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Background and objectives Identification of latent tuberculosis infection (LTBI) is a critical step of tuberculosis surveillance, especially in low incidence countries, and is limited to situations with a higher probability of developing active disease, e.g., patients with hematological malignancies. According to guidelines, in TB non-endemic countries no clear screening program is established at diagnosis for patients with acute leukemia (AL). The primary endpoint of this study was to establish the LTBI incidence in patients with diagnosis of AL using QuantiFERON (QFT)-TB. Secondarily, TB-specific prophylaxis efficacy and safety, and features driving increased risk of LTBI were evaluated. Methods QFT-TB screening was performed before induction, consolidation or during follow-up, in all patients with AL (myeloid and lymphoid), treated at our Institution between October 2019 and August 2023. Results We accrued 62 patients, of whom 7 (11,3%) tested positive, without any symptoms or signs of active TB, and 2 (3,2%) resulted as indeterminate. All positive patients started prophylaxis with isoniazid 300 mg/die, while patients whose test was indeterminate did not receive any prophylaxis. Active TB was excluded by imaging, as well as microscopic, cultural, and molecular examination on bronchoalveolar lavage. During the 46-month period of observation, none of the patients developed TB reactivation. Conclusions In our country, LTBI is not uncommon as expected. Despite the low sample size, 1 out of 10 of our patients had prior TB exposure. This finding suggests implementing TB screening in the pre-treatment setting, particularly in a time when more numerous active treatments are becoming available also for patients ineligible to intensive chemotherapy.

Abstract Background Pneumocystis jirovecii pneumonia (PCP) and SARS-CoV2 share some similarities in their effects on the respiratory system, clinical presentation, and management. The COVID-19 pandemic required rapid action to curb transmission and mitigate its lethiferous impact. Non-pharmaceutical interventions (NPIs) were globally adopted. We hypothesized that these measures reduced the transmission and acquisition of P. jirovecii in both hospital and community settings. Methods We conducted a retrospective observational study on 2950 respiratory specimens from patients with suspected pulmonary infection, analyzed at the Laboratory of Parasitology Unit of the Policlinico Tor Vergata of Rome, Italy, from January 2014 to December 2022. Results We show a significant reduction in the frequency of PCP in the COVID-19 pandemic era compared to the previous period. Among the four sequence types of P. jirovecii identified, genotype 1 was the most prevalent (37%). We observed a non-significant trend of decreasing cases with genotype 1 and increasing cases with genotype 3 over the study period. Conclusions The nationwide implementation of NPIs against COVID-19 may have changed the microbiological landscape of exposure, thereby decreasing the exposure to P. jirovecii and consequently reducing the incidence of PCP.

Abstract. Background: Colonization by multidrug-resistant organisms (MDRO) is a frequent complication in hematologic departments, which puts patients at risk of life-threatening bacterial sepsis. Fever of unknown origin (FUO) is a condition related to the delivery of chemotherapy in hematologic malignancies, in which the use of antibiotics is debated. The incidence, risk factors, and influence on the outcome of these conditions in patients with acute myeloid leukemia (AML) are not clearly defined. Methods: We retrospectively analyzed 132 consecutive admissions of non-promyelocytic AML patients at the Hematology Unit of the University Tor Vergata in Rome between June 2019 and February 2022. MDRO swab-based screening was performed in all patients on the day of admission and once weekly after that. FUO was defined as fever with no evidence of infection. Results: Of 132 consecutive hospitalizations (69 AML patients), MDRO colonization was observed in 35 cases (26%) and resulted independently related to a previous MDRO colonization (p=0.001) and length of hospitalization (p=0.03). The colonization persistence rate in subsequent admissions was 64%. MDRO-related bloodstream infection was observed in 8 patients (23%) and correlated with grade III/IV mucositis (p=0.008) and length of hospitalization (p=0.02). FUO occurred in 68 cases (51%) and correlated with an absolute neutrophilic count

In acute myeloid leukemia (AML) many patients experience relapse, despite the achievement of morphological complete remission; therefore, conventional morphologic criteria are currently considered inadequate for assessing the quality of the response after treatment. Quantification of measurable residual disease (MRD) has been established as a strong prognostic marker in AML and patients that test MRD negative have lower relapse rates and better survival than those who test positive. Different techniques, varying in their sensitivity and applicability to patients, are available for the measurement of MRD and their use as a guide for selecting the most optimal post-remission therapy is an area of active investigation. Although still controversial, MRD prognostic value promises to support drug development serving as a surrogate biomarker, potentially useful for accelerating the regulatory approval of new agents. In this review, we will critically examine the methods used to detect MRD and its potential role as a study endpoint.

Using a multiparametric flow cytometry assay, we assessed the predictive power of a threshold calculated applying the criteria of limit of detection (LOD) and limit of quantitation (LOQ) in adult patients with acute myeloid leukemia. This was a post-hoc analysis of 261 patients enrolled in the GIMEMA AML1310 prospective trial. According to the protocol design, using the predefined measurable residual disease (MRD) threshold of 0.035% bone marrow residual leukemic cells (RLC) calculated on mononuclear cells, 154 (59%) of the 261 patients were negative (MRD

Informed treatment decision-making in acute myeloid leukemia (AML) requires a comprehensive evaluation of all clinical and biological features that may affect the outcome with any given type or intensity of therapy [...]

Information regarding the incidence and the prognostic impact of thrombotic events (TE) in non-promyelocytic acute myeloid leukemia (AML) is sparse. Although several risk factors associated with an increased risk of TE development have been recognized, we still lack universally approved guidelines for identification and management of these complications. We retrospectively analyzed 300 consecutive patients with newly diagnosed AML. Reporting the incidence of venous TE (VTE) and arterial TE (ATE) was the primary endpoint. Secondarily, we evaluated baseline patient- and disease-related characteristics with a possible influence of VTE-occurrence probability. Finally, we evaluated the impact of TE on survival. Overall, the VTE incidence was 12.3% and ATE incidence was 2.3%. We identified three independent predictors associated with early-VTE: comorbidities (p = 0.006), platelets count >50 × 109/L (p = 0.006), and a previous history of VTE (p = 0.003). Assigning 1 point to each variable, we observed an overall cumulative incidence of VTE of 18.4% in the high-risk group (≥2 points) versus 6.4% in the low-risk group (0–1 point), log-rank = 0.002. Overall, ATE, but not VTE, was associated with poor prognosis (p < 0.001). In conclusion, TE incidence in AML patients is not negligible. We proposed an early-VTE risk score that could be useful for a proper management of VTE prophylaxis.

Hypofibrinogenemia (HF) in adult acute lymphoblastic leukemia (ALL) of B lineage is uncommon and mostly associated with asparaginase (ASP) delivery. Since we noticed a significant reduction in fibrinogen (FBG) plasma levels even before the first ASP dose, we aim to assess the levels of FBG during induction treatment and explore if the FBG fall correlated with therapies other than asparaginase and/or specific leukemia biological features. We retrospectively analyzed FBG levels in 115 patients with B-ALL. In 74 (64%) out of 115 patients FBG decline occurred during the steroid prephase. In univariate analysis, such a steroid-related HF was significantly associated with BCR-ABL1 rearrangement (p = 0.00158). None of those experiencing HF had significant modifications of liver function tests during induction treatment. Our retrospective study suggests that in B-ALL, steroid therapy can also induce HF and that such an event is preferentially observed in patients carrying BCR-ABL1 rearrangements. The pathogenesis of this phenomenon is still unclear. We attempt to explain it by applying the International Society of Thrombosis and Hemostasis-Disseminated Intravascular Coagulation score (ISTH-DIC score); nonetheless additional studies are needed to clarify further the mechanisms of HF in this subset of patients.

In acute lymphoblastic leukemia, flow cytometry detects more accurately leukemic cells in patients' cerebrospinal fluid compared to conventional cytology. However, the clinical significance of flow cytometry positivity with a negative cytology - occult central nervous system disease - is not clear. In the framework of the national Campus ALL program, we retrospectively evaluated the incidence of occult central nervous system disease and its impact on outcome in 240 adult patients with newly diagnosed acute lymphoblastic leukemia. All cerebrospinal fluid samples were investigated by conventional cytology and flow cytometry. The presence of ≥10 phenotypically abnormal events, forming a cluster, was considered as flow cytometry positivity. No central nervous system involvement was documented in 179 patients, while 18 were positive by conventional morphology and 43 were occult central nervous system disease positive. The relapse rate was significantly lower in central nervous system disease negative patients and the disease-free and overall survival were significantly longer in central nervous system disease negative patients than in those with manifest or occult central nervous system disease positive. In multivariate analysis, the status of manifest and occult central nervous system disease positivity was independently associated with a worse overall survival. In conclusion, we demonstrate that in adult acute lymphoblastic leukemia patients at diagnosis flow cytometry can detect occult central nervous system disease at high sensitivity and that the status of occult central nervous system disease positivity is associated with an adverse outcome. (Clinicaltrials.gov NCT03803670)

Background: although bronchoalveolar lavage (BAL) measurements of galactomannan antigen (GM) seems to be more sensitive than serum testing to detect invasive pulmonary aspergillosis (IPA), a consensus on the most appropriate diagnostic threshold of the BAL GM test is still unclear. Moreover, there is uncertainty as to whether BAL is a safe procedure in patients with hematological malignancies (HM) and thrombocytopenia (TC). Objectives: based on this background, 102 adult patients with HM and associated thrombocytopenia were retrospectively analyzed with the twin aims of 1) determining whether BAL is a safe and feasible procedure; and, 2) identifying the most appropriate threshold for GM positivity in the diagnosis of IPA. Patients/Methods: each BAL was considered as one case/patient. One hundred twelve BALs were carried out in 102 HM patients: at the time of the BAL, the median platelets count (PLTs) in all patients was 47x109/L (1-476) and 31 patients (27%) had PLTs< 20x109/L. Results: complications from the BAL were infrequent (3.5%) and mild. No bleeding was reported. The BAL GM cut off of >0.8 was associated with the best diagnostic accuracy (sensitivity 72.97% and specificity 80%). Antifungal treatment of patients with BAL GM >0.8resulted in a clinical-radiological improvement in 35/41patients (85%). Conclusions: BAL was a safe procedure also in thrombocytopenic patients, permitting an IPA diagnosis not otherwise identifiable using EORTC/MSG criteria. Our data suggest that a BAL GM value of>0.8 represents the most useful cut-off in terms of sensibility and specificity. Further prospective studies on a larger number of patients are needed to confirm these results.

Measurable residual disease (MRD) is increasingly employed as a biomarker of quality of complete remission (CR) in intensively treated acute myeloid leukemia (AML) patients. We evaluated if a MRD-driven transplant policy improved outcome as compared to a policy solely relying on a familiar donor availability. High-risk patients (adverse karyotype, FLT3-ITD) received allogeneic hematopoietic cell transplant (alloHCT) whereas for intermediate and low risk ones (CBF-AML and NPM1-mutated), alloHCT or autologous SCT was delivered depending on the post-consolidation measurable residual disease (MRD) status, as assessed by flow cytometry. For comparison, we analyzed a matched historical cohort of patients in whom alloHCT was delivered based on the sole availability of a matched sibling donor. Ten-years overall and disease-free survival were longer in the MRD-driven cohort as compared to the historical cohort (47.7% vs. 28.7%, p = 0.012 and 42.0% vs. 19.5%, p = 0.0003). The favorable impact of this MRD-driven strategy was evident for the intermediate-risk category, particularly for MRD positive patients. In the low-risk category, the significantly lower CIR of the MRD-driven cohort did not translate into a survival advantage. In conclusion, a MRD-driven transplant allocation may play a better role than the one based on the simple donor availability. This approach determines a superior outcome of intermediate-risk patients whereat in low-risk ones a careful evaluation is needed for transplant allocation.

Acute myeloid leukemia (AML), with an incidence increasing with age, is the most common acute leukemia in adults. Concurrent comorbidities, mild to severe organ dysfunctions, and low performance status (PS) are frequently found in older patients at the onset, conditioning treatment choice and crucially influencing the outcome. Although anthracyclines plus cytarabine-based chemotherapy, also called “7 + 3” regimen, remains the standard of care in young adults, its use in patients older than 65 years should be reserved to selected cases because of higher incidence of toxicity. These adverse features of AML in the elderly underline the importance of a careful patient assessment at diagnosis as a critical tool in the decision-making process of treatment choice. In this review, we will describe selected recently approved drugs as well as examine prognostic algorithms that may be helpful to assign treatment in elderly patients properly.