Citations

Abstract Introduction: Allogeneic stem cell transplant is an intensive procedure, offered in a limited number of medical centres. We sought to describe how sociodemographic variables impacted access to transplant across the United States, and if disadvantaged populations had inferior access to transplant. Methods: Data from the Surveillance, Epidemiology and End Results Program (SEER) and the Center for International Blood and Marrow Transplant Research (CIBMTR) was integrated to determine the rate of unrelated donor transplantation between 2000 and 2010 in each of the 612 counties included in the SEER registry. Patients under the age of 65 with AML, ALL, and MDS were included, and the analysis was restricted to unrelated donors due to limited availability of ZIP code in CIBMTR data. New incident cases were determined from SEER, and the number of transplants was determined from CIBMTR. The transplant rate was calculated (transplants performed divided by incident cases) for each county. County attributes (percent minority, rural/urban status, percentage below the poverty line, and median family size) were obtained from US Census data. Poisson regression was used to describe how county attributes impacted transplant rates. Transplant rates were calculated separately for AML, White residents, and pediatric ALL. Results: 3147 patients were identified in the CIBMTR dataset that met inclusion criteria. The estimated ZIP code completeness was 75%. There were 30,468 new incident diagnoses of ALL, AML, and MDS. For AML, patients from rural areas (less than 20,000 residents) and patients from areas with higher poverty levels had lower transplant rates (Table 1). Minority status and family size did not impact transplant rate. In regression models, higher levels of poverty remained associated with lower transplant rates, while rurality did not (Table 2). The results were similar among White residents. In contrast, in pediatric ALL, no county attributes (poverty, rurality, percent minority, and family size) were significantly associated with a difference in transplant rate (Table 1). However, numbers of transplants were smaller, limiting power. Discussion: Patients with AML from disadvantaged areas had lower rates of unrelated donor transplant. While patients from disadvantaged areas were also more likely to be non-White, and non-White Americans are less likely to have an available unrelated donor, this difference was also seen in White Americans from disadvantaged areas. This suggests the lower transplant rate is due impaired access to transplant. Poverty rate was the most important predictor of transplant rate. The results of this study suggest that improving access to transplant in disadvantaged populations should be a priority for health care administrators. Based on these results, approximately 2500 Americans do not undergo allogeneic transplant annually due to inferior access associated with higher poverty rates. Table 1 Univariate Analysis Table 1. Univariate Analysis Table 2 Acute Myeloid Leukemia, Regression Model * Metropolitan = county > 50,000 people, micropolitan = county > 20,000, rural county < 20,000. Table 2. Acute Myeloid Leukemia, Regression Model. / * Metropolitan = county > 50,000 people, micropolitan = county > 20,000, rural county < 20,000. Disclosures Hahn: Novartis: Equity Ownership; NIH: Research Funding.

Abstract #the authors contributed equally to this work While survival outcomes after HLA-matched unrelated donor (URD) blood and marrow transplant (BMT) have significantly improved over the last two decades, about 40% of patients die before 1-year post URD BMT. Previously we performed a genome-wide association study (GWAS) named DISCOVeRY-BMT (Determining the Influence of Susceptibility COnveying Variants Related to one-Year mortality after BMT) to investigate the contributions of common genetic variants on survival outcomes. To address the specific contributions of low frequency (≤ 1%) exonic variants on survival outcomes, we used the DISCOVeRY-BMT cohorts typed with the Illumina HumanExome BeadChip containing 242,901 variants, which are mainly protein-coding variants. We used a gene-based test (the optimal sequence kernel association test (SKAT-O)) to evaluate the cumulative effects of multiple genetic variants within a gene on overall survival (OS), transplant-related mortality (TRM), and disease-related mortality (DRM) 1 year after URD BMT. SKAT-O measures the overall significance of the gene and allows the variants to have different directions and magnitude of effects. We used a 2-stage study design: SKAT-O analysis was carried out in Cohort 1 consisting of 1,972 AML, ALL or MDS patients reported to the Center for International Blood and Marrow Transplant Research from 2000 to 2008 and their 2,006 10/10 HLA-matched URD. Genes with a suggestive association with each outcome (P < 1×10-3) entered the final meta-analysis including Cohort 1 and an independent cohort (Cohort 2), consisting of 503 recipients and 520 10/10 HLA-matched URD from 2009 to 2011. The analysis included recipients and URD of European descent due to the low frequency of other populations. All association models included age at BMT, diagnosis (AML, ALL, MDS), disease status at BMT, cell source (peripheral blood, marrow), year of BMT, and principal components from EIGENSTRAT to control for population stratification. Only coding variants (missense and nonsense) with minor allele frequency ≤ 1% were included in our analysis, which resulted in > 12,000 genes tested in our gene-based analysis in recipients and donors. Exome-wide significance was set at Pmeta< 4.10×10-6 after Bonferroni correction for the total number of genes tested. The likely pathogenicity of these variants was determined in silico using SIFT and PolyPhen. In recipients, we identified OR51D1, a member of the olfactory receptor gene family, as significantly associated with both OS and TRM. The OS association with ORD51D1 is driven by TRM as the same six missense variants contribute to both TRM and OS, but not to DRM. In donors, four (ALPP, EMID1, SLC44A5, LRP1), one (HHAT), and two (LYZL4, NT5E) genes were significantly associated with OS, TRM, and DRM, respectively (Table). ALPP encodes an alkaline phosphatase. SLC44A5 is a member of the solute carrier gene family. LRP1 (low density lipoprotein receptor-related protein 1) encodes an endocytic receptor involved in several cellular processes, including intracellular signaling, lipid homeostasis, and clearance of apoptotic cells. HHAT encodes an enzyme that acts within the hedgehog secretory pathway, which is involved in hematologic malignancy. LYZL4 is a member of a family of lysozyme-like genes, which have a protective role in host defense. The encoded protein of NT5E, CD270, is used as a determinant of lymphocyte differentiation. The likely pathogenicity of several of the functional variants in all significant genes identified was predicted to be both (possibly or probably) damaging and deleterious (Table), thus indicating that the amino acid substitution of the variant may not be well tolerated. One damaging variant in LRP1 has been identified as a somatic mutation in hematopoietic and lymphoid tissue. Our study is the first analysis of the low-frequency coding variant contribution to URD BMT survival outcomes. We found that the missense variants contributing to many of these significant gene associations shows evidence of pathogenicity and thus it is biologically plausible these variants are contributing to survival outcomes. Further confirmation of these findings, and studies of the functional consequences of protein-coding changes in these genes, may provide more individualized risk prediction and prognosis as well as alternative donor selection strategies. Table. Table. Disclosures McCarthy: Gamida Cell: Honoraria, Membership on an entity's Board of Directors or advisory committees; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; The Binding Site: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hahn:Novartis: Equity Ownership; NIH: Research Funding. Sucheston-Campbell:NIH/NCI: Research Funding.

Abstract Over the past decade, there have been numerous published candidate gene association studies of non-HLA variants, genes and/or pathways in relation to BMT survival outcomes. Most of these studies investigated a small number of candidate single nucleotide polymorphisms (SNPs), chosen based on known gene function, in a limited number of cases without replication. Here we test the association of previously reported SNPs with survival outcomes (overall survival (OS), progression-free survival (PFS), death due to disease (DD) or transplant-related mortality (TRM)) after URD BMT using data from the DISCOVeRY-BMT (Determining the Influence of Susceptibility Conveying Variants Related to one-Year mortality after BMT) study which included 2,052 European descent recipient-unrelated donor pairs (Cohort 1) and 763 recipient-unrelated donor pairs (Cohort 1) reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) between 2000-2009 and 2009-2011, respectively. DISCOVeRY-BMT is a Genome Wide Association Study (GWAS) that includes over 9 million typed or imputed SNPs. This represents the largest study to date and is well powered to test both SNP and gene-based association hypotheses. We conducted an extensive literature review of PubMed using MESH terms related to transplant and hematologic disease which yielded 76 candidate gene association studies that investigated a total of 46 genes with any survival outcome. Of the 46 genes, 11 genes (CTLA4, CYP2B6, CYP2C19, GSTM1, GSTT1, IL23R, IL6, MTHFR, NOD2/CARD15, TNFSRF1B, and VDR) were studied in at least 2 publications. A total of 16 SNPs in 8 of these genes reported a significant (P< 0.05) association with at least one survival outcome (OS, PFS, DD or TRM). We tested these 16 SNPs for an association with the survival outcome originally reported in each article (Table 1). All association models included age at BMT, diagnosis (AML, ALL, MDS), disease status at BMT, cell source (blood, bone marrow) and year of BMT. P-values from Cohorts 1 and 2 were combined using a fixed-effects model in METAL software. Since the candidate gene studies have a gene-based hypothesis, we also performed gene-level testing using the VErsatile Gene-Based Association Study (VEGAS2) software to measure the aggregate effect of all available typed and imputed SNPs from our GWAS data in these 8 genes. The candidate gene association studies included heterogeneous patient populations of autologous and/or allogeneic (related or unrelated donors) BMT for a variety of hematologic diseases. Most candidate gene studies performed genotyping on both donors and recipients, and SNPs were tested either independently for donor or recipient genomes, or considering the total number of variant alleles the recipient-donor pair had at a given locus (0-4) (Table 1). The 16 SNPs from the previous candidate gene association studies were not significantly associated at a nominal P<0.05 to either the survival outcome reported in the original published paper, or to any survival outcome (Table 1). Likewise, the VEGAS2 gene-based analysis did not reveal any statistically significant associations for any of the 8 genes at P<0.05. Our study also corroborated prior reports of SNPs and genes that were not associated with survival outcomes. Candidate gene association studies use a priori biological knowledge to select genes that are likely associated with outcome and subsequently SNPs within the gene thought likely to affect function based on knowledge at the time of the investigation. Our findings suggest that neither the genetic variation tested in these candidate genes, nor other individual SNPs in the gene independently or collectively are not associated with survival outcomes in recipients of URD BMT. Our failure to replicate the prior candidate gene studies may be due to these SNPs being dependent on the underlying disease (ie. AML, ALL, etc), the donor relation (related, unrelated, autologous), or that there is no true association of these SNPs with the outcomes studied. #These authors contributed equally Table 1. Table 1. Disclosures McCarthy: Gamida Cell: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; The Binding Site: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hahn:Novartis: Equity Ownership; NIH: Research Funding. Sucheston-Campbell:NIH/NCI: Research Funding.

Abstract Background: Sickle cell anemia (SCA) is a genetically inherited disorder that can lead to severe sequelae in any organ system. The most clinically devastating complications, e.g. stroke, are managed with chronic red blood cell (RBC) transfusions as curing the underlying SCA is often not an option. Chronic RBC exchange (RBCx), is an effective alternative to simple transfusions and often performed every 4-5 weeks. Isovolemic Hemodilution-Red Blood Cell Exchange (IHD-RBCx) is a modified RBCx method used at UT Southwestern Medical Center (UTSW) and increases the time interval between transfusions, i.e. inter-procedure interval (IPI), up to 9 weeks while maintaining the desired hemoglobin S targets at safe levels. This minimizes the overall lifetime procedures and blood exposures. The standard operating procedure for IHD-RBCx is published (Matevosyan et al, 2012). However, we observed IPI variability between patients in this chronic IHD-RBCx program. We sought to analyze hematologic characteristics in a cohort of adult SCA patients that may be associated with this noted variability. Methods: This IRB approved cross-sectional study evaluated medical and blood bank records of adult patients with SCA, i.e. hemoglobin SS or Sβ0 thalassemia genotypes, undergoing chronic IHD-RBCx at UTSW adult hospital sites between January 1, 2012 and December 31, 2013. Excluded participants were those with autoimmune disease, non-compliance with IHD-RBCx leading to delays > 7 days, or use of hydroxyurea or steroids within four months of the study period. Patients with < 5 exchanges were excluded as several procedures are needed to determine baseline IPIs. The primary indication for IHD-RBCx was secondary stroke prevention. Three subjects had alternative indications (i.e. recurrent severe acute chest syndrome that failed hydroxyurea therapy, intractable pain and severe anemia ineligible for iron chelation due to end-stage renal disease). Median values during the 2 year study were determined for the IPI, laboratory, and RBC properties for use in subsequent analyses. Correlation and multiple regression analyses were performed to determine variables predictive of IPI. Results: Twenty-four SCA patients in this chronic IHD-RBCx transfusion program met inclusion criteria of which 14 (58.3%) were female with age range 18-41 years. Three subjects had incomplete data. The median number of packed RBC (pRBC) units per IHD-RBCx was 8 (range: 6-11 units). The median volume per unit of pRBCs was 304.5 mL (range: 298.8-326.5 mL) with average age of the pRBCs 5.8 days ± 0.7 days. The median IPI was 55.8 days (range: 36.0-65.5 days). The strongest correlation with IPI was the change from the mid to post-procedure hemoglobin and hematocrit values, r=0.56, p=0.005 and r=0.57, p=0.003, respectively. Participants with documented direct antiglobulin test positivity (n=7), compared to those who remained negative (n=16), had 4.9 days increased IPI. This difference was not statistically significant, p=0.19. ABO differences in blood type also did not show statistical significant differences. However, A+ subjects had a 58 day interval compared to 51, 52, 53 days for B+, O+, O- respectively (Figure). In multiple regression models, log blood urea nitrogen (BUN) and post-procedure white blood cell count (WBC) were found to be independent predictors of IPI, beta=-11.3, p=0.04 and -2.1, p=0.03 respectively, with adjusted R2=0.31. Conclusions: Chronic IHD-RBCx effectively treats severe SCA complications. Discontinuing transfusions lead to repeat stroke events or the recurrence of disease manifestations making chronic transfusion programs an indefinite therapy. Outside of the expected correlation between the IPI and hemoglobin/hematocrit, WBC and BUN were found to have negative associations with IPIs. The decrease in WBCs is likely due to the direct clearing effect by the operating system. The association between BUN and IPI may imply relationship with renal function. Interestingly, association with creatinine was not statistically significant. The study is limited by the small sample size. Future studies of similar cohorts should prospectively evaluate target mechanisms which may lead to interventions that can minimize lifetime blood exposures given the growing demands for continued RBCx in severe SCA. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Key PointsIKZF1 associations with high-risk B-ALL may differ by age and sex. A novel variant on chromosome 14, rs189434316, is associated with over a 3.5-fold risk of normal cytogenetic B-ALL.

Abstract BACKGROUND: Azacitidine and decitabine are indicated for the first line treatment of intermediate and high risk MDS. About 40% to 47% of patients respond to 1st line hypomethylating agents. The median duration of response is 13 months. There are no effective therapies for patients who fail to respond to or progress on hypomethylating agents. A phase II trial of high dose lenalidomide (50mg/day) induction therapy followed by low dose (10mg/day) maintenance therapy in elderly patients with AML had demonstrated a high CR/CRi of 30%. CR was restricted to patients with presenting WBC counts <10000/µL, peripheral blast counts <1000/ µL and < 30%, many of whom could have been classified as having MDS rather than AML by FAB criteria. With the rationale that MDS and AML represent a continuum of disease, and the promising results in AML we aimed to assess the clinical activity of high dose lenalidomide by conducting a clinical trial of high dose Lenalidomide induction followed by low dose maintenance in patients with hypomethylating agent refractory MDS. METHODS: We conducted an open label, single arm, multi-center phase II trial of high dose lenalidomide induction (50mg/day for two 28 day cycles) followed by low dose lenalidomide maintenance therapy (10mg/day for 12 cycles) for patients with MDS (as defined by FAB criteria) refractory to hypomethylating agents. Patients who had failed to show CR, PR or HI (hematological improvement) after at least 6 cycles of azacytidine or decitabine or who had progressed on treatment were considered eligible. Patients were enrolled in a Simon's optimal two-stage design with an intended sample size of 43. The primary endpoint was proportion of confirmed responses (CR, PR or HI), as defined by international working group criteria, during the 14 cycles of treatment. RESULTS: 24 patients were enrolled in the first stage of the study. 16 patients completed at least one cycle of therapy and were considered evaluable for efficacy. Efficacy: Characteristics and outcomes of patients are detailed in Table 1. There were no complete or partial remissions. Marrow complete remission (MCR) was seen in 8/16 patients (50%). One of the 8 patients with a MCR had 5q- karyotype; 3/8 had trisomy 8 and one patient had a complex karyotype with monosomy 7. Median duration of MCR was 70 days (range 28-336 days). MCR lasted beyond the high dose induction period in 2 patients, one of whom had a 5q interstitial deletion (112 days) and one patient with trisomy 8 (336 days). Hematologic improvement (HI) was seen in 2/16 patients (12.5%) (Refer to table below). Toxicity: ≥grade 3 toxicities included pneumonia (12/24, 50%), sepsis (4/24, 17%), febrile neutropenia (8/24, 33%), rash (2/24, 8%), thromboembolic event (1/24), MI (1/24), new cancer -mammary analogue salivary carcinoma- (1/24). TABLE 1 Pt No: Age IPSS Prior cycles of 5-aza/ decitabine Cycles of Lenalidomide Reason off trial Best Response 1 69 1.5 2 4 Pancytopenia MCR 2 78 3 8 1 Death-Unrelated SD 3 73 2 7 1 Consent withdrawn SD 4 87 2 14 12 Progression MCR, HI-p&n 6 72 2 13 2 Thrombocytopenia MCR 7 69 2 13 1 PE SD 8 75 1 7 2 New Cancer MCR 9 74 1 4 3 Progression SD 10 75 2 0 2 Progression SD 11 72 1 13 3 Thrombocytopenia MCR 12 75 3 6 1 Progression PD 13 78 1 9 3 Gr3 Fatigue MCR 14 70 0 19 2 Progression MCR, HI-p 15 72 1 23 1 Progression PD 16 73 1 8 2 Gr 3 fatigue MCR CONCLUSIONS: High dose lenalidomide followed by standard dose maintenance in hypomethylating agent refractory MDS resulted in a marrow complete remission rate of 50% and hematological improvement rate of 12.5%. Future protocols should explore whether an extended schedule of intermittent dosing of high dose lenalidomide would allow for improved efficacy with acceptable toxicity. Disclosures Off Label Use: Lenalidomide is used in this study in patients with MDS both with and without deletion 5q.Use in patients without deletion 5q is off label use.. Tibes:Tetralogic Pharmaceuticals: Research Funding. Stockerl-Goldstein:Celgene: Speakers Bureau. Jacoby:Norvo Nordisk: Consultancy. Cashen:Celgene: Speakers Bureau. Vij:Onyx: Honoraria, Research Funding; Sanofi: Honoraria; Jannsen: Honoraria; Novartis: Honoraria; Millennium: Honoraria; Celgene: Honoraria, Research Funding.

Abstract Background: The association of clinical trial participation with outcomes in cancer patients is controversial, with some studies reporting better outcomes for trial participants while others do not. It is possible that the difference in outcomes is due to differences in baseline characteristics of participants and non-participants. The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 trial was a large randomized, multi-center study comparing peripheral blood (PB) with bone marrow (BM) for hematopoietic cell transplantation (HCT) from HLA-matched or 1 allele mismatched unrelated donors (URD) in patients with acute leukemia, chronic myeloid leukemia and myelodysplastic syndromes. The trial reported no significant survival differences between PB and BM; there was decreased risk of graft failure but increased risk of chronic graft-versus-host disease (GVHD) with PB grafts (Anasetti et al NEJM 2012). Methods: We compared characteristics of BMT CTN 0201 study participants (n=494) with HCT recipients who did not participate on the trial (n=1384) but were potentially eligible by virtue of known characteristics. These patients received similar conditioning and GVHD prophylaxis as trial participants at 38 United States trial centers during the study time-period. Centers that had no eligible non-trial participants were excluded. Outcomes between patients on and off trial were compared using Cox proportional hazards regression models. Data were obtained from the Center for International Blood and Marrow Transplant Research (CIBMTR) that collects patient data on all trial and non-trial allogeneic HCT recipients through its registry function. Results: Approximately 29% [494/1878] of apparently eligible patients were randomized and analyzed as part of the trial. There were no significant differences between study participants and non-participants in age or sex distribution, disease types, HLA or sex matching, comorbidities, or interval from diagnosis to HCT. Higher proportions of non-participants were Hispanic, had a lower performance status and lower disease risk, and received myeloablative conditioning and antithymocyte globulin (ATG) or Campath than the study participants. PB was used more commonly as the graft source in the non-participants as compared to the study participants (65% vs. 50%, p<0.001). In multivariate models, overall mortality (HR 1.09, 95% CI 0.95-1.25, p=0.22), transplant-related mortality (HR 1.08, 95% CI 0.89-1.32, p=0.42) and risks of acute grade II-IV (HR 0.96, 95% CI 0.82-1.12, p=0.57) and chronic GVHD (HR 1.06, 95% CI 0.92-1.23, p=0.41) were comparable between study non-participants and participants. Non-participants were at higher risk for relapse than participants (HR 1.24, 95%CI 1.04-1.49, p=0.02) in the multivariate analysis adjusted for disease risk and other clinical variables. Center effect was examined and was not found to be significant (p=0.10). There was no significant interaction between graft source and trial participation (P=0.22) and the risk of mortality was comparable for BM (HR 0.99, 95% CI 0.80-1.22, p=0.90) and PB recipients (HR 1.17, 95% CI 0.97-1.41, p=0.09) whether on trial or off trial. (Figure) Conclusion: Approximately 29% of patients who appeared eligible and were treated with conditioning and GVHD prophylaxis regimens allowed on the trial were enrolled. Despite some differences in clinical characteristics, most of the outcomes of non-trial participants were comparable to trial participants, suggesting that there is no definitive evidence that the outcomes of patients in a clinical trial are superior to those of the non-participants treated in a similar fashion. The comparable outcomes also indicate that the results of this trial were not seriously affected by selection bias and are therefore representative of the larger population. Figure 1: Adjusted overall survival in BMT CTN 0201 trial participants and non-participants Figure 1:. Adjusted overall survival in BMT CTN 0201 trial participants and non-participants Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years from diagnosis. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. The best outcomes are observed in patients whose primary treatment includes complete resection of all visible disease plus combination platinum-based chemotherapy. Research efforts are focused on primary neoadjuvant treatments that may improve resectability, as well as systemic therapies providing improved long-term survival. These NCCN Guidelines Insights focus on recent updates to neoadjuvant chemotherapy recommendations, including the addition of hyperthermic intraperitoneal chemotherapy, and the role of PARP inhibitors and bevacizumab as maintenance therapy options in select patients who have completed primary chemotherapy.

ABSTRACT Here, we show that cells expressing the adherens junction protein nectin-1 capture nectin-4-containing membranes from the surface of adjacent cells in a trans-endocytosis process. We find that internalized nectin-1–nectin-4 complexes follow the endocytic pathway. The nectin-1 cytoplasmic tail controls transfer: its deletion prevents trans-endocytosis, while its exchange with the nectin-4 tail reverses transfer direction. Nectin-1-expressing cells acquire dye-labeled cytoplasmic proteins synchronously with nectin-4, a process most active during cell adhesion. Some cytoplasmic cargo remains functional after transfer, as demonstrated with encapsidated genomes of measles virus (MeV). This virus uses nectin-4, but not nectin-1, as a receptor. Epithelial cells expressing nectin-4, but not those expressing another MeV receptor in its place, can transfer infection to nectin-1-expressing primary neurons. Thus, this newly discovered process can move cytoplasmic cargo, including infectious material, from epithelial cells to neurons. We name the process nectin-elicited cytoplasm transfer (NECT). NECT-related trans-endocytosis processes may be exploited by pathogens to extend tropism. This article has an associated First Person interview with the first author of the paper.

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.