Impact of bortezomib-based versus lenalidomide maintenance therapy on outcomes of patients with high-risk multiple myeloma.

BACKGROUND: Lenalidomide maintenance after autologous stem cell transplant (ASCT) in multiple myeloma (MM) results in superior progression-free survival and overall survival. However, patients with high-risk multiple myeloma (HRMM) do not derive the same survival benefit from lenalidomide maintenance compared with standard-risk patients. The authors sought to determine the outcomes of bortezomib-based maintenance compared with lenalidomide maintenance in patients with HRMM undergoing ASCT. METHODS: In total, the authors identified 503 patients with HRMM who were undergoing ASCT within 12 months of diagnosis from January 2013 to December 2018 after receiving triplet novel-agent induction in the Center for International Blood and Marrow Transplant Research database. HRMM was defined as deletion 17p, t(14;16), t(4;14), t(14;20), or chromosome 1q gain. RESULTS: Three hundred fifty-seven patients (67%) received lenalidomide alone, and 146 (33%) received bortezomib-based maintenance (with bortezomib alone in 58%). Patients in the bortezomib-based maintenance group were more likely to harbor two or more high-risk abnormalities and International Staging System stage III disease (30% vs. 22%; p = .01) compared with the lenalidomide group (24% vs. 15%; p < .01). Patients who were receiving lenalidomide maintenance had superior progression-free survival at 2 years compared with those who were receiving either bortezomib monotherapy or combination therapy (75% vs. 63%; p = .009). Overall survival at 2 years was also superior in the lenalidomide group (93% vs. 84%; p = .001). CONCLUSIONS: No superior outcomes were observed in patients with HRMM who received bortezomib monotherapy or (to a lesser extent) in those who received bortezomib in combination as maintenance compared with lenalidomide alone. Until prospective data from randomized clinical trials are available, post-transplant therapy should be tailored to each patient with consideration for treating patients in clinical trials that target novel therapeutic strategies for HRMM, and lenalidomide should remain a cornerstone of treatment.

Inappropriate use of statistical power.

INTRODUCTION: We are pleased to add this typescript, Inappropriate use of statistical power by Raphael Fraser to the BONE MARROW TRANSPLANTATION Statistics Series. The authour discusses how we sometimes misuse statistical analyses after a study is completed and analyzed to explain the results. The most egregious example is post hoc power calculations.When the conclusion of an observational study or clinical trial is negative, namely, the data observed (or more extreme data) fail to reject the null hypothesis, people often argue for calculating the observed statistical power. This is especially true of clinical trialists believing in a new therapy who wished and hoped for a favorable outcome (rejecting the null hypothesis). One is reminded of the saying from Benjamin Franklin: A man convinced against his will is of the same opinion still.As the authour notes, when we face a negative conclusion of a clinical trial there are two possibilities: (1) there is no treatment effect; or (2) we made a mistake. By calculating the observed power after the study, people (incorrectly) believe if the observed power is high there is strong support for the null hypothesis. However, the problem is usually the opposite: if the observed power is low, the null hypothesis was not rejected because there were too few subjects. This is usually couched in terms such as: there was a trend towards… or we failed to detect a benefit because we had too few subjects or the like. Observed power should not be used to interpret results of a negative study. Put more strongly, observed power should not be calculated after a study is completed and analyzed. The power of the study to reject or not the null hypothesis is already incorporated in the calculation of the p value.The authour use interesting analogies to make important points about hypothesis testing. Testing the null hypothesis is like a jury trial. The jury can find the plaintiff guilty or not guilty. They cannot find him innocent. It is always important to recall failure to reject the null hypothesis does not mean the null hypothesis is true, simply there are insufficient evidence (data) to reject it. As the author notes: In a sense, hypothesis testing is like world championship boxing where the null hypothesis is the champion until defeated by the challenger, the alternative hypothesis, to become the new world champion.The authour include a discussion of what is a p-value, a topic we discussed before in this series and elsewhere [1, 2]. Finally, there is a nice discussion of confidence intervals (frequentist) and credibility limits (Bayesian). A frequentist interpretation views probability as the limit of the relative frequency of an event after many trials. In contrast, a Bayesian interpretation views probability in the context of a degree of belief in an event . This belief could be based on prior knowledge such as the results of previous trials, biological plausibility or personal beliefs (my drug is better than your drug). The important point is the common mis-interpretation of confidence intervals. For example, many researchers interpret a 95 percent confidence interval to mean there is a 95 percent chance this interval contains the parameter value. This is wrong. It means, if we repeat the identical study many times 95 percent of the intervals will contain the true but unknown parameter in the population. This will seem strange to many people because we are interested only in the study we are analyzing, not in repeating the same study-design many times.We hope readers will enjoy this well-written summary of common statistical errors, especially post hoc calculations of observed power. Going forth we hope to ban statements like there was a trend towards… or we failed to detect a benefit because we had too few subjects from the Journal. Reviewers have been advised. Proceed at your own risk. Robert Peter Gale MD, PhD, DSc(hc), FACP, FRCP, FRCPI(hon), FRSM, Imperial College London, Mei-Jie Zhang PhD, Medical College of Wisconsin.

Understanding Influenza and SARS-CoV-2 Vaccine Hesitancy in Racial and Ethnic Minority Caregivers.

(1) Background: We compared influenza and SARS-CoV-2 vaccine hesitancy levels in Black, Hispanic, and White parents/caregivers and identified barriers and facilitators to vaccine acceptance. (2) Methods: This was a mixed methods study. A cross-sectional survey of ED caregivers presenting with children 6mo−18yo compared vaccine hesitancy levels among diverse caregivers. Six focus groups of survey participants, stratified by caregiver race/ethnicity and caregiver intent to receive SARS-CoV-2 vaccine, assessed facilitators and barriers of vaccination, with thematic coding using the Consolidated Framework for Implementation Research (CFIR). (3) Results: Surveys (n = 589) revealed Black caregivers had significantly higher vaccine hesitancy rates than White caregivers for pediatric influenza (42% versus 21%) and SARS-CoV-2 (63% versus 36%; both p < 0.05). Hispanic caregivers were more hesitant than White caregivers (37% flu and 58% SARS-CoV-2), but this was not significant. Qualitative analysis (n = 23 caregivers) identified barriers including vaccine side effects, lack of necessity, inadequate data/science, and distrust. Facilitators included vaccine convenience, fear of illness, and desire to protect others. (4) Conclusions: Minority caregivers reported higher levels of vaccine hesitancy for influenza and SARS-CoV-2. We identified vaccine facilitators and barriers inclusive of Black and Hispanic caregivers, which may guide interventions designed to equitably improve acceptance of pediatric vaccines.

A phase 2 trial of a topical antiseptic bundle in head and neck cancer surgery: Effects on surgical site infection and the oral microbiome.

BACKGROUND: Head and neck cancer (HNC) surgery remains an important component of management but is associated with a high rate of surgical site infection (SSI). We aimed to assess the safety and efficacy of a topical mucosal antiseptic bundle in preventing SSI and evaluate microbial predictors of infection through a genomic sequencing approach. METHODS: This study was an open-label, single-arm, single-center, phase 2 trial of a topical mucosal antiseptic bundle in patients with HNC undergoing aerodigestive tract resection and reconstruction. Patients underwent topical preparation of the oral mucosa with povidone-iodine (PI) and chlorhexidine gluconate (CHG) pre- and intra-operatively followed by oral tetracycline ointment every 6 hours for 2 days post-operatively. The primary outcome was change in bacterial bioburden at the oral surgical site. Secondary outcomes included safety, SSI, and microbial predictors of infection. FINDINGS: Of 27 patients screened between January 8, 2021, and May 14, 2021, 26 were enrolled and 25 completed the study. There were no antiseptic-related adverse events. The topical mucosal antiseptic bundle significantly decreased oral bacterial colony-forming units from pre-operative levels (log10 mean difference 4·03, 95%CI 3·13-4·;92). There were three SSI (12%) within 30 days. In correlative genomic studies, a distinct set of amplicon sequence variants in the post-operative microbiome was associated with SSI. Further, despite no instance of post-operative orocervical fistula, metagenomic sequence mapping revealed the oral cavity as the origin of the infectious organism in two of the three SSI. INTERPRETATION: The bacterial strains which subsequently caused SSI were frequently identified in the pre-operative oral cavity. Accordingly, a topical antiseptic bundle decreased oral bacterial bioburden throughout the peri-operative period and was associated with a low rate of SSI, supporting further study of topical antisepsis in HNC surgery. FUNDING: Alliance Oncology.

Does recipient body mass index inform donor selection for allogeneic haematopoietic cell transplantation?

It is not known whether obesity has a differential effect on allogeneic haematopoietic cell transplantation outcomes with alternative donor types. We report the results of a retrospective registry study examining the effect of obesity [body mass index (BMI) > 30] on outcomes with alternative donors (haploidentical related donor with two or more mismatches and receiving post-transplant cyclophosphamide [haplo] and cord blood (CBU)] versus matched unrelated donor (MUD). Adult patients receiving haematopoietic cell transplantation for haematologic malignancy (2013-2017) (N = 16 182) using MUD (n = 11 801), haplo (n = 2894) and CBU (n = 1487) were included. The primary outcome was non-relapse mortality (NRM). The analysis demonstrated a significant, non-linear interaction between pretransplant BMI and the three donor groups for NRM: NRM risk was significantly higher with CBU compared to haplo at BMI 25-30 [hazard ratio (HR) 1.66-1.71, p < 0.05] and MUD transplants at a BMI of 25-45 (HR, 1.61-3.47, p < 0.05). The results demonstrated that NRM and survival outcomes are worse in overweight and obese transplant recipients (BMI ≥ 25) with one alternative donor type over MUD, although obesity does not appear to confer a uniform differential mortality risk with one donor type over the other. BMI may serve as a criterion for selecting a donor among the three (MUD, haplo and CBU) options, if matched sibling donor is not available.

Racial Disparities in the Emergency Department Evaluation of Adolescent Girls.

OBJECTIVE: Racial disparities and differences exist in emergency care. Obtaining a sexual history is standard of care for adolescents with abdominal pain. Testing for sexually transmitted infections (STIs) and pregnancy should be based on historical findings. The objective of this study was to determine whether differential care was provided to adolescent female patients with abdominal pain based on patient race or healthcare provider characteristics by evaluating the documentation of sexual history, STI testing, and pregnancy testing. METHODS: This was a retrospective chart review of female patients between the ages of 14 and 18 years with abdominal pain presenting to a pediatric emergency department. Patient and provider characteristics, sexual history documentation, STI, and pregnancy testing were abstracted. Data were analyzed using χ 2 test and logistic regression model. RESULTS: Eight hundred eighty-six encounters were included in the analysis. Median patient age was 16 years (range, 14-18 years); 359 (40.5%) were non-White. Differential care was provided. Non-White patients compared with White patients were more likely to have a documented sexual history (59.9% vs 44.0%, P < 0.001), STI testing (24.8% vs 7.8%, P < 0.001), and pregnancy testing (76.6% vs 66.2%, P < 0.001). Among sexually active female patients, the racial disparity for STI testing persisted ( P = 0.010). Provider type and sex did not result in differences in sexual history documentation, STI, or pregnancy testing for non-White compared with White patients ( P > 0.05). CONCLUSIONS: Differential care was provided to non-White adolescents with abdominal pain compared with White adolescents. They were more likely to have a documented sexual history, STI testing, and pregnancy testing. Healthcare provider characteristics did not impact patient care. This racial disparity resulted in better medical care for non-White adolescents, but this may be the consequence of underlying implicit bias.

Impact of Induction Therapy with VRD versus VCD on Outcomes in Patients with Multiple Myeloma in Partial Response or Better Undergoing Upfront Autologous Stem Cell Transplantation.

Bortezomib-based triplet regimens-specifically bortezomib, lenalidomide, and dexamethasone (VRD) and bortezomib, cyclophosphamide, and dexamethasone (VCD)-are the 2 most common induction regimens used in transplantation-eligible patients with newly diagnosed multiple myeloma (NDMM), with conflicting data on comparative efficacy and outcomes in this population. We compared long-term outcomes of patients with NDMM receiving VRD induction and those receiving VCD induction prior to autologous stem cell transplantation (ASCT). Patients registered with the Center for International Blood and Marrow Transplant Registry were included if they had undergone ASCT for MM within 6 months of diagnosis between January 2013 and December 2018, received VRD or VCD induction, and achieved a pretransplantation partial or better response. Of 1135 patients, 914 received VRD and 221 received VCD. The patients receiving VCD were more likely to have renal impairment and International Staging System (ISS) stage III disease and less likely to receive full-dose melphalan (200 mg/m2) conditioning (69% versus 80%; P < .001). Very good partial response rates pretransplantation, post-transplantation, and at best response were not significantly different in the 2 groups. Maintenance use was more common after VRD induction (88% versus 76%; P < .001), with lenalidomide the most common agent (80% versus 63%). Patients in the VRD group had a higher rate of renal recovery (74% versus 43%; P < .001), possibly due to a rapid reduction of light chains in the VRD group or improvement in renal function with VCD, which allowed a switch over to VRD, as patients who switched were classified in the VRD group. Patients receiving VRD had better survival on univariate analysis, with a median progression-free survival (PFS) from transplantation of 44.6 months versus 34.1 months (P = .004) and median 5-year overall survival (OS) of 79% versus 60% (P < .001). Multivariate analysis showed no significant survival difference, with a hazard ratio for VCD versus VRD induction of 1.22 (95% CI, 0.96 to 1.55; P = .10) for PFS and 1.33 (95% CI, 0.93 to 1.92, P = .12) for OS. Maintenance use was independently associated with superior PFS and OS, along with ISS stage, cytogenetics, and pretransplantation response (PFS only). In patients with MM undergoing upfront ASCT after VRD or VCD induction, no independent survival difference was seen based on the induction therapy received after adjusting for other prognostic factors. The use of maintenance treatment was uniformly associated with superior outcomes. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Maintenance therapy after second autologous hematopoietic cell transplantation for multiple myeloma. A CIBMTR analysis.

The role of maintenance therapy after high-dose chemotherapy and first autologous transplantation in multiple myeloma (MM) is well established. We explored the effect of maintenance therapy on outcomes after salvage second autologous hematopoietic cell transplant (AHCT2) using the Center for International Blood and Marrow Transplant Research registry. Outcomes of interest included non-relapse mortality (NRM), relapse/progression (REL), progression-free and overall survival (PFS, OS). Of 522 patients who underwent AHCT2 between 2010 and 2018, 342 received maintenance therapy and 180 did not. Maintenance regimens included lenalidomide (42%), pomalidomide (13%), and bortezomib (13%). Median follow up was 58 months in the maintenance group and 61.5 months in the no-maintenance group. Univariate analysis showed superior outcomes at 5 years in maintenance compared to the no-maintenance group: NRM 2 (0.7-3.9)% vs 9.9 (5.9-14.9)%, (p < 0.01), REL 70.2 (64.4-75.8)% vs 80.3 (73.6-86.3)% (p < 0.01), PFS 27.8 (22.4-33.5)% vs. 9.8 (5.5-15.2)% (p < 0.01), and OS 54 (47.5-60.5)% vs 30.9 (23.2-39.2)% (p < 0.01), respectively. Use of maintenance therapy retained its association with improved outcomes in multivariate analysis. There was no difference in second cancers in the two groups (p = 0.39). We conclude that maintenance after AHCT2 is associated with improved 5-year outcomes.

A note on median regression for complex surveys.

There is a great need for statistical methods for analyzing skewed responses in complex sample surveys. Quantile regression is a logical option in addressing this problem but is often accompanied by incorrect variance estimation. We show how the variance can be estimated correctly by including the survey design in the variance estimation process. In a simulation study, we illustrate that the variance of the median regression estimator has a very small relative bias with appropriate coverage probability. The motivation for our work stems from the National Health and Nutrition Examination Survey where we demonstrate the impact of our results on iodine deficiency in females compared with males adjusting for other covariates.

Ecological Study of Variability in the Relationship between Liver Cancer Mortality and Racial Residential Segregation.

Racial segregation has been identified as a predictor for the burden of cancer in several different metropolitan areas across the United States. This ecological study tested relationships between racial segregation and liver cancer mortality across several different metropolitan statistical areas in Wisconsin. Tract-level liver cancer mortality rates were calculated using cases from 2003-2012. Hotspot analysis was conducted and segregation scores in high, low, and baseline mortality tracts were compared using ANOVA. Spatial regression analysis was done, controlling for socioeconomic advantage and rurality. Black isolation scores were significantly higher in high-mortality tracts compared to baseline and low-mortality tracts, but stratification by metropolitan areas found this relationship was driven by two of the five metropolitan areas. Hispanic isolation was predictive for higher mortality in regression analysis, but this effect was not found across all metropolitan areas. This study showed associations between liver cancer mortality and racial segregation but also found that this relationship was not generalizable to all metropolitan areas in the study area.

Myeloablative versus Reduced-Intensity Conditioning for Hematopoietic Cell Transplantation in Acute Myelogenous Leukemia and Myelodysplastic Syndromes-Long-Term Follow-Up of the BMT CTN 0901 Clinical Trial.

Several prospective randomized trials comparing conditioning intensity before allogeneic hematopoietic cell transplantation (HCT) have been performed, with conflicting results. Although reduced-intensity conditioning (RIC) leads to lower treatment-related mortality (TRM), this is offset by higher rates of relapse. Long-term follow-up of randomized comparative trials are limited. Here we present long-term follow-up of a randomized comparison of myeloablative conditioning (MAC) compared with RIC before HCT for acute myelogenous leukemia (AML) or myelodysplasia (MDS). Long-term comparative analyses of overall survival, relapse, and relapse-free survival were performed. Patients age 18 to 65 years with <5% marrow myeloblasts were randomized to receive MAC (n = 135) or RIC (n = 137), followed by HCT from an HLA-matched donor. The primary endpoint of the trial was an 18-month pointwise comparison of overall survival. The analyses were performed using a proportional hazards model. The median follow-up of the entire cohort was 51 months. At 4 years, the transplant-related mortality (TRM) was 25.1% for MAC, compared with 9.9% for RIC (P < .001). Patients who received RIC had a significantly higher risk of relapse compared to those who received MAC (hazard ratio [HR], 4.06; 95% CI, 2.59 to 6.35; P < 0.001). Among the patients who relapsed after HCT, postrelapse survival was similar at 3 years (24% for MAC and 26% for RIC). Overall survival was superior for patients who received MAC compared to those who received RIC (HR, 1.54; 95% CI, 1.07 to 2.2; P = .03). Our data show that patients who received MAC were at higher risk of late TRM compared with those who received RIC; however, because of the exceedingly high rates of relapse in the RIC arm, overall survival remained significantly better for patients who received MAC. Among patients with MDS or AML eligible for either MAC or RIC regimens, long-term follow up demonstrates a survival advantage for patients who received MAC.

Bortezomib-Based Induction Is Associated with Superior Outcomes in Light Chain Amyloidosis Patients Treated with Autologous Hematopoietic Cell Transplantation Regardless of Plasma Cell Burden.

The benefits of pre-transplant induction chemotherapy in light chain (AL) amyloidosis, a low burden plasma cell (PC) neoplasm associated with multiorgan dysfunction, is debatable, although with the availability of bortezomib, this approach is being increasingly pursued. We analyzed the outcomes of AL amyloidosis patients undergoing autologous hematopoietic cell transplant between 2014 and 2018 that were reported to the Center for International Blood and Marrow Transplant Research database. Of 440 patients, 294 received bortezomib-based induction, and 146 received no induction. Patients receiving induction had greater PC burden compared to no induction (PC 10% or more, 39% versus 11%; P < .01). At 2 years, the induction group compared to no induction had lower relapse/progression: 13% (9% to 18%) versus 23% (16% to 32%) (P = .02); better progression-free survival (PFS): 82% (77% to 87%) versus 69% (61% to 77%) (P < .01); and similar overall survival (OS): 92% (88% to 95%) versus 89% (84% to 94%) (P = .22), findings that were confirmed on multivariate analysis. A subset analysis limited to patients with <10% PC also showed superior relapse/progression (hazard ratio [HR], .43; 95% confidence interval [CI], .24 to .78; P < .01) and PFS (HR, .43; 95% CI, .26 to .72; P < .01) for induction compared to no induction. Thus, we conclude that pre-transplant bortezomib-based induction was associated with improved relapse/progression and PFS in AL amyloidosis. Longer survival follow-up is warranted, as OS was excellent in both cohorts at 2 years.

Multimedia Evaluation of EMT-Paramedic Assessment and Management of Pediatric Respiratory Distress.

BACKGROUND: The prehospital care of asthma, bronchiolitis and croup is directed by evidence-based Emergency Medical Services (EMS) protocols. Determining the appropriate intervention for these conditions requires Emergency Medical Technicians-Paramedics (EMT-Ps) to correctly differentiate asthma/bronchospasm, bronchiolitis, and croup. The diagnostic accuracy of EMT-Ps for these pediatric respiratory distress conditions is unknown. OBJECTIVE: We hypothesized increasing provider age, years of provider experience, higher volume of pediatric cases, self-reported comfort with pediatric patients, and having children of one's own would be associated with increased accuracy in diagnosis on a validated multimedia questionnaire. METHODS: This is a cross-sectional study of paramedics from a single EMS agency who completed a validated, case-based questionnaire between July and September 2018. The multimedia questionnaire consisted of four cases, each of which included patient videos and lung sound recordings. Paramedics were asked to assess the severity of distress and ascribe the correct diagnosis and prehospital intervention for each case. Each paramedic completed the questionnaire independently. We defined high questionnaire performance a priori as correctly identifying the diagnosis for ≥75% of cases and used multivariate regression to assess factors associated with high questionnaire performance. Provider age and EMS experience were reported in years and analyzed as continuous variables. Volume of pediatric cases was dichotomized to <1 and ≥1 case per shift and having children was dichotomized to either having children or not having children. RESULTS: Of 514 paramedics, 420 (82%) completed the questionnaire. Overall, paramedics correctly assessed the severity of respiratory distress 92% of the time. However, they only ascribed the correct diagnosis 50% and selected the correct intervention(s) 38% of the time. Increasing age, years of experience, higher volume of pediatric cases, self-reported comfort with pediatric patients, and having children of their own were not associated with questionnaire performance. CONCLUSION: Paramedics accurately assessed severity of distress in multimedia cases of asthma/bronchospasm, bronchiolitis and croup in children, but showed significant room for improvement in correctly identifying the diagnosis and in selecting appropriate intervention(s). Age, years of EMS experience, higher volume of clinical pediatric cases, self-reported comfort with pediatric patients, and having children of their own were not associated with questionnaire performance.

African Americans with translocation t(11;14) have superior survival after autologous hematopoietic cell transplantation for multiple myeloma in comparison with Whites in the United States.

BACKGROUND: Multiple myeloma (MM) with the translocation t(11;14) may have inferior outcomes in comparison with other standard-risk MM, and it has been suggested to portend a worse prognosis in African Americans in comparison with Whites. This study used the Center for International Blood and Marrow Transplant Research (CIBMTR) database to examine the impact of t(11;14) on the clinical outcomes of patients with MM of African American and White descent. METHODS: This study evaluated 3538 patients who underwent autologous hematopoietic cell transplantation (autoHCT) for MM from 2008 to 2016 and were reported to the CIBMTR. Patients were analyzed in 4 groups: African Americans with t(11;14) (n = 117), African Americans without t(11;14) (n = 968), Whites with t(11;14) (n = 266), and Whites without t(11;14) (n = 2187). RESULTS: African Americans with t(11;14) were younger, had lower Karnofsky scores, and had more advanced stage MM with a higher Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI). Fewer African Americans with t(11;14) (21%) had a coexistent high-risk marker in comparison with Whites with t(11;14) (27%). In a multivariate analysis, race and t(11;14) had no association with progression-free survival. However, overall survival was superior among African Americans with t(11;14) in comparison with Whites with t(11;14) (hazard ratio, 0.53; 95% confidence interval, 0.30-0.93; P = .03). Survival was also associated with female sex, stage, time from diagnosis to transplant, a low HCT-CI, and receipt of maintenance. CONCLUSIONS: Race may have a differential impact on the survival of patients with t(11;14) MM who undergo autoHCT and needs to be further studied.

Novel prognostic scoring system for autologous hematopoietic cell transplantation in multiple myeloma.

We studied 2,528 patients with upfront autologous haematopoietic cell transplantation (AHCT) for multiple myeloma (MM) from 2008-2017 to develop a prognostic model to predict outcomes. High-risk cytogenetics included t(4;14), t(14;16), t(14;20), del13q on karyotype, del17p, +1q or 1pdel. A Cox model identified factors prognostic of progression/relapse in a training subset (n = 1,246). A weighted score using these factors was assigned to a validation cohort (n = 774). Presence of high-risk cytogenetics [hazard ratio, (HR) 1·68 (1·3-2·17)] and pre-AHCT bone marrow plasma cells (BMPCs) ≥10% [1·68 (1·33-2·12)] were assigned 4 points each; albumin at diagnosis <3·5 g/dl [1·31 (1·07-1·61)] 2; standard risk cytogenetics 1, and no cytogenetics abnormality, BMPCs <10% at AHCT and albumin ≥3·5 g/dl at diagnosis 0 points each. A three-category system with low risk (0-3), intermediate risk (4-8) and high risk (9-10) showed 3-year progression-free survival in the low vs. intermediate vs. high risk of 58% (95% CI: 52-63) vs. 49% (95% CI: 43-56) vs. 31% (95% CI: 12-51), P < 0.001 respectively, and 3-year OS in low vs. intermediate vs. high risk of 88% (95% CI: 84-91) vs. 81% (95% CI: 76-86) vs. 64% (95% CI: 39-80); P < 0·001. Our prognostic scoring system can identify MM patients at risk for early relapse after AHCT.

The association between timely opioid administration and hospitalization in children with sickle cell disease presenting to the emergency department in acute pain.

INTRODUCTION: The National Heart, Lung, and Blood Institute guidelines for sickle cell disease (SCD) pain crisis management recommend opioids within 60 minutes of emergency department (ED) registration and every 30 minutes thereafter until acute pain is managed. These guidelines are based on expert opinion without published, supporting data. OBJECTIVE: To evaluate the association between timely ED opioid administration and hospitalization rates in children with SCD. METHODS: Retrospective cohort of children presenting to a children's hospital ED with SCD pain between January 1, 2014, and April 30, 2018. Visits were extracted using ICD codes, chief complaints, and receipt of at least one opioid, and then reviewed to confirm the visit was an uncomplicated pain crisis. The primary outcome was hospitalization, yes or no. Generalized estimating equations were used to determine adjusted odds of hospitalization for the timely administration of initial and second doses of opioids. RESULTS: Of the 902 eligible visits, 368 (40.8%) resulted in hospitalization. The mean (SD) age was 11.9 (± 5.2) years. The first opioid was administered within 60 minutes of arrival in 601 (66.6%) visits. The second opioid was administered within 30 minutes of the first in 84 (12.3%) visits. Receipt of the first opioid within 60 minutes of arrival was not associated with decreased hospitalization (1.30 [0.96-1.76]). However, receipt of the second dose within 30 minutes of the first was associated with decreased hospitalization (0.56 [0.33-0.94]). CONCLUSION: This study suggests an association between children with SCD receiving a second dose within 30 minutes of the first opioid dose and decreased hospitalizations.