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We previously conducted a single-arm feasibility study (STRIDE1) of myeloablative bone marrow transplantation (BMT) in adolescents and young adults with sickle cell disease (SCD). The trial identified donors before entry, enrolled well, and found no unexpected regimen-related toxicity. Although many single-arm studies have been published, there are no controlled trials of either BMT or gene therapy in SCD. Therefore, we designed a comparative trial by biological assignment (available donor versus no donor). This multicenter National Institutes of Health-funded study (Blood and Marrow Transplant Clinical Trials Network 1503; STRIDE2) enrolled patients between 2016 and 2021 at 35 sites. Lagging recruitment led to study closure, and here we report the impediments to accrual. The BMT regimen and entry criteria were from STRIDE1, and 2-year survival was the primary endpoint. To minimize selection bias from prior HLA typing, STRIDE2 excluded individuals with previously identified donors. Accrual was stopped at 69% of target (138 enrolled; assigned 28 with donor, 96 with no donor). Barriers to enrollment included lower than expected frequency of HLA-matched related and unrelated donors; loss of enrollees owing to previously identified donors; conventional care arm dissuading some seeking BMT; challenging short-term endpoints in SCD, including incomplete documentation of sickle pain episodes; state Medicaid (primary insurers of SCD) denial of BMT coverage for adult SCD despite the study having secured Coverage with Evidence Development from the Center for Medicare & Medicaid Services; slowed accrual in 2019 to 2021 during the Coronavirus disease 2019 pandemic; and restriction of BMT resourcing for nonmalignant diseases by academic medical (cancer) centers. Social obstacles and access to BMT centers also limited entry, as did practitioner and participant concerns over suitability, cost, and toxicity. Planning for future controlled trials of curative therapy in SCD and ot

Previous naturalistic driving studies have shown that visual and manual secondary tasks increase driving crash risk. With the increasing use of infotainment systems in vehicles, secondary tasks requiring cognitive executive demand may increase crash risk, especially for young and older drivers. Naturalistic driving data were examined to determine if secondary tasks with increasing cognitive executive demand would result in increasing crash risk. Data were extracted from the Second Strategic Highway Research Program Naturalistic Driving Study, where vehicles were instrumented to record driving behavior and crash/near-crash data. Cognitive executive and visual-manual tasks paired with a second cognitive executive task were compared to the cognitive executive and visual-manual tasks performed alone. Crash/near-crash odds ratios were computed by comparing each task condition to driving without presence of any secondary task. Dual cognitive executive tasks resulted in greater odds ratios than those for single cognitive executive tasks. The dual visual-manual tasks odds ratios did not increase from single task odds ratios. These effects were only found for young drivers. These findings help validate that cognitive executive secondary task load increases crash/near-crash risk, especially in dual task situations for young drivers. Future research should be conducted to minimize cognitive task load associated with vehicle infotainment systems using such technologies as voice commands.

Immunocompromised individuals, particularly autologous hematopoietic stem cell transplant (auHSCT) recipients, are at high risk for herpes zoster (HZ). We provide an in-depth description of humoral and cell-mediated immune (CMI) responses by age (protocol-defined) or underlying disease (post-hoc) as well as efficacy by underlying disease (post-hoc) of the adjuvanted recombinant zoster vaccine (RZV) in a randomized observer-blind phase III trial (ZOE-HSCT, NCT01610414). 1846 adult auHSCT recipients were randomized to receive a first dose of either RZV or placebo 50-70 days post-auHSCT, followed by the second dose at 1-2 months (M) later. In cohorts of 114-1721 participants, at 1 M post-second vaccine dose: Anti-gE antibody geometric mean concentrations (GMCs) and median gE-specific CD4[2+] T-cell frequencies (CD4 T cells expressing ≥2 of four assessed activation markers) were similar between 18-49 and ≥50-year-olds. Despite lower anti-gE antibody GMCs in non-Hodgkin B-cell lymphoma (NHBCL) patients, CD4[2+] T-cell frequencies were similar between NHBCL and other underlying diseases. The proportion of polyfunctional CD4 T cells increased over time, accounting for 79.6% of gE-specific CD4 T cells at 24 M post-dose two. Vaccine efficacy against HZ ranged between 42.5% and 82.5% across underlying diseases and was statistically significant in NHBCL and multiple myeloma patients. In conclusion, two RZV doses administered early post-auHSCT induced robust, persistent, and polyfunctional gE-specific immune responses. Efficacy against HZ was also high in NHBCL patients despite the lower humoral response.

BackgroundDespite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma.MethodsWe randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants). The primary end point was a global rank composite score comparing participants with each other on the basis of a hierarchy of disease features assessed at 54 months: death, event-free survival (survival without respiratory, renal, or cardiac failure), forced vital capacity, the score on the Disability Index of the Health Assessment Questionnaire, and the modified Rodnan skin score.ResultsIn the intention-to-treat population, global rank composite scores at 54 months showed the superiority of transplantation (67% of 1404 pairwise comparisons favored transplantation and 33% favored cyclophosphamide, P=0.01). In the per-protocol population (participants who received a transplant or completed ≥9 doses of cyclophosphamide), the rate of event-free survival at 54 months was 79% in the transplantation group and 50% in the cyclophosphamide group (P=0.02). At 72 months, Kaplan-Meier estimates of event-free survival (74% vs. 47%) and overall survival (86% vs. 51%) also favored transplantation (P=0.03 and 0.02, respectively). A total of 9% of the participants in the transplantation group had initiated disease-modifying antirheumatic drugs (DMARDs) by 54 months, as compared with 44% of those in the cyclophosphamide group (P=0.001). Treatment-related mortality in the transplantation group was 3% at 54 months and 6% at 72 months, as compared with 0% in the cyclophosphamide group.ConclusionsMyeloablative autologous hematopoietic stem-cell transplantation achiev

Background: A phase 2 trial of tocilizumab showed preliminary evidence of efficacy in systemic sclerosis. We assessed skin fibrosis and systemic sclerosis-associated interstitial lung disease (SSc-ILD) in a phase 3 trial to investigate the safety and efficacy of tocilizumab, an anti-interleukin-6 receptor antibody, in the treatment of systemic sclerosis. Methods: In this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial, participants were recruited from 75 sites in 20 countries across Europe, North America, Latin America, and Japan. Adults with diffuse cutaneous systemic sclerosis for 60 months or less and a modified Rodnan skin score (mRSS) of 10–35 at screening were randomly assigned (1:1) with a voice-web-response system to receive subcutaneous tocilizumab 162 mg or placebo weekly for 48 weeks, stratified by IL-6 levels; participants and investigators were masked to treatment group. The primary endpoint was the difference in change from baseline to week 48 in mRSS. Percentage of predicted forced vital capacity (FVC% predicted) at week 48, time to treatment failure, and patient-reported and physician-reported outcomes were secondary endpoints. This trial is registered with ClinicalTrials.gov (number NCT02453256) and is closed to accrual. Findings: Between Nov 20, 2015, and Feb 14, 2017, 210 individuals were randomly assigned to receive tocilizumab (n=104) or placebo (n=106). In the intention-to-treat population, least squares mean [LSM] change from baseline to week 48 in mRSS was −6·14 for tocilizumab and −4·41 for placebo (adjusted difference −1·73 [95% CI −3·78 to 0·32]; p=0·10). The shift in distribution of change from baseline in FVC% predicted at week 48 favoured tocilizumab (van Elteren nominal p=0·002 vs placebo), with a difference in LSM of 4·2 (95% CI 2·0–6·4; nominal p=0·0002), as did time to treatment failure (hazard ratio 0·63 [95% CI 0·37–1·06]; nominal p=0·08). Change in LSM from baseline to week 48 in Health Assessment Ques

We conducted a multicenter pilot investigation of the safety and feasibility of bone marrow transplantation (BMT) in adults with severe sickle cell disease (SCD) (NCT 01565616) using a reduced toxicity preparative regimen of busulfan (13.2 mg/kg), fludarabine (175 mg/m2 ) and thymoglobulin (6 mg/kg) and cyclosporine or tacrolimus and methotrexate for graft-vs-host disease (GVHD) prophylaxis. Twenty-two patients (median age 22 years; range 17-36) were enrolled at eight centers. Seventeen patients received marrow from an HLA-identical sibling donor and five patients received marrow from an 8/8 HLA-allele matched unrelated donor. Before BMT, patients had stroke, acute chest syndrome, recurrent pain events, were receiving regular red blood cell transfusions, or had an elevated tricuspid regurgitant jet (TRJ) velocity, which fulfilled eligibility criteria. Four patients developed grades II-III acute GVHD (18%) and six developed chronic GVHD (27%) that was moderate in two and severe in one patient. One patient died of intracranial hemorrhage and one of GVHD. Nineteen patients had stable donor chimerism, 1-year post-transplant. One patient who developed secondary graft failure survives disease-free after a second BMT. The one-year overall survival and event-free survival (EFS) are 91% (95% CI 68%-98%) and 86% (95% CI, 63%-95%), respectively, and 3-year EFS is 82%. Statistically significant improvements in the pain interference and physical function domains of health-related quality of life were observed. The study satisfied the primary endpoint of 1-year EFS ≥70%. This regimen is being studied in a prospective clinical trial comparing HLA-matched donor BMT with standard of care in adults with severe SCD (NCT02766465).

ObjectiveTo assess survival and identify predictors of survival in patients with systemic sclerosis-interstitial lung disease (SSc-ILD) who participated in the Scleroderma Lung Studies (SLS) I and II.MethodsSLS I randomised 158 patients with SSc-ILD to 1 year of oral cyclophosphamide (CYC) vs placebo. SLS II randomised 142 patients to 1 year of oral CYC followed by 1 year of placebo vs 2 years of mycophenolate mofetil. Counting process Cox proportional hazard modelling identified variables associated with long-term mortality in SLS I and II. Internal validation was performed using joint modelling.ResultsAfter a median follow-up of 8 years, 42% of SLS I patients died, and when known the cause of death was most often attributable to SSc. There was no significant difference in the time to death between treatment arms in SLS I or II. Higher baseline skin score, older age, and a decline in the forced vital capacity (FVC) and the diffusing capacity for carbon monoxide (DLCO) over 2 years were independently associated with an increased risk of mortality in SLS I. The Cox model identified the same mortality predictor variables using the SLS II data.ConclusionIn addition to identifying traditional mortality risk factors in SSc (skin score, age), this study demonstrated that a decline in FVC and DLCO over 2 years was a better predictor of mortality than baseline FVC and DLCO. These findings suggest that short-term changes in surrogate measures of SSc-ILD progression may have important effects on long-term outcomes.

For patients with acute lymphoblastic leukemia (ALL), allogeneic hematopoietic cell transplantation (alloHCT) offers a potential cure. Life-threatening complications can arise from alloHCT that require the application of sophisticated health care delivery. The impact of country-level economic conditions on post-transplantation outcomes is not known. Our objective was to assess whether these variables were associated with outcomes for patients transplanted for ALL. Using data from the Center for Blood and Marrow Transplant Research, we included 11,261 patients who received a first alloHCT for ALL from 303 centers across 38 countries between the years of 2005 and 2013. Cox regression models were constructed using the following macroeconomic indicators as main effects: Gross national income per capita, health expenditure per capita, and Human Development Index (HDI). The outcome was overall survival at 100 days following transplantation. In each model, transplants performed within lower resourced environments were associated with inferior overall survival. In the model with the HDI as the main effect, transplants performed in the lowest HDI quartile (n = 697) were associated with increased hazard for mortality (hazard ratio, 2.42; 95% confidence interval, 1.64 to 3.57; P < .001) in comparison with transplants performed in the countries with the highest HDI quartile. This translated into an 11% survival difference at 100 days (77% for lowest HDI quartile versus 88% for all other quartiles). Country-level macroeconomic indices were associated with lower survival at 100 days after alloHCT for ALL. The reasons for this disparity require further investigation.

Advances in allogeneic hematopoietic cell transplantation for sickle cell disease have improved outcomes, but there is limited analysis of healthcare utilization in this setting. We hypothesized that, compared to late transplantation, early transplantation (at age < 10 years) improves outcomes and decreases healthcare utilization. We performed a retrospective study of children transplanted for sickle cell disease in the USA during 2000-2013 using two large databases. Univariate and Cox models were used to estimate associations of demographics, sickle cell disease severity, and transplant-related variables with mortality and chronic graft-versus-host disease, while Wilcoxon, Kruskal-Wallis, or linear trend tests were applied for the estimates of healthcare utilization. Among 161 patients with a 2-year overall survival rate of 90% (95% confidence interval [CI] 85-95%) mortality was significantly higher in those who underwent late transplantation versus early (hazard ratio (HR) 21, 95% CI 2.8-160.8, P=0.003) and unrelated compared to matched sibling donor transplantation (HR 5.9, 95% CI 1.7-20.2, P=0.005). Chronic graftversus host disease was significantly more frequent among those translanted late (HR 1.9, 95% CI 1.0-3.5, P=0.034) and those who received an unrelated graft (HR 2.5, 95% CI 1.2-5.4; P=0.017). Merged data for 176 patients showed that the median total adjusted transplant cost per patient was $467,747 (range: $344,029-$ 799,219). Healthcare utilization was lower among recipients of matched sibling donor grafts and those with low severity disease compared to those with other types of donor and disease severity types (P<0.001 and P=0.022, respectively); no association was demonstrated with late transplantation (P=0.775). Among patients with 2-year pre-and post-transplant data (n=41), early transplantation was associated with significant reductions in admissions (P<0.001), length of stay (P<0.001), and cost (P=0.008). Early transplant outcomes need

Although a number of published trials exist of HLA-identical sibling hematopoietic cell transplantation (HCT) for sickle cell disease (SCD) that span 2 decades, when and for whom this therapy should be pursued is a subject of debate. Assessments of the risks of transplant-related complications that include infertility and debilitating graft-versus-host disease and long-term quality of life after successful HCT are difficult to perform without prospective trials in transplant and nontransplant cohorts. However, it is possible to assess the risk of mortality and to compare published rates of survival in individuals with SCD treated and not treated by HCT. In this brief review, projections about mortality risk based on recent published reports are reviewed and summarized. The published data show overall survival and event-free survival rates of 95% and 92%, respectively, in children treated by HLA-identical sibling HCT. The overall survival rates in the Center for International Blood and Marrow Transplant Research (N = 412) and European Blood and Marrow Transplant (N = 487) registries were 91% and 95%, respectively. These results provide broad support for the therapeutic value of HLA-identical sibling HCT for children with SCD and serve as the basis for a strong recommendation in favor of the option of HCT when a suitable donor is available. The experience of HLA-identical sibling HCT in adults with SCD is limited but appears to be similar to results in children. These preliminary observations, however, warrant further investigation.

An investigation of sites, uses and practices for literacy in the lives of Pasifika students Lower test scores on school measures of literacy for Pasifika students than for the majority of students in New Zealand are a cause for concern. As part of a wider attempt to address this problem the Ministry of Education has argued that teachers need to be better informed of out-of-school literacy practices. This thesis considers what can be learned when this guidance is followed and it investigates students' social and cultural uses of literacy in family and community settings. It explores the argument that knowledge of these out-of-school literacies will inform teachers and through incorporation (McNaughton, 2002) teachers may be able to make effective connections for students to school literacy. A sociocultural perspective is used to investigate the social and cultural practices of the students while the study also uses Cremin's (1976) concept of configurations of sites to consider how learning is mediated for students in different settings. Rogoff's (1995) three planes of analysis provide a tool to examine students' practices at the community, interpersonal, and personal levels. The investigation sought the students' own perspective of how they appropriate knowledge about literacy as they collected information with cameras and journals on their own practices. The participants were 14 Pasifika students aged 11 and 12 years (mostly Samoan) as well as three adult Samoan church representatives and teachers from the students' school. Students' photos were used to elicit rich description in semi-structured interviews and interview schedules were also used with students and adult participants. The findings illustrate how the students were socialised into particular practices that are contextualised in the sites of family, church and neighbourhood. They reveal that for the students there was both overlapping of values and conflict between their sites of literacy practice. The c

We report outcomes after myeloablative haematopoietic cell transplantation (HCT) from human leucocyte antigen (HLA)-matched sibling donors in 67 patients with sickle cell disease transplanted between 1989 and 2002. The most common indications for transplantation were stroke and recurrent vaso-occlusive crisis in 38% and 37% of patients respectively. The median age at transplantation was 10 years and 67% of patients had received >10 red blood cell transfusions before HCT. Twenty-seven percent of patients had a poor performance score at transplantation. Ninety-four percent received busulfan and cyclophosphamide-containing conditioning regimens and bone marrow was the predominant source of donor cells. Most patients achieved haematopoietic recovery and no deaths occurred during the early post-transplant period. Rates of acute and chronic graft-versus-host disease were 10% and 22% respectively. Sixty-four of 67 patients are alive with 5-year probabilities of disease-free and overall survival of 85% and 97% respectively. Nine patients had graft failure with recovery of sickle erythropoiesis, eight of who had recurrent sickle-related events. This report confirms and extends earlier reports that HCT from HLA-matched related donors offers a very high survival rate, with few transplant-related complications and the elimination of sickle-related complications in the majority of patients who undergo this therapy., Journal Article, Multicenter Study, Research Support, N.I.H. Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., SCOPUS: ar.j, FLWIN, info:eu-repo/semantics/published

In the 1990s there was public speculation that New Zealand schools and businesses were establishing new and more relationships. Three broad public discourses sought to articulate this shift and its effects. They collectively represented business motives for school-business relationships as commercial, social, or operationally focused, or mixtures of these. This thesis argues with evidence from literature and original research, and with special attention on the activities of the food industry, that the prime business motive for school-business relationships was commercial. This motive is explored within the interwoven cultural contexts of changing businesses, changing childhoods and changing schools. In recent years businesses have assumed greater power as corporate meaning-makers in childhood identities as the boundaries between the cultural categories of advertising, entertainment and education collapse and new hybrid forms emerge including new school-business relationship forms. As business integrate public relations with their marketing objectives, this meaning-making role in an information society has intensified and fulfils a wide range of objectives from increased sales to management of public opinion. Businesses with the most fragile public profiles have gravitated to schools the most, and school children have become both key producers and key consumers of the sign value of the socially responsible business. Childhood is considered within a social constructionist perspective and it is argued that businesses influence childhood identity through the transgressive pedagogies of children's popular culture, and the commercialized adult discourses of child development and innocence. The tensions between these are being brought to some resolution in the increasingly popular commercialized edutainment pedagogies offered to students in schools, which simultaneously address adult and child desires. Responding to school-business relationships in New Zealand from 1990 wa

The history of the relationship between Maori (the indigenous minority) and Pakeha (the dominant majority) is one that is encapsulated in processes of mediation. Pakeha resolve issues that favour kawanatanga solutions (article 1 of the Treaty) while Maori recommendations almost always line up with solutions that uphold questions to do with tino rangatiratanga (article 2 of the Treaty). Each takes into account forms of accommodation of the other but these compromise positions are usually the tasks for the public servants who are by definition, working for the government of the day, and therefore, on the side of kawanatanga. The point of articulation is critical in the nature of the relationship between Maori and Pakeha. The legal academic, Alex Frame (2002) describes this position as important for those New Zealanders "who have tried to walk in both worlds, thereby not only honouring and strengthening their own and each other's cultures, but also bringing to life a third and co-existing culture of interaction in Aotearoa". A study of a variety of mediating structures, explores the relationship between Maori and Pakeha and analyses the effects these have on both parties, especially as these pertain to developments in Maori education. An approach to settling the conundrum of prioritising one agenda without creating new grievances for redress is argued throughout the study. It is argued, further, that a major re-think is needed of what an education will mean in order to meet the requirements of a contemporary Polynesian/Western society that both honours the tenets of its foundation document as well as providing a rational basis for meeting commitments in the modern global society.

Relocatable targets are mobile targets that will stay in a discrete location for an unknown, random length of time before moving to another location. Such targets include mobile missile launchers, air defense units, fuel trucks and other high value targets (e.g. maneuver forces). Using a combination of multiagent simulation and a multiobjective evolutionary algorithm, we evolve optimal submunition design characteristics for attacking relocatable target examined three types of target concealment, and discovered that high probability of detection, short delay times, and multiple submunitions are required for successful engagement., Presented at MORS Symposium, Working Group 11, 15 November, 2004.

The benefits of network-centric warfare are addressed in many publications, but few of these publications actually demonstrate how to quantify these alleged benefits. This report proposes an analytical framework to quantify the value-added of network-centric warfare; that framework is queueing theory, which is based on the concept of a demand-for-service process. Most warfare tasks can be characterized as demand-for-service processes. This report shows how queueing theory can be applied to demand-for-service warfare tasks and thus provide the basis for analyzing and quantifying those tasks. In addition, this report demonstrates how the functions of many of the independent and dependent variables and associated warfare metrics can be translated into the characteristics and metrics of queues., The original document contains color images. All DTIC reproductions will be in black and white.

QSIM is a queueing theory model developed to interpret the various undertakings involved in military operations. The multiple probability distribution functions (PDFs) for arrival, service, and renege rates not only allow QSIM to analyze a variety of specific warfare tasks (especially those characterized by nonexponential PDFs), but they also ensure that the model is applicable to many other situations. Moreover, the relatively efficient run times permit the user to analyze a range of input values quickly., The original document contains color images. All DTIC reproductions will be in black and white.

In 2001 the Maritime Systems Group of The Technical Cooperation Program (TTCP) set-up an Action Group (AG-1) to examine the exponential increases in warfighting capability claimed for Network-Centric Maritime Warfare (NCMW). Analysis of NCMW is a two-stage process of finding analysis processes for estimating the NCMW effects on the scenario parameters and then applying appropriate warfare models to relate NCMW-sensitive scenario parameters to force effectiveness. This paper will report on the results of a modeling workshop held by AG-1 in November 2002. The workshop's focus was to investigate the usefulness of applying a queueing model to Maritime Interdiction Operations (MIO) within the context of the NCMW concept of tactical collaborative planning. Both analytical and simulation-based queueing models were examined, and the theoretical model was applied parametrically to two MIO scenarios. Using the steady-state probability of target vessel interdiction (i.e., service) as the primary measure of effectiveness, the workshop was able to demonstrate the usefulness of queueing to relate NCMW application measures to force effectiveness. In addition, the queueing models provided valuable insight into the aspects of the MIO task where NCMW concepts might be applied. Thus, queueing is directly applicable to the second stage of analysis for operations that can be viewed as a demand for service, and provides direction in the process of refining NCMW concepts into testable applications. The parametric results from the workshop provide general bounds on expected improvements in effectiveness; however, specific results will depend upon the particular NCMW applications and how they are used., The original document contains color images. Presented at the 8th International Command and Control Research and Technology Symposium (ICCRTS 2003) held in Washington, DC on 17-19 2003. Published in the Proceedings of the 8th International Command and Control Research and Technology Symposium (ICCRTS 2003).

This study of school bullying provides an overview of the development of international anti-bullying initiatives, an in-depth analysis of the state of antibullying approaches in New Zealand and a description of the impact of such approaches on the behaviour in one secondary school community. Its findings endorse the use of effective, school-based, anti-bullying interventions, in particular, those developed in Scandinavia and Britain during the last twenty years. The efforts to combat bullying in New Zealand are reviewed. While some New Zealand programmes are found to be effective, the anti-bullying initiatives of the Ministry of Education and the Education Review Office are found wanting, as is their failure to respond effectively to the growing public concern over bullying. A number of anti-bullying interventions undertaken within one school community are evaluated. While generally found to reduce bullying, the limitations of these interventions became evident when one class group was viewed in greater depth in a study which discovered an entrenched bullying ‘culture’ and provided insights into the bullying dynamic. The communication difficulties experienced when a small number of powerful individuals capture the dynamics of power and abuse, and in effect establish the relationship style for the whole group, are then highlighted. As a result of the understandings gained through this classroom-based study, a number of conclusions are developed about the importance of the role played by leaders, both teacher and pupil.

info:eu-repo/semantics/published

We retrospectively studied 340 fit patients with multiple myeloma (MM) who underwent autologous stem cell transplantation (ASCT). We hypothesized that progression-free survival (PFS) of older patients was non-inferior to that of younger patients after ASCT. Our null hypothesis was that the PFS hazard ratio (HR) for a 5-year increase in age was ≥1.05; the alternative (non-inferiority) hypothesis was that the HR was ≤1. The observed HR was 0.94 (95% confidence interval [CI] 0.86-1.03); since the CI upper bound was <1.05, we reject the null hypothesis and conclude that PFS in older patients was at least as good as in younger patients. We cannot reject an analogous null hypothesis for overall survival (HR 1.06 [95% CI 0.94-1.19]), since the CI upper bound >1.05. Toxicity was similar across ages and transplant-related mortality was minimal. 28% of subjects <65 versus 45% of those ≥65 received maintenance therapy. In summary, ASCT prolongs PFS equally well in older vs. younger adults. Although we cannot exclude maintenance as a confounder, these data support ASCT for fit seniors with MM.

We retrospectively studied 340 fit patients with multiple myeloma (MM) who underwent autologous stem cell transplantation (ASCT). We hypothesized that progression-free survival (PFS) of older patients was non-inferior to that of younger patients after ASCT. Our null hypothesis was that the PFS hazard ratio (HR) for a 5-year increase in age was ≥1.05; the alternative (non-inferiority) hypothesis was that the HR was ≤1. The observed HR was 0.94 (95% confidence interval [CI] 0.86-1.03); since the CI upper bound was <1.05, we reject the null hypothesis and conclude that PFS in older patients was at least as good as in younger patients. We cannot reject an analogous null hypothesis for overall survival (HR 1.06 [95% CI 0.94-1.19]), since the CI upper bound >1.05. Toxicity was similar across ages and transplant-related mortality was minimal. 28% of subjects <65 versus 45% of those ≥65 received maintenance therapy. In summary, ASCT prolongs PFS equally well in older vs. younger adults. Although we cannot exclude maintenance as a confounder, these data support ASCT for fit seniors with MM.