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The lack of standardized criteria for measuring therapeutic response is a major obstacle to the development of new therapeutic agents for chronic graft-versus-host disease (cGVHD). National Institutes of Health (NIH) consensus criteria for evaluating therapeutic response were published in 2006. We report the results of 4 consecutive pilot trials evaluating the feasibility and estimating the interrater reliability and minimum detectable change of these response criteria. Hematology-oncology clinicians with limited experience in applying the NIH cGVHD response criteria (n = 34) participated in a 2.5-hour training session on response evaluation in cGVHD. Feasibility and interrater reliability between subspecialty cGVHD experts and this panel of clinician raters were examined in a sample of 25 children and adults with cGVHD. The minimum detectable change was calculated using the standard error of measurement. Clinicians' impressions of the brief training session, the photo atlas, and the response criteria documentation tools were generally favorable. Performing and documenting the full set of response evaluations required a median of 21 minutes (range: 12-60 minutes) per rater. The Schirmer tear test required the greatest time of any single test (median: 9 minutes). Overall, interrater agreement for skin and oral manifestations was modest; however, in the third and fourth trials, the agreement between clinicians and experts for all dimensions except movable sclerosis approached satisfactory values. In the final 2 trials, the threshold for defining change exceeding measurement error was 19% to 22% body surface area (BSA) for erythema, 18% to 26% BSA for movable sclerosis, 17% to 21% BSA for nonmovable sclerosis, and 2.1 to 2.6 points on the 15-point NIH Oral cGHVD scale. Agreement between clinician-expert pairs was moderate to substantial for the measures of functional capacity and for the gastrointestinal and global cGVHD rating scales. These results suggest that the NIH response criteria are feasible for use, and these reliability estimates are encouraging, because they were observed following a single 2.5-hour training session given at multiple transplant centers, with no opportunity for iterative training and calibration. Research is needed to evaluate inter- and intrarater reliability in larger samples, and to evaluate these response criteria as predictors of outcomes in clinical trials., (Published by Elsevier Inc.)

Although xerostomia is a commonly reported complaint in patients with chronic graft-versus-host disease (cGVHD), criteria for evaluating the prevalence and characteristics of salivary gland involvement have not been well defined in this patient population. Previous studies also have made no distinction between salivary and mucosal oral cGVHD. We systematically evaluated signs and symptoms of sicca in a large cohort of patients with cGVHD (n = 101) using instruments widely used to study Sjogren's syndrome. Xerostomia was reported in 60 (77%) patients reporting ocular and 52 (67%) patients reporting oral complaints [corrected]. The salivary flow rate was < or =0.2 mL/min in 27%, and < or =0.1 mL/min in 16%. Histopathological changes, consisting of mononuclear infiltration and/or fibrosis/atrophy, were present in all patients with salivary dysfunction. Importantly, there was no correlation of salivary and oral mucosal involvement in cGVHD. Patients with cGVHD-associated salivary gland involvement had diminished oral cavity-specific quality of life and lower body mass index. Salivary gland involvement is a common and clinically distinct manifestation of cGVHD. Formal evaluation of salivary function using standardized criteria is needed, and this could be incorporated as an outcome measure in clinical trials of cGVHD., (Published by Elsevier Inc.)

Inflammatory breast cancer (IBC) is a rare clinicopathologic entity with a poor prognosis, lagging far behind any other form of nonmetastatic breast cancer. Since the advent of systemic chemotherapy over 35 years ago, only minimal progress has been made in long-term outcome. Although multiple randomized trials of high-dose chemotherapy and autologous progenitor cell transplantation (ASCT) for the treatment of breast cancer have yielded disappointing results, these data are not necessarily relevant to IBC, a distinct clinical and pathologic entity. Therefore, the optimal multimodality therapy for IBC is not well established, and remains unsatisfactory. We treated 21 women with nonmetastatic IBC with a multimodality strategy including high-dose melphalan (Mel)/etoposide and ASCT. The treatment was overall tolerated with acceptable morbidity, and no post-ASCT 100-day mortality. With a median potential follow-up of approximately 8 years, the estimated progression-free survival (PFS), event-free survival (EFS), and overall survival (OS) at 6 years from on-study date are: 67%, 55%, and 69%, respectively. These results from a small phase II study are among the most promising of mature outcome data for IBC. They strongly suggest, along with results of several already published phase II trials, that ASCT could play a significant role in the first line treatment of IBC.