[Show abstract][Hide abstract] ABSTRACT: Blood Cancer Journal is a peer-reviewed, open access online journal publishing pre-clinical and clinical work in the field of hematology with ramifications into translational biology research down to new therapies
Blood Cancer Journal 08/2015; 5(8):e344. DOI:10.1038/bcj.2015.70 · 3.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The relationship of socioeconomic status (SES) with long-term outcomes in allogeneic hematopoietic cell transplantation (HCT) survivors has not been well described. We studied the association of SES with the outcomes of 283 consecutive allogeneic HCT recipients transplanted between 2003 and 2012 who had survived for at least 1 year in remission. Median annual household income was estimated using Census tract data and from ZIP code of residence. SES categories were determined by recursive partitioning analysis (low SES (<$51 000/year), N=203; high SES (⩾$51 000/year), N=80). In multivariable analyses, low SES patients had higher risks of all-cause mortality (hazard ratio (HR) 1.98, P=0.012) and non-relapse mortality (NRM) (HR 2.22, P=0.028), but similar risks of relapse mortality (HR 1.01, P=0.97) compared with high SES patients. A trend toward better survival and lower NRM for high SES patients with no chronic GVHD was observed; low SES patients without GVHD had similar survival as patients with chronic GVHD. In allogeneic HCT survivors who survive in remission for at least 1 year, SES is associated with long-term survival that is primarily mediated through higher risks of NRM. More research is needed to understand the mechanisms of health-care disparities and interventions to mitigate them.Bone Marrow Transplantation advance online publication, 20 July 2015; doi:10.1038/bmt.2015.166.
Bone marrow transplantation 07/2015; DOI:10.1038/bmt.2015.166 · 3.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Quality of life (QOL) is an important outcome for hematopoietic cell transplantation (HCT) recipients. Whether pre-HCT QOL adds prognostic information to patient and disease related risk factors has not been well described. We investigated the association of pre-HCT QOL with relapse, non-relapse mortality (NRM), and overall mortality after allogeneic HCT. From 2003 to 2012, the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale instrument was administered before transplantation to 409 first allogeneic HCT recipients. We examined the association of the three outcomes with (1) individual QOL domains, (2) trial outcome index (TOI) and (3) total score. In multivariable models with individual domains, functional well-being (hazard ratio (HR) 0.95, P=0.025) and additional concerns (HR 1.39, P=0.002) were associated with reduced risk of relapse, no domain was associated with NRM, and better physical well-being was associated with reduced risk of overall mortality (HR 0.97, P=0.04). TOI was not associated with relapse or NRM but was associated with reduced risk of overall mortality (HR 0.93, P=0.05). Total score was not associated with any of the three outcomes. HCT-comorbidity index score was prognostic for greater risk of relapse and mortality but not NRM. QOL assessments, particularly physical functioning and functional well-being, may provide independent prognostic information beyond standard clinical measures in allogeneic HCT recipients.Bone Marrow Transplantation advance online publication, 1 June 2015; doi:10.1038/bmt.2015.122.
Bone marrow transplantation 06/2015; 50(9). DOI:10.1038/bmt.2015.122 · 3.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nonsurgical treatment of advanced supraglottic laryngeal cancer is widely used as part of a larynx preservation protocol. However, recent studies have suggested that nonsurgical treatment may be associated with inferior survival. Furthermore, it is not clear whether preservation of the larynx provides superior voice or swallowing function in the long term.
To test the hypothesis that surgical treatment of advanced-stage squamous cell carcinoma of the supraglottic larynx is associated with superior overall survival (OS), freedom from recurrence (FFR), and noninferior voice and swallowing function.
Retrospective medical record review of patients treated for stage III or IV squamous cell carcinoma of the supraglottic larynx between January 1990 and June 2013 at a tertiary referral center: 97 patients underwent surgical treatment and 138, nonsurgical treatment. Exclusion criteria included prior definitive treatment for laryngeal cancer or evidence of distant metastatic disease at presentation. The median follow-up for all 235 patients was 63 months.
Surgical or nonsurgical therapy.
Freedom from recurrence (FFR), OS, larynx preservation, voice graded from 1 to 5, and swallowing graded from 1 to 6 using our voice and swallowing function scales.
Surgical treatment was associated with superior FFR (5-year FFR: 75% vs 55%; P = .006) but not OS (5-year OS: 52% vs 52%; P = .61). The larynx was preserved in 83% of patients in the nonsurgical group vs 42% of patients in the surgical group (P < .001). Voice function was superior in the nonsurgical group at all time points through 5 years after treatment (mean voice score, 3.8 vs 2.6; P < .001). Swallowing function was comparable between surgical and nonsurgical groups. Multivariable analysis revealed that advanced age (hazard ratio [HR], 1.43 per 10-year increment; 95% CI, 1.19-1.72) and clinical N stage (HR, 1.17 per 1-level increment; 95% CI, 1.05-1.30) were associated with worse OS, while treatment with chemotherapy was associated with superior OS (HR, 0.61; 95% CI, 0.41-0.92).
Compared with surgical treatment, nonsurgical treatment as part of a larynx preservation protocol is associated with a higher likelihood of recurrence but has similar OS and should continue to be viewed as a viable alternative for the treatment of advanced supraglottic laryngeal cancer.
JAMA Otolaryngology - Head and Neck Surgery 05/2015; DOI:10.1001/jamaoto.2015.0663 · 1.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The impact of race on outcome has been identified in a number of cancers, with African Americans having poorer survival compared with whites. We conducted a study to investigate the association of race with allogeneic hematopoietic cell transplant (HCT) outcomes. We identified 789 patients (58 African Americans and 731 whites) who underwent allogeneic HCT for hematologic disorders. There were no significant differences between African Americans and white patients in gender, performance status or comorbidity score. However, African Americans were younger than whites (median 40 years versus 47 years, P=0.003) and were more likely to be in remission at HCT (74% versus 57%, P=0.011), to have an HLA-mismatched donor (36% versus 14%, P<0.001), to have positive donor or recipient CMV serostatus (90% versus 69%, P<0.001) and to have received a cord blood transplant (21% versus 6%, P<0.001). In univariate analysis, African Americans had worse overall survival (OS) (HR 1.41, P=0.026) compared with whites, with no significant differences in acute or chronic GvHD, non-CMV infection or relapse. However, after adjusting for several transplant and disease-related factors in multivariate analysis, the OS difference between African Americans and whites became nonsignificant (HR 1.27, P=0.18). These results suggest that race in and of itself does not lead to worse survival post HCT.Bone Marrow Transplantation advance online publication, 23 March 2015; doi:10.1038/bmt.2015.44.
Bone marrow transplantation 03/2015; 50(6). DOI:10.1038/bmt.2015.44 · 3.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obesity continues to be an increasing global health issue contributing to the complexity of chemotherapy dosing in the field of SCT. Investigation into the optimal dosing weight used to calculate chemotherapy doses in obese patients undergoing SCT is limited and inconclusive. Our single-center, retrospective study compared safety and efficacy outcomes by body mass index (BMI) for 476 adult lymphoma patients who underwent auto-SCT with a myeloablative chemotherapeutic regimen of BU, CY and etoposide dosed using adjusted body weight. Three weight groups categorized based on BMI were defined: normal/underweight ⩽24.9 kg/m(2), overweight 25-29.9 kg/m(2) and obese ⩾30 kg/m(2). Severity of mucositis, incidence of secondary malignancy, incidence of bacteremia and median hospital length of stay did not differ among the groups. The median times to absolute neutrophil count and platelet recovery were 10 days (P=0.75) and 14 days (P=0.17), respectively. Obese patients had a lower 100-day mortality compared with other weight groups, although this did not translate into an OS benefit. OS and disease relapse were similar among the groups. Our study demonstrates that use of adjusted body weight to calculate chemotherapy doses does not negatively have an impact on outcomes in obese patients undergoing auto-SCT with BU, CY and etoposide.Bone Marrow Transplantation advance online publication, 9 February 2015; doi:10.1038/bmt.2014.327.
Bone Marrow Transplantation 02/2015; 50(5). DOI:10.1038/bmt.2014.327 · 3.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic hematopoietic cell transplantation (HCT) despite current prophylaxis. Methotrexate (MTX) with a calcineurin inhibitor (CNI) is the current standard, however, has several toxicities. Mycophenolate mofetil (MMF) is frequently used in reduced-intensity HCT, but data in myeloablative transplants is limited. We thus retrospectively identified 241 patients who underwent myeloablative HCT from an HLA-identical sibling donor; 174 patients received cyclosporine (CSA) + MMF and 67 received CSA +MTX. Patients receiving MMF+CSA had rapid neutrophil (median 11 versus 19 days with MTX+CSA), and platelet recovery (median 19 versus 25 days), lower incidence of severe mucositis by OMAS (19% versus 53%), and shorter length of hospital stay (median 25 versus 36 days) (p<0.001 for all comparisons). There were no significant differences in incidence of grade 2-4 (MMF+CSA 37% versus MTX+CSA 39%) or 3-4 acute GVHD (17% versus 12%), chronic GVHD (46% versus 56%), relapse (28% versus 27%), non-relapse mortality (20% versus 27%) or overall survival (47% versus 44%) (p=NS for all). However, in multivariable analysis, the use of MMF+CSA was associated with an increased risk of severe grade 3-4 acute GVHD (HR 2.92, 95% CI 1.2-7.15, p=0.019). There were no differences between the two regimens in multivariable analyses for other survival outcomes. This analysis demonstrates that the use of MMF in myeloablative sibling donor transplantation is well tolerated. However, there may be an increased risk of severe GVHD with MMF+CSA compared to MTX+CSA. Further studies evaluating optimal dosing strategies are needed.
American Journal of Hematology 02/2015; 90(2). DOI:10.1002/ajh.23882 · 3.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The clinical relevance of mismatches at the major histocompatibility complex class I-related chain A (MICA) in hematopoietic stem cell transplantation (HSCT) remains unclear. We investigated the association of MICA donor/recipient mismatch and whether there is an interaction between these and HLA-DPB1 mismatch on clinical outcomes following unrelated donor HSCT. Our study included 227 patients who underwent unrelated donor allogeneic HSCT at our institution between 2000 and 2010. Among these, 177 (78%) received HSCT from a 10/10 HLA-matched donor. MICA genotyping was performed using commercially available kits. In univariable analysis, the risk of grade II-IV acute GvHD was greater for patients with MICA mismatch (hazard ratio (HR) 1.73, p=0.02) than for HLA-DPB1 mismatch (HR 1.62, p=0.07). When MICA and HLA-DPB1 were assessed simultaneously, patients mismatched at both loci had the greatest risk (HR 2.51, p<0.01) and those mismatched at only one locus had somewhat greater risk (HR 1.53, p=0.12) than patients matched at both loci; this remained significant in multivariable analysis. 100-day incidence was 66%, 45%, and 31% (p=0.03). Results were similar for grade III-IV acute GvHD, with 100-day incidence 34%, 16%, and 8% (p=0.01). These results are clinically pertinent to donor selection strategies and indicate that patients with mismatch at both MICA and HLA-DPB1 are at increased risk for acute GvHD.
Biology of Blood and Marrow Transplantation 11/2014; 20(11). DOI:10.1016/j.bbmt.2014.07.019 · 3.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Of the serrated polyps, the origin, morphologic features, molecular alterations, and natural history of traditional serrated adenomas (TSAs) are the least understood. Recent studies suggest that these polyps may arise from precursor lesions. The frequencies of KRAS and BRAF mutations vary between these studies, and only 1 small study has measured CpG island methylation using current markers of methylation. Mutations in GNAS, a gene commonly mutated in colorectal villous adenomas, have not been fully evaluated in TSAs. Finally, the expression of annexin A10 (ANXA10), a recently discovered marker of sessile serrated adenomas/polyps, has not been studied in these polyps. To further characterize these polyps, 5 gastrointestinal pathologists reviewed 55 left-sided polyps diagnosed as TSA at a single institution. Pathologists assessed various histologic features including cytoplasmic eosinophilia, ectopic crypt foci, presence of conventional dysplasia, and presence of precursor serrated lesions. KRAS, BRAF, and GNAS mutational analysis was performed, as well as CpG island methylation and ANXA10 immunohistochemistry. Ectopic crypt foci were seen in 62% of TSAs. Precursor lesions were seen in 24% of the study polyps, most of which were hyperplastic polyps. KRAS and BRAF mutations were common and were present in 42% and 48% of polyps, respectively. GNAS mutations occurred in 8% of polyps, often in conjunction with a BRAF mutation. Unlike sessile serrated adenomas/polyps, TSAs rarely had diffuse expression of ANXA10. Importantly, BRAF-mutated TSAs had more widespread methylation of a 5-marker CpG island panel compared with KRAS-mutated polyps. However, ectopic crypt foci, a proposed defining feature of TSA, were not associated with any specific molecular alteration.
American Journal of Surgical Pathology 09/2014; 38(9):1290-7. DOI:10.1097/PAS.0000000000000253 · 5.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Preoperative chemoradiotherapy improves local control in patients with locoregionally advanced adenocarcinoma of the esophagus and gastroesophageal junction (GEJ). Distant failure remains common, however, suggesting potential benefit from additional chemotherapy. This phase II study investigated the addition of induction chemotherapy to surgery and adjuvant chemoradiotherapy.
Patients with cT3-4 or N1 or M1a (American Joint Committee on Cancer 6th edition) adenocarcinoma of the esophagus and GEJ were eligible. Induction chemotherapy, with epirubicin 50 mg/m/d, oxaliplatin 130 mg/m/d, and fluorouracil 200 mg/m/d continuous infusion for 3 weeks, was given every 21 days for three courses, followed by surgery. Adjuvant chemoradiotherapy consisted of 50 to 55 Gy at 1.8 to 2.0 Gy/d and two courses of cisplatin (20 mg/m/d) and fluorouracil (1000 mg/m/d) during weeks 1 and 4 of radiotherapy.
Between February 2008 and January 2012, 60 evaluable patients enrolled. Resection was accomplished in 54 patients (90%) and adjuvant chemoradiotherapy in 48 (80%) patients. Toxicity included unplanned hospitalization in 18% of patients during induction chemotherapy and 19% of patients during adjuvant chemoradiotherapy. There was one chemotherapy-related and two postoperative deaths. With a median follow-up of 43 months, the projected 3-year locoregional control is 88%, distant metastatic control 46%, relapse-free survival 41%, and overall survival 47%. Symptomatic response to chemotherapy and the percentage of remaining viable tumor at surgery proved the strongest predictors of survival and distant control.
Chemotherapy, surgery, and adjuvant chemoradiotherapy are feasible and produce outcomes similar to other multimodality treatment schedules in locoregionally advanced adenocarcinoma of the esophagus and GEJ. Symptomatic response and less residual tumor at surgery were associated with improved outcomes.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 08/2014; 9(10). DOI:10.1097/JTO.0000000000000312 · 5.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vancomycin-resistant enterococcus (VRE) is a well-known infectious complication among immunocompromised patients. We performed a retrospective analysis to identify risk factors for the development of VRE bacteremia (VRE-B) within 15 months after allogeneic hematopoietic cell transplantation (alloHCT) and to determine its prognostic importance for other post-transplant outcomes. Eight hundred consecutive adult patients who underwent alloHCT for hematologic diseases from 1997 to 2011 were included. Seventy-six (10%) developed VRE-B at a median of 46 days post transplant. Year of transplant, higher HCT comorbidity score, a diagnosis of ALL, unrelated donor and umbilical cord blood donor were all significant risk factors on multivariable analysis for the development of VRE-B. Sixty-seven (88%) died within a median of 1.1 months after VRE-B, but only four (6%) of these deaths were attributable to VRE. VRE-B was significantly associated with worse OS (hazard ratio 4.28, 95% confidence interval 3.23-5.66, P<0.001) in multivariable analysis. We conclude that the incidence of VRE-B after alloHCT has increased over time and is highly associated with mortality, although not usually attributable to VRE infection. Rather than being the cause, this may be a marker for a complicated post-transplant course. Strategies to further enhance immune reconstitution post transplant and strict adherence to infection prevention measures are warranted.Bone Marrow Transplantation advance online publication, 11 August 2014; doi:10.1038/bmt.2014.150.
Bone Marrow Transplantation 08/2014; 49(10). DOI:10.1038/bmt.2014.150 · 3.57 Impact Factor