Publications

Human T cell lymphotropic virus type 1 (HTLV1)-associated adult T cell leukemia/lymphoma (ATLL) is an aggressive malignant disorder. Intensive conventional chemotherapy regimens and autologous hematopoietic cell transplantation (HCT) have failed to improve outcomes in ATLL. Allogeneic HCT (allo-HCT) is commonly offered as front-line consolidation despite lack of randomized controlled trials. We performed a comprehensive search of the medical literature using PubMed/Medline, EMBASE, and Cochrane reviews on September 10, 2018. We extracted data on clinical outcomes related to benefits (complete response [CR], overall survival [OS], and progression-free survival [PFS]) and harms (relapse and nonrelapse mortality [NRM]), independently by 2 authors. Our search strategy identified a total of 801 references. Nineteen studies (n = 2446 patients) were included in the systematic review; however, only 18 studies (n = 1767 patients) were included in the meta-analysis. Reduced intensity conditioning regimens were more commonly prescribed (52%). Bone marrow (50%) and peripheral blood (40%) were more frequently used as stem cell source. The pooled post-allografting CR, OS, and PFS rates were 73% (95% confidence interval [CI], 57% to 87%), 40% (95% CI, 33% to 46%), and 37% (95% CI, 27% to 48%), respectively. Pooled relapse and NRM rates were 36% (95% CI, 28% to 43%) and 29% (95% CI, 21% to 37%), respectively. The heterogeneity among the included studies was generally high. These results support the use of allo-HCT as an effective treatment for patients with ATLL, yielding pooled OS rates of 40%, but relapse still occurs in over one-third of cases. Future studies should evaluate strategies to help reduce relapse in patients with ATLL undergoing allo-HCT.

BACKGROUND: The outcomes for patients with diffuse large B-cell lymphoma (DLBCL) with adverse clinical prognostic factors such as a high age-adjusted International Prognostic Index (aaIPI) are not optimal. In the current study, the authors performed a systematic review and meta-analysis to assess the totality of evidence pertaining to the efficacy of autologous hematopoietic stem cell transplantation (auto-HCT) consolidation for patients with DLBCL in first remission.

METHODS: The authors searched the Cochrane and MEDLINE/PubMed databases through December 1, 2018, for studies comparing conventional chemotherapy with rituximab (R-chemo) versus R-chemo and auto-HCT. Two authors independently reviewed all references for study inclusion and extracted data related to benefits (overall survival, progression-free survival, and response rates) and harms (treatment-related mortality and adverse events).

RESULTS: Four studies (1173 patients) met the inclusion criteria and were included in the current analysis. The median duration of follow-up ranged from 42 to 76 months. There was no difference noted with regard to the overall survival (hazard ratio, 1.01; 95% CI, 0.74-1.37), progression-free survival (hazard ratio, 0.77; 95% CI, 0.58-1.04), or response rates (risk ratio, 0.98; 95% CI, 0.92-1.04) between patients who received R-chemo and auto-HCT and those who received R-chemo alone. The risk of mortality and therapy failure was not found to be different when the analysis was limited to high aaIPI between the 2 groups. Although there was no difference noted with regard to the risk of treatment-related mortality, there was a significantly higher incidence of CTCAE grade 3 or 4 adverse events in patients who received R-chemo and auto-HCT compared with patients treated with R-chemo alone.

CONCLUSIONS: The findings from what to the authors' knowledge is the first meta-analysis performed in the rituximab era demonstrated no beneficial effect of upfront auto-HCT consolidation in patients with aggressive B-cell non-Hodgkin lymphoma, including high-risk clinical groups (high aaIPI).

BACKGROUND: Multidrug resistance tuberculosis (MDR-TB) is an important public health problem for India but there is a paucity of data related to the prevalence of MDR-TB in India. This systematic review and meta-analysis was designed to synthesize evidence regarding the prevalence of MDR-TB in adult patients in India.

METHODS: PubMed and Google Scholar were searched to find different observational studies reporting MDR-TB prevalence in India. Data related to MDR-TB prevalence were pooled for the analysis. PubMed was searched by using different MeSH words. Prevalence was reported with 95% confidence interval (CI). A separate analysis was done for new cases and previously treated cases. Random effect model was used and heterogeneity was assessed by I2 and Cochran Q test.

RESULTS: MDR-TB prevalence in new cases were 3% (95% CI 2%-5%, I2 = 95.3%). There was difference in prevalence between different methods of measurement of MDR-TB and study designs. MDR-TB prevalence in previously treated cases was found to be 35% (95% CI 29%-41%, I2 = 98.7%). Results vary with the method of measurement as well as the study design.

CONCLUSION: MDR-TB prevalence in previously treated patients was found higher compared to the reported values in national surveys. There is a need for large scale cross-sectional study to verify the findings observed in this review.

Graft-versus-host disease (GVHD) remains a limiting factor for successful allogeneic hematopoietic cell transplantation (allo-HCT). Conflicting data exist on the benefit of ATG on post-transplant survival. We performed a systematic review of randomized controlled trials (RCTs) to assess benefits and harms of thymoglobulin and Fresenius (re-branded as Grafalon) ATG formulations in patients undergoing allo-HCT for a variety of hematologic malignancies and bone marrow failure syndromes. A comprehensive search of MEDLINE, EMBASE, and Cochrane Library was performed. Data on methodological quality, benefits, and harms were extracted for each trial and pooled under a random-effects model. Eight RCTs (1134 patients) met the inclusion criteria. Methodological quality ranged from moderate to very low. Pooled results showed no difference in overall survival (OS) with the use of ATG (hazard ratio (HR) = 0.97; 95% confidence interval (CI) = 0.74-1.28; P = 0.83). ATG reduced grade II/III acute GVHD (risk ratio (RR) = 0.61; 95% CI = 0.48-0.77; P < 0.0001), grade III/IV acute GVHD (RR = 0.52; 95% CI = 0.34-0.81; P = 0.004), and chronic GVHD (RR = 0.52; 95% CI = 0.40-0.69; P < 0.00001) without an increase in non-relapse mortality (NRM) (RR = 0.91; 95% CI = 0.74-1.13; P = 0.40). Future studies with better methodological quality are needed to provide conclusive answers related to optimal dosing and timing of ATG for prevention of GVHD.

BACKGROUND AND OBJECTIVES: The determinants of guideline panels' recommendations remain uncertain. The objective of this study was to investigate factors considered by members of 8 panels convened by the American Society of Hematology (ASH) to develop guidelines using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.

STUDY DESIGN AND SETTING: Web-based survey of the participants in the ASH guidelines panels.

ANALYSIS: two-level hierarchical, random-effect, multivariable regression analysis to explore the relation between GRADE and non-GRADE factors and strength of recommendations (SOR).

RESULTS: In the primary analysis, certainty in evidence [OR = 1.83; (95CI% 1.45-2.31)], balance of benefits and harms [OR = 1.49 (95CI% 1.30-1.69)] and variability in patients' values and preferences [OR = 1.47 (95CI% 1.15-1.88)] proved the strongest predictors of SOR. In a secondary analysis, certainty of evidence was associated with a strong recommendation [OR = 3.60 (95% CI 2.16-6.00)] when panel members recommended "for" interventions but not when they made recommendations "against" interventions [OR = 0.98 (95%CI: 0.57-1.8)] consistent with "yes" bias. Agreement between individual members and the group in rating SOR varied (kappa ranged from -0.01 to 0.64).

CONCLUSION: GRADE's conceptual framework proved, in general, to be highly associated with SOR. Failure of certainty of evidence to be associated with SOR against an intervention, suggest the need for improvements in the process.

BACKGROUND: Insurance type has been reported to be an independent predictor of overall survival in lung cancer patients. We studied the effect of insurance type on patient outcomes after minimally invasive pulmonary lobectomy for lung cancer.

METHODS: We retrospectively analyzed 433 consecutive patients who underwent robotic-assisted pulmonary lobectomy by one surgeon during an 80-month period. Perioperative outcomes and intraoperative and postoperative complications were noted. Disposition at discharge after surgery (favorable, eg, transfer to home with self-care or with home health nursing and/or physical therapy, versus unfavorable, eg, long-term acute care or rehabilitation facility, hospice, or death) and 5-year overall survival (5-years OS) were also recorded. We used Pearson χ2, analysis of variance (ANOVA), and Kruskal-Wallis test to compare variables and Cox regression for survival analysis.

RESULTS: There were 107 patients (mean age 57.5 years) with private insurance, 118 (mean age 70.3 years) with public insurance (Medicare or Medicaid), 196 (mean age 71.8 year; P < .001) with combination insurance plans (Medicare plus a privately supplied supplemental), and 12 patients with no insurance (excluded owing to low sample size). There were more current smokers in the public insurance group, more former smokers in the combination insurance group, and more nonsmokers in the private insurance group (P = .03). There were more comorbidities in the public and combination insurance groups versus the private insurance group, including gastroesophageal reflux disease (P = .003), hypertension (P = .01), and hyperlipidemia (P < .001). The groups had no differences in tumor size or pathologic stage. There were higher numbers of intraoperative conversions to open lobectomy in the private and public insurance groups versus the combination insurance group (P = .001). Also, the private and combination insurance groups had more cases of favorable disposition at discharge after surgery compared with the public insurance group (P < .001). Multivariable regression analyses identified private insurance type as an independent predictor of favorable disposition at discharge (public versus private plan; odds ratio, 0.43; 95% confidence interval [CI], 0.22-0.85, P = .02) and 5-year OS (combination versus private plan; hazard ratio, 2.68; 95% CI, 1.26-5.67, P = .01; public versus private plan; HR, 2.84; 95% CI, 1.37-5.89; P = .01).

CONCLUSION: Although public or combination insurance type was associated with greater risk of all-cause mortality, and public insurance type was associated with less favorable disposition at discharge after surgery and overall conversion to open lobectomy, insurance type was not associated with increased intraoperative complications, hospital duration of stay, or in-hospital mortality after minimally invasive robotic-assisted pulmonary lobectomy.

BACKGROUND AND AIMS: Patients with spinal cord injury (SCI) suffer significant morbidity from neurogenic bowel. Chronic constipation has long-been a proposed risk factor for polyp development. We performed a retrospective cohort study in veterans with SCI to assess polyp presence in the setting of colonic stasis.

METHODS: All consecutive patients at the James A. Haley Veterans Affairs Hospital with SCI and neurogenic bowel who completed screening colonoscopy between January 1, 2004 to June 30, 2013 were included. Colonoscopies were excluded if they were aborted, not completed to the cecum, of less than adequate preparation, or if polypectomy was precluded. Patient data included level, duration, and completeness of SCI. Polyp data included number, location, and histology.

RESULTS: 325 patients ultimately met inclusion criteria. Most were male (96%). The average age at screening colonoscopy was 62.8 years. The majority of patients had injury to the cervical spine (41.5%). Colon polyps were detected in 130 patients (40%). Adenomatous change was seen in 95 (73%) of these patients. The adenoma detection rate (ADR) across all patients was 29.2%. Polyp presence and ADR demonstrated no statistically significant correlation with level, degree, or duration of SCI. Only patient age at time of screening colonoscopy had a significant correlation with polyp and adenoma presence (P<0.05).

CONCLUSIONS: SCI had no statistically significant correlation with polyp or adenoma presence. The ADR in our veteran SCI population with chronic constipation is comparable with that reported in the general population.

Prognostic biomarkers in allogeneic hematopoietic cell transplantation (allo-HCT) are needed to improve risk assessment and help guide therapeutic and surveillance strategies to mitigate the risk of death from the procedure. We previously identified hypoalbuminemia at day +90 post-transplantation as an independent predictor of increased nonrelapse mortality (NRM) and inferior overall survival (OS) in patients with acute myelogenous leukemia and myelodysplastic syndrome who were treated with an allo-HCT. Here, we aim to confirm the prognostic significance of day +90 hypoalbuminemia in 783 patients, median age 52 years (range, 18 to 76), who received an allo-HCT for various hematologic malignancies and bone marrow failure syndromes. Multivariate analysis for NRM demonstrated a negative effect of low serum albumin levels (<3.0 versus 3.0 to 3.5 versus >3.5 g/dL) at day +90 post-transplantation (hazard ratios, 8.03 [95% CI, 3.59 to 17.97] versus 2.84 [95% CI, 1.59 to 5.08] versus reference; P < .0001). This was also the case for OS (hazard ratios, 6.86 [95% CI, 4.24 to 11.10] versus 1.52 [95% CI, 1.05 to 2.20] versus reference; P < .0001). Patients with hypoalbuminemia at day +90 post-transplantation are more likely to die from causes other than relapse, particularly infections. This large study confirms the ability of day +90 serum hypoalbuminemia to predict worse NRM and inferior OS. Presence of hypoalbuminemia at day +90 should drive a more rigorous real-time surveillance strategy considering the anticipated high-risk of NRM and poor survival in these patients. Future studies should consider incorporating day +90 serum albumin levels in prognostic models of NRM and OS.

INTRODUCTION: It is common practice to refer patients to transplantation centers for allogeneic hematopoietic cell transplantation (allo-HCT) for blastic plasmacytoid dendritic-cell neoplasm (BPDCN) despite lack of randomized controlled trials. We performed a systematic review to assess the totality of evidence pertaining to the efficacy of allo-HCT in BPDCN.

METHODS: We searched the Cochrane, PubMed, and Embase databases through January 5, 2018, for studies on allo-HCT for BPDCN. Two authors independently reviewed all references for inclusion and extracted data related to benefits (overall [OS] and progression-free/disease-free [PFS/DFS] survival) and harms (relapse and nonrelapse mortality) from included studies. When appropriate, data were pooled using random-effects model.

RESULTS: Four studies (128 patients) were included in analysis. Pooled OS rate was 50% (95% confidence interval [CI], 41-59) for all patients. Among patients who underwent allografting whose disease was in first complete remission (CR1), pooled OS and PFS/DFS rates were 67% (95% CI, 52-80) and 53% (95% CI, 29-76), respectively. For patients who underwent allografting in > CR1, pooled OS and PFS/DFS rates were 7% (95% CI, 0-32) for both outcomes. Relapse rates were higher when reduced-intensity regimens were used (40% [95% CI, 25-56] vs. 18% [95% CI, 7-31]).

CONCLUSION: This systematic review represents the best available evidence supporting allo-HCT in BPDCN, especially when offered in CR1. Use of myeloablative allo-HCT results in lower pooled relapse rates (18% vs. 40%). A prospective comparative study will be needed to determine the impact of intensity of the conditioning regimen on postallograft relapse.

BACKGROUND: Tissue expander and implant remains the most common technique for breast reconstruction. A controversial topic within this method is routine use of acellular dermal matrix (ADM). Acellular dermal matrices have increased risks of infection, seroma, hematoma, skin flap necrosis, and total complications.

METHODS: After an institutional review board approval, a retrospective chart review was conducted of 756 tissue expander with implant cases from November 2010 to November 2016 at Moffitt Cancer Center with 2 breast reconstruction surgeons. Patients were grouped in 2 groups: tissue expander alone reconstruction (TE) and tissue expander with ADM (TE + ADM). Complications were defined by return visits to the operating room for irrigation and debridement as well as for subsequent tissue expander placement.

RESULTS: There were 703 patients in the TE group and 53 in the TE + ADM group. Patients undergoing TE + ADM reconstruction were 3 times more likely to experience return to operating room compared with patients undergoing TE alone (7.5% vs 2.4%). Patients were significantly more likely to undergo 3 or more subsequent tissue expander placement procedures with TE + ADM (54.7%) compared with TE alone (4.8%) (P < 0.0001).

CONCLUSIONS: Although ADM may be appropriate for specific patients, its use in tissue expander breast reconstruction should be judiciously selected, because there is an observed increase in complications needing return to the operating room.