Citations

Key PointsHigh-circulating AREG (≥33 pg/mL) reclassifies additional patients into HR categories and further refines the Minnesota aGVHD risk score. Patients with aGVHD and AREG ≥33 pg/mL have lower rates of steroid response, higher NRM, and poorer OS.

LBA1 Background: In hormone receptor (HR)-positive, HER2-negative, axillary node (AN)-negative breast cancer, the 21-gene expression assay (Oncotype DX Recurrence Score [RS]) is prognostic for distant recurrence, prognostic for low recurrence with endocrine therapy alone if low (0-10), and predictive of chemotherapy benefit if high (26 or higher). We performed a prospective, randomized trial of endocrine therapy (ET) versus chemoendocrine therapy (CET) in women with a mid-range RS of 11-25. Methods: Eligibility criteria included women 18-75 years of age with HR-positive, HER2-negative, axillary node (AN)-negative breast cancer and tumors 1.1-5.0 cm in size (or 0.6-1.0 cm and int/high grade) and agreed to have chemotherapy assigned or randomized based on the RS. Women with a mid-range RS (11-25) were randomized to receive ET or CET. The primary endpoint was invasive disease-free survival (iDFS), and the trial was designed to show non-inferiority for ET alone by not rejecting equality (hazard ratio [HR] margin up to 1.322 for omission of chemotherapy, 1-sided type I error rate 10%, type II error rate 5%). The target sample size was adjusted to compensate for non-adherence to randomized treatment, and the protocol-specified final analysis was triggered after 835 iDFS events. Results: Of the 10,253 eligible women enrolled between 4/7/06-10/6/10, 6711 (65.5%) had a RS of 11-25 and adequate information. There were 836 iDFS events at final analysis with a median followup of 90 months. ET was non-inferior to CET for iDFS (HR 1.08, 95% confidence intervals [CI] 0.94, 1.24, p=0.26) in the intention-to-treat (ITT) population. ET was also non-inferior for distant recurrence-free interval (DRFI; HR 1.03, p=0.80), recurrence-free interval (RFI; HR 1.12, p=0.28), and overall survival (OS; HR 0.97, p=0.80). Nine year rates were similar for iDFS (83.3% vs. 84.3%), DRFI (94.5% vs. 95.0%), RFI (92.2% vs. 92.9%), and OS (93.9% vs. 93.8%). Recurrence accounted for 338 (41.6%) the first iDFS event, of which 199 (23.8%) were distant recurrences. Treatment interaction tests were significant for age (iDFS p=0.03; RFI p= 0.02), but not menopause, tumor size, grade, or RS (continuous or RS 11-15, 16-20, 21-25). Conclusions: In women with HR-positive, HER2-negative, AN-negative breast cancer and a RS of 11-25, adjuvant ET was not inferior to CET in the ITT analysis. (Funded by NCI, BCRF, and Komen Foundation.) Clinical trial information: NCT00310180.

Key Points Over the last decade, allogeneic HCT has been increasingly administered in the United States to adults aged 70 and older with hematologic malignancies. Allogeneic transplant outcomes were reasonable; high comorbidity and ablative conditioning regimens were associated with inferior outcomes.

BACKGROUNDTo evaluate the impact of depression before autologous and allogeneic hematopoietic cell transplantation (HCT) on clinical outcomes post‐transplantation.METHODSWe analyzed data from the Center for International Blood and Marrow Transplant Research to compare outcomes after autologous (n = 3786) or allogeneic (n = 7433) HCT for adult patients with hematologic malignancies with an existing diagnosis of pre‐HCT depression requiring treatment versus those without pre‐HCT depression. Using Cox regression models, we compared overall survival (OS) between patients with or without depression. We compared the number of days alive and out of the hospital in the first 100 days post‐HCT using Poisson models. We also compared the incidence of grade 2‐4 acute and chronic graft‐versus‐host disease (GVHD) in allogeneic HCT.RESULTSThe study included 1116 (15%) patients with pre‐transplant depression and 6317 (85%) without depression who underwent allogeneic HCT between 2008 and 2012. Pre‐transplant depression was associated with lower OS (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.04‐1.23; P = 0.004) and a higher incidence of grade 2‐4 acute GVHD (HR, 1.25; 95% CI, 1.14‐1.37; P < 0.0001), but similar incidence of chronic GVHD. Pre‐transplant depression was associated with fewer days‐alive‐and‐out‐of‐the hospital (means ratio [MR] = 0.97; 95% CI, 0.95‐0.99; P = 0.004). There were 512 (13.5%) patients with Pre‐transplant depression and 3274 (86.5%) without depression who underwent autologous HCT. Pre‐transplant depression in autologous HCT was not associated with OS (HR, 1.15; 95% CI, 0.98‐1.34; P = 0.096) but was associated with fewer days alive and out of the hospital (MR, 0.98; 95% CI, 0.97‐0.99; P = 0.002).CONCLUSIONPre‐transplant depression was associated with lower OS and higher risk of acute GVHD among allogeneic HCT recipients and fewer days alive and out of the hospital during the first 100 days after autologous and allogeneic HCT. Patients with pre‐transplant depression represent a population that is at risk for post‐transplant complications. Cancer 2017;123:1828–1838. © 2017 American Cancer Society.

Key Points Under current treatment approaches, patients with LA GVHD have poor overall and failure-free survival. Levels of AREG are elevated in LA GVHD, and the AREG/EGF ratio is predictive of overall survival and nonrelapse mortality in LA GVHD.

Purpose To develop a system prognostic of outcome in those undergoing allogeneic hematopoietic cell transplantation (allo HCT) for myelodysplastic syndrome (MDS). Patients and Methods We examined 2,133 patients with MDS undergoing HLA-matched (n = 1,728) or -mismatched (n = 405) allo HCT from 2000 to 2012. We used a Cox multivariable model to identify factors prognostic of mortality in a training subset (n = 1,151) of the HLA-matched cohort. A weighted score using these factors was assigned to the remaining patients undergoing HLA-matched allo HCT (validation cohort; n = 577) as well as to patients undergoing HLA-mismatched allo HCT. Results Blood blasts greater than 3% (hazard ratio [HR], 1.41; 95% CI, 1.08 to 1.85), platelets 50 × 109/L or less at transplantation (HR, 1.37; 95% CI, 1.18 to 1.61), Karnofsky performance status less than 90% (HR, 1.25; 95% CI, 1.06 to 1.28), comprehensive cytogenetic risk score of poor or very poor (HR, 1.43; 95% CI, 1.14 to 1.80), and age 30 to 49 years (HR, 1.60; 95% CI, 1.09 to 2.35) were associated with increased hazard of death and assigned 1 point in the scoring system. Monosomal karyotype (HR, 2.01; 95% CI, 1.65 to 2.45) and age 50 years or older (HR, 1.93; 95% CI, 1.36 to 2.83) were assigned 2 points. The 3-year overall survival after transplantation in patients with low (0 to 1 points), intermediate (2 to 3), high (4 to 5) and very high (≥ 6) scores was 71% (95% CI, 58% to 85%), 49% (95% CI, 42% to 56%), 41% (95% CI, 31% to 51%), and 25% (95% CI, 4% to 46%), respectively (P < .001). Increasing score was predictive of increased relapse (P < .001) and treatment-related mortality (P < .001) in the HLA-matched set and relapse (P < .001) in the HLA-mismatched cohort. Conclusion The proposed system is prognostic of outcome in patients undergoing HLA-matched and -mismatched allo HCT for MDS.

Abstract Purpose: Cutaneous sclerosis occurs in 20% of patients with chronic graft-versus-host disease (GVHD) and can compromise mobility and quality of life. Experimental design: We conducted a prospective, multicenter, randomized, two-arm phase II crossover trial of imatinib (200 mg daily) or rituximab (375 mg/m2 i.v. weekly × 4 doses, repeatable after 3 months) for treatment of cutaneous sclerosis diagnosed within 18 months (NCT01309997). The primary endpoint was significant clinical response (SCR) at 6 months, defined as quantitative improvement in skin sclerosis or joint range of motion. Treatment success was defined as SCR at 6 months without crossover, recurrent malignancy or death. Secondary endpoints included changes of B-cell profiles in blood (BAFF levels and cellular subsets), patient-reported outcomes, and histopathology between responders and nonresponders with each therapy. Results: SCR was observed in 9 of 35 [26%; 95% confidence interval (CI); 13%–43%] participants randomized to imatinib and 10 of 37 (27%; 95% CI, 14%–44%) randomized to rituximab. Six (17%; 95% CI, 7%–34%) patients in the imatinib arm and 5 (14%; 95% CI, 5%–29%) in the rituximab arm had treatment success. Higher percentages of activated B cells (CD27+) were seen at enrollment in rituximab-treated patients who had treatment success (P = 0.01), but not in imatinib-treated patients. Conclusions: These results support the need for more effective therapies for cutaneous sclerosis and suggest that activated B cells define a subgroup of patients with cutaneous sclerosis who are more likely to respond to rituximab. Clin Cancer Res; 22(2); 319–27. ©2015 AACR.

Purpose Autologous hematopoietic cell transplantation, or autotransplantation, is effective in light-chain amyloidosis (AL), but it is associated with a high risk of early mortality (EM). In a multicenter randomized comparison against oral chemotherapy, autotransplantation was associated with 24% EM. We analyzed trends in outcomes after autologous hematopoietic cell transplantation for AL in North America. Patients and Methods Between 1995 and 2012, 1,536 patients with AL who underwent autotransplantation at 134 centers were identified in the Center for International Blood and Marrow Transplant Research database. EM and overall survival (OS) were analyzed in three time cohorts: 1995 to 2000 (n = 140), 2001 to 2006 (n = 596), and 2007 to 2012 (n = 800). Hematologic and renal responses and factors associated with EM, relapse and/or progression, progression-free survival and OS were analyzed in more recent subgroups from 2001 to 2006 (n = 197) and from 2007 to 2012 (n = 157). Results Mortality at 30 and 100 days progressively declined over successive time periods from 11% and 20%, respectively, in 1995 to 2000 to 5% and 11%, respectively, in 2001 to 2006, and to 3% and 5%, respectively, in 2007 to 2012. Correspondingly, 5-year OS improved from 55% in 1995 to 2000 to 61% in 2001 to 2006 and to 77% in 2007 to 2012. Hematologic response to transplantation improved in the latest cohort. Renal response rate was 32%. Centers performing more than four AL transplantations per year had superior survival outcomes. In the multivariable analysis, cardiac AL was associated with high EM and inferior progression-free survival and OS. Autotransplantation in 2007 to 2012 and use of higher dosages of melphalan were associated with a lowered relapse risk. A Karnofsky score less than 80 and creatinine levels 2 mg/m2 or greater were associated with worsened OS. Conclusion Post-transplantation survival in AL has improved, with a dramatic reduction in early post-transplantation mortality and excellent 5-year survival. The risk-benefit ratio for autotransplantation has changed, and randomized comparison with nontransplantation approaches is again warranted.