Citations

Abstract Background: Outcomes in multiple myeloma (MM) have significantly improved, leading to higher prevalence of this disease. Increasing efforts have been made by various agencies to educate patients (pts), manage quality of life (QoL) and survivorship. A global impact of these efforts including pt awareness, disease knowledge and participation in their care, as well as the physical and emotional impact of MM and its treatments (Rx) has not been assessed. We undertook an international, pt-reported survey to investigate these factors and understand any underlying disparities. Methods: A 61-question patient-reported questionnaire (MM-Q), addressing global aspects of MM pts care (components in Figure 1) was used. MM-Q was administered in collaboration with the International Myeloma Foundation (IMF). To limit responses by MM pt only, “SmartPatient” MM community members and IMF Support Group Leader list were invited to complete the survey. Some of the questions were mandatory, and those with missing responses were withdrawn from the final analysis of that pts MM-Q. Categorical and continuous variables were compared among groups using the Chi-square and Kruskal-Wallis tests, respectively using SAS software (v9.3) with a two-sided significance level of 0.05. Results: Survey responses are available from 894/1240 (72%) individuals thus far. Average survey completion time was 16 minutes. Data from 746 MM-Q was included in this analysis with 466 (62.5%) complete responses. Pts from United States (US) represented 85.7% of the responders (majority from New York State). Ethnicity (n=590) was reported as non-Latino by 97%, race (n=580) was reported as White by 95%, family history of MM was reported by 19 pts and 81 reported prior history of a primary malignancy (most common, 37% non-melanoma skin cancer). Living situation questions (n=538) revealed majority were in a household of 2 (62%), were unemployed/on public assistance (53.5%), travelled alone to medical appointments (74%), with travel times varying from <30 min (55%) to >1 hr (17%). Majority (83%) had no prior knowledge of MM, 63% were patient support group members, and 92% did MM-related research on internet. With respect to MM Rx (n=524), 70% had been on Rx within 3 months and 12% reported non-compliance. Prior Rx included thalidomide (30%), lenalidomide (66%), pomalidomide (11.5%), bortezomib (63.5%), carfilzomib (11%), steroids (100%), and clinical trial participation in 25% pts. Side effects from Rx/QoL in prior 3 months (n=403) are summarized in figure 2. Pts satisfaction with Rx/treating staff (n=378) revealed majority felt their Rx to be effective (92%), right for them (87%) and side effects were as expected (84%). In general, pts acknowledged positive attributes of the Rx staff (worked towards same goal; 91%, participated in decisions; 81%, honesty 89%, confidence; 92%), and their doctor's explanations regarding Rx (benefits; 84%, side effects; 74%, test results; 83%), with the exception of emotional effects of Rx (48%). 94% pts rated their care as good/excellent and 95% were willing to participate in a follow-up survey. Stratification of statistically significant responses by geographical categories, age and time since diagnosis are shown in table 1 and analysis by occupation and educational status is ongoing. Conclusions: We conducted a large patient-reported survey to understand the current state of awareness among MM pts and a global impact of the diagnosis and its Rx on them. We showed that majority of pts who accessed the survey responded (72%), which may be a product of literacy, education and access to technology. Majority of the pts were White and non-Latino, highlighting the possible role of access and awareness in ethnic minorities. We report the large prevalence of psychophysical burden of MM and its Rx in MM pts. In general, MM pts had a high rate of satisfaction related to the Rx and their healthcare providers, but the frequency of discussion regarding emotional effects of Rx between doctors and pts was conspicuously low (48%) and the more recently diagnosed pts were less likely to be satisfied with their treating staff. We also demonstrated significant behavioral pattern differences in geographical, age and time-since-diagnosis subgroups, some of which may be sociocultural, while others may be a result of more patient awareness and understanding of the disease. This knowledge will be very helpful in devising MM survivorship strategies. Disclosures No relevant conflicts of interest to declare.

Abstract Abstract 602 Although, MM remains the most common indication for ASCT in the US, a controversy exists about the timing of ASCT. Since early ASCT (eASCT) versus delayed ASCT (dASCT) results in similar progression free survival (PFS) and overall survival (OS) in the novel agent era, economic assessment of one strategy over the other may help both clinicians and policy makers in establishing guidelines in the MM treatment paradigm. Here we designed a study to model a decision tree of both the strategies and estimate their cost-effectiveness. A decision tree was developed to compare the outcomes of ASCT in newly diagnosed transplant eligible MM patients after chemotherapy with novel drug lenalidomide which formed the base case. The survival data was obtained from our published data on eASCT versus dASCT in MM patients who underwent initial therapy with dexamethasone + immunomodulatory agents (IMiDs). The initial decision node on the decision tree model was dichotomized based on the cutoff of 12 months for eASCT versus dASCT. The probabilities of events during the length of follow up (60 months) period which formed our base case were: (a) eASCT cohort: Induction chemotherapy for median of 6 months - ASCT - median 30 months to relapse (drug free interval) followed by median therapy of 24 months for relapsed MM; (b) dASCT cohort: Median initial therapy for 36 months - ASCT - median 24 months to relapse (drug free interval). The cost analysis was done from a US third party payer perspective. The cost data for MM ASCT was obtained from the published data in which direct hospital costs were obtained from Nationwide Inpatient Sample and were converted to Medicare cost-to-charge ratio for urban hospitals. Chemotherapy cost consisted of actual drug costs that calculated based on average wholesale prices AWP (2008), costs of medical oncology visits, and the costs of managing adverse events. Post-ASCT maintenance costs were not included in the analysis. TreeAge Pro 2012 software was used to perform a static decision analysis. The outcomes were expressed in the units of health utility values obtained from phase III HOVON trial which measured quality of life (QoL) using EORTC QLQ-C30 & EuroQoL-5D. All scales and items were linearly transformed to range from 0 to 100. The utilities measured by the EuroQol-5D ranged from 0.40 before induction therapy to 0.70 after ASCT and translated to QALYs using area under the curve method. Using a Consumer Price Index (CPI), the costs of ASCT and chemotherapy were converted into 2012 US$. The robustness of the decision model was tested through univariate analyses and tornado diagram to identify those variables which if varied across clinically relevant measures may result in difference in outcomes. The expected cost of providing treatment to newly diagnosed MM patients for a period of 5 years when they undergo eASCT after induction with IMiDs was calculated to be $211,869. This was $52,454 less than the expected cost of undergoing dASCT. Patients who underwent eASCT had an expected benefit of 2.06 QALYs following treatment, which was 0.19 QALYs more than the patients who received dASCT. This implies that eASCT is preferred over (dominates) dASCT. One-way sensitivity analysis was undertaken to identify factors that were found to be most influential and included OS, overall response rate (ORR) and 1 year ASCT related mortality rate (TRM). Specifically, eASCT showed dominance even if the probability of OS was lowered to 52.1% from the actual case base of 65%, or the probability of ORR was lowered to ≥ 75.8% from the actual case base of 92%, or the probability of 1 year TRM was increased to 11.5% from actual case base of 2%, indicating the robustness of the model favoring cost effectiveness of eASCT. In absence of a survival benefit, the cost savings of early ASCT as measured by ICER would favor this approach, and it would help clinicians, patients, policy makers and third party payers in decision making. Future prospective studies in MM ASCT should incorporate economic and QOL components in the analysis and also focus on the added cost of post-ASCT maintenance therapies with respect to ICER and QALYs. Disclosures: No relevant conflicts of interest to declare.

Abstract Machine learning (ML) offers opportunities to advance pathological diagnosis, especially with increasing trends in digitalizing microscopic images. Diagnosing leukemia is time‐consuming and challenging in many areas globally and there is a growing trend in utilizing ML techniques for its diagnosis. In this review, we aimed to describe the literature of ML utilization in the diagnosis of the four common types of leukemia: acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and chronic myelogenous leukemia (CML). Using a strict selection criterion, utilizing MeSH terminology and Boolean logic, an electronic search of MEDLINE and IEEE Xplore Digital Library was performed. The electronic search was complemented by handsearching of references of related studies and the top results of Google Scholar. The full texts of 58 articles were reviewed, out of which, 22 studies were included. The number of studies discussing ALL, AML, CLL, and CML was 12, 8, 3, and 1, respectively. No studies were prospectively applying algorithms in real‐world scenarios. Majority of studies had small and homogenous samples and used supervised learning for classification tasks. 91% of the studies were performed after 2010, and 74% of the included studies applied ML algorithms to microscopic diagnosis of leukemia. The included studies illustrated the need to develop the field of ML research, including the transformation from solely designing algorithms to practically applying them clinically.

Abstract Presumably, reduced-intensity/nonmyeloablative conditioning (RIC/NMA) for allogeneic hematopoietic cell transplantation (alloHCT) results in reduced infections compared with myeloablative conditioning (MAC) regimens; however, published evidence is limited. In this Center for International Blood and Marrow Transplant Research study, 1755 patients (aged ≥40 years) with acute myeloid leukemia in first complete remission were evaluated for infections occurring within 100 days after T-cell replete alloHCT. Patients receiving RIC/NMA (n = 777) compared with those receiving MAC (n = 978) were older and underwent transplantation more recently; however, the groups were similar regarding Karnofsky performance score, HCT–comorbidity index, and cytogenetic risk. One or more infections occurred in 1045 (59.5%) patients (MAC, 595 [61%]; RIC/NMA, 450 [58%]; P = .21) by day 100. The median time to initial infection after MAC conditioning occurred earlier (MAC, 15 days [range, &lt;1-99 days]; RIC/NMA, 21 days [range, &lt;1-100 days]; P &lt; .001). Patients receiving MAC were more likely to experience at least 1 bacterial infection by day 100 (MAC, 46% [95% confidence interval (CI), 43-49]; RIC/NMA, 37% [95% CI, 34-41]; P = .0004), whereas at least a single viral infection was more prevalent in the RIC/NMA cohort (MAC, 34% [95% CI, 31-37]; RIC/NMA, 39% [95% CI, 36-42]; P = .046). MAC remained a risk factor for bacterial infections in multivariable analysis (relative risk, 1.44; 95% CI, 1.23-1.67; P &lt; .0001). Moreover, the rate of any infection per patient-days at risk in the first 100 days (infection density) after alloHCT was greater for the MAC cohort (1.21; 95% CI, 1.11-1.32; P &lt; .0001). RIC/NMA was associated with reduced infections, especially bacterial infections, in the first 100 days after alloHCT.

SummaryBone marrow damage is an important consequence of exposure to acute high‐dose whole‐body radiation. As such, haematologists can play an important role in managing this complication. However, these accident and incident scenarios are complex and often involve injuries to other organs and tissues from heat, projectiles and chemicals. In the case of a large‐scale event there will likely be severe infrastructure disruptions and injury or death to medical personnel. Accurate estimates of dose and uniformity of exposure are needed to intelligently direct appropriate interventions, which range from antibiotics, antifungals and anti‐virus drugs, molecularly‐cloned haematopoietic growth factors and, in rare instances, haematopoietic cell transplants. These therapies are ones that haematologists often use in the context of anti‐cancer therapy, especially therapy of haematological cancers like leukaemia. However, most haematologists have little knowledge of radiation biology and should consider updating this aspect of their expertise in continuing medical education. As in other areas of medicine, prevention is better than cure and haematologists should be active in decreasing risks of a nuclear war.

Abstract HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cy–based Haplo-HCT and 869 underwent MSD using calcineurin inhibitor–based graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs 7%), consistent with current practice. In multivariable analysis, Haplo-HCT and MSD groups were not different with regard to overall survival (P = .15), leukemia-free survival (P = .50), nonrelapse mortality (P = .16), relapse (P = .90), or grade II-IV acute GVHD (P = .98). However, the Haplo-HCT group had a significantly lower rate of chronic GVHD (hazard ratio, 0.38; 95% confidence interval, 0.30-0.48; P &lt; .001). Results of subgroup analyses by conditioning intensity and graft source suggested that the reduced incidence of chronic GVHD in Haplo-HCT is not limited to a specific graft source or conditioning intensity. Center effect and minimal residual disease–donor type interaction were not predictors of outcome. Our results indicate a lower rate of chronic GVHD after PT-Cy–based Haplo-HCT vs MSD using calcineurin inhibitor–based GVHD prophylaxis, but similar other outcomes, in patients with AML in CR1. Haplo-HCT is a viable alternative to MSD in these patients.

AbstractBackgroundThe occurrence of chemotherapy‐related adverse cutaneous reactions in the setting of capillary leak syndrome (CLS) is quite rare. Our objective was to identify the type of skin reactions associated with CLS.MethodsLeukemia or hematopoietic stem cell transplant patients between January 2010 and December 2017 were identified, and medical records were reviewed for a dermatology consultation occurring concomitantly with CLS.ResultsFive patients were identified, two with a diagnosis of toxic erythema of chemotherapy (TEC) and three others with a skin diagnosis of toxic epidermal necrolysis (TEN). Pathology of all patients was available for clinical‐pathologic confirmation.ConclusionsAlthough TEC is generally self‐limited, both TEC and TEN can present with severe adverse skin manifestations during CLS secondary to toxicity from chemotherapy.