Background Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19. Methods This multicentre, retrospective, cohort study included adult patients (aged ≥18 years) with diagnosis of a WHO-defined haematological malignancy admitted to 66 Italian hospitals between Feb 25 and May 18, 2020, with laboratory-confirmed and symptomatic COVID-19. Data cutoff for this analysis was June 22, 2020. The primary outcome was mortality and evaluation of potential predictive parameters of mortality. We calculated standardised mortality ratios between observed death in the study cohort and expected death by applying stratum-specific mortality rates of the Italian population with COVID-19 and an Italian cohort of 31 993 patients with haematological malignancies without COVID-19 (data up to March 1, 2019). Multivariable Cox proportional hazards model was used to identify factors associated with overall survival. This study is registered with ClinicalTrials.gov, NCT04352556, and the prospective part of the study is ongoing. Findings We enrolled 536 patients with a median follow-up of 20 days (IQR 10-34) at data cutoff, 85 (16%) of whom were managed as outpatients. 440 (98%) of 451 hospitalised patients completed their hospital course (were either discharged alive or died). 198 (37%) of 536 patients died. When compared with the general Italian population with COVID-19, the standardised mortality ratio was 2•04 (95% CI 1•77-2•34) in our whole study cohort and 3•72 (2•86-4•64) in individuals younger than 70 years. When compared with the non-COVID-19 cohort with haematological malignancies, the standardised mortality ratio was 41•3 (38•1-44•9). Older age (hazard ratio 1•03, 95% CI 1•01-1•05); progressive disease status (2•10, 1•41-3•12); diagnosis of acute myeloid leukaemia (3•49, 1•56-7•81), indolent non-Hodgin lymphoma (2•19, 1•07-4•48), aggressive non-Hodgkin lymphoma (2•56, 1•34-4•89), or plasma cell neoplasms (2•48, 1•31-4•69), and severe or critical COVID-19 (4•08, 2•73-6•09) were associated with worse overall survival. Interpretation This study adds to the evidence that patients with haematological malignancies have worse outcomes than both the general population with COVID-19 and patients with haematological malignancies without COVID-19. The high mortality among patients with haematological malignancies hospitalised with COVID-19 highlights the need for aggressive infection prevention strategies, at least until effective vaccination or treatment strategies are available. Funding Associazione italiana contro le leucemie, linfomi e mieloma-Varese Onlus.

Purpose The initial results of the APL0406 trial showed that the combination of all- trans-retinoic acid (ATRA) and arsenic trioxide (ATO) is at least not inferior to standard ATRA and chemotherapy (CHT) in first-line therapy of low- or intermediate-risk acute promyelocytic leukemia (APL). We herein report the final analysis on the complete series of patients enrolled onto this trial. Patients and Methods The APL0406 study was a prospective, randomized, multicenter, open-label, phase III noninferiority trial. Eligible patients were adults between 18 and 71 years of age with newly diagnosed, low- or intermediate-risk APL (WBC at diagnosis ≤ 10 × 10/L). Overall, 276 patients were randomly assigned to receive ATRA-ATO or ATRA-CHT between October 2007 and January 2013. Results Of 263 patients evaluable for response to induction, 127 (100%) of 127 patients and 132 (97%) of 136 patients achieved complete remission (CR) in the ATRA-ATO and ATRA-CHT arms, respectively ( P = .12). After a median follow-up of 40.6 months, the event-free survival, cumulative incidence of relapse, and overall survival at 50 months for patients in the ATRA-ATO versus ATRA-CHT arms were 97.3% v 80%, 1.9% v 13.9%, and 99.2% v 92.6%, respectively ( P < .001, P = .0013, and P = .0073, respectively). Postinduction events included two relapses and one death in CR in the ATRA-ATO arm and two instances of molecular resistance after third consolidation, 15 relapses, and five deaths in CR in the ATRA-CHT arm. Two patients in the ATRA-CHT arm developed a therapy-related myeloid neoplasm. Conclusion These results show that the advantages of ATRA-ATO over ATRA-CHT increase over time and that there is significantly greater and more sustained antileukemic efficacy of ATO-ATRA compared with ATRA-CHT in low- and intermediate-risk APL.