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Background KPC- K.pneumoniae bloodstream infection (KPC-KpBSI) mortality rate in patients with hematological malignancies is reported about 60%. The initial treatment active against KPC- K.pneumoniae is crucial for survival and KPC- K.pneumoniae rectal colonization usually precedes KPC-KpBSI. We evaluated the impact on KPC-KpBSI mortality of the preemptive use of antibiotics active against KPC- K.pneumoniae , as opposed to inactive or standard empiric antibiotics, for the empiric treatment of febrile neutropenia episodes in patients with hematological malignancy identified as KPC- K.pneumoniae intestinal carriers. Methods We compared the outcomes of KPC-KpBSIs occurring in high-risk hematological patients known to be colonized with KPC- K.pneumoniae , during two time periods: March2012-December2013 (Period 1, initial approach to KPC- K.pneumoniae spread) and January2017-October2018 (Period 2, full application of the preemptive strategy). The relative importance of the various prognostic factors that could influence death rates were assessed by forward stepwise logistic regression models. Results KPC-KpBSI-related mortality in hematological patients identified as KPC- K.pneumoniae carriers dropped from 50% in Period 1 to 6% in Period 2 (p < 0.01), from 58 to 9% in acute myeloid leukemia carriers(p < 0.01). KPC-KpBSIs developed in patients identified as KPC- K.pneumoniae carriers were initially treated with active therapy in 56% and 100% of cases in Period 1 and Period 2, respectively (p < 0.01), in particular with an active antibiotic combination in 39 and 94% of cases, respectively(p < 0.01). The 61% of KPC-KpBSI observed in Period 1 developed during inactive systemic antibiotic treatment (none in Period 2, p < 0.01), fatal in the 73% of cases. Overall, KPC-KpBSI-related mortality was 88% with no initial active treatment, 11.5% with at least one initial active antibiotic (p < 0.01), 9% with initial active combination. Only the initial active treatment resulted independently associated with survival. Conclusions In high-risk hematological patients colonized by KPC- K.pneumoniae , the empiric treatment of febrile neutropenia active against KPC- K.pneumonia e reduced KPC-KpBSI-related mortality to 6% and prevented fatal KPC-KpBSI occurrence during inactive systemic antibiotic treatment.

BackgroundAutologous stem cell transplantation (ASCT) has gained growing consideration as a treatment option for favorable-risk acute myeloid leukemia (FR-AML) in first complete remission (CR1), compared with chemotherapy.Materials and MethodsWe report the long-term outcomes of 117 consecutive patients with FR-AML fit for intensive chemotherapy diagnosed in our center between 1999 and 2020, who underwent ASCT.ResultsSixty-five of the 117 were eligible for intensive post-remission treatment, and 42 of those 65 received ASCT. Median follow up was 132 months. Overall survival (OS) and disease-free survival (DFS) were 75% and 76%. Higher doses of CD34 + stem cell infusions negatively impacted DFS in multivariate analysis. Core-binding factor (CBF) leukemia was an independent prognostic factor for improved DFS. No differences based on pre-transplant measurable residual disease (MRD) were observed. In CBF leukemia, 10-year DFS is 72% for MRD-positive patients versus 100% for MRD negative patients.ConclusionsASCT is effective and safe in FR-AML patients. In CBF leukemia, ASCT provides excellent results regardless of achievement of bone marrow MRD negativity. In NPM1-mutated/FLT3-wild type (mNPM1) AML, early molecular response seems to have more impact on prognosis. Prospective investigation of the role of gemtuzumab ozogamicin in this setting is ongoing.

To evaluate the benefits and safety of the empiric antibiotic treatment (EAT) active against KPC- in febrile neutropenic patients with acute leukaemia (AL) who are colonised by KPC- A 7-year (2013-2019) retrospective observational cohort study was conducted at the Haematology, Sapienza Rome University (Italy) on 94 febrile neutropenia episodes (FNE) in AL patients KPC- carriers treated with active EAT. Eighty-two (87%) FNE were empirically treated with antibiotic combinations [38 colistin-based and 44 ceftazidime-avibactam (CAZAVI)-based], 12 with CAZAVI monotherapy. Successful outcomes were observed in 88/94 (94%) FNE, 46/49 (94%) microbiologically documented infections, and 24/27 (89%) gram-negative bloodstream infections (GNB-BSI). Mortality due to infective causes was 4.2% (2.1% within 1 week). KPC infections caused 28/94 FNE (30%) and KPC BSI was documented in 22 FNE (23.4%) (85% of GNB-BSI), in all cases patients received active EAT, and 21 survived. KPC BSI mortality rate was 4.5%. CAZAVI-based EAT showed better results than colistin-based EAT (55/56 vs 33/38, p = 0.037), overall and without EAT modification (41/56 vs 20/38, p = 0.02). Empirical combinations including CAZAVI were successful in 98% of cases (43/44 vs 33/38 for colistin-based EAT, p = 0.01), without modifications in 82% (36/44 vs 20/28, p = 0.02). All deaths occurred in patients treated with colistin-based EAT (4/38 vs 0/56, p = 0.02). CAZAVI-containing EAT was the only independent factor for an overall successful response (HR 0.058, CI 0.013-1.072, p = 0.058). Nephrotoxicity occurred in 3(8%) patients undergoing colistin-based EAT (none in those undergoing CAZAVI-based EAT, p = 0.02). KPC- infections are frequent in colonised AL patients with FNE. EAT with active antibiotics, mainly CAZAVI-based combinations, was effective, safe, and associated with low overall and KPC BSI-related mortality.

Background Achieving complete remission (CR) is the main goal in AML treatment and a prerequisite for successful autologous stem cell transplantation (ACT). Methods Comparing results of peripheral blood ACT in patients with AML in CR1 attained following 1 versus 2 chemotherapy courses transplanted in 2000–2019. Results Patients 1532 (84%) with one and 293 (16%) patients with two induction chemotherapies courses (a total of 1825 patients) were included in the study. Follow‐up was 7.9 (95% CI: 7.4–8.4) and 7.7 (95% CI: 7.0–8.6) years (p = 0.8). Time from diagnosis to ACT was 4.7 (range, 3.9–5.8) versus 5.7 (range, 4.7–7.1) months (p < 0.001), respectively. Leukemia free survival (LFS) and overall survival (OS) at 5 years were inferior for patients achieving CR1 with 2 versus 1 course of chemotherapy: 26.6% versus 41.7% (HR = 1.42 [95% CI: 1.22–1.66], p < 0.001) and 36.2% versus 53.3%, (HR = 1.48 [95% CI: 1.25–1.75], p < 0.001), and 5‐year relapse incidence (RI) was higher: 67.2% versus 52.3%, (HR = 1.46 [95% CI: 1.25–1.72], p < 0.001). Five‐year non‐relapse mortality (NRM) was 6.2% versus 6.0% for patients with 2 versus 1 chemotherapy courses, and did not differ significantly (HR = 1.31 [95% CI: 0.81–2.10], p = 0.27). Conclusions LFS and OS were inferior and relapse rate was higher in AML patients who received two inductions chemotherapy courses to reach CR1 before being autografted. AML patients who required 2 induction courses to achieve remission, may be offered allogeneic transplantation rather than an autologous one in an attempt to reduce their high RI and improve outcomes. Autologous transplantation outcome in leukemic patients that achieve complete remission after two induction courses is inferior to outcome of patients achieving remission after one induction course. AML patients who need two induction chemotherapy courses to reach first complete remission may be offered allogeneic transplantation rather than autologous one aiming in reducing disease recurrence and improving transplantation outcome.

Abstract Background Despite improvements in survival outcomes for acute myeloid leukemia (AML), limited evidence is available on health-related quality of life (HRQoL) and health problems experienced by long-term survivors. Patients and methods This international, cross-sectional study evaluated HRQoL, comorbidities, and lifestyle behaviors among long-term AML survivors enrolled from 24 centers across 6 countries. Health-related quality of life was assessed using the SF-36 and the EORTC QLQ-C30 questionnaires, while comorbidities were measured with an adapted version of the validated self-administered comorbidity questionnaire. Lifestyle factors, including physical activity, diet, smoking, alcohol consumption, and body mass index, were also assessed. Results Overall, 225 AML survivors were enrolled, with a median time since diagnosis of 8.8 years (IQR 6.4-11.9) and a median age of 58.9 years (IQR 49.0-67.0). Compared with the general population, AML survivors exhibited clinically relevant impairments in SF-36 physical functioning (Δ = −8.09, P < .001) and role physical scales (Δ = -11.09, P < .001), as well as clinically relevant lower physical component summary scores (Δ = -3.94, P < .001). Survivors treated with alloSCT reported worse HRQoL profiles compared with those treated with autoSCT or chemotherapy only. Comorbidities were highly prevalent (88.5%), with impaired vision, back pain, and arthrosis/arthritis being the most frequent. Analysis of lifestyle behaviors showed that 66.2% of AML survivors were physically inactive, 80.2% did not meet dietary recommendations, and 55.3% were overweight/obese. Multivariate analysis identified physical inactivity as the only independent factor associated with worse HRQoL (β = −6.3, P < .001). Conclusion Our study shows that AML survivors experience physical limitations and a high comorbidity burden even many years after diagnosis, and it provides insights to better inform survivorship care programs. Further research examining the relationship between physical activity and HRQoL in long-term AML survivors is warranted.

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 Gemtuzumab ozogamicin (GO), is an anti-CD33 monoclonal antibody, approved for AML CD33 + , those patients with low and intermediate-risk who obtain a complete response may also be candidated for consolidation with autologous stem cell transplantation (ASCT). However, there are scant data on the mobilization of hemopoietic stem cells (HSC) after fractionated GO. We retrospectively studied data from five Italian centers and identified 20 patients (median age 54 years, range 29–69, 15 female, 15 NPM1mutated) that attempted HSC mobilization after fractionated doses of GO + “7 + 3” regimen and 1–2 cycles of consolidation (GO + HDAC + daunorubicin). After chemotherapy and standard G-CSF, 11/20 patients (55%) reached the threshold of 20 CD34 + /µL, and HSC were successfully harvested, while 9 patients (45%) failed. The median day of apheresis was Day + 26 from the start of chemotherapy (range 22–39 days). In good mobilizer patients, the median circulating CD34 + cells were 35.9 cells/µL and the median CD34 + harvested were 4.65 × 106/kg of patients’ body weight. With a median follow-up of 12.7 months, at 24 months from the first diagnosis, 93.3% of all 20 patients were alive and the median overall survival was 25 months. The 2-year RFS rate from the timepoint of the first CR was 72.6%, while the median RFS was not reached. However, only five patients underwent ASCT and achieved full engraftment.In conclusion, in our cohort of patients, the addition of GO reduced HSC mobilization and harvesting, which was reached in about 55% of patients. Nevertheless, further studies are warranted to evaluate the effects of fractionated doses of GO on HSC mobilization and ASCT outcomes.

A Correction to this paper has been published: https://doi.org/10.1038/s41409-021-01242-9