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Summary: All‐trans‐retinoic acid (ATRA) and arsenic trioxide (ATO) represent the standard of care for low‐intermediate risk acute promyelocytic leukaemia (APL). Leucocytosis during induction with ATRA‐ATO represents a common complication with an incidence of up to 60%. To identify predictive factors for this complication, we studied a cohort of 65 low‐intermediate risk APL patients treated with ATRA‐ATO in three highly specialized Italian centres. Overall, 39/65 (60%) patients developed leucocytosis, with a peak in leucocyte count being most frequent in the second week from diagnosis. All cases were successfully managed with hydroxyurea. Predictive factors for leucocytosis in univariate analysis were lower platelet counts (odds ratio [OR] 0.98, 0.97–1.00, p = 0.018), lower fibrinogen levels (OR 0.36, 0.17–0.66, p = 0.003), higher bone marrow blast infiltration (OR 1.03, 1.01–1.07, p = 0.021) and CD117 expression by flow (OR 1.04, 1.01–1.08, p = 0.012). Multivariate analysis confirmed lower levels of fibrinogen at diagnosis as the strongest predictive factor for the development of leucocytosis (OR 0.36, 0.15–0.72, p = 0.009). Differentiation syndrome (DS) occurred only in patients developing leucocytosis showing a strict correlation with rising leucocytes counts (16/39 vs. 0/26, p < 0.001). In addition, other treatment‐related complications including QTc prolongation, cardiac events, liver, and haematological toxicities were significantly more frequent in patients experiencing leucocytosis (22/39 vs. 3/26, p < 0.001). In conclusion, APL patients undergoing ATRA‐ATO therapy with lower fibrinogen levels and platelet counts at diagnosis and with a massive bone marrow blast infiltrate should be carefully monitored for the development of leucocytosis during induction. DS and other treatment‐related complications seem to occur almost exclusively in patients developing leucocytosis, who should necessarily receive DS prophylaxis and more intensive monitoring and supportive therapy to prevent treatment complications. [ABSTRACT FROM AUTHOR]

Simple Summary: Relapses of acute promyelocytic leukemia (APL) remain a challenge despite the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Given the variability in salvage therapies and emerging evidence supporting the deferral of hematopoietic cell transplantation (HCT) in patients receiving ATO, we analyzed the outcomes of a multicentric cohort of 67 relapsed APL patients. Better outcomes were reported with ATO ± ATRA compared to chemo-based regimens and ATRA ± Gemtuzumab ozogamicin (GO). A significant survival advantage was observed for patients undergoing HCT in the chemo-based cohort (p = 0.017), but not in the ATO-based group (p = 0.12). Achieving molecular complete remission (CR) post salvage therapy emerged as the main prognostic factor for second relapses in both univariate and multivariate analyses. Our findings support the efficacy of ATO-based therapies in first relapse and enhance the role of molecular remission as an independent outcome predictor in both first and second APL relapses. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: FLT3 mutations are common in acute myeloid leukemia (AML) and are often associated with poorer outcomes and higher relapse rates. This study examined the long-term outcomes of FLT3-mutated (FLT3m) AML patients who received intensive treatment at our institution over the past 24 years, comparing the results in patients who received standard chemotherapy alone with those who received a FLT3 inhibitor (FLT3i). Our single-center, real-life experience confirms the impact of FLT3i administration on survival, both in frontline and salvage settings. In addition, our results underline that the proper positioning of allogeneic stem cell transplantation in the therapeutic algorithm is still an unmet need. These findings suggest that incorporating FLT3-targeting agents into treatment plans may improve outcomes for AML patients while highlighting the need for the continued optimization of treatment strategies to enhance patient survival and quality of life. We analyzed 140 patients with a median age of 51 years; 21% had WBC ≥ 100 × 109/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 × 109/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. [ABSTRACT FROM AUTHOR]

This article discusses the risk of early death (ED) in patients with acute promyelocytic leukemia (APL). The study found that the mortality rate was significantly higher in high-risk and very high-risk patients compared to low-risk patients. The analysis did not reveal any differences in bone marrow morphology or cytometric markers between ED and non-ED patients, suggesting that these factors may not play a role in determining the risk of early mortality. The study also evaluated the effectiveness of the ED risk score in patients treated with the ATO+ATRA regimen and found no premature deaths in this group. The article concludes that the ED risk score is effective in predicting early mortality and emphasizes the importance of timely diagnosis and treatment in improving outcomes for APL patients. [Extracted from the article]

P9 showed a different molecular profile, I FLT3-TKD+/NPM1 i + at diagnosis and I FLT3/TKD i and I NPM1 i wild type at relapse; however, at relapse the patient presented as myeloid sarcoma of the skin. At diagnosis, this patient received intensive chemotherapy followed by PBSCT; at relapse, he was treated with high dose cytarabine plus intrathecal therapy followed by an allogeneic transplant. The occurrence of an acute myeloid leukemia (AML) relapse is generally observed within 2-3 years after complete remission (CR) and affects the overall survival rate of these patients [[1]]. Aim of our study was to evaluate, in a large series of AML patients diagnosed at our Center, the incidence of very late AML relapses, in addition, the therapeutic strategies and the outcome of these patients. [Extracted from the article]

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