Clonal hematopoiesis (CH) is common in the general population and associated with various health risks, but its prevalence and clinical implications in acute myeloid leukemia (AML) long-term survivors (LTS; ≥5-year survival) are unknown. We analyzed CH in 373 AML-LTS with a median 11.6-year follow-up from diagnosis using a sensitive targeted sequencing assay based on single-molecule molecular inversion probes. CH variants were detected in 61.9% of survivors, with 26% having small-clone CH (SC-CH, variant allele frequency (VAF) < 2%) and 35.9% CH of indeterminate potential (≥2% VAF). CH was more prevalent in survivors treated with chemotherapy only (75.7%) compared to those who received allogeneic stem cell transplantation (alloSCT, 54.0%) and to age group-matched healthy controls. In chemotherapy-treated survivors, CH prevalence increased with age, whereas in alloSCT recipients, it most closely associated with hematopoietic age (i.e., the sum of donor age and time since transplantation). The variant spectrum also differed by treatment, with TP53 and PPM1D variants being more common in the chemotherapy group. CH variants ≥10% VAF associated with increased risks of diabetes in alloSCT recipients and secondary neoplasms in chemotherapy-treated survivors. This study provides insights into the high prevalence and potential clinical relevance of CH in AML-LTS.

We performed a questionnaire-based cross-sectional study to analyze Acute Myeloid Leukemia (AML) long-term survivor (LTS) outcomes, including psychosocial well-being and somatic health status. Four-hundred-twenty-seven former AML patients participated (response rate, 63%) ≥5 years[y] and up to 18.6 y past their leukemia diagnosis (median, 11.3 y). Median age at study participation was 61 y (range 28y–93y), 23% had experienced disease relapse, and 63% had received allogeneic hematopoietic stem cell transplantation (alloHSCT). Overall, quality of life (QoL) and general life satisfaction (gLS) summary scores were higher in AML LTS (p < 0.001) compared to age-/sex-matched reference cohorts, although differences were small and likely not clinically relevant. However, we identified subgroups of survivors reporting impaired QoL (27%), gLS (13%) and health-related life satisfaction (hrLS; 17%). Using multivariable regression models, we identified predisposing and protective factors for each of these outcomes. Treatment with alloHSCT did not adversely impact QoL, gLS, or hrLS. In summary, global QoL and LS in AML LTS are comparable to the general population, irrespective of treatment modality, although some survivors report clinically significant impairment of global QoL and/or in specific domains. We identified factors associated with impaired outcomes (e.g., comorbidity and fatigue), delineating a subgroup of survivors with unmet needs ≥5 y after their AML diagnosis.

Background and Methods In the German AMLCG Survivorship study, we included former AML patients from the AMLCG 1999, 2004, 2008 trials and the AMLCG patient registry, who survived at least 5 years after their initial diagnosis (AML-LTS). Our participants provided information on life satisfaction, quality of life as well as a number of psychological outcomes. Here, we analyzed the hospital anxiety and depression scale questionnaire and present results with respect to severity of observed anxiety (HADS-A) and depression scores (HADS-D), as well as an exploratory analysis to identify major risk factors. We analyzed our data using absolute and relative frequencies. Categorical variables were compared by chi-squared tests. Univariate and multivariable logistic regression models were fitted to analyze the risk of increased anxiety or depression scores. Results 427 AML-LTS participated in this study 5 to 18.6 years after their initial AML diagnosis. Overall, long term survivors showed HADS depression values between 0 and 19 with higher values indicating more severe depression. On average, former patients scored 4.35 (SD=3.8) points. Based on the classification proposed by Zigmond et al., 77.5% (331/420) showed normal depression scores (range: 0-7), 12.9% (55/420) borderline depression scores (8-10) and 8% (34/420) high scores (>10). Anxiety scores ranged between 0 and 20. Average score was 5.55 (SD: 4.01). Anxiety seem to be a more prominent problem in former AML patients. 73.3% (313/418) showed a normal score, 13.3% (57/418) a borderline score and 11.2% (48/418) a high score. While depression severity was equally distributed between sexes (P >.05), anxiety is more prominent in women (male cases 10/182, 5.5% vs. female cases 38/236, 16.1%, P = .003). Older participants show a decreased risk for high (>10) anxiety scores (odds ratio per 10 years of age (OR): .776, 95% confidence interval (CI): .618-.970), but not for depression (P >.05). Time since initial diagnosis did not associate with depression or anxiety (P > .05). The equivalence income (household income in EUR, dependent on household size) was associated with depression risk (OR: .54, 95%CI: .34-.88, per 1000 EUR), but not with anxiety (P > .05). Changes in the occupational situation (due to AML) impacts the chance for high depression (P = .001) and high anxiety scores (P < .001). Especially, being unable to work at all showed an elevated risk for high depression (5/24, 21%) and anxiety (9/24, 37%) scores. Worsening of the participant's financial situation was associated with an increased risk for high depression (19/128, 14.8%, P < .001) and high anxiety (25/127, 19.7%, P < .001). Furthermore, AML- and therapy-related variables (de novo AML, cytogenetic risk, allogeneic stem cell transplantation vs chemotherapy only, as well as experiencing one or more relapses) were not associated with depression or anxiety (P > .05) in this univariate analysis. All factors analyzed above were also used as risk factors in multivariable logistic regression models, within a backward variable selection approach with likelihoods ratio test. The final model for increased depression scores (HADS-D >10) contained the equivalence income (P = .056) as well as change in the financial situation (OR: 2.7, 95%CI: 1.28-5.69, P = .009) (Figure 1A). The latter confirmed the univariate finding that worsening financial situation is a risk factor for increased depression risk in long term survivors. The final model for increased anxiety scores (HADS-A >10) confirmed female sex (OR: 2.79, 95%CI: 1.29-6.02, P = .009), change in the occupational situation (P < .001, ORs are given in Figure 1B for the individual characteristics) as major risk factors for increased anxiety. Experiencing one or more relapses after AML seems to reduce the risk for anxiety (OR: .23, 95%CI: .08-.64, P = .005) (Figure 1B). Discussion Our data shows that anxiety and depression are relevant health problems for ca. 20%-25% of long-term survivors. Furthermore, women seems to be more prone to exhibit anxiety after AML. Interestingly, experiencing at least one relapse seems to reduce the chance for increased anxiety. The association of occupational and/or financial situation with increased anxiety or depression risk suggests a need for the management of these factors to mitigate adverse effects. Overall, our data may be useful to guide aftercare for former AML patients with respect to their psychological well-being. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Durch modernere Behandlungsoptionen hat sich die Prognose der akuten myeloischen Leukämie (AML) verbessert. Dadurch gewinnen Spätfolgen der Erkrankung und ihrer Behandlung immer mehr an Bedeutung. Zurzeit ist keine umfassende Nachsorgeempfehlung verfügbar, da die Datengewinnung unter anderem durch die relative Seltenheit der Erkrankung erschwert wird. Aus Untersuchungen von Langzeitüberlebenden verschiedener anderer Tumorentitäten sind bereits häufig auftretende gesundheitliche Spätfolgen und Problembereiche bekannt. Einige davon konnten auch bei AML-Überlebenden identifiziert werden. Aus psychosozialer Sicht können basierend auf den vorhandenen Daten eine erhöhte Prävalenz von Depression, Angst und Fatigue sowie vermehrte finanzielle Sorgen beobachtet werden. Zudem ist das Risiko für verschiedene somatische Komorbiditäten wie kardiovaskuläre Erkrankungen und Sekundärmalignome bei AML-Langzeitüberlebenden erhöht. Ergänzend zu regelmäßigen Kontrollen des Remissionsstatus sollten bei der Behandlung von Langzeitüberlebenden einer AML auch psychosoziale und somatische Begleit- und Folgeerkrankungen in der Nachsorge berücksichtigt werden. Außerdem sollte eine Ausweitung des intensiven Nachsorgeintervalls länger als fünf Jahre seit der Erstdiagnose erwogen werden. Weitere Studien zu Langzeitfolgen der Erkrankung sind zur Optimierung der Nachsorge von ehemaligen AML-Patienten nötig.

Background: An increasing proportion of patients with acute myeloid leukemia (AML) become long-term survivors. Somatic and psycho-social outcomes in survivors are therefore becoming increasingly important, but little is known about the long-term effects of the disease and its treatment. Aims: The primary aim of this study was to compare quality of life (QoL, measured by the FACT-G questionnaire) and general and health-related life satisfaction (gLS/hLS, measured by the FLZ-M questionnaire) of AML-LTS with normative data of German adults who were not diagnosed with AML. Methods: We designed a comprehensive analysis of AML survivorship outcomes including psycho-social well-being and somatic health status and conducted a questionnaire-based study collecting data from AML long term survivors (AML-LTS). This report focuses on overall and health-related quality of life. Somatic morbidity in AML-LTS is reported separately (Moret et al.). Results: 427 former AML patients who had been enrolled in AMLCG trials (AMLCG-1999, AMLCG-2004, AMLCG-2008) or the AMLCG patient registry, participated in this study between 5 and 18.6 years (y) after their initial AML diagnosis (median, 11.3y). Median age of AML-LTS was 61y (range 28y-93y), and 56% were female. Thirty-eight percent of participants had been treated with chemotherapy alone, while 62% received at least one allogeneic stem cell transplant (alloHSCT). A relapse occurred in 24% of the participants. Unexpectedly, age- and sex-normalized quality of life and general life satisfaction summary scores were significantly higher in AML-LTS (p<.001) compared to adults without the diagnosis of AML. Raw score points of AML-LTS on the FACT-G summary scale also were higher than in age and sex-matched normal adults by a median of 4.7 points (95% CI: 2.82 – 7.2) – a differences that likely is clinically not relevant, considering an established cutoff for clinical relevance of 7 raw score points. No difference between AML-LTS and normal adults was found for health-related life satisfaction (hLS). Using the cutoff for clinical importance (i.e., 7 points below age- and sex-matched population norm), 26.1% of participants reported relevant impairment of overall QoL. To identify factors potentially associated with poor overall QoL, we constructed a logistic regression model including pre-specified cofactors (age, sex, time since initial diagnosis, relapse and alloHSCT) and additional covariables that associated with QoL in univariate analyses (Figure 1). We found that participants with no children, lower educational level, shorter time since diagnosis and altered financial situation reported significantly lower QoL. No influence was found for disease- and treatment related factors including treatment (alloHSCT vs. no alloHSCT), previous relapse, or de novo vs secondary or therapy-related AML. Image:Summary/Conclusion: Unlike previous studies of AML survivorship, our large cohort included a diverse spectrum of patients regarding age, time since diagnosis, and treatment modalities, which allows for new insight into long-term QoL. Our study establishes that overall QoL in AML long-term survivors is comparable to the general population, with further improvement from five years post diagnosis onwards. Importantly, disease- and treatment-related factors, such as prior relapse or alloHSCT, are not associated with overall QoL. However, we were able to identify risk factors for worse QoL, delineating a subgroup of patients that may still have a need for targeted psycho-social interventions five or more years after an AML diagnosis.

Introduction: As outcomes of patients with acute myeloid leukemia (AML) have improved, the fraction of patients surviving long-term is increasing. Information on somatic and psycho-social health consequences of AML and its treatment is sparse. The aim of our study was to perform a multi- dimensional analysis of health outcomes in AML long-term survivors (AML-LTS). This report focuses on secondary neoplasms (SN) after AML. Data on psychosocial outcomes and clonal hematopoiesis are presented by Telzerow et al., Görlich et al. and Krauss et al. Methods: We conducted a cross-sectional study including AML survivors who had been enrolled in clinical trials or the patient registry of the AML-CG study group, and were alive ≥5 years after initial diagnosis. Data concerning somatic health status were collected through patient questionnaires, assessments by the patients' physicians, and medical and laboratory reports. (DRKS00023991) Results: Data on somatic health status is available for 355 AML-LTS, 58% female, aged 28 to 93 years [y] (median 60y), 5 to 19y after initial diagnosis (median, 11.6y). Sixteen percent were initially diagnosed with secondary AML (sAML) or therapy-related AML (tAML) and 38% were treated with chemotherapy only while 62% had undergone allogeneic stem cell transplantation (alloHSCT). Fifty-five AML-LTS (15.5%) had developed SN after AML, that manifested 3 months to 18y after initial diagnosis (median, 12.4y), at age 31 to 83y (median 59y). Forty-two percent of AML-LTS with SN were female, 66% had undergone alloHSCT and 24% were initially diagnosed with sAML or tAML. At the time of study participation, 96% percent of all AML-LTS and 90 % of those diagnosed with SN fulfilled CR criteria (neutrophils >1G/L and thrombocytes >100G/L). Most common tumor types were non-melanoma skin cancers (30%), breast cancer (11%, all female, 25% of female AML-LTS with SN), head and neck cancers (7%) and, in 5% each, cancers of the esophagus, lung, bladder and prostate (9.4% of male AML-LTS with SN). Kaplan-Meier-Analyses show a 20%-risk of AML-LTS to develop SN 15 years after initial diagnosis, with no significant difference between patients treated by alloHSCT or chemotherapy only (log-rank p=.26; Fig. 1). However, 10y-risk was 5.6% and 15y-risk was 18.5% for AML-LTS treated with chemotherapy only, whereas for AML-LTS treated with alloHSCT 10y-risk was 12% and 15y-risk was 21%. AML-LTS >60y at the time of AML diagnosis had a significantly higher risk to develop secondary cancer, with a 10y-risk of 17.7% compared to 7.9% for AML-LTS aged 30-60y and 6.6% aged <30y at initial diagnosis (Fig. 2). Using Cox regression models, we analyzed the influence of age at AML diagnosis, sex, smoking status, sAML/tAML vs. de novo-AML, AML relapse (as time-dependent covariable) and treatment with alloHSCT vs. chemotherapy only on the risk of developing secondary malignancies after AML. Only older age at initial diagnosis (OR=1.03 per year, 95% CI: 1.01 - 1.05, p=.01) and male sex (OR=1.93, 95%-CI: 1.12 - 3.37, p=.02), but none of the diagnosis- and treatment-related factors significantly associated with higher risks for secondary malignancies. However, AML-LTS diagnosed with sAML/tAML tended to develop SN earlier after initial diagnosis than those diagnosed with de novo AML. Ten-years-risk was 9% and 15y-risk was 20% for AML-LTS diagnosed with de-novo-AML, whereas for AML-LTS diagnosed with sAML/tAML 10y-risk was 14% and 15y-risk was 23% (log-rank p=.08). Conclusion: Our study includes a large cohort of AML-LTS representing a wide age range, a long follow-up period of 5 to nearly 20 years, and heterogeneous therapy regimens (chemotherapy + autoHSCT vs. alloHSCT), close to real-life clinical settings. We found that the 15y-risk to develop a SN after AML is ~20%, with men having a 2-fold higher risk, and older age at the time of diagnosis being a negative predictor. We did not identify diagnosis- or treatment-related factors associated with increased risks for SN, although SN tended to occur earlier in patients who received alloHSCT compared to those treated with chemo only. We hope that our results may guide future recommendations for risk-adapted follow-up of AML-LTS. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Objective To improve allocation of psychosocial care and to provide patient-oriented support offers, identification of determinants of elevated distress is needed. So far, there is a lack of evidence investigating the interplay between individual disposition and current clinical and psychosocial determinants of distress in the inpatient setting. Methods In this cross-sectional study, we investigated 879 inpatients with different cancer sites treated in a German Comprehensive Cancer Center. Assessment of determinants of elevated distress included sociodemographic, clinical and psychosocial characteristics as well as dimensions of personality. Multiple linear regression was applied to identify determinants of psychosocial distress. Results Mean age of the patients was M = 61.9 (SD = 11.8), 48.1% were women. In the multiple linear regression model younger age (beta = -0.061, p = 0.033), higher neuroticism (beta = 0.178, p = <0.001), having metastases (beta = 0.091, p = 0.002), being in a worse physical condition (beta = 0.380, p = <0.001), depressive symptoms (beta = 0.270, p = <0.001), not feeling well informed about psychological support (beta = 0.054, p = 0.046) and previous uptake of psychological treatment (beta = 0.067, p = 0.020) showed significant associations with higher psychosocial distress. The adjusted R-2 of the overall model was 0.464. Conclusion Controlling for sociodemographic characteristics and dispositional vulnerability, that is neuroticism, current clinical and psychosocial characteristics were still associated with hospitalized patients' psychosocial distress. Psycho-oncologists should address both, the more transient emotional responses, such as depressive symptoms, as well as more enduring patient characteristics, like neuroticism.

Background: As outcomes of patients with acute myeloid leukemia (AML) have improved, the fraction of patients surviving long-term are increasing. Information on somatic and psycho-social health consequences of AML and its treatment is sparse. Aims: Our aim was to perform a multi-dimensional analysis of health outcomes in AML long-term survivors (AML-LTS). This report focuses on somatic morbidity; overall and health-related quality of life are reported separately (Telzerow et al.). Methods: We conducted a cross-sectional study including AML survivors who had been enrolled in clinical trials or the patient registry of the AML-CG study group and were alive ≥5 years after initial diagnosis. Data concerning somatic health status were collected through patient questionnaires, assessment by the patients’ physicians, and medical and laboratory reports. An age- and sex-matched control cohort was derived from German population-based health surveys (Robert Koch Institute, DEGS1 survey; n=6013). Results: Data on somatic health status was available for 355 survivors, aged 28-93 years, who participated 5 to 19 years after their AML diagnosis. Thirty-eight percent of survivors were treated with chemotherapy with or without an autologous transplant, whereas 62% had undergone allogeneic transplantation (alloSCT). We compared the prevalence of somatic diseases between AML-LTS and the general German population (DEGS1 sample), focusing on cardiovascular diseases and risk factors due to their relevance for overall morbidity and mortality, and their known association with survivorship in other cancers. Using age- and sex-adjusted multivariate models (Figure A), we found that AML survivors had a 2-fold higher risk of type 1/2 diabetes (DM 1/2), and a 3.5-fold increased risk of congestive heart failure (CHF) compared to the general population. Prevalence of hypertension, coronary artery disease (CAD) and myocardial infarction were similar between the groups. To identify factors associated with development of CHF among AML-LTS, we constructed multivariate models incorporating patient- and treatment-related covariables. We found an increased risk of CHF for AML-LTS who have had AML relapse (OR, 3.16; 95% CI: 1.46 – 6.83; P=0.004) and, in trend, for patients with sAML or tAML (OR 2.19; 95%CI: 0.92 – 5.22, P=0.076). Disease- or treatment-related factors did not significantly associate with any of the other comorbidities we studied. Furthermore, AML-LTS had significantly impaired kidney function, as assessed by the glomerular filtration rate (eGFR) estimated using the CKD-EPI-formula. Figure B displays the median eGFR according to age groups for AML-LTS and DEGS1. For each age group AML-LTS had significantly lower eGFR in comparison to DEGS1. We did not find an association between kidney function and time since diagnosis (p=.5) and no differences between AML-LTS treated by chemotherapy or alloSCT (p=.5), survived a relapse (p=.9) or were diagnosed with de novo-AML vs. sAML/tAML (P=.6). Image:Summary/Conclusion: Compared to the German general population, AML-LTS had increased risks of CHF and diabetes, but not hypertension or CAD. We identified AML relapse as a risk factor for developing of CHF, suggesting that cumulative chemotherapy exposure might be causally involved. Notably, AML-LTS who had undergone alloSCT did not have increased risks of CHF, CAD, hypertension or diabetes, compared to survivors treated with chemotherapy only. In addition, AML-LTS had a higher prevalence of impaired renal function. We did not identify treatment- or disease-related factors that might cause the lower kidney function in AML-LTS.

Abstract Introduction An increasing proportion of patients with Acute Myeloid Leukemia (AML) become long-term survivors. Somatic and psycho-social outcomes are therefore becoming increasingly important, but little is known about the long-term effects of the disease and its treatment. Methods We designed a comprehensive analysis of AML survivorship outcomes including psycho-social well-being and somatic health status and conducted a questionnaire-based study collecting data from AML long term survivors (AML-LTS) and their physicians. This report focuses on overall and health-related quality of life. Somatic, especially cardiovascular, morbidity in AML-LTS are reported separately (Moret et al.). The primary aim of this study was to compare quality of life (QoL, measured by the FACT-G questionnaire) and general and health-related life satisfaction (gLS/hLS, measured by the FLZ-M questionnaire) of AML-LTS with normative data of German adults who were not diagnosed with AML (Holzner et al. 2009; Daig et al. 2009). FLZ-M and FACT-G scores were standardized relative to the normal population mean and standard deviation, stratified by sex and age. These z-scores were then tested against the fixed value 0 (indicating no difference between AML-LTS and the general population) using Mann-Whitney U-tests. Our statistical design incorporated a sequentially rejective testing procedure to maintain the multiple testing significance level at 5%, using a graphical model as described by Bretz et al. (2009). Results 427 former AML patients who had been enrolled in AMLCG trials (AMLCG-1999, AMLCG-2004, AMLCG-2008) or the AMLCG patient registry, participated in this study between 5 and 18.6 years [y] after their initial AML diagnosis (median, 11.3y). Median age of AML-LTS was 61y (range 28y-93y), and 56% were female. Thirty-eight percent of participants had been treated with chemotherapy alone, while 62% received at least one allogeneic stem cell transplant (alloSCT). A relapse occurred in 24% of the participants. Unexpectedly, quality of life and general life satisfaction summary scores were significantly higher in AML-LTS (p<.001) compared to adults without the diagnosis of AML, although most differences on QoL subscales relative to the general population were small and very likely not clinically relevant. No statistical difference between AML-LTS and normal adults was found for health-related life satisfaction (hLS). Notably, a subgroup of participants (26%) reported poor physical well-being (PWB), indicated by a FACT PWB subscore more than one standard deviation (SD) below the age- and sex-matched general population value (Figure A). This resulted in poor overall QoL (i.e. >1 SD below normal) for 13% of the participants (Figure B). To identify factors potentially associated with poor overall QoL, we constructed a logistic regression model including pre-specified cofactors (age, sex, time since initial diagnosis, relapse and alloSCT) and additional covariables that associated with QoL in univariate analyses (Table C). We found that participants with younger age, male sex, lower educational level, shorter time since diagnosis and a altered financial situation reported significantly lower QoL. No influence was found for other characteristics including treatment (alloSCT vs. no alloSCT), previous relapse, or de novo vs. secondary or therapy-related AML. Discussion Unlike previous studies of AML survivorship, our large cohort included a diverse spectrum of patients regarding age, time since diagnosis, and treatment modalities, which allows for new insight into long-term quality of life. Our study establishes that overall QoL in AML long-term survivors is comparable to the general population. Improvement of QoL continues beyond five years post diagnosis. Importantly, disease- and treatment-related factors, such as prior relapse or status post allogeneic transplantation, are not associated with overall QoL. However, we were able to identify risk factors for worse QoL (younger age, male sex, alteration of the financial situation), delineating a subgroup of patients that may still have a need for targeted psycho-social interventions five or more years after an AML diagnosis. Figure 1 Figure 1. Disclosures Berdel: Philogen S.p.A.: Consultancy, Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees. Hiddemann: Janssen: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Metzeler: AbbVie: Honoraria; Astellas: Honoraria; Daiichi Sankyo: Honoraria; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy; Pfizer: Consultancy; Celgene/BMS: Consultancy, Honoraria, Research Funding.

Background: Clonal hematopoiesis (CH), the outgrowth of hematopoietic stem cells and their progeny with somatically acquired gene mutations, is a common phenomenon in elderly individuals without known hematological disorders. CH has been linked to an increased risk of developing myeloid neoplasia and cardiovascular diseases, resulting in higher all-cause mortality. More specifically, clonal hematopoiesis of indeterminate potential (CHIP) has been defined by hematopoietic clones with a variant allele frequency (VAF) ≥2% in the absence of hematologic disease. CH is also known to be common in patients with acute myeloid leukemia (AML) briefly after therapy, but prevalence and relevance of CH in AML long-term survivors (AML-LTS) has not been investigated so far. Aims: We aimed to study CH in a cohort of 380 AML-LTS using a targeted next generation sequencing (NGS) assay utilizing single-molecule Molecular Inversion Probes (smMIPs), and to analyze determinants of CH and its effects on somatic health outcomes. Methods: We employed smMIP-technology, which follows a hybridization-capture protocol for NGS library preparation to selectively enrich and amplify hundreds of genomic target loci covering 82 regions in 24 CH and AML-related genes in a single reaction. Unique molecular identifiers (UMIs) within probes enabled computational correction of sequencing errors to significantly increase precision of variant calls. Results: We successfully established a UMI-based smMIP NGS assay as well as a custom computational analysis pipeline to enable the reliable detection of variants ≥0.5% VAF. In whole blood specimens from 380 AML-LTS we detected CH in 61.4% of individuals, including CHIP (VAF ≥2%) in 35.8%. Stratification by treatment group, i.e. chemotherapy/autologous hematopoietic stem cell transplantation only (chemo) vs. allogeneic hematopoietic stem cell transplantation (alloSCT), revealed a significantly lower prevalence of CHIP in the alloSCT group (26.0% vs. 52.1%; p<.001). Concordantly, median VAF of CH mutations after alloSCT was significantly lower than in the chemo group (1.2% vs. 1.8%; p=.005). CHIP prevalence increased with age in the chemo group, from 21.7% (<50 years) to 70.0% (≥70 years), whereas it was independent of patient age in the alloSCT group (Figure A). Conversely, CHIP prevalence was independent from time since start of therapy in the chemo group, but increased with time after transplantation in the alloSCT group, from 18.4% (0-5 years) to 46.2% (16-18 years; Figure B). In both treatment groups, the known CHIP driver genes DNMT3A and TET2 were most frequently mutated. Notably, PPM1D (p<.001) and TP53 (p<.001) were more frequently mutated in the chemo group (Figure C). We did not detect significant differences in complete blood counts of AML survivors according to CH status. While most somatic comorbidities showed no clear association with CH status, prevalence of diabetes and development of secondary cancer after leukemia therapy were increased in patients with CH (VAF <2%), and more so in those with CHIP (Figure D). Image:Summary/Conclusion: We report a high prevalence of CH in AML long-term survivors, particular in those treated with chemotherapy without alloSCT. CHIP prevalence increases with age in patients treated with chemotherapy, and with time elapsed after transplantation in patients who underwent alloSCT. We reveal distinct mutation spectra for both groups. Although associations between CH and somatic morbidities seem to be weak overall, we found associations with diabetes and the development of secondary cancer after leukemia treatment, which warrant further exploration.

Background With the increasing number of long-term survivors after acute myeloid leukemia (AML), long-term effects of the disease and its treatment become increasingly important. Due to various factors, like the rareness of the disease, guidelines for survivorship care plans are difficult to establish on the basis of existing studies. Results Looking at various studies including cancer survivors of various cancer entities, different problem areas have already been identified in long-term survivors. Some of those can be added to the data available for AML long-term survivors. From a psychosocial point of view, higher prevalence for depression, anxiety, fatigue and financial toxicity have been observed. In addition, the risk for certain somatic comorbidities, like cardiovascular comorbidities and secondary malignancies, is increased. Conclusion Aside from regular monitoring of the remission status, psychosocial and somatic comorbidities should also be monitored by the physician when caring for long-term survivors after AML. In addition, intensive aftercare intervals should be extended further than 5 years after initial diagnosis. Future research on long-term effects of the disease is still needed to optimize care for AML long-term survivors.

Introduction: As outcomes of patients with acute myeloid leukemia (AML) have improved over the past decades, the fraction of patients surviving long-term is increasing. Information on long-term somatic and psycho-social health consequences of AML and its treatment is sparse. Previous studies suggested a higher prevalence of cardiovascular diseases in AML survivors, especially those treated with allogeneic stem cell transplantation (alloHSCT). The aim of our study was to perform a multi-dimensional analysis of health outcomes in AML long-term survivors (AML-LTS). This report focuses on somatic, especially cardiovascular, morbidity in AML-LTS. Overall and health-related quality of life are reported separately (Telzerow et al.).

OBJECTIVE:Many distressed cancer patients do not want or, finally, do not use psychological support. This study aimed at identifying factors associated with the decline of psychological support during hospital stay. METHODS:This cross-sectional study included inpatients with different cancer diagnoses. Distress was assessed using the short form of the Questionnaire on Stress in Cancer Patients-Revised (QSC-R10) and the Distress Thermometer (DT). Multivariable logistic regression was used to identify factors associated with decline. RESULTS:Of 925 patients, 71.6% (n = 662) declined psychological support. Male sex (OR = 2.54, 95% CI = 1.69-3.80), low psychosocial distress (OR = 3.76, CI = 2.50-5.67), not feeling depressed (OR = 1.93, CI = 1.24-2.99), perceived overload (OR = 3.37, CI = 2.19-5.20), no previous psychological treatment (OR = 1.88, CI = 1.25-2.83), and feeling well informed about psychological support (OR = 1.66, CI = 1.11-2.46) were associated with decline. Among the patients who indicated clinical distress (46.2%), 53.9% declined psychological support. Male sex (OR = 2.96, CI = 1.71-5.12), not feeling depressed (OR = 1.87, CI = 1.12-3.14), perceived overload (OR = 5.37, CI = 3.07-9.37), agreeableness (OR = 0.70, CI = 0.51-0.95), and feeling well informed about psychological support (OR = 1.81, CI = 1.07-3.07) were uniquely associated with decline in this subgroup. CONCLUSIONS:Decline of psychological support is primarily due to psychological factors. Feeling well informed about support emerged as a relevant factor associated with decline. Thus, design of informational material and education about available psychological services seem crucial.