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Background: The introduction of all- trans retinoic acid (ATRA) and arsenic trioxide (ATO) has radically improved the prognosis of acute promyelocytic leukemia (APL), with cure rates above 80%. While relapse occurs in less than 20% of cases, addressing this issue remains challenging. Identifying effective salvage therapies for relapsed APL is crucial to improve patient outcomes., Methods: A retrospective analysis was performed on a multicentric cohort of 67 APL patients in first relapse, treated in three Italian hematology centers from June 1981 to November 2021. The overall survival (OS) and cumulative incidence of relapse (CIR) were calculated, and predictive factors were assessed using Cox regression models., Results: Overall, 61 patients (91%) received ATO ± ATRA (40.3%), chemo-based regimens (40.3%), or ATRA ± Gemtuzumab ozogamicin (GO) (10.4%). Complete remission (CR) was achieved in 98.2% of patients (molecular CR, n = 71.4%). With a median follow-up time of 54.5 months, the 5-year OS was 73% in the ATO ± ATRA group, 44% in the chemo-based group, and 29% in the ATRA ± GO group ( p = 0.035). The 5-year OS rate was also higher for transplant recipients vs. non-recipients within the chemo-based cohort (50% vs. 33%, p = 0.017), but not in the ATO-based cohort ( p = 0.12). ATO-based salvage therapy resulted in better OS in both univariate ( p = 0.025) and multivariate analyses ( p = 0.026). The 2-year CIR was higher in patients without molecular CR vs. patients in molecular CR (66% vs. 24%, p = 0.034). Molecular CR was a significant predictor of second relapse in both univariate ( p = 0.035) and multivariate analyses ( p = 0.036)., Conclusions: Our findings support the efficacy of ATO-based therapies in first relapse of APL and confirm the achievement of molecular remission as an independent outcome predictor in both first and second APL relapse.

We analyzed 140 patients with a median age of 51 years; 21% had WBC ≥ 100 × 10 9 /L, and 52% had an NPM1 co-mutation. Until 2018, 101 patients received chemotherapy; thereafter, 39 received 3+7+midostaurin. The overall CR rate was 64%, higher in NPM1 mutant patients (73%). Univariate analysis showed that NPM1 mutation ( p = 0.032) and WBC < 100 × 10 9 /L ( p = 0.013) positively influenced the response, with a trend for FLT3i administration ( p = 0.052). Multivariate analysis confirmed WBC count as an independent prognostic factor ( p = 0.017). In CR1, 41/90 patients underwent allogeneic and 18 autologous transplantation. The median EFS was 1.1 vs. 1.6 years in autografted and allografted patients, respectively ( p = 0.9). The one-year non-relapse mortality was 0.00% for autologous and 28% for allogeneic transplants ( p = 0.007); CIR at 1 and 3 years was higher in autologous transplants (39% vs. 15% and 57% vs. 21%, p = 0.004). The median survival was not reached in the FLT3i group. Overall, 69 patients received stem cell transplantation (18 autologous, 51 allogeneic). Post-transplant FLT3i was resumed in eight patients, all alive after a median of 65 months. Allogeneic transplantation is crucial in FLT3-mutated AML, but the next challenge will be to identify which patients can benefit from transplants in CR1 and in which to intensify post-transplant therapy.

Introduction: Chronic myeloid leukemia (CML) prevalence is currently increasing due to the great efficacy of tyrosine kinase inhibitor (TKI) therapy. Discontinuation of treatment in the long-term, owing to avoid off-target side effects or treatment-free remission (TFR), has become an additional treatment goal in CML patients who achieved a deep molecular response (DMR). Second-generation TKIs (2 G-TKIs) have a significantly higher rate of DMR than imatinib. Hence, especially in young patients with a strategy of TFR, 2 G-TKIs are becoming the most frequently used TKIs and may increase TFR attempts in the future., Areas Covered: In this review, the main findings extrapolated from clinical trials and real-life evidence regarding 2 G-TKIs discontinuation were discussed, through broad research on Medline, Embase, and archives from EHA and ASH congresses., Expert Opinion: Overall, TFR rate after 2 G-TKIs is ranging from 40% to 60% for selected patients with sustained DMR and it can be considered a safe procedure, that have become, nowadays, a daily practice. However, many crucial aspects regarding treatment choices, timings, as well as predictive factors, patient communication, and optimal strategies need to be better clarified to improve successful TFR rate.

COVID-19 disease has a strong impact on hematological patients; those receiving autologous hematopoietic stem cell transplantation (aHSCT) represent a particularly vulnerable group, in which the effectiveness of vaccination is very variable. Chiarucci et al. showed that patients affected by non-Hodgkin lymphoma (NHL) and treated with rituximab experienced a lower rate of immunization against SARS-CoV-2 (54%), as well as significantly lower IgG antibody titers. In our multicenter retrospective observational study, we included 82 patients who underwent aHSCT, divided into two groups: 58 patients vaccinated after aHSCT (group A) and 24 vaccinated before getting transplantation (group B). In group A, 39 (67%) patients had positive serology, and the rate of positivity increased with time after aHSCT. In the subgroup of patients with NHL, the administration of rituximab predicted negative serology, particularly when administered in the 6 months before vaccination (13% response rate). Patients affected by plasma cells had a higher rate of positivity (83% overall), independently of the time to aHSCT. In group B, no patient who initially showed positive serology became negative after transplantation, so the aHSCT did not affect the response to the vaccination. Our study confirmed the role of rituximab as a negative predictor of response to SARS-CoV-2 vaccination, whereas the conditioning and transplantation procedure itself seemed to be less important., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Autore, Stirparo, Innocenti, Papa, Marchesi, Togni, Mariani, Torrieri, Salvatori, Fazio, Metafuni, Giammarco, Sora, Falcucci, Ferrari, Trisolini, Capria, Tafuri, Chiusolo, Sica and Laurenti.)

Objective: To characterize skin integrity among coronavirus disease 2019 (COVID-19) patients treated in the intensive care unit (ICU), and identify risk factors for skin failure (SF) in these patients. Design: The characteristic, profound pro-inflammatory, hypercoagulable state of COVID-19 is manifested by the high severity of illness and extensive organ dysfunction observed in these patients. SF in critically ill patients, although described previously, exhibits a uniquely complex pathogenesis in this population. Patients: Retrospective review of all COVID-19 patients (confirmed positive for severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]) admitted to a single surgical ICU for at least 48 hours between March-June 2020. Interventions: Data were extracted from a COVID-19 institutional data repository that harvested data from electronic health records and other clinical data sources. Demographics; coagulation/inflammation biomarkers; number, location, and stage of SF lesions; resource utilization; and outcomes were captured. Measurements and Main Results: 64 patients met inclusion criteria; 51 (80%) developed SF (SF+ ). Forty-three (85%) developed stage 3 or higher SF (χ 2   =  22.66, P  < .0001). Thirty-nine of 51 (76%) SF+ patients developed more than one SF lesion (χ 2   =  13.26, P   =  .0003). SF+ patients manifested a profound pro-inflammatory, hypercoagulable phenotype (lower serum albumin and higher ferritin, interleukin [IL]-6 and D-dimer concentrations [all, P  < .001]). Durations of mechanical ventilation, vasopressor therapy, and ICU length of stay were significantly longer (all, P  < .05) in the SF + patients. Conclusions: The unique characteristics of COVID-19 dermatopathology and the strong correlation between markers of inflammation and development of SF reflect COVID-19-related organ dysfunction and its deleterious effects on the microcirculation. Considering that skin is invaded directly by SARS-CoV-2 and affected by COVID-19-related immune complex deposition and microthrombosis, SF may reflect disease as opposed to pressure injuries related to processes of care. In the context of COVID-19 critical illness, SF should not be considered a "never event."