Efficacy of conventional chemoimmunotherapy is limited in patients with Richter syndrome (RS) with anticipated median overall survival (OS) of less than 10 months. Allogeneic hematopoietic cell transplantation (allo-HCT) is commonly offered as a consolidative treatment option in RS. To our knowledge, there are no randomized controlled studies that have compared allo-HCT against other therapies in RS; available allo-HCT data are limited to small case series from single-institution or registry studies. We performed a systematic review and meta-analysis to assess the totality of evidence regarding the efficacy (or lack thereof) of allo-HCT for RS. We extracted data on post-allograft outcomes related to benefits (overall response rate [ORR], complete remission [CR], OS, and progression-free survival [PFS]). For harms, data were extracted on non-relapse mortality (NRM) and relapse post-allografting. Our search strategy identified 240 studies, but only four studies (n = 72 patients) met our inclusion criteria. Pooled ORR, CR, OS, and PFS rates were 79%, 33%, 49%, and 30%, respectively. Pooled NRM and relapse rates were 24% and 28%, respectively. Results of this systematic review and meta-analysis indicate that allo-HCT yields encouraging OS in RS, thus remaining a reasonable treatment option in fit patients whose disease demonstrates a chemosensitive response to pre-transplant salvage therapies. Novel strategies are certainly needed to reduce the risk of relapse to further improve outcomes in these patients.
Publications
2021
BACKGROUND: Upfront surgery is the current standard for resectable intrahepatic cholangiocarcinoma (ICC) despite high treatment failure with this approach. We sought to examine the use of neoadjuvant chemotherapy (NAC) as an alternative strategy for this population.
METHODS: The National Cancer Database was used to identify patients with resectable ICC undergoing curative-intent surgery (2006-2014). Utilization trends were examined and survival estimates between NAC and upfront surgery were compared; propensity score-matched models were used to examine the association of NAC with overall survival (OS) for all patients and risk-stratified cohorts. Models accounted for clustering within hospitals, and results represent findings from a complete-case analysis.
RESULTS: Among 881 patients with ICC, 8.3% received NAC, with no changes over time (Cochran-Armitage p = 0.7). Median follow-up was 50.9 months, with no difference in unadjusted survival with NAC versus upfront surgery (median OS 51.8 vs. 35.6 months, and 5-year OS rates of 38.2% vs. 36.6%; log rank p = 0.51), and no survival benefit in the propensity score-matched analysis (hazard ratio [HR] 0.78, 95% CI 0.54-1.11; p = 0.16). However, for patients with stage II-III disease, NAC was associated with a trend towards improved survival (median OS of 47.6 months vs. 25.9 months, and 5-year OS rates of 34% vs. 25.7%; log-rank p = 0.10) and a statistically significant survival benefit in the propensity score-matched analysis. (HR 0.58, 95% CI 0.37-0.91; p = 0.02).
CONCLUSION: NAC is associated with improved OS over upfront surgery in patients with resectable ICC and high-risk of treatment failure. These data support the need for prospective studies to examine NAC as an alternative strategy to improve OS in this population.
OBJECTIVE: To determine various morphometric parameters like transverse and sagittal pedicle width; interpedicular distance; antero-posterior and transverse canal diameter and canal surface area at thoracolumbar junction (T11, T12, L1, L2) in central Indian population and compare results with similar studies available in literature.
MATERIAL AND METHODS: A prospective, computerized tomography scan based morphometric analysis of thoracolumbar junction was conducted at medical college and tertiary care centre in central India. All asymptomatic cases more than 18 years age with normal lateral radiograph and CT scan of thoracolumbar junction and free from any spinal pathology or trauma were included in the study. Parameters measured were transverse and sagittal pedicle width; interpedicular distance; antero-posterior and transverse canal diameter and canal surface area at thoracolumbar junction (T11, T12, L1, L2).
RESULTS: Mean transverse pedicle width was maximum at T11 and minimum at L1 in both males and females, whereas sagittal width was maximum at T11 and minimum at L2 in both the groups. Interpedicular distance was largest at L1 in both the groups. All the measurements were significantly different (P < 0.05) in males and females. Mean antero-posterior and transverse diameter was maximum at T12 and L2 respectively in both male and female study population. Canal surface area was maximum at L1 among males (230.10 mm2) as well as females (209.02 mm2).
CONCLUSION: There is significant variation in morphometric parameters of thoracolumbar junction in different races and population. Thorough knowledge of morphometry of a particular population is essential for dealing with pathology or trauma of thoracolumbar junction.
OBJECTIVE(S): To determine the association of pharmacist medication counseling with medication adherence, 30-day hospital readmission, and mortality.
METHODS: The initial search identified 21,590 citations. After applying the inclusion and exclusion criteria, 62 randomized controlled trials (RCTs) (49 for the meta-analysis) were included in the final analysis. Data were pooled using a random-effects model.
RESULTS: The participants in most of the studies were older patients with chronic diseases who, therefore, were taking many drugs. The overall methodologic quality of evidence ranged from low to very low. Pharmacist medication counseling versus no such counseling was associated with a statistically significant 30% increase in relative risk (RR) for medication adherence, a 24% RR reduction in 30-day hospital readmission (number needed to treat = 4.2), and a 30% RR reduction in emergency department visits. RR reductions for primary care visits and mortality were not statistically significant.
CONCLUSION: The evidence supports pharmacist medication counseling to increase medication adherence and to reduce 30-day hospital readmissions and emergency department visits. However, higher-quality RCT studies are needed to confirm or refute these findings.
In patients with lymphoma, third-space fluid accumulations may develop or worsen during cytokine release syndrome (CRS) associated with chimeric antigen receptor (CAR) T cell therapy. Pre-existing symptomatic pleural effusions were excluded by the ZUMA-1 trial of axicabtagene ciloleucel for large B cell lymphoma (LBCL) and variants. The incidence and management of effusions during CAR T cell therapy for LBCL are unknown. We performed a single-center retrospective study evaluating 148 patients receiving CD19-directed CAR T cell therapy for LBCL between May 2015 and September 2019. We retrospectively identified patients who had radiographic pleural, pericardial, or peritoneal effusions that were present prior to the time of CAR T infusion (pre-CAR T) or that newly developed during the first 30 days after CAR T-cell infusion (post-CAR T). Of 148 patients, 19 patients had a pre-CAR T effusion, 17 patients without pre-existing effusion developed a new infusion after CAR T, and 112 patients had no effusions. Comparing pre-CAR T effusions to new effusions post-CAR T, pre-CAR T effusions were more often malignant (84% versus 12%), persistent beyond 30 days (95% versus 18%), and required interventional drainage after CAR T infusion (79% versus 0%). Compared to patients with no effusion, patients with pre-CAR T therapy effusions had a higher frequency of high-risk baseline characteristics, such as bulky disease and high International Prognostic Index. Similarly, patients with pre-CAR T therapy effusions had a higher rate of toxicity with grade 3 or higher CRS occurring in 32% of patients. On multivariate analysis adjusting for age, Eastern Cooperative Oncology Group status, bulky disease, albumin, and lactate dehydrogenase, a pre-CAR T therapy effusion was associated with reduced overall survival (hazard ratio, 2.34; 95% confidence interval, 1.09 to 5.03; P = .03). Moreover, there was higher non-relapse mortality (11% versus 1%; P = .005). Post-CAR T effusions were not associated with significant difference in survival. Effusions commonly complicate CAR T cell therapy for lymphoma. Malignant effusions that occur prior to CAR T therapy are frequently persistent and require therapeutic intervention, and patients have a higher rate of toxicity and death. Effusions that newly occur after CAR T therapy can generally be managed medically and tend not to persist.
INTRODUCTION: Lenalidomide maintenance, commonly prescribed in the postautologous transplantation (AHCT) setting for multiple myeloma (MM), is associated with development of secondary primary malignancies (SPM). Proteasome inhibitor maintenance (PIM) has also been evaluated in MM. We conduct a systematic review/meta-analysis to assess the efficacy of PIM in MM.
METHODS: Performing a comprehensive search of the medical literature using PubMed/Medline and EMBASE on September 11, 2019, we extracted data on clinical outcomes related to benefits (OS, PFS, and depth of hematologic response [DOHR]) and harms (SPM and adverse events). 2144 references were identified; three studies were eligible for inclusion.
RESULTS: A total of 1760 patients were included in the analysis; 507 patients received bortezomib and 395 received ixazomib maintenance. Control arms were either placebo (n = 261) or thalidomide (n = 358). PIM did not improve OS (HR 0.88, 95% CI 0.73-1.05, P = .15) but improved PFS (HR 0.77, 95% CI 0.69-0.86, P ≤ .00001) and DOHR (HR 0.88, 95% CI 0.79-0.98, P = .02) compared with control. There were no significant differences between PIM and control regarding SPM (p = NS) and ≥grade 3 peripheral neuropathy (PN) (p = NS).
CONCLUSIONS: PIM following AHCT in MM improves PFS and DOHR without an increase in development of SPM or severe PN compared with placebo/thalidomide.
AIM: The aim of this study is to explore the therapeutic potential of S-allylcysteine (SAC) organosulphur compound as a potent immune checkpoint inhibitor PD-L1.
BACKGROUND: Natural compounds have been showing tremendous anticancerous potential via suppressing the expression of genes involved in the development and progression of several carcinomas. This has further motivated us to explore the therapeutic potential of organosulphur compounds as potent immune checkpoint inhibitors.
OBJECTIVE: Our study was designed to elucidate the potential of S-allylcysteine (SAC) as significant PD-L1 (immune checkpoint) inhibitor in human lung cancer A549 cancer cell line by using both the in vitro and in silico approaches.
METHODS: Anticancerous effect of the SAC on lung cancer cells was determined by using the MTT cell viability. Apoptotic induction was confirmed by Hoechst staining, percent caspase-3 activity as well as gene expression analysis by real time PCR. Reactive Oxygen Species (ROS) was estimated by DCFDA method. Additionally, ligand-target protein interaction was analysed by molecular docking.
RESULT: Cell growth and proliferation was significantly reduced in SAC treated A549 cells in a concentration and time.dependent manner. The effect of SAC on apoptotic induction was analyzed by enhanced nuclear condensation, increased percent caspase-3 activity as well as modulation of apoptotic genes. Furthermore, SAC treatment also resulted in reduced expression of PD-L1 and HIF-1α. Additionally, in silico analysis also supported the in vitro findings by showing efficient docking with PD-L1 immune checkpoint target.
CONCLUSION: Therefore, our results clearly suggested that SAC could serve as a novel chemotherapeutic candidate for the treatment of lung cancer by inhibiting immune checkpoint target PD-L1 in human lung cancer cells. Additionally, our study also explained a novel molecular mechanism of its antitumor activity.
BACKGROUND: Carriers of deleterious mutations in breast cancer predisposition genes are presented with critical choices regarding cancer risk management. Risk-reduction mastectomy is a major preventative strategy in this population. Understanding the decision-making process for prophylactic mastectomy is essential in patient-centered care for high-risk carriers and patients with breast cancer. We sought to provide insight into influential factors underlying preventative surgery decisions among individuals with high breast cancer risk.
MATERIALS AND METHODS: We conducted a retrospective chart review of pathogenic carriers of high-risk breast cancer genes who presented to the Moffitt GeneHome clinic between March 2017 and June 2020. Associations between preventative mastectomy choice and influence variables were analyzed via unadjusted and adjusted logistic regression models.
RESULTS: Of 258 high-risk mutation carriers, 104 (40.3%) underwent risk-reduction mastectomy. A significantly higher proportion of mastectomy patients reported prior history of breast cancer (68.9% vs. 16.5%; P < .001) and history of other risk-reduction or noncancer-related surgeries (61.7% vs. 25.8%; P < .001). Significant predictors affecting surgery decision included previous breast cancer history (adjusted odds ratio [aOR], 10.48; 95% confidence interval [CI], 5.59-19.63; P < .0001), other risk-reduction or noncancer-related surgical history (aOR, 4.65; 95% CI, 2.28-9.47; P < .0001), and age at presentation to the genetics clinic (< 35 years old: aOR, 2.77; 95% CI, 1.04-7.4; P = .042; 35-55 years old: aOR, 2.48; 95% CI, 1.19-5.18; P = .016).
CONCLUSIONS: Preventive mastectomy decisions are highly personal and complex. In our sample, we observed prior history or concurrent breast cancer, history of other risk-reduction surgery or noncancer-related surgery, and younger age at presentation to the GeneHome clinic to be predictive of mastectomy uptake.
BACKGROUND: Deep inferior epigastric perforator flap (DIEP) for breast reconstruction is a widely accepted technique for breast reconstruction. Secondary benefit of this technique is abdominal contour improvement. Because of direct access, abdominal plication can be performed at the time of abdominal closure. Our goal was to investigate if this addition affected the complications.
METHODS: A retrospective chart review was performed on all DIEP flap reconstructions performed by a single surgeon at a cancer center, from March 2011 through February 2020. Presence of abdominal plication, age, and body mass index were compared with reoperation due to abdominal wound or hernia, procedure length in minutes, and length of stay. The association between the dependent and independent variables for the unadjusted and adjusted analysis was performed using the binary logistic regression analysis.
RESULTS: Three hundred fifty-eight DIEP flaps performed on 233 patients for breast reconstruction were analyzed. Flap loss was 1.7%. Abdominal plication was performed in 178 flaps (49.7%) and not performed in 180 flaps (50.3%). Thirty-nine percent were immediate; 61% were delayed. The results did not show a statistically significant association between abdominal plication and the need to reoperate (P = 0.3). Results from the adjusted analysis (age, body mass index) also did not show a significant association between the plication, need to reoperate, procedure duration, or hospital stay (P = 0.4).
CONCLUSIONS: Abdominal plication can improve cosmetic outcomes without increasing the duration of surgery, hospital stay, or reoperation rates due to abdominal complications. Therefore, it can be a valuable addition in DIEP flap breast reconstructions.
BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to stress the health care system. Neutralizing monoclonal antibodies (mAbs) were effective in reducing COVID-19-related hospitalizations and emergency department (ED) visits in their respective clinical trials. However, these results have yet to be reproduced in a practical setting following implementation of current US Food and Drug Administration (FDA) guidance.
METHODS: This retrospective cohort study included outpatients with confirmed COVID-19 infection, who had mild/moderate symptoms for 10 days or less, and who were deemed high-risk for severe COVID-19 under FDA's Emergency Use Authorization for mAbs. Patients who received either bamlanivimab or casirivimab/imdevimab from 18 November 2020 through 5 January 2021 were included (n = 200). This was compared against a control cohort of randomly selected high-risk COVID-19 outpatients who declined or were not referred for mAb treatment during the same period (n = 200). The primary outcome was a composite of 29-day COVID-19-related hospitalizations and/or ED visits. Prespecified secondary outcomes included the individual components of the primary endpoint, 29-day all-cause mortality, and serious adverse drug events.
RESULTS: Patients treated with mAbs were significantly less likely to be hospitalized or visit the ED compared with patients not treated with mAb (13.5% vs 40.5%; odds ratio, 0.23 [95% confidence interval, .14-.38]; P < .001). The mortality rate was 0% in the mAb group compared with 3.5% in the control group (P = .02). Only 2 patients receiving mAb experienced a serious adverse event requiring treatment.
CONCLUSIONS: Among high-risk COVID-19 outpatients with mild/moderate symptoms, early administration of mAbs can potentially reduce the strain on the health care system during the current pandemic.