Rethinking the definition of 'less intensive' for venetoclax-combining regimens in acute myeloid leukaemia patients.

Invasive fungal infections (IFIs), mainly due to pulmonary aspergillosis, are considered a serious complication in acute leukaemia, with an unfavourable impact on patient. In this well-conducted retrospective study, Reynolds et al. suggest that the use of posaconazole prophylaxis in association with venetoclax plus hypomethylating agents or chemotherapy leads to a reduction of IFI incidence. Therapeutic drug monitoring of posaconazole levels is suggested, even if no correlation with IFI risk has been demonstrated. Commentary on: Reynolds et al. Invasive fungal infection following venetoclax and posaconazole co-administration. Br J Haematol 2023;203:593-598.

Comparison between azacitidine and decitabine as front-line therapy in elderly acute myeloid leukemia patients not eligible for intensive chemotherapy.

We compared the efficacy of azacitidine (AZA) and decitabine (DEC) in elderly patients with untreated AML, diagnosed according to WHO criteria. In the two groups, we evaluated complete remission (CR), overall survival (OS) and disease free survival (DFS). The AZA and DEC groups included 139 and 186 patients, respectively. To minimize the effects of treatment selection bias, adjustments were made using the propensity-score matching method, which yielded 136 patient pairs. In the AZA and DEC cohort, median age was 75 years in both, (IQR, 71-78 and 71-77), median WBCc at treatment onset 2.5 × 109/L (IQR, 1.6-5.8) and 2.9 × 109/L (IQR, 1.5-8.1), median bone marrow (BM) blast count 30% (IQR, 24-41%) and 49% (IQR, 30-67%), 59 (43%) and 63 (46%) patients had a secondary AML, respectively. Karyotype was evaluable in 115 and 120 patients: 80 (59%) and 87 (64%) had intermediate-risk, 35 (26%) and 33 (24%) an adverse risk karyotype, respectively. Median number of cycles delivered was 6 (IQR, 3.0-11.0) and 4 (IQR, 2.0-9.0), CR rate was 24% vs 29%, median OS and 2-year OS rates 11.3 (95% CI 9.5-13.8) vs 12.0 (95% CI 7.1-16.5) months and 20% vs 24%, respectively. No differences in CR and OS were found within the following subgroup: intermediate- and adverse-risk cytogenetic, frequency of WBCc at treatment ≥ 5 × 10^9 L and < 5 × 10^9/L, de novo and secondary AML, BM blast count < and ≥ 30%. Median DFS for AZA and DEC treated patients was 9.2 vs 12 months, respectively. Our analysis indicates similar outcomes with AZA compared to DEC.

Biological versus Clinical Risk Factors in Acute Myeloid Leukemia: Is There a Winner?

We present a case of a patient with a three-month history of peripheral blood cytopenia without a confirmed diagnosis of myelodysplastic syndrome, who developed a favourable-risk acute myeloid leukemia (AML), according to the European Leukemia Net (ELN) criteria. The patient achieved a complete remission with incomplete platelet recovery (CRi) after induction. The patient achieved the morphological CR after the first consolidation and completed the first-line treatment with a syngeneic stem cell transplantation (SCT). A disease relapse occurred after one year of CR (blast cell count in the bone marrow 15%), and the patient was offered a haplo-SCT, which he refused due to personal reasons. In this paper, we discuss the interplay between clinical and biological risk factors in non-high-risk AML patients and speculate that some old clinical risk factors (e.g., age of the patient, achievement of CR after induction, and previous history of myelodysplastic syndrome) may still impact on the treatment decision algorithm of some of these patients.

P. aeruginosa bloodstream infections among hematological patients: an old or new question?

Pseudomonas aeruginosa is a well-known cause of severe and potentially life-threatening infections among hematological patients. A prospective epidemiological surveillance program ongoing at our Hematology Unit revealed an increase over time of P. aeruginosa bloodstream infections (BSI). Their impact on outcome and antibiotic susceptibility was analyzed. BSI which consecutively occurred at our institution during a 70-month period were evaluated and correlated with type of pathogen, status of underlying disease, neutropenia, previous antibiotic therapy, resistance to antibiotics, and outcome. During the observation period, 441 BSI were recorded. Frequency of Gram-negative BSI was higher than that of other pathogens (57.3%). Overall, 66 P. aeruginosa BSI were recorded; 22 out of 66 were multiresistant (MR P. aeruginosa). Thirty-day mortality for all BSI was 11.3%; it was 27.3% for P. aeruginosa BSI and 36.4% for MR P. aeruginosa. At multivariate analysis, only active hematological disease and P. aeruginosa BSI were associated to an increased risk of death. For MR P. aeruginosa, BSI mortality was 83.3% vs. 18.8% when empiric therapy included or not an antibiotic with in vitro activity against P. aeruginosa (p=0.011). Together with active disease, the emergence of P. aeruginosa BSI, particularly if multiresistant, was responsible for an increased risk of death among hematological patients at our institution. In this scenario, reconsidering the type of combination antibiotic therapy to be used as empiric treatment of neutropenic fever was worthwhile.

Recent changes in bacterial epidemiology and the emergence of fluoroquinolone-resistant Escherichia coli among patients with haematological malignancies: results of a prospective study on 823 patients at a single institution.

BACKGROUND: Regular monitoring of bacterial epidemiology allows evaluation of antibacterial strategies adopted. The aim of this study was to disclose evolving trends in the epidemiology of infections and emerging antibiotic resistance in unselected inpatients with haematological cancers. METHODS: Febrile/infectious episodes occurring in 823 patients consecutively admitted to a single institution during a 16 month period were analysed. Levofloxacin prophylaxis was used in patients with >7 days expected neutropenia. RESULTS: Fever developed in 364 patients (44.2%) and an infection was documented in 187 (22.7%), either clinically (6.1%) or microbiologically (16.6%). Levofloxacin prophylaxis, used in 39.4% of cases, caused a reduction in febrile episodes only among neutropenic patients and no difference in the frequency of documented infections. Among 164 pathogens isolated, gram-negative (49.4%) outweighed gram-positive bacteria (40.9%), Escherichia coli being most frequent (23.2%). Fluoroquinolone resistance and methicillin resistance were the most frequent types of antibiotic resistance, occurring in 56.1% of bacterial isolates and in 66.7% of staphylococci, respectively. Fluoroquinolone-resistant E. coli accounted for 20.1% of all isolates and for 86.8% of E. coli. Multivariate analysis of risk factors for fluoroquinolone resistance identified prophylaxis (P < 0.001) and neutropenia >7 days (P = 0.02) as independent. Methicillin resistance was independently associated with prophylaxis (P = 0.041) and central venous catheters (P = 0.036). Infections by fluoroquinolone-resistant strains did not show a worse outcome. CONCLUSIONS: A shift towards gram-negative bacteria has been occurring in recent years in the bacterial epidemiology of haematological patients. Fluoroquinolone resistance is emerging as a major type of antibacterial resistance, particularly among E. coli strains. Further investigation is needed to explore the consequences of such epidemiological changes.

Fatal hemophagocytic syndrome related to active human herpesvirus-8/Kaposi sarcoma-associated herpesvirus infection in human immunodeficiency virus-negative, non-transplant patients without related malignancies.

Hemophagocytic syndrome (HS) may occur as a consequence of herpes viral infections. Human herpesvirus 8 (HHV-8)/Kaposi sarcoma-associated herpesvirus has so far been recognized as a trigger of HS only in immunosuppressed subjects or in patients with Kaposi sarcoma and/or HHV-8-related lymphoproliferative diseases. We report two Italian human immunodeficiency virus (HIV)-negative elderly men who developed an HS with a rapidly fatal course, following treatment with corticosteroids for autoimmune hemolytic anemia. An overwhelming active infection with HHV-8 was unequivocally documented by molecular and immunohistochemical methods, in the absence of HHV-8-related tumors. The occurrence of HHV-8-associated HS, although rare, may be considered, even out of the HIV or the transplantation settings, at least in areas endemic for HHV-8 infection.

Oral cavity lymphomas in immunocompetent and human immunodeficiency virus infected patients.

Oral cavity lymphoma (OCL) seems to occur more frequently in HIV-positive patients, but it is presently unknown whether HIV-related immune deficit plays a role in modifying the prevalence and the characteristics of these lymphomas. To clarify this issue, we compared OCL occurring in immunocompetent and HIV-positive patients. A comparison was made between cases of OCL occurring among 543 and 123 NHL consecutively diagnosed at a single center in immunocompetent and HIV-positive patients respectively. The prevalence of oral cavity involvement at diagnosis was significantly lower in the immunocompetent subgroup (HIV-negative: 1.66%; HIV-positive: 7.3%, P = 0.002). Extranodal T/NK nasal-nasal-type lymphoma (ET/NK-NL) was observed in 3 of 9 immunocompetent patients, whereas plasmablastic lymphoma (PBL) was observed in 3 of 9 HIV-positive patients. EBV expression correlated with HIV-positivity. Response to treatment was similar between the two subgroups, but the overall prognosis was significantly worse among HIV-positive patients. Median survival was 34 months in immunocompetent vs. 9 months in HIV-positive patients (P < 0.01). A higher frequency of oral cavity lymphoma was associated with HIV infection. ET/NK-NL and PBL seemed to be clinical entities characteristically related to immunocompetent and HIV-positive subgroups, respectively. Chemotherapy was feasible and effective in both subgroups, although a poor prognosis was associated with immunodeficiency.

[LAT (linker for activation of T cells): a useful marker for megakaryocyte evaluation on bone marrow biopsies]. / LAT (linker for activation of T cells): un utile marcatore per l'identificazione di megacariociti in biopsie osteomidollari.

Detection of atypical megakaryocytes in bone marrow biopsies, especially in cases of myelodysplastic syndromes (MDS), chronic myeloproliferative disorders (CMPD) and acute leukemias, is facilitated by staining for markers such as Ulex europaeus agglutinin (UEA)-J, CD31, CD61 and von Willebrand factor (VWF), the latter being considered the most sensitive. Recently, LAT (linker for activation of T cells), a molecule involved in T-cell activation and platelet aggregation, was found to be expressed by megakaryocytes and platelets in tissue sections. We compared VWF and LAT immunoreactivity on megakaryocytes in 64 bone marrow biopsies from 12 normal controls (NC), and from patients with MDS (n=18), CMPD (n=21) and acute megakaryocytic leukemia (AML-M7, n=13). Immunostaining was performed on paraffin sections with polyclonal antibodies against VWF and LAT. Immunoreactivity was evaluated by counting positive megakaryocytes in 10 high-power fields, and values were compared using Student's t test for paired data. Both VWF and LAT predominantly stained the cytoplasm of megakaryocytes, although LAT was also recognizable on the cell membrane. In most biopsies, the immunoreactivity of the two antibodies was quite similar. No significant differences were noticed between the mean values of VWF+ and LAT+ megakaryocytes. However, in 22 cases (5 NC; 5 MDS; 6 CMPD; 6 AML-M7), the number of LAT+ megakaryocytes was at least 30% higher than VWF+cells, while in 3 cases opposite findings were found. In 3 AML-M7 cases, anti-LAT antibodies stained numerous megakaryocytes, but anti-VWF staining was practically negative; in another 5 AML-M7 cases, anti-LAT labeling was much stronger than anti-VWF staining. LAT represents a useful immunohistochemical marker for megakaryocytes in normal and pathological conditions. It seems to be expressed by megakaryocytes more than VWF in most cases and, particularly, in conditions associated with poorly differentiated megakaryocytes, such as acute megakaryocytic leukemias. The use of LAT staining should be recommended in association with other megakaryocyte markers in the study of bone marrow biopsies in cases of hematopoietic disorders.