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Objetivo: Analizar la relación entre los síntomas depresivos y la prevalencia de fragilidad medida como fenotipo de fragilidad. Material y métodos: Este es un estudio secundario de la encuesta SABE Colombia 2015. Se utilizaron las puntuaciones de la escala Yesavage como variable independiente, la prevalencia de fragilidad calculada con el fenotipo de fragilidad de Fried. Realizamos un análisis descriptivo y bivariado de la muestra, seguido de un análisis multivariado ajustando por variables de confusión. Resultados: Analizamos información de un total de 19,004 participantes mayores de 60 años, participantes sin deterioro cognitivo de la encuesta, a quienes se les administró la escala Yesavage. La media de edad fue 69.25 años, el 56% de los participantes eran mujeres, la prevalencia de fragilidad fue del 12% y se encontró síntomas depresivos en 57,4% de la muestra. En el análisis multivariado encontramos asociaciones estadísticamente significativas entre las puntuaciones más altas de la escala Yesavage y la presencia de fragilidad (Yesavage 5-10) OR 1.20 (0.98-1.46) p valor 0.066 y (Yesavage >10) 2.05 (1.46-2.89)

Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P = .01; HR, 1.71; P < .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P = .002, and HR, 1.47; P < .001), as was overall survival (HR, 1.32; P < .001, and HR, 1.45; P < .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.

Does geriatric syndrome have an association with subclinical hypothyroidism. This study showed a greater incidence of GS in subjects 50 years and older with sub-clinical hypothyroidism, when compared to those with normal thyroid function. Endocrine assessment should be taken in account in frail individuals as part of an integral evaluation for patients. To determine the incidence of geriatric syndromes (GS) in community dwelling older adults with subclinical hypothyroidism. This is an analysis from the Mexican Health and Aging Study, of a subsample of 2089 subjects with TSH determination. From this last subsample, we included 1628 individuals with TSH levels in the subclinical range (4.5–10 µU/ml). The multivariate analysis showed that when comparing data obtained from the 2012 wave with the 2015 wave results, there was a significant incidence of some GS such as falls (OR 1.79, CI 1.16–2.77, p = 0.0116), fatigue (OR 2.17, CI 1.40–3.38, p = 0.0348) and depression (OR 1.70, CI 1.06–2.71, p = 0.0246) among the subclinical hypothyroidism group. This study showed a greater incidence of GS in subjects 50 years and older with sub-clinical hypothyroidism, when compared to those with normal thyroid function.

Epstein-Barr virus (EBV) reactivation and EBV-related post-transplantation lymphoproliferative disorder (PTLD) are often fatal complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The risk of EBV reactivation may be mitigated by depletion of B cells with rituximab. Starting in January 2020, allo-HSCT recipients undergoing T-cell depletion with alemtuzumab received 1 dose of rituximab before transplantation. The objective of this study was to evaluate the cumulative incidence of EBV reactivation and EBV-PTLD in recipients of allo-HSCT and in vivo T-cell depletion with alemtuzumab who received pre-HSCT rituximab compared to patients who did not. This was a single-center retrospective analysis of adult patients who consecutively received an HLA-identical allo-HSCT between January 2019 and May 2021 and in vivo T-cell depletion with alemtuzumab. Patients were included in the rituximab cohort if they received rituximab within 6 months before their transplantation. The primary endpoint was incidence of EBV reactivation at day 180 among those receiving pre-HSCT rituximab versus those not receiving rituximab. Secondary endpoints included cumulative incidence of EBV-PTLD at 1 year, time to engraftment, immune reconstitution, and incidence of infections and acute graft-versus-host disease (aGVHD) at day 180. Eighty-six consecutive patients who received an allo-HSCT with alemtuzumab T-cell depletion were reviewed; 43 patients who received pre-HSCT rituximab after our protocol modification were compared to 43 patients who did not receive pre-HSCT rituximab before this change. Median age was 57 (interquartile range [IQR] 40-69) years, and the majority of patients had acute myeloid leukemia or myelodysplastic syndrome. Baseline characteristics were similar between the cohorts. EBV reactivation at day 180 occurred in 23 (53%) patients without prior rituximab exposure versus 0 patients with pre-HSCT rituximab exposure (P.0001). Similarly, 6 patients without prior rituximab exposure developed PTLD at 1 year compared to no cases of PTLD among patients receiving pre-HSCT rituximab. There was no difference in neutrophil engraftment, incidence of infections, or aGVHD at day 180 between the 2 cohorts. There was a delay in time to platelet engraftment in the rituximab cohort (median 16 [IQR 15-20] days versus 15 [IQR 14-17] days; P = .04). Administration of pre-HSCT rituximab before allo-HSCT in patients receiving T-cell depletion with alemtuzumab was associated with a significant decrease in the risk for EBV reactivation and EBV-PTLD, without increasing aGVHD or infection rates.

Background Levofloxacin prophylaxis is recommended to prevent gram-negative bloodstream infections (BSIs) in patients with prolonged chemotherapy-induced neutropenia. However, increasing fluoroquinolone resistance may decrease the effectiveness of this approach. Methods We assessed the prevalence of colonization with fluoroquinolone-resistant Enterobacterales (FQRE) among patients admitted for hematopoietic cell transplantation (HCT) from November 2016 to August 2019 and compared the risk of gram-negative BSI between FQRE-colonized and noncolonized patients. All patients received levofloxacin prophylaxis during neutropenia. Stool samples were collected upon admission for HCT and weekly thereafter until recovery from neutropenia, and underwent selective culture for FQRE. All isolates were identified and underwent antimicrobial susceptibility testing by broth microdilution. FQRE isolates also underwent whole-genome sequencing. Results Fifty-four of 234 (23%) patients were colonized with FQRE prior to HCT, including 30 of 119 (25%) allogeneic and 24 of 115 (21%) autologous HCT recipients. Recent antibacterial use was associated with FQRE colonization (P = .048). Ninety-one percent of colonizing FQRE isolates were Escherichia coli and 29% produced extended-spectrum β-lactamases. Seventeen (31%) FQRE-colonized patients developed gram-negative BSI despite levofloxacin prophylaxis, compared to only 2 of 180 (1.1%) patients who were not colonized with FQRE on admission (P Conclusions Nearly one-third of HCT recipients with pretransplant FQRE colonization developed gram-negative BSI while receiving levofloxacin prophylaxis, and infections were typically caused by their colonizing strains. In contrast, levofloxacin prophylaxis was highly effective in patients not initially colonized with FQRE.

Allogeneic hematopoietic cell transplantation (alloHCT) for multiple myeloma (MM), with its underlying graft-versus-tumor capacity, is a potentially curative approach for high-risk patients. Relapse is the main cause of treatment failure, but predictors for postrelapse survival are not well characterized. We conducted a retrospective analysis to evaluate predictors for postrelapse overall survival (OS) in 60 MM patients who progressed after myeloablative T cell-depleted alloHCT. The median patient age was 56 years, and 82% had high-risk cytogenetics. Patients received a median of 4 lines of therapy pre-HCT, and 88% achieved at least a partial response (PR) before alloHCT. Of the 38% who received preemptive post-HCT therapy, 13 received donor lymphocyte infusions (DLIs) and 10 received other interventions. Relapse was defined as very early ( 24 months; 22%). At relapse, 27% presented with extramedullary disease (EMD). The median postrelapse overall survival (OS) by time to relapse was 4 months for the very early relapse group, 17 months for the early relapse group, and 72 months for the late relapse group (P = .002). Older age, relapse with EMD

Covid-19 vaccination is recommended in allogeneic transplant recipients, but many questions remain regarding its efficacy. Here we studied serologic responses in 145 patients who had undergone allogeneic transplantation using in vivo T-cell depletion. Median age was 57 (range 21-79) at transplantation and 61 (range 24-80) at vaccination. Sixty-nine percent were Caucasian. One third each received transplants from HLA-identical related (MRD), adult unrelated (MUD), or haploidentical-cord blood donors. Graft-versus-host disease (GVHD) prophylaxis involved in-vivo T-cell depletion using alemtuzumab for MRD or MUD transplants and anti-thymocyte globulin for haplo-cord transplants. Patients were vaccinated between January 2021 and January 2022, an average of 31 months (range 3-111 months) after transplantation. Sixty-one percent received the BNT162b2 (bioNtech/Pfizer) vaccine, 34% received mRNA-1273 (Moderna), and 5% received JNJ-78436735 (JohnsonJohnson). After the initial vaccinations (2 doses for BNT162b2 and mRNA-1273, 1 dose for JNJ-7843673), 124 of the 145 (85%) patients had a detectable SARS-CoV-2 spike protein (S) antibody, and 21 (15%) did not respond. Ninety-nine (68%) had high-level responses (≥100 binding antibody units [BAU]/mL)m and 25 (17%) had a low-level response (100 BAU/mL). In multivariable analysis, lymphocyte count less than 1 × 10

Resumen Dentro de los principales desafíos relacionados con el envejecimiento se encuentran la fragilidad y el deterioro cognitivo, condiciones que se han relacionado con aumento en la declinación funcional, la discapacidad y el deterioro en la calidad de vida. Durante los últimos años se ha demostrado la relación bidireccional entre estas dos condiciones clínicas y dentro del Grupo de Consenso Internacional en Toulouse, Francia, surgió el término fragilidad cognitiva, en el 2013. Ese estado reversible se ha considerado un nuevo síndrome geriátrico, caracterizado por la coexistencia entre fragilidad física y deterioro cognitivo; sin embargo, aún sin criterios diagnósticos definidos. El objetivo es realizar una aproximación de la definición, fisiopatología, herramientas diagnósticas y su respectiva asociación con desenlaces adversos, para realizar un diagnóstico oportuno y aplicar intervenciones multidominio centradas en la actividad física, el enfoque nutricional y el entrenamiento cognitivo, que puedan modificar el curso de este estado dinámico y reversible, previniendo el deterioro funcional y mejorando la calidad de vida de las personas mayores. Abstract The main challenges facing the increase of elderly population are the frailty and cognitive impairment, which are related to increasing disability, worse quality of life and cognitive decline. During the last years, it has been proved the two-way relationship between frailty and cognitive impairment, hence the concept cognitive frailty emerged by an international consensus group on 2013 in Toulouse (France). This reversible stage has been considered a new geriatric syndrome characterized by the coexistence between physical frailty and cognitive impairment, however, there is no consensus regarding diagnostic criteria. The objective of this study is to make an approach to the definition pathophysiology, and diagnostic instruments, and their respective association with adverse outcomes, to make an opportune diagnosis and apply multi-domain interventions focused on physical activity, nutritional focus and cognitive training, which can modify the course of this dynamic and reversible state by preventing functional impairment and improving the quality of life for the elderly.

Tuberculosis (TB) is a pathology prevalent at a global level in our society, the elderly population being one of the most susceptible to develop it given the presence of special conditions such as: immunosenescence, pluripatology, polypharmacy, malnutrition, among others. The case of an elderly patient who is admitted to the emergency department due to clinical deterioration secondary to altered state of consciousness is presented below. Primary causes such as TBI, bleeding or cerebral ischemic events and seizure status are ruled out. Upon interrogation, long-standing respiratory symptoms were found with radiographic findings of tuberculosis, confirmed by chest CT, with subsequent neuroinfection findings given the persistence of altered state of consciousness and the report of lumbar puncture.

Allogeneic hematopoietic cell transplantation (alloHCT) for multiple myeloma (MM), with its underlying graft-versus-tumor capacity, is a potentially curative approach for high-risk patients. Relapse is the main cause of treatment failure, but predictors for postrelapse survival are not well characterized. We conducted a retrospective analysis to evaluate predictors for postrelapse overall survival (OS) in 60 MM patients who progressed after myeloablative T cell-depleted alloHCT. The median patient age was 56 years, and 82% had high-risk cytogenetics. Patients received a median of 4 lines of therapy pre-HCT, and 88% achieved at least a partial response (PR) before alloHCT. Of the 38% who received preemptive post-HCT therapy, 13 received donor lymphocyte infusions (DLIs) and 10 received other interventions. Relapse was defined as very early (6 months; 28%), early (6 to 24 months; 50%), or late (24 months; 22%). At relapse, 27% presented with extramedullary disease (EMD). The median postrelapse overall survival (OS) by time to relapse was 4 months for the very early relapse group, 17 months for the early relapse group, and 72 months for the late relapse group (P = .002). Older age, relapse with EMD,PR before alloHCT,PR by day +100, and no maintenance were prognostic for inferior postrelapse OS on univariate analysis. On multivariate analysis adjusted for age and sex, very early relapse (hazard ratio [HR], 4.37; 95% confidence interval [CI], 1.42 to 13.5), relapse with EMD (HR, 5.20; 95% CI, 2.10 to 12.9), and DLI for relapse prevention (HR, .11; 95% CI, 2.10 to 12.9) were significant predictors for postrelapse survival. Despite their shared inherent high-risk status, patients with MM have significantly disparate post-HCT relapse courses, with some demonstrating long-term survival despite relapse.

Introduction: Acute myeloid leukemia (AML) is heterogenous disease with a range of cytogenetic and molecular changes. Several molecular mutations identified in AML patients at diagnosis have prognostic implications and play important roles in guiding induction and consolidative treatment decisions. The prognostic impact of mutations peri allogeneic stem cell transplant are less well characterized. In this study, we examine the significance of pre and by D100 Post-transplant mutation status in AML patients underwent Fludarabine/Melphalan conditioned reduced intensity allogeneic stem cell transplant (SCT). Methods: AML patients who are in morphologic complete remission (CR1 or greater) with available molecular mutation at diagnosis, within 6 weeks prior to allogeneic SCT, and by 100 days post-transplant were included. Variables analyzed included baseline demographics, clinical variables (CIBMTR disease risk index (DRI), type of transplant, ELN risk, performance status) and 23 recurring molecular mutations. Analysis was also performed by grouping mutations into six pre-defined gene groups based on gene function (Table 2). Multivariable cox regression analysis was adjusted for age, gender, DRI and molecular mutation. Backward selection method was used to select the best combination of genes that is associated with overall survival (OS) and relapse-free survival (RFS). Results : A total of 142 AML patients with molecular genetic data available from 2014 to June, 2020 at Weill Cornell Medicine/New York Presbyterian Hospital were analyzed. Clinical characteristics of the patients are summarized in Table 1. The median age was 58 years (range 20 -78). Total of 261 mutations were detectable at diagnosis (Table 3). Prior to allo SCT and by D100, the detectable mutations were 87 and 40 respectively, which represent 56 and 26 patients. High-dose chemotherapy was less effective on clearing DNMT3A, ASXL1, TET2 (DAT) or IDH mutations, resulting in over-representation of DAT and IDH mutations prior to transplant. With a median follow-up time of 25 months, the median overall survival for the group was 40.8 months. The presence of mutations in TP53 at diagnosis was associated with worse OS by both univariate (HR 3.67, p=0.0030, CI 1.56-8.68) and multivariate analysis (HR 4.75, p=0.0014, CI 1.82-12.39) with median OS reduced from 49.3 to 19.3 months (p=0.002). High CIBMTR DRI (HR 0.17, p=0.0018, CI 0.05-0.51) predicted reduced OS and RFS, and Age >60 at diagnosis was associated with worse OS (HR 1.7 CI 1.04-3, p 0.03). Presence of any molecular mutation prior to transplant did not impact OS or RFS. For patients with any persistent mutations by D100 post-transplant, both OS ( HR 2.04, p 0.027, CI 1.08-3.8) and RFS (HR 1.99, p 0.025, CI 1.09-3.6,) were reduced in the univariate analysis, but not on multivariate analysis (HR 1.88, p 0.5, CI 0.99-3.49). Analysis based on six mutational groups (table 2) did not show any difference in their OS or RFS. However, worse RFS was independently associated with persistent IDH1 (HR 3.8, p 0.004, CI 1.07-56,), TET2 (HR 3.9, P 0.04, CI 1.04-14.1), and FLT3-ITD (HR 4.5, p 0.01, CI 1.7-52). Worse OS was independently associated with persistent TET2 (HR 3.9, p 0.013, CI 1.04-14.1), with a trend towards worse OS for IDH1, FLT3-ITD, with a trend towards worsening OS and RFS for ASXL1 (OS HR 7.4, p 0.06, CI 0.86 -63; RFS HR 4.9, p 0.06, CI 0.9-26) and DNMT3A (OS HR 2.3, p 0.12, CI 0.86-6.9; RFS 2.9, p 0.08, CI 0.98-8). Association with worse clinical outcomes remained significant after multivariate analysis for TET2 (both OS HR 3.98 p 0.041, CI1.07- 32 and RFS HR 5.8, p 0.032, CI 1.1- 29), IDH1 (RFS HR 8.02, p 0.049, CI 1.02 - 65) and FLT3-ITD (RFS HR 11.4, p0.010, CI 2.2- 80). Conclusions: Presence of TP53 mutations was associated with worse OS. Presence of pre-transplant mutation did not impact RFS or OS. Persistent presence of mutations in TET2, IDH1 and FLT3-ITD after Fludarabine/melphalan conditioning regimen allogeneic SCT were associated with shorter RFS and OS (in the case of TET2) independent of CIBMTR DRI. This analysis supports association of adverse outcomes in AML patients with selected persistent mutations by D100 post-transplant in reduced intensity transplant setting. Post-transplant strategies that can further eliminate persistent mutations should be investigated in prospective studies. Figure 1 Figure 1. Disclosures Lee: Pin Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Innate: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees. Desai: Kura Oncology: Consultancy; Bristol Myers Squibb: Consultancy; Agios: Consultancy; Takeda: Consultancy; Janssen R&D: Research Funding; Astex: Research Funding. Ritchie: Protaganist: Consultancy, Honoraria; Incyte: Consultancy, Honoraria, Speakers Bureau; Celgene/BMS: Consultancy, Other: travel support, Speakers Bureau; Bristol Myers Squibb: Consultancy, Research Funding; ARIAD Pharmaceuticals: Ended employment in the past 24 months, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria; Astellas: Consultancy, Research Funding; NS Pharma: Research Funding; Abbvie: Consultancy, Honoraria; Jazz: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding. Roboz: MEI Pharma - IDMC Chair: Consultancy; Daiichi Sankyo: Consultancy; Helsinn: Consultancy; Jazz: Consultancy; Bristol Myers Squibb: Consultancy; Glaxo SmithKline: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Otsuka: Consultancy; Celgene: Consultancy; Mesoblast: Consultancy; Blueprint Medicines: Consultancy; Jasper Therapeutics: Consultancy; AbbVie: Consultancy; Actinium: Consultancy; Agios: Consultancy; Amgen: Consultancy; Astex: Consultancy; Astellas: Consultancy; AstraZeneca: Consultancy; Bayer: Consultancy; Janssen: Research Funding; Pfizer: Consultancy; Roche/Genentech: Consultancy.

Introduction: Pulmonary complications constitute a major cause of morbidity and mortality in the post-hematopoietic cell transplant (HCT) period. While Chest X-ray (CXR) is customarily used for screening, we have utilized chest computed tomography (CT) within one month of transplant. Here we aim to characterize the prevalence of abnormalities and their impact on the eligibility for allogenic (allo) HCT and outcomes post-transplant. Methodology: We conducted a single center retrospective study of all patients who were evaluated for allogenic HCT from January 2013 through December 2020 in New York Presbyterian Hospital - Weill Cornell Medicine (NYP-WCM). All patients who had chest CT as part of their pre-transplant evaluation were included for analysis. Results: We identified 478 patients who had Chest CT screening. In 396 CT chest was normal or confirmed previous abnormalities. Eighty-two patients (17%) had previously undetected abnormalities (Figure 1). The most frequent abnormalities were pulmonary nodules (defined as nodules of 4 mm or greater) in 27 patients (31%), ground-glass opacities (GGO) in 21 patients (25%), Pneumonia in 18 patients (21%). Miscellaneous findings not related to the primary disease were found in 12 patients (14%) including thyroid nodules, breast nodules and hemangioma of the liver. A new malignancy was found in 6 patients (7%) and incidental pulmonary embolism (PE) in 2 patients (2%) (Figure 2). There were 5 (6%) patients who were ultimately excluded from transplant due to CT chest findings (simultaneous CXR showed abnormalities in only 1 out of 5). Three of those patients were found to have invasive fungal infection, and the other two had unrecognized metastatic lung cancer. For 19 patients (23%), transplant was delayed for diagnostic procedure and/or treatment of pulmonary findings (CXR showed abnormalities in only 3 patients out of 19). The most common reason for delay was lung infection requiring treatment. Thirty-two patients (41%) out of 77 patients with abnormal CT scan who eventually underwent transplant, have died . Sixteen died after relapse, and 16 from non-relapse mortality (NRM) with pulmonary complications playing a role in 13 patients (Figure 3). Conclusion: 17% of patients who had a pre-transplant CT chest had abnormalities that warranted further evaluation. In 23% of these patients, these findings led to a delay in transplant for further optimization. Six percent were deemed ineligible for transplant due to absolute contraindications that were incidentally discovered on chest CT. Initial screening CXR failed to identify a significant number of abnormalities. Our data suggests that chest CT imaging should be part of the routine pre-transplant evaluation. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background Ph-like ALL is a recently recognized high risk B-ALL subgroup, defined by a gene expression profile similar to Ph (+) ALL that activates tyrosine kinase or cytokine receptor signaling. Several studies have described inferior outcomes with conventional chemotherapy and although small series suggest that it is responsive to targeted therapies, stem cell transplant (SCT) remains the only potentially curative option. However, the SCT outcomes of Ph-like ALL are not well defined and it remains unknown whether SCT is able to overcome the adverse prognosis associated with it. Methods We retrospectively identified 77 adult patients with Ph (-) B-ALL that received a SCT at Memorial Sloan Kettering, 2008-2018, and reviewed their cytogenetic and molecular reports at diagnosis. Testing for Ph-like ALL is employed in an algorithmically driven approach at our institution including cytogenetics, chromosomal microarray and next generation sequencing (NGS). Ph-like ALL was defined by the presence of abnormalities including ABL-class fusions that phenocopy BCR-ABL (ABL1, ABL2, CSF1R and PDGFRB) or alterations of CRFL2, JAK2 and EPOR that activate JAK/STAT signaling. We then analyzed the SCT outcomes of Ph-like patients and compared them to Ph (-) patients. Results A Ph-like signature was identified in 13 of 77 (16.9%) patients by NGS (n=7), cytogenetics (n=1), both NGS/cytogenetics (n=2) or microarray (n=3). Median age of all 13 patients was 42.7 (range 23.9-67.7) years and 6 (46.2%) patients were adolescents/young adults ( At a median follow up of 17.3 (range 0.5-109.3) months, overall survival (OS) was comparable between the Ph-like and Ph (-) groups with one-year OS rates of 74% and 70% (p=0.534) respectively (Fig 2A). Causes of death in Ph-like patients were relapse (n=2) and infectious complications (n=1). One-year cumulative incidence of relapse was 32.7% in Ph-like vs 17.3% in Ph (-) patients, however it did not reach statistical significance (p=0.94, Fig 3). Among the 4 Ph-like patients who relapsed, 1 had refractory disease prior to SCT, 2 were in second remission and 1 in first remission. One-year disease free survival was also comparable between the 2 groups (67% for Ph-like vs 65% for Ph (-), p=0.719) (Fig 2B). Finally, acute GVHD rates by day 100 were 69.2% in Ph-like (n=9) vs 53.1% (n=34) in Ph (-) patients (p=0.3). Conclusions Our findings suggest that SCT overcomes the adverse prognosis associated with the Ph-like signature and should be incorporated in the treatment of patients with this disease entity.

Background Studies evaluating the impact of 11q23 / KMT2A / MLL translocations on post-transplant outcomes as compared to other intermediate- and adverse-risk cytogenetic characteristics are lacking. Methods We considered 8709 AML patients from the CIBMTR database for inclusion. We evaluated relapse, non-relapse mortality (NRM), disease-free survival (DFS), and overall survival (OS) for patients who were transplanted in CR1 stratified by presence of 11q23 rearrangement, intermediate- or adverse-risk disease. Assignment of cytogenetic risk was performed by hand, based on the 2010 AML-MRC Classification System. A multivariate analysis was performed using a Cox proportional hazards model. Results Characteristics of 3779 patients, selected based on disease and donor type, HSCT in CR1, and availability of data, are shown in Figure 1. Of these, 426 patients had an 11q23-rearrangement, 2384 had intermediate-risk disease, and 969 had adverse-risk disease. Of the patients with 11q23 translocations, 112 (26%) had t(9;11), 62 (15%) had t(11;19), 41 (10%) had t(6;11), 28 (7%) had t(10;11), and 47 (11%) had other partners. No partner was provided in 136 cases (32%). Figures 2 and 3 show the DFS, OS, NRM, and relapse data stratified by cytogenetic category. Based on the multivariate analysis, DFS was lowest in adverse-risk patients (HR for death 1.47, 1.26 for MLL, p Stratification of outcomes by translocation partner did not yield any statistically significant differences between groups, however a descriptive analysis of these data will be presented. Measurable residual disease (MRD) status did not appear to play an independent role in NRM or in OS. However, the multivariate HR for relapse in patients with MRD-positivity was 1.23, p Conclusions Patients with MLL-rearranged AML had post-HSCT DFS and OS that were more similar to patients with adverse-risk disease than to those with intermediate-risk characteristics. MLL patients had a higher probability of relapse than intermediate-, but not adverse-risk, patients. NRM was similar among all groups. Both prognostic classification and MRD status independently contributed to the risk of relapse and DFS, but MRD was not an independent factor in predicting NRM or OS. Our study suggests that patients with MLL rearrangements do almost as poorly as those with adverse-risk disease and that novel approaches for this high-risk population represent an urgent unmet clinical need.

Allogeneic hematopoietic stem cell transplantation (HCT), defined by its underlying graft-versus-multiple myeloma (MM) effect, is a potentially curative approach for high-risk pts. However, relapse remains the main cause of treatment failure. Predictors for post-relapse survival after HCT are not well characterized, and we hypothesized that the time to relapse and the patterns of relapse are prognostic for post-relapse survival. Methods: All pts with MM who underwent a CD34+-selected alloHCT at Memorial Sloan Kettering Cancer Center on protocol (NCT 01131169/01119066) or off study from 01/2010 to 12/2017 and progressed after alloHCT were included. Pts were conditioned with busulfan (0.8 mg/kg x 10), melphalan (70 mg/m2 × 2), and fludarabine (25mg/m2 × 5). The K-M method was used to estimate OS post-HCT relapse. Significant predictors were considered in a Cox model. Results: Of the 115 transplanted pts, 60 (52%) relapsed and were analyzed. The median age was 56 yrs (35- 66), 62% male and 82% with high-risk cytogenetics (CG). KPS was ≥ 80 in 100% and ≥ 90 in 52%. Pts received a median of 4 lines of therapy pre-HCT (1-10), with 88% achieving at least a partial response (PR) prior to alloHCT. All pts had received at least one autoHCT. Of the 38% who received a planned or preemptive post-HCT therapy, 13 received DLI and 10 other strategies. Relapse was characterized as very early ( 24 mo, 22%). At relapse, 27% presented with extramedullary disease (EMD). Median post-relapse OS was significantly different for pts who relapsed very early, early, or late; 4 mo, 17 mo, and 72 mo, respectively (p = 0.002). Age ≥55, relapse with EMD, lower KPS, Conclusion: For this very high-risk group of MM pts, differences in time to relapse after alloHCT define very distinct post-relapse survival patterns. Very early relapses were associated with greater chemoresistance and dismal prognosis. In contrast, the median post-relapse OS for late relapses was 6 yrs, suggesting different underlying disease biology and/or host/donor characteristics. Similar to the post-auto setting, relapse with EMD conferred poor prognosis. Of note, post-relapse OS was superior for pts who received a DLI as planned post-HCT therapy prior to relapse. Efforts to characterize optimal post-relapse therapeutic strategies and mechanism(s) driving relapses are ongoing.