Abstract: Abstract 1019 Poster Board I-41 INTRODUCTION: Erythroleukemia is characterized by a peculiar marrow feature: a proliferation of erythroblasts greater than 50% and of myeloblasts greater than 30%, according to the FAB classification. Treatment strategies are usually indistinct from other forms of acute myeloid leukemia (AML), with the exception of acute promyelocytic leukemia. Although generally considered as a very aggressive subtype of AML, very few data are available concerning epidemiologic features and specific outcome of erythroleukemia among AMLs. MATERIALS AND METHODs: Adult patients with AML consecutively enrolled in the GIMEMA trials AML10 and LAM99p were retrospectively analyzed with the aim of evaluating the epidemiologic features and outcome of acute erythroid leukemia (FAB M6) characterized by morphological/cytochemical criteria after central revision, in comparison with non-M6 AML. RESULTs: Among 1675 AML patients, 59 (3.6%) were identified as M6; 39 were males and 20 females, the median age was 49 years (range 25.9-60.8), the median WBC count at diagnosis 2.7 × 109/l (range 0.7-41.8), the median Hb level 7.8 gr/dl (range 5.1-11.8) and the median platelet count 38 × 109/l (range 6-245). Univariate analysis showed a statistical difference between the M6 cases and the non-M6 series enrolled in these two clinical trials with regard to: incidence of male gender (p=0.03), prevalence of older age (p=0.001), leukopenia at diagnosis (p 〈 0.0001), decreased levels of Hb (p=0.0006), lower platelet count (p=0.05), peripheral blast count (p 〈 0.0001) and increased PMN count (p 〈 0.0001). A previous myelodisplastic phase was reported in 5.6% of M6 cases compared to 1.7% in the other AML subtypes (p=0.07). Analysis of response to intensive chemotherapy, evaluated as ITT, showed that 64.4% of M6 patients achieved a complete remission (CR) compared to 69.6% in the other FAB subtypes (p=0.39); a similar induction death rate (13.5%) was observed in both groups. Overall survival (OS) at 60 months was 29.5% in M6 patients and 34% in the other FAB types (p=0.75), as shown in the figure; no significant difference was recorded also with regard to disease-free survival (DFS): 44% in M6 vs 39.7% in the other FAB types after 60 months of follow-up (p=0.59). For patients who obtained a CR, the cumulative incidence of relapse (CIR) showed no statistical differences: 45% at 60 months in M6 vs 46.9% in the other types, p=089). Also the cumulative incidence of non-relapse mortality (CINRM) at 60 months was similar in both groups: 10.7% in M6 vs 13.4% in the other types, p=0.62. CONCLUSIONs: Despite the higher incidence of some risk factors - higher age, higher proportion of myelodisplastic pre-phase and cytopenias - in this rare form of AML the CR duration and the OS are similar to those observed in the other more frequent forms of AML. Based on this analysis, the prognosis of this form of acute leukemia does not differ from that of the other subtypes. Disclosures: No relevant conflicts of interest to declare.

Abstract: Background: Comorbidities and body mass index (BMI) are significantly associated with outcome in patients (pts) who receive continue treatment with tyrosine kinase inhibitors (TKIs), such as in Ph+ leukemias. Ruxolitinib (RUX) is the first JAK1/2 inhibitor that may induce spleen/symptom responses and improve quality of life in pts with myelofibrosis (MF). Up-to-date, no data are available on the impact of comorbidities and BMI on pts treated with RUX. Aims: To evaluate the impact of comorbidities and BMI on responses, overall survival (OS) and maintenance of RUX dose in a large cohort of pts. Methods: Data were extracted from an electronic database that included retrospective data on pts treated before January 2015 in 16 Italian Hematology centers. Response to RUX was evaluated according to IWG-MRT criteria. BMI was calculated at the time of start of RUX and classified according to WHO criteria. Comorbidities were recorded at the time of start of RUX and classified according to the Charlson Comorbidity Index (CCI). Overall survival (OS) was calculated from the date of RUX start to the time of death or to last follow-up, whichever came first. Results: Between June 2011 and Apr 2016, 289 pts with PMF (52.6%), or PET-MF (17%) or PPV-MF (30.4%) were treated with RUX in participating Centers. At RUX start, median age was 68.4 years (range 39-89) with a male prevalence (56.4%); International Prognostic Score System (IPSS) was intermediate (intm)-1 (15.6%), intm-2 (45.3%), high (39.1%). Transfusion dependence and spleen enlargement were present in 26.6% and 96.9% of pts, respectively (69.6% with spleen≥ 10 cm). Median total symptom score (TSS) was 20 (range 0-70). JAK2V617F was present in 80.3% of 234 evaluable pts. Median follow-up from MF diagnosis was 3.8 yr (range 0.3-29.6) and median RUX exposure was 20 months (3-56.2). Overall, comorbidities were evaluable in 275 pts. CCI stratification showed the absence of comorbidities in 100 pts (36.4%), one comorbidity in 63 pts (22.9%) and two or more in 112 pts (40.7%). Compared to pts with CCI 〈 2, pts with CCI ≥2 were more frequently: male (66.1% vs 49.1%, p=0.005), ≥65y (74.1% vs 54%, p=0.001), at intm2/high IPSS risk (90.2% vs 81%, p=0.03) and transfusion-dependent (36.6% vs 20.2%, p=0.003). Notably, the percentage of pts starting RUX 〉 2y from MF diagnosis was lower if CCI≥2 (33.9% vs 54%, p=0.001). Higher CCI did not correlate with lower spleen response (achieved by 45.2% vs 34.7%, p=0.09), TSS response (90.1% vs 83.2%, p=0.11), and higher incidence of RUX-induced anemia (Hb 〈 10 g/dl in pts with baseline Hb ≥10 g/dl) (48% vs 41%, p=0.33). RUX starting and titrated doses at 12-wks were similar in the two groups (p=0.44 and p=0.81, respectively). OS was significantly higher in pts with CCI 〈 2 (96.7% vs 87.8% at 2 yr, p 〈 0.001). After stratification according to CCI (below or above 2) and the achievement of a spleen response, both factors remained significantly associated with survival. Indeed, in pts with CCI 〈 2 OS at 2 yr was 92.7% and 79.1%, depending on the achievement of a spleen response (SR) or not (NR), respectively (p=0.034). Analogously, in pts with CCI≥2 the achievement of a spleen response significantly increased survival (79.2% vs 55.3% in pts without spleen response, p=0.011). Notably, OS was comparable in pts with lower CCI /no spleen response and in pts with higher CCI/spleen response (79.1% vs 79.2%) (Figure 1). BMI was evaluable in 269 pts: 169 pts (62.8%) were classified as under-weight/normal for a BMI 〈 25, whereas 100 pts were overweight/obese (BMI ≥25). Pts with BMI≥25 were more frequently male (71% vs 47.3%, p 〈 0.001) and with a lower incidence of anemia (30% vs 42%, p=0.049). BMI stratification did not correlate with differences in spleen response (p=0.83) and TSS (p=0.18) or onset of anemia/infections during treatment (p=0.49 and p=0.28). Starting and median doses, as well as percentage of pts reducing RUX dose over time, were similar in the two groups. Summary: In MF pts treated with RUX, BMI and comorbidities did not influence the achievement of spleen/symptom responses, maintenance of RUX dose or onset of drug-related anemia. Although CCI stratification correlated with survival, as in Ph+ leukemias treated with TKIs, the achievement of a spleen response was able to counterbalance the negative prognostic effect of a higher CCI. Consequently, higher BMI and CCI should not be regarded as contraindication to RUX therapy. Figure Figure. Disclosures Breccia: Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Ariad: Honoraria; Pfizer: Honoraria. Tiribelli:Ariad Pharmaceuticals: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Bonifacio:Ariad Pharmaceuticals: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; Bristol Myers Squibb: Consultancy; Novartis: Research Funding. Cimino:Bristol-Mayer: Honoraria; Celgene: Honoraria. Latagliata:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Janssen: Consultancy, Honoraria; Shire: Honoraria. Cavo:Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Millennium: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria.

Abstract: Different biologic features have been associated with a more or less aggressive clinical course in chronic lymphocytic leukemia (CLL). In the present study, 20 patients with highly stable CLL observed at a single institution over a period of 10 to 23 years and who never required treatment were extensively characterized. The aim was to identify a distinct and reproducible biologic profile associated with disease stability that may be used to recognize at presentation CLL patients who are likely to have a very benign clinical course and for whom treatment is not indicated. The results obtained indicate that numerous parameters are closely associated with disease stability: a typical CLL morphology and immunophenotype, the lack of expression of the CD38 antigen, the mutated immunoglobulin (Ig) heavy (H) chain variable (V) pattern, the absence of p53 mutations, a CD4/CD8 ratio more than 1, the lack of 17p and 11q deletions and of complex karyotypic aberrations, and the occurrence of the 13q14 deletion. No case displayed the VH3-21 gene, linked in mutated CLL with a poor outcome. In addition, the VH1-69 gene associated with unmutated CLL cases was never detected. These biologic features were coupled with an indolent clinical course characterized by an unmodified clinical stage over time, and by lack of autoimmune phenomena and of major infections requiring parental antibiotics. At a time when aggressive therapeutic strategies are always more frequently used in the management of CLL, the distinctive features of patients with long-lived stable disease should be prospectively identified at presentation.

Abstract: Background There is now great interest in using digital health tools to monitor patients' health status in real-world practice. Such tools often include electronic-patient-reported outcome (ePRO) systems in which symptoms questions are included into online interfaces for patient self-reporting, with real-time alerts triggered to the treating physician if severe symptoms or problems are reported. However, there is little information about the clinical utility and user perceptions of these systems, and this is particularly true in the area of hematology. Objectives This study investigates physicians' perceptions of usability and clinical utility of using remote ePROs in routine practice of patients with hematologic malignancies and explored implications in the delivery of patient care. Patients and Methods Remote ePROs are being gathered since December 2020 by the ALLIANCE Digital Health Platform, whose details of the development process have been previously described (Efficace F. et al., JMIR Res Protoc. 2021 Jun 1;10:e25271). Adult patients diagnosed with any hematologic malignancy are eligible to enter the platform, after having provided written informed consent. Aspects related to health-related quality of life (HRQoL), symptoms and medication adherence are assessed via validated PRO measures. The platform allows for real-time graphical presentation to physicians of individual patient symptoms and HRQoL outcomes. Based on a pre-defined algorithm, which includes the presence of clinically important problems and symptoms, the platform triggers automated alerts to the treating haematologists and medical staff. The definition of clinically important problems and symptoms is based on previously defined evidence-based thresholds (Giesinger J. et al., J Clin Epidemiol. 2020 Feb;118:1-8). We asked treating haematologists a feedback about their experience in using the platform, by an ad hoc web-survey consisting of 27 items covering several domains, including: usability and benefits, current use, evaluation of patient health-status, symptoms and adverse events, as well as physician-patient communication. We summarized characteristics of enrolled patients and treating haematologists by proportions, mean, median and range. We also used logistic regression analysis to check the possible association of characteristics of haematologists with survey results. Results Of the 201 patients invited to participate between December 2020 and June 2021 (cut-off date for current analysis), 180 (90%) accepted to enter the ALLIANCE platform, currently activated in 19 centers. The median age of patients was 57 years (range 21-91) and 58% were males. The majority were diagnosed with chronic myeloid leukemia (n=32, 18%) and multiple myeloma (n=31, 17%) and were in stable disease (n=89, 49%). Twenty-three hematologists (44% males) with a median age of 42 years (range 31-63) and an average 17 years (range 5-34) of experience in clinical practice, completed the survey. The majority of physicians (78%) accessed the platform at least once per month (of whom 39% at least once per week), regardless the alerts sent by the system about patients' clinically relevant problems. The frequency of access on a regular basis was also independent of physician sex (p=0.393) and years of experience in clinical practice (p=0.404). Overall, 57% of hematologists discussed often or very often ePROs with their patients, while 83% and 61% deemed this information helpful to better identify symptomatic adverse events (AEs) of grade 1-2 or of grade 3-4, respectively (see figure). Also, 87% and 91% of hematologists found ePROs useful to improve physician-patient communication and the accuracy of documentation of symptomatic AEs (regardless of severity), respectively. Physicians' responses to selected items of the survey are reported in the figure. Conclusions: Current findings support the clinical utility, from the perspective of the treating physician, of integrating ePROs into routine cancer care of patients with hematologic malignancies. Figure 1 Figure 1. Disclosures Efficace: Takeda: Consultancy; Janssen: Consultancy; Abbvie: Consultancy, Other: Grants (to Institution); Amgen: Consultancy, Other: Grants (to Institution). Breccia: Bristol Myers Squibb/Celgene: Honoraria; Pfizer: Honoraria; Abbvie: Honoraria; Incyte: Honoraria; Novartis: Honoraria. Fazio: Janseen: Honoraria. Petrucci: Karyopharm: Honoraria, Other: Advisory Board; GSK: Honoraria, Other: Advisory Board; Amgen: Honoraria, Other: Advisory Board; Takeda: Honoraria, Other: Advisory Board; BMS: Honoraria, Other: Advisory Board; Janssen-Cilag: Honoraria, Other: Advisory Board; Celgene: Honoraria, Other: Advisory Board. Rigacci: Merck: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Gilead Science: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Menarini: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Tafuri: Roche: Research Funding; Celgene: Research Funding; Novartis: Research Funding. Siragusa: Novartis, CSL, Behring, Amgen, Novonoridsk, SOBI, Bayer: Consultancy, Honoraria, Speakers Bureau. Patriarca: Incyte: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Argenix: Honoraria. Luppi: Abbvie: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; MSD: Honoraria; Gilead Science: Honoraria, Other: Travel grant; Daiichi-Sankyo: Honoraria; Jazz Pharma: Honoraria. Vignetti: Novartis: Honoraria; Incyte: Honoraria; Amgen: Consultancy, Honoraria.

Abstract: Introduction: Polycythemia Vera (PV) is a myeloproliferative neoplasm characterized by excessive red cell production and release of pro-inflammatory cytokines resulting in increased thrombotic risk, presence of systemic symptoms and reduced overall survival (OS). Abnormal body mass index (BMI) and comorbidities, as categorized by the Charlson Comorbidity Index (CCI), were found to influence treatment success and survival in several hematological malignancies, including myelofibrosis (MF). We evaluated the impact of CCI and BMI on the outcome of PV pts on the basis of real-world data. Methods: A network called "PV-NET" started in January 2019 including clinical/laboratory data of 2016 WHO-defined PV pts diagnosed and followed in 16 European Hematology Centers. Data cut-off was June 2019. OS was calculated from PV diagnosis to last contact or death (log-rank p). Cumulative incidences of events (thromboses, hemorrhages, infections, second neoplasia, and evolution into blast phase [BP] or MF) were conducted with Fine & Gray model with death as competing risk. Therapies were treated as time-to-event variables. Results: A total of 530 PV pts were collected. Median follow-up was 5.4 yrs (0.5-34) (total observation: 3633 pt-yrs). Main characteristics at diagnosis were: median age: 62.4 yrs (18.3-89.5); males: 53.4%; median (range) leukocyte/platelet count, x109/l: 9.8 (1.1-33)/448 (143-1386); median hemoglobin (g/dl)/hematocrit (%): 18.6/56 (males); 17.6/54.4 (females). Sixty-four (12.1%) and 34 (6.4%) pts had a thrombosis prior to or at diagnosis, respectively. At least one cardiovascular risk factor (CVRF) among smoke, diabetes, and hypertension was present in 343 pts (64.7%). Age-adjusted CCI was 0 (15.9%), 1 (18.9%), 2 (23.8%), and ≥3 (41.5%). Median BMI was 24 (17.4-37.3); 3.3%, 51.2%, 35.9% and 9.6% were underweight (BMI 〈 18.5), normal weight (18.5-24.9), overweight (BMI≥25) or obese (BMI≥30), respectively. Baseline features were comparable across BMI and CCI categories, but male pts were significantly more likely to have a BMI≥25 than female (p 〈 0.001). During follow-up, 64 all-grades thromboses (arterial, 56.3%), 29 bleedings, 56 infections and 66 second neoplasia were recorded. Overall, 13 pts progressed to BP and 32 to MF. Thirty-three pts died, because of BP (27.3%), second neoplasia (24.2%), MF (15.2%), old age (9.1%), thrombosis (6.1%) or other causes (18.1%). Incidence rates per 100 pt-yrs of all-grades events were: 1.5 (thromboses), 0.7 (bleedings), 1.4 (infections), 1.6 (second neoplasia), 0.4 (BP) and 0.9 (MF). Pts with CCI≥2 had a significantly higher rate of second neoplasia (p=0.01) and infections (p=0.03) over time and a worse OS (p 〈 0.001) compared to pts with CCI 〈 2. A BMI 〈 25 was associated with a higher probability of MF progression (p=0.02) and with reduced OS (p=0.04) (Fig.1). Notably, thrombotic risk was not influenced by CCI (p=0.16) and BMI (p=0.43). Pts received phlebotomies (PHL) (92.1%), hydroxyurea (HU) (82.6%), interferon (IFN) (7.9%), busulfan (2.6%), and ruxolitinib (RUX) (10.9%). Pts with CCI≥2 were significantly less treated with IFN (p 〈 0.001) and received more frequently HU (p 〈 0.001); notably, CCI did not influence the decision to start RUX (p=0.41). All pts treated with IFN but two had a BMI 〉 18.5; both underweight pts discontinued IFN due to intolerance. Overall, 0.8%, 19.4%, and 38.1% of pts had grade≥2 toxicity and/or stopped therapy because of intolerance during PHL, HU, and IFN, respectively. IFN intolerance tended to be more frequent in pts with CCI≥2 (p=0.06). Conclusions: CCI and BMI are rarely assessed in PV but may influence treatment strategy and survival. Particularly, CCI/BMI oriented the choice of IFN, but not RUX. Overweight PV pts had an improved survival, mimicking the "obesity paradox" observed in non-malignant CV diseases (Elagizi, et al. 2018). However, BMI may not be a reliable measure of adiposity. In cancer pts, an under/normal-weight may mask a hypercatabolic state with lean mass loss caused by a more aggressive disease, as supported by a higher rate of MF evolutions in pts with BMI 〈 25. Quantified body composition and careful control of comorbid conditions can improve PV management, prognostication and outcome. Disclosures Benevolo: Novartis Pharmaceuticals: Consultancy. Elli:Novartis: Membership on an entity's Board of Directors or advisory committees. Latagliata:Novartis: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Pfizer: Honoraria. Tiribelli:Pfizer: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Heidel:Celgene: Consultancy; CTI: Consultancy; Novartis: Consultancy, Research Funding. Cavazzini:Pfize: Honoraria; Incyte: Honoraria; Novartis: Honoraria. Bonifacio:Pfizer: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Amgen: Honoraria; BMS: Honoraria. Crugnola:Incyte: Honoraria; Novartis: Honoraria. Cuneo:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Krampera:Novartis: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Cavo:amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; bms: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; novartis: Honoraria. Breccia:Celgene: Honoraria; Incyte: Honoraria; Pfizer: Honoraria; BMS: Honoraria; Novartis: Honoraria. Palumbo:Hospira: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Teva: Honoraria; Novartis: Honoraria; Celgene: Honoraria. Palandri:Novartis: Consultancy, Honoraria.

Abstract: VEXAS is a prototypic hemato‐inflammatory disease combining rheumatologic and hematologic disorders in a molecularly defined nosological entity. In this nationwide study, we aimed at screenshotting the current diagnostic capabilities and clinical‐genomic features of VEXAS, and tracked UBA1 longitudinal clonal dynamics upon different therapeutics, including allogeneic hematopoietic cell transplant. We leveraged a collaboration between the Italian Society of Experimental Hematology and of Rheumatology and disseminated a national survey to collect clinical and molecular patient information. Overall, 13/29 centers performed UBA1 genomic testing locally, including Sanger sequencing (46%), next‐generation sequencing (23%), droplet digital polymerase chain reaction (8%), or combination (23%). A total of 41 male patients were identified, majority (51%) with threonine substitutions at Met41 hotspot, followed by valine and leucine (27% and 8%). Median age at VEXAS diagnosis was 67 years. All patients displayed anemia (median hemoglobin 9.1 g/dL), with macrocytosis. Bone marrow vacuoles were observed in most cases (89%). The most common rheumatologic association was polychondritis (49%). A concomitant myelodysplastic neoplasm/syndrome (MDS) was diagnosed in 71% of patients ( n = 28), chiefly exhibiting lower Revised International Prognostic Scoring System risk profiles. Karyotype was normal in all patients, except three MDS cases showing ‐Y, t(12;16)(q13;q24), and +8. The most frequently mutated gene was DNMT3A ( n = 10), followed by TET2 ( n = 3). At last follow‐up, five patients died and two patients progressed to acute leukemia. Longitudinal UBA1 clonal dynamics demonstrated mutational clearance following transplant. We collected a nationwide interdisciplinary VEXAS patient cohort, characterized by heterogeneous rheumatologic manifestations and treatments used. MDS was diagnosed in 71% of cases. Patients exhibited various longitudinal UBA1 clonal dynamics.

Abstract: The main objective of this study was to compare the long-term health-related quality of life of patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) vs ATRA plus standard chemotherapy. Patients previously enrolled in the randomized controlled trial APL0406 were considered eligible for this follow-up study. The following patient-reported outcome measures were used: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30), the EORTC Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20), and the Short Form Health Survey 36 (SF-36). The prevalence of late comorbidities and health problems was also assessed. The clinical significance of differences was evaluated based on predefined thresholds. A total of 161 of 232 potentially eligible patients were analyzed, of whom 83 were treated with ATRA-ATO and 78 were treated with ATRA chemotherapy. The median time since diagnosis of the study sample was 8 years. The 2 largest clinically meaningful differences in the EORTC QLQ-C30 were observed for role functioning (Δ = 8.4; 95% confidence interval [CI], 0.5 to 16.3) and dyspnea (Δ = −8.5; 95% CI, −16.4 to −0.7), favoring patients treated with ATRA-ATO. With regard to the SF-36 results, a clinically relevant better physical component score (Δ = 4.6; 95% CI, 1.3 to 7.8) was observed in patients treated with ATRA-ATO, but this was not the case for the mental component score. The 2 groups showed similar profiles in the scores of the EORTC QLQ-CIPN20 scales and in the prevalence of late comorbidities. Overall, our findings suggest that the greater and more sustained antileukemic efficacy of ATRA-ATO is also associated with better long-term patient-reported outcomes than ATRA chemotherapy. This study was registered at www.clinicaltrials.gov as #NCT03096496.