Background: HD IL-2 is an approved immunotherapy that can achieve durable cures in MM pts. Due to toxicity and low ORR, identification of predictors of clinical benefit would enhance pt selection and outcomes with HD IL-2. Recent research identified a positive correlation for ALC ≥ 1000 (either at baseline or at dose 3) with OS among MM pts treated with the immunotherapy agent ipilimumab. We tested the hypothesis that ALC (≥ 1000) or other hematological parameters correlates with clinical benefit from HD IL2. Methods: Results of hematologic testing in patients (n=98) treated with HD IL2 at MD Anderson Cancer Center were collected, including absolute levels of neutrophils (ANC), lymphocytes (ALC), monocytes (AMC), eosinophils (AEC), and platelets (APC) at baseline, after cycle 1 (C1), and after cycle 2 (C2) of HD IL-2; changes in each parameter for each interval were also calculated. Hematologic values were assessed as categorical (for ALC, ≥ 1000 Yes/No; other parameters, above upper limit of normal [ULN] Yes/No) and continuous variables. Associations between these parameters and PFS and ORR were analyzed. Results: ALC was≥ 1000 in 75 pts (76%) at baseline, in 81 (83%) after C1, and in 80 of 86 pts (93%) after completion of C2 of HD IL-2. PFS was not significantly associated with ALC ≥ 1000 at baseline (HR 0.69, p=0.13), after C1 (HR 1.32, p=0.33), or after C2 (HR 1.01, p=0.98). ALC ≥ 1000 at each timepoint was not significantly associated with ORR or OS. There was no significant difference in the change in ALC with HD IL2 treatment among responders versus non-responders. Among baseline hematological factors, APC > ULN was significantly associated with PFS (p=0.001), but it was rare (2/98 patients). Exploratory analyses identified significantly shorter PFS for patients with baseline APC > 300 (11%, HR 2.75, p=0.002). Analysis of hematologic factors as continuous values identified significant associations with PFS for AMC (HR 2.42, p=0.03) and AEC (HR 1.73, p=0.009) after C2. Conclusions: ALC ≥ 1000 did not correlate with PFS, ORR, or OS with HD IL-2 therapy in this cohort of metastatic melanoma pts.