Fluoroquinolone prophylaxis’s (FQ-P) usefulness in patients with neutropenia is controversial. In recent decades, Italian epidemiological data has shown worrisome rates of FQ resistance. A single-center cohort study on 136 autologous stem cell transplantations (ASCTs) and 223 allogeneic hematopoietic stem cell transplantations (allo-HSCTs) was performed from January 2018 to December 2020. Piperacillin/tazobactam was the first-line therapy for febrile neutropenia (FN). Since February 2019, FQ-P has been omitted. We evaluated the day +30 posttransplant cumulative incidence function (CIF) of gram-negative bacteria pre-engraftment bloodstream infections (PE-BSIs) and any changes in antimicrobial resistance, FN, and infection-related mortality (IRM). In ASCTs, ≥1 FN episode occurred in 74.3% of transplants, without differences among groups (P = .66). CIF of gram-negative bacteria PE-BSI was 10.1%, with a significant difference according to FQ-P (0% [LEVO-group] vs 14.1% [NO-LEVO-group], P = .016). CIF of IRM was 0% in both groups. In allo-HSCTs, ≥1 FN episode occurred in 96.4% of transplants, without differences among groups (P = .72). CIF of gram-negative bacteria PE-BSI was 28%, significantly higher without FQ-P (14.7% [LEVO-group] vs 34.4% [NO-LEVO-group], P = .003). CIF of IRM was 5%, superimposable in both groups (P = .62). Comparing antimicrobial resistance among gram-negative bacteria of allo-HSCT setting, in the group without FQ-P, a significantly higher proportion of pathogens was susceptible to piperacillin/tazobactam (71% vs 30%, P = .026), FQ (49% vs 10%, P = .03), and carbapenems (95% vs 50%, P = .001). FQ-P discontinuation increased gram-negative bacteria PE-BSI but did not impact IRM, both in the ASCT and allo-HSCT settings; importantly, it concurred to significantly decrease antimicrobial resistance in gram-negative bacteria.

The management of patients with acute myeloid leukemia (AML) relapsed post allogeneic hematopoietic stem cell transplantation (HSCT) remains a clinical challenge. Intensive treatment approaches are limited by severe toxicities in the early post-transplantation period. Therefore, hypomethylating agents (HMAs) have become the standard therapeutic approach due to favorable tolerability. Moreover, HMAs serve as a backbone for additional anti-leukemic agents. Despite discordant results, the addition of donor lymphocytes infusions (DLI) generally granted improved outcomes with manageable GvHD incidence. The recent introduction of novel targeted drugs in AML gives the opportunity to add a third element to salvage regimens. Those patients harboring targetable mutations might benefit from IDH1/2 inhibitors Ivosidenib and Enasidenib as well as FLT3 inhibitors Sorafenib and Gilteritinib in combination with HMA and DLI. Conversely, patients lacking targetable mutations actually benefit from the addition of Venetoclax. A second HSCT remains a valid option, especially for fit patients and for those who achieve a complete disease response with salvage regimens. Overall, across studies, higher response rates and longer survival were observed in cases of pre-emptive intervention for molecular relapse. Future perspectives currently rely on the development of adoptive immunotherapeutic strategies mainly represented by CAR-T cells.

The introduction of novel agents dramatically improved response and outcomes of multiple myeloma (MM) and led to a sharp decline in the use of allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Thus, recent guidelines do not recommend anymore allo-HSCT as consolidation in the first-line treatment of newly diagnosed MM, even in high-risk patients. In a relapsed/refractory setting, allo-HSCT is not routinely recommended but should only be performed within clinical trials in young and high-risk patients. Nonetheless, allo-HSCT still represents a potential curative approach that has been used for decades in the treatment of MM and plasma cell neoplasms with favorable results and may still represent a treatment option for carefully selected patients. Despite that promising results were obtained with CAR T-cell therapies and bispecific antibodies in triple- and penta-exposed/refractory MM, these patients will inevitably relapse. To date, less is known about outcomes of allo-HSCT in patients exposed to novel immunotherapeutic drugs. Therefore, allo-HSCT could represent a reasonable treatment choice for younger and high-risk patients who have relapsed after CAR T-cell therapies and bispecific antibodies as well as an alternative for patients not eligible to these treatments and in those countries where immunotherapies are not yet available. In the choice of conditioning, reduced intensity conditioning regimens are currently recommended for the lower toxicity and mortality. Moreover, the use of alternative donors, particularly haploidentical, has progressively increased in last years with results comparable to full matched donors. Finally, post-transplantation maintenance strategies are encouraged whenever feasible.

Background/Objectives: Treatments for multiple myeloma (MM) have expanded in the last decade, and the overall survival (OS) of MM patients (pts) is in continuous improvement. With the availability of new treatments and the use of high-dose chemotherapy, followed by autologous hematopoietic stem cell transplantation (ASCT), the median OS of newly diagnosed MM (NDMM) pts is 6–8 years. To date, approximately 50% and 28% of MM patients are still alive at 5 years and 10 years. Few data are reported concerning the characteristics of the long-term survival MM pts. Methods: the aim of this observational multicenter study is to analyze the clinical profile of MM pts who have survived 10 years or longer, to identify possible predictors of long-term survival. Conclusions: this is a real-life observation of a cohort of 344 long-term survivors with MM. The median age of the entire cohort was 59 years (range 27–83). The median years from diagnosis was 13.4 (range 11.3–16.3). Our analysis identified age more than 60 years, hypoalbuminemia at diagnosis, and a number of anti-myeloma therapies equal or more than 3 as significant independent prognostic factors for reduced OS. These finding underline the importance of designing prospective studies to identify clinical, biological, and molecular characteristics that could be used to better stratify newly diagnosed multiple myeloma pts in order to incorporate reproducible biomarkers and to identify tailored optimal target therapies.

We retrospectively analysed cytogenetics by fluorescence in situ hybridization (FISH) in 1.026 patients with multiple myeloma treated in real-world with the aim to establish its role in daily clinical practice. Thirty-seven percent of patients had no FISH data available. Based on median PFS of each cytogenetic abnormality found, we identified 3 group of patients with a significantly different PFS and determined which patients can best benefit from anti-CD38 regimens and double transplant. These findings support cytogenetic testing in all patients at diagnosis. Cytogenetics by fluorescence in situ hybridization (FISH) plays an increasing prognostic role in multiple myeloma (MM). we analysed cytogenetics and its implications in 1.026 patients treated in real-world from 2019 to 2023. Low-risk (LR) patients had normal cytogenetic or del(13q); intermediate-risk (IR) had t(11;14), hyperdiploidy, gain(1q) or del(1p); high-risk (HR) group had del(17p)/TP53, amp1q21, t(4;14), t(14:16) or t(14;20). Co-existence of 2 high risk abnormalities was named double hit. FISH data were not evaluable in 383 patients (37%). Out of 643 evaluable patients, chromosome 1 alterations were observed in 119 (18.5%), high risk chromosome 14 translocations in 65 (10%), del(17p)/TP53 in 37 (6%) and double-hit in 7 patients (1%). Cytogenetic was normal or hyperdiploid in 252 (39%) and 59 (13%) patients, respectively. Median PFS of LR, IR and HR group were 57.5, 43.2 and 30.5 months, respectively (P < .001). Although anti-CD38 regimens resulted in significantly longer PFS in both TE and NTE pts, in the former significant benefit was documented in the LR and IR group but not in HR group while in the latter only in the LR group. Tandem transplantation did not improve PFS both overall and in the 3 risk groups. Multivariate Cox regression analysis selected ECOG-PS ≥2, R-ISS II-III and our cytogenetic score HR as factors affecting PFS. in real world, more than one third of MM patients do not have baseline FISH data. Nevertheless, cytogenetics and ECOG PS can be used for prognostic staging and for tailoring therapy.