Impact of Absolute Lymphocyte Count at Time of Antithymocyte Globulin on Outcomes of Allogeneic Unrelated Hematopoietic Cell Transplantation with Busulfan and Fludarabine Myeloablative Conditioning

Introduction:

Allogeneic hematopoietic stem cell transplant is curative in several benign and malignant hematological disorders with predominant complications of graft versus host disease (GVHD) and infections. Antithymocyte globulin (ATG) has been shown in a number of prospective trials to be effective in decreasing acute and chronic GVHD. Recently, it has been suggested that recipient peripheral blood absolute lymphocyte count (ALC) on the day of ATG administration interacts with the dose of ATG administered and predicts transplantation outcomes. This interaction may depend on the preparative regimen and the dose of ATG used. We sought to determine if ALC at time of administration of ATG could impact clinical outcomes in a population treated with busulfan fludarabine myeloablative regimen and a fixed dose of 4mg/kg of ATG.

Methods:

Seventy consecutive pts who underwent a matched unrelated donor transplant with ATG at the University of Iowa were retrospectively analyzed. All pts received rabbit ATG (Thymoglobulin®) at 0.5 mg/kg on day -3, 1.5 mg/kg on day -2 and 2 mg/kg on day -3 in addition to tacrolimus and methotrexate. All received a myeloablative preparative regimen with busulfan (130 mg/m2 days -6 to -3) and fludarabine (40 mg/m2 daily for 4 days). All but one pt received peripheral blood as graft source. The effect of patient, disease, and transplant characteristics on 2-year outcomes was evaluated using Cox and Fine and Gray regression models. For relapse, GVHD, and infections, death was considered a competing risk. Estimated effects of predictors are reported as hazard ratios (HR) along with 95% confidence intervals.

Results:

Median age was 59 years (range 20-68). Underlying diagnoses were AML (n=47), MDS (n=20) and CML (n=3). Disease Risk index showed 25 high risk, 24 intermediate risk and 21 low risk patients in this study. The median peripheral blood ALC on day -3 was 100 × 102/µL (range 0-1144 × 102/µL). Univariate analysis showed no significant impact of ALC (100+ vs <100) on 2-year risk of developing GVHD (HR 1.49, 95%CI: 0.77 - 2.86), 2-year overall infection risk (HR 0.86, 95%CI: 0.51-1.46), 2-year bacterial (HR 0.78, 95%CI: 0.43-1.42), viral (HR 0.81, 95%CI: 0.41-1.60) and fungal (HR 0.63, 95% CI: 0.17-2.33) infections. Univariate analysis also showed no significant influence on 2-year relapse-free survival (HR 0.67, 95%CI: 0.21-2.14) and overall survival (HR 0.84, 95%CI: 0.34-2.06). Significantly worse survival is seen in MDS in comparison to leukemic pts, and high disease risk in comparison to low disease risk.

Conclusion:

Our single center experience using busulfan and fludarabine myeloablative regimen and rabbit ATG dosed at 4 mg/kg showed no interaction between the recipient peripheral blood ALC and ATG to predict GVHD, infections, overall and relapse free survival.