Bassett, Roland L.

AbstractEnumeration of blasts and promonocytes is essential for World Health Organization (WHO) classification of myelomonocytic neoplasms. The accuracy of distinguishing blasts, promonocytes and monocytes, including normal vs abnormal monocytes, remains controversial. The objective of this analysis is to assess concordances between experienced hematopathologists in classifying cells as blasts, promonocytes, and monocytes according to WHO criteria. Each of 11 hematopathologists assessed glass slides from 20 patients [12 with chronic myelomonocytic leukemia (CMML) and 8 with acute myeloid leukemia (AML)] including blood and BM aspirate smears, and limited nonspecific esterase (NSE) stains. All cases were blindly reviewed. Fleiss’ extension of Cohen's kappa for multiple raters was used on these variables, separately for peripheral blood (PB) and bone marrow (BM). Spearman's rank correlation was used to assess correlations between each pair of hematopathologists for each measurement. For the classification based on the sum of blasts and promonocytes in the BM, Fleiss’ kappa was estimated as 0.744. For PB, categorizing patients according to the sum of blasts and promonocytes, Fleiss’ kappa was estimated as 0.949. Distinction of abnormal monocytes from normal monocytes in PB did not achieve a good concordance and showed strong evidence of differences between hematopathologists (P < .0001). The hematopathologists achieved a good concordance rate of 74% in CMML vs AML classification and a high k rate, confirming that criteria for defining the blasts equivalents (blasts plus promonocytes) could be applied consistently. Identification of monocyte subtypes (abnormal vs normal) was not concordant. Our results support the practice of combining blasts/promonocytes into a single category.

9096 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.

Abstract Purpose: Emerging data from cooperative group trials suggests that not all patients with a positive SLN require completion axillary lymph node dissection (ALND). The controversy regarding who will benefit from additional nodal clearance continues, suggesting a need for improved tools to predict non-SLN involvement. We hypothesized that the size of a SLN metastasis evaluated as a continuous variable would be an important predictor of non-SLN involvement. The goal of this study was to determine clinicopathologic factors including SLN metastasis size that predicted non-SLN involvement and to use these factors to construct an improved predictive nomogram. Methods: Using a prospective database, we identified 509 patients with invasive breast cancer from 1996 - 2007 with a positive SLN who underwent ALND. Patients receiving neoadjuvant therapy were excluded. Clinicopathologic data including age, primary tumor size, presence of multifocal disease, histology (invasive ductal vs. invasive lobular vs. mixed invasive), tumor grade, estrogen receptor, progesterone receptor, and HER2/neu status, presence of lymphovascular invasion (LVI), the number of SLNs identified, number of positive SLNs, the maximum SLN metastasis size and the presence of extranodal extension were recorded. For SLNs described only as containing isolated tumor cells, size was recorded as 0.1 mm. Univariate and multivariate logistic regression analyses were performed to identify factors predictive of positive non-SLNs. Using these variables, a nomogram was constructed and subsequently validated using an external cohort of 464 patients. Results: On univariate analysis, the following factors were predictive of positive non-SLNs: number of SLN identified (p&lt;.001), number of positive SLN (p&lt;.001), maximum SLN metastasis size (p&lt;.001), extranodal extension (p&lt;.001), primary tumor size (p=.001), LVI (p=.019) and histology (p=.034). On multivariate analysis, all factors remained significant at the 5% level except LVI. A nomogram was created using these variables. When applied to an external cohort, the nomogram was accurate and discriminating with an area under the receiver operating characteristic curve of .73 (95% CI: .68 - .77). Conclusions: SLN metastasis size is predictive for identifying additional disease in the axilla. These data have been incorporated into a nomogram that accurately predicts the likelihood of having additional, non-SLN metastasis suggesting that routine reporting of the SLN metastasis size would assist with clinical decision making regarding the need to perform a completion ALND. Figures available in online version. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD06-08.