerism by day 30 post HSCT compared to 76% of patients in normal WBC, suggesting that the abnormal WBC reflects poor donor engraftment or persistence of underlying disease. There was a weak correlation between WBC and ALC at 1 month (correlation coefficient = 0.46). Low ALC is associated with poor outcome, but not high ALC.

Conclusion:
Out data suggest that WBC at 1 month after allogeneic HSCT predicts transplant outcomes independent of ALC and chimerism.

Disclosures:
No relevant conflicts of interest to declare.