Maintain Efficacy and Spare Toxicity: Traditional and New Radiation-Based Conditioning Regimens in Hematopoietic Stem Cell Transplantation.

Novelty in total body irradiation (TBI) as part of pre-transplant conditioning regimens lacked until recently, despite the developments in the field of allogeneic stem cell transplants. Long-term toxicities have been one of the major concerns associated with TBI in this setting, although the impact of TBI is not so easy to discriminate from that of chemotherapy, especially in the adult population. More recently, lower-intensity TBI and different approaches to irradiation (namely, total marrow irradiation, TMI, and total marrow and lymphoid irradiation, TMLI) were implemented to keep the benefits of irradiation and limit potential harm. TMI/TMLI is an alternative to TBI that delivers more selective irradiation, with healthy tissues being better spared and the control of the radiation dose delivery. In this review, we discussed the potential radiation-associated long-term toxicities and their management, summarized the evidence regarding the current indications of traditional TBI, and focused on the technological advances in radiotherapy that have resulted in the development of TMLI. Finally, considering the most recent published trials, we postulate how the role of radiotherapy in the setting of allografting might change in the future.

Treatment of primary plasma cell leukaemia with carfilzomib and lenalidomide-based therapy (EMN12/HOVON-129): final analysis of a non-randomised, multicentre, phase 2 study.

BACKGROUND: Primary plasma cell leukaemia is a rare and aggressive plasma cell disorder with a poor prognosis. The aim of the EMN12/HOVON-129 study was to improve the outcomes of patients with primary plasma cell leukaemia by incorporating carfilzomib and lenalidomide in induction, consolidation, and maintenance therapy. METHODS: The EMN12/HOVON-129 study is a non-randomised, phase 2, multicentre study conducted at 19 academic centres and hospitals in seven European countries (Belgium, Czech Republic, Denmark, Italy, Norway, The Netherlands, and the UK) for previously untreated patients with primary plasma cell leukaemia aged 18 years or older. Inclusion criteria were newly diagnosed primary plasma cell leukaemia (defined as >2 ×109 cells per L circulating monoclonal plasma cells or plasmacytosis >20% of the differential white cell count) and WHO performance status 0-3. Patients aged 18-65 years (younger patients) and 66 years or older (older patients) were treated in age-specific cohorts and were analysed separately. Younger patients were treated with four 28-day cycles of carfilzomib (36 mg/m2 intravenously on days 1, 2, 8, 9, 15, and 16), lenalidomide (25 mg orally on days 1-21), and dexamethasone (20 mg orally on days 1, 2, 8, 9, 15, 16, 22, and 23). Carfilzomib-lenalidomide-dexamethasone (KRd) induction was followed by double autologous haematopoietic stem-cell transplantation (HSCT), four cycles of KRd consolidation, and then maintenance with carfilzomib (27 mg/m2 intravenously on days 1, 2, 15, and 16 for the first 12 28-day cycles, and then 56 mg/m2 on days 1 and 15 in all subsequent cycles) and lenalidomide (10 mg orally on days 1-21) until progression. Patients who were eligible for allogeneic HSCT, could also receive a single autologous HSCT followed by reduced-intensity conditioning allogeneic HSCT and then carfilzomib-lenalidomide maintenance. Older patients received eight cycles of KRd induction followed by maintenance therapy with carfilzomib and lenalidomide until progression. The primary endpoint was progression-free survival. The primary analysis population was the intention-to-treat population, irrespective of the actual treatment received. Data from all participants who received any study drug were included in the safety analyses. The trial was registered at www.trialregister.nl (until June 2022) and https://trialsearch.who.int/ as NTR5350; recruitment is complete and this is the final analysis. FINDINGS: Between Oct 23, 2015, and Aug 5, 2021, 61 patients were enrolled and received KRd induction treatment (36 patients aged 18-65 years [20 (56%) were male and 16 (44%) female], and 25 aged ≥66 years [12 (48%) were male and 13 (52%) female]). With a median follow-up of 43·5 months (IQR 27·7-67·8), the median progression-free survival was 15·5 months (95% CI 9·4-38·4) for younger patients. For older patients, median follow-up was 32·0 months (IQR 24·7-34·6), and median progression-free survival was 13·8 months (95% CI 9·2-35·5). Adverse events were most frequently observed directly after treatment initiation, with infections (two of 36 (6%) younger patients and eight of 25 (32%) older patients) and respiratory events (two of 36 [6%] younger patients and four of 25 [16%] older patients) being the most common grade 3 or greater events during the first four KRd cycles. Treatment-related serious adverse events were reported in 26 (72%) of 36 younger patients and in 19 (76%) of 25 older patients, with infections being the most common. Treatment-related deaths were reported in none of the younger patients and three (12%) of the older patients (two infections and one unknown cause of death). INTERPRETATION: Carfilzomib and lenalidomide-based therapy provides improved progression-free survival compared with previously published data. However, results remain inferior in primary plasma cell leukaemia compared with multiple myeloma, highlighting the need for new studies incorporating novel immunotherapies. FUNDING: Dutch Cancer Society, Celgene (a BMS company), and AMGEN.

Graft-Versus-Host Disease Prophylaxis with Antithymocyte Globulin in Patients Receiving Stem Cell Transplantation from Unrelated Donors: An Observational Retrospective Single-Center Study.

Graft-versus-host disease (GVHD) is one of the most important complications of allogeneic hematopoietic stem cell transplantation. Rabbit antilymphocyte serum (ATG/ATLG) is recommended for GVHD prophylaxis, while its appropriate dosing is debated. We performed a retrospective single-center study to examine the outcome of patients receiving ATG at the dose of 5 mg/kg as GVHD prophylaxis for unrelated donor (URD) HSCT. We collected data from all consecutive adult patients with hematological malignancies who had undergone allogeneic HSCT from URDs at the Stem Cell Transplant Center of the Città della Salute e della Scienza Hospital of Torino between July 2008 and July 2021. The primary aim was to ascertain the cumulative incidence (CI) for acute GVHD (aGVHD) and chronic GVHD (cGVHD); the secondary aim was to ascertain the CI for NRM (Non-Relapse Mortality) and RI (Relapse Incidence), as well the overall survival (OS) and infection incidence within 30 days of transplantation. We included in the analysis 226 patients who collectively underwent 231 HSCTs. The CI of grade II-IV aGVHD was found to be 29.9%, while that of moderate to severe cGVHD was 29.8%. The CI of NRM recorded at 1, 2, and 3 years after transplant was 18.2%, 19.6%, and 20.2%, respectively. The CI of RI at 1, 2, and 3 years from transplant was recorded to be 17.8%, 21.0%, and 21.6%, respectively. The median follow-up was 56 months, while the median OS for the whole cohort was not established; the OS at 1, 3, and 5 years from transplant was 69.6%, 59.3%, and 57.2%, respectively. We registered 88 bacteremias in 82/231 patients (35.5%), while invasive fungal infections occurred in 12/231 patients (5.2%). Our study suggests that the use of ATG at 5 mg/kg is highly effective in limiting the occurrence of both aGVHD and cGVHD, ensuring a low NRM, RI, and infection incidence.

Real-World Validation of Molecular International Prognostic Scoring System for Myelodysplastic Syndromes.

PURPOSE: Myelodysplastic syndromes (MDS) are heterogeneous myeloid neoplasms in which a risk-adapted treatment strategy is needed. Recently, a new clinical-molecular prognostic model, the Molecular International Prognostic Scoring System (IPSS-M) was proposed to improve the prediction of clinical outcome of the currently available tool (Revised International Prognostic Scoring System [IPSS-R]). We aimed to provide an extensive validation of IPSS-M. METHODS: A total of 2,876 patients with primary MDS from the GenoMed4All consortium were retrospectively analyzed. RESULTS: IPSS-M improved prognostic discrimination across all clinical end points with respect to IPSS-R (concordance was 0.81 v 0.74 for overall survival and 0.89 v 0.76 for leukemia-free survival, respectively). This was true even in those patients without detectable gene mutations. Compared with the IPSS-R based stratification, the IPSS-M risk group changed in 46% of patients (23.6% and 22.4% of subjects were upstaged and downstaged, respectively).In patients treated with hematopoietic stem cell transplantation (HSCT), IPSS-M significantly improved the prediction of the risk of disease relapse and the probability of post-transplantation survival versus IPSS-R (concordance was 0.76 v 0.60 for overall survival and 0.89 v 0.70 for probability of relapse, respectively). In high-risk patients treated with hypomethylating agents (HMA), IPSS-M failed to stratify individual probability of response; response duration and probability of survival were inversely related to IPSS-M risk.Finally, we tested the accuracy in predicting IPSS-M when molecular information was missed and we defined a minimum set of 15 relevant genes associated with high performance of the score. CONCLUSION: IPSS-M improves MDS prognostication and might result in a more effective selection of candidates to HSCT. Additional factors other than gene mutations can be involved in determining HMA sensitivity. The definition of a minimum set of relevant genes may facilitate the clinical implementation of the score.

Bacterial Bloodstream Infections after Allogeneic Hematopoietic Stem Cell Transplantation: Etiology, Risk Factors and Outcome in a Single-Center Study.

Background-Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are subject to major risks for bacterial bloodstream infections (BSIs), including emergent multidrug-resistant (MDR) organisms, which still represent the main cause of morbidity and mortality in transplanted patients. METHODS: We performed an observational, retrospective, single-center study on patients undergoing allo-HSCT between 2004 and 2020 at the Stem Cell Transplant Unit in Turin to assess the incidence, etiology, and outcomes of BSIs and to explore any risk factors for bacteriaemia. RESULTS: We observed a total of 178 bacterial BSIs in our cohort of 563 patients, resulting in a cumulative incidence of 19.4%, 23.8%, and 28.7% at 30, 100, and 365 days, respectively. Among isolated bacteria, 50.6% were Gram positive (GPB), 41.6% were Gram negative (GNB), and 7.9% were polymicrobial infections. Moreover, BSI occurrence significantly influenced 1-year overall survival. High and very high Disease Risk Index (DRI), an haploidentical donor, and antibacterial prophylaxis were found as results as independent risk factors for bacterial BSI occurrence in multivariate analysis. CONCLUSIONS: In our experience, GNB have overwhelmed GPB, and fluoroquinolone prophylaxis has contributed to the emergence of MDR pathogens. Local resistance patterns and patients' characteristics should therefore be considered for better management of bacteremia in patients receiving an allogeneic HSCT.

Cost-Effectiveness of Targeted Prophylaxis among Allogenic Stem Cell Transplant Recipients.

Bloodstream infections (BSI) are life-threatening complications for onco-hematologic patients. Fluoroquinolones prophylaxis (FQP) was recommended for patients with neutropenia. Later, it was correlated with increased resistance rates among this population and its role became debated. While the role of FQ prophylaxis is still being studied, its cost-effectiveness is also unknown. The objective of this study was to evaluate the costs and effects associated with two alternative strategies (FQP vs. no prophylaxis) for patients with hematological malignancies undergoing allogenic stem cell transplant (HSCT). A decision-tree model was built integrating retrospectively collected data from a single transplant center, part of a tertiary teaching hospital in Northern Italy. Probabilities, costs and effects were considered in the assessment of the two alternative strategies. Probabilities of colonization, BSIs, extended-spectrum beta lactamase (ESBL) and Klebsiella pneumoniae carbapenemase (KPC) BSIs and mortality associated with infection, as well as median duration of length of stay (LOS) were calculated based on data collected between 2013 and 2021. The center applied the strategy of FQP between 2013 and 2016, and of no prophylaxis between 2016 and 2021. Data on 326 patients were collected during the considered time period. Overall, the rates of colonization, BSI, KPC/ESBL BSI, and mortality were 6.8% (95% confidence interval (CI) 2.7-13.5), 42% (9.9-81.4) and 20.72 (16.67-25.26), respectively. A mean bed-day cost of 132€ was estimated. Considering no prophylaxis vs. prophylaxis, the difference in costs ranged between additional 33.61 and 80.59€ per patient, whereas the difference in effects ranged between 0.11 and 0.03 life-years (LYs) lost (around 40 and 11 days). Given the small differences in terms of costs and effects between the two strategies, no prophylaxis seems an appropriate choice. Furthermore, this analysis did not consider the broader effect on hospital ecology of multiple doses of FQP, which could provide further support for the strategy of no prophylaxis. Our results suggest that the necessity for FQP in onco-hematologic setting should be determined based on local antibiotic resistance patterns.

Busulfan or Treosulfan Conditioning Platform for Allogeneic Stem Cell Transplantation in Patients Aged >60 Y With Acute Myeloid Leukemia/Myelodysplastic Syndrome: A Subanalysis of the GITMO AlloEld Study.

The conditioning regimens with different alkylators at different doses can influence the outcome of allogeneic stem cell transplantation (SCT), but conclusive data are missing. Methods: With the aim to analyze real-life allogeneic SCTs performed in Italy between 2006 and 2017 in elderly patients (aged >60 y) with acute myeloid leukemia or myelodysplastic syndrome, we collected 780 first transplants data. For analysis purposes, patients were grouped according to the type of alkylator included in the conditioning (busulfan [BU]-based; n = 618; 79%; treosulfan [TREO]-based; n=162; 21%). Results: No significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival, although in the TREO-based group, we observed a greater proportion of elderly patients (P < 0.001); more active diseases at the time of SCT (P < 0.001); a higher prevalence of patients with either hematopoietic cell transplantation-comorbidity index ≥3 (P < 0.001) or a good Karnofsky performance status (P = 0.025); increased use of peripheral blood stem cells as graft sources (P < 0.001); and greater use of reduced intensity conditioning regimens (P = 0.013) and of haploidentical donors (P < 0.001). Moreover, the 2-y cumulative incidence of relapse with myeloablative doses of BU was significantly lower than that registered with reduced intensity conditioning (21% versus 31%; P = 0.0003). This was not observed in the TREO-based group. Conclusions: Despite a higher number of risk factors in the TREO group, no significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival according to the type of alkylator, suggesting that TREO has no advantage over BU in terms of efficacy and toxicity in acute myeloid leukemia and myelodysplastic syndrome.

Post-Transplant Lymphoproliferative Disease (PTLD) after Allogeneic Hematopoietic Stem Cell Transplantation: Biology and Treatment Options.

Post-transplant lymphoproliferative disease (PTLD) is a serious complication occurring as a consequence of immunosuppression in the setting of allogeneic hematopoietic stem cell transplantation (alloHSCT) or solid organ transplantation (SOT). The majority of PTLD arises from B-cells, and Epstein-Barr virus (EBV) infection is present in 60-80% of the cases, revealing the central role played by the latent infection in the pathogenesis of the disease. Therefore, EBV serological status is considered the most important risk factor associated with PTLDs, together with the depth of T-cell immunosuppression pre- and post-transplant. However, despite the advances in pathogenesis understanding and the introduction of novel treatment options, PTLD arising after alloHSCT remains a particularly challenging disease, and there is a need for consensus on how to treat rituximab-refractory cases. This review aims to explore the pathogenesis, risk factors, and treatment options of PTLD in the alloHSCT setting, finally focusing on adoptive immunotherapy options, namely EBV-specific cytotoxic T-lymphocytes (EBV-CTL) and chimeric antigen receptor T-cells (CAR T).

Impact of second-degree related donor on the outcomes of T cell-replete haploidentical transplantation with post-transplant cyclophosphamide.

Donor selection may contribute to improve clinical outcomes of T cell-replete haploidentical stem cell transplantation (Haplo-SCT) with post-transplant cyclophosphamide (PT-Cy). Impact of second-degree related donor (SRD) was not fully elucidated in this platform. We retrospectively compared the outcome of patients receiving Haplo-SCT either from a SRD (n = 31) or a first-degree related donor (FRD, n = 957). Median time to neutrophil and platelet recovery did not differ between a SRD and a FRD transplant (p = 0.599 and 0.587). Cumulative incidence of grade II-IV acute graft-versus host disease (GVHD) and moderate-severe chronic GVHD was 13% and 19% after SRD vs 24% (p = 0.126) and 13% (p = 0.395) after FRD transplant. One-year cumulative incidence of non-relapse mortality (NRM) was 19% for SRD and 20% for FRD (p = 0.435) cohort. The 3-year probability of overall survival (OS) and progression-free survival (PFS) was 42% vs 55% (p = 0.273) and 49% vs 35% (p = 0.280) after SRD and FRD transplant, respectively. After propensity score adjustment or matched pair analysis, the outcome of patients receiving Haplo-SCT from a SRD or a FRD did not differ in terms of NRM, OS, PFS, acute and chronic GVHD. Our results suggest that a SRD is a viable option for Haplo-SCT with PT-Cy when a FRD is not available.

Sorafenib maintenance after hematopoietic stem cell transplantation improves outcome of FLT3-ITD-mutated acute myeloid leukemia.

In a retrospective analysis, 21 acute myeloid leukemia patients receiving single-agent sorafenib maintenance therapy in complete remission (CR) after hematopoietic stem cell transplantation (HSCT) were compared with a control group of 22 patients without maintenance. Sorafenib was initiated a median of 3 months (IQR: 2.3-3.5) after allogeneic HSCT with a median daily dosage of 400 mg (range: 200-800) orally, and lasted a median of 11.3 months (IQR: 3.3-24.4). No significant increase in graft versus host disease or toxicity was observed. Adverse events were reversible with dose adjustment or temporary discontinuation in 19/19 cases. With a median follow-up of 34.7 months (IQR: 16.9-79.5), sorafenib maintenance significantly improved cumulative incidence of relapse (p = 0.028) as well as overall survival (OS) (p = 0.016), especially in patients undergoing allogeneic HSCT in CR1 (p < 0.001). In conclusion, sorafenib maintenance after allogeneic HSCT is safe and may improve cumulative incidence of relapse and OS in FLT3-ITD-mutated AML.

Oral health status after hematopoietic stem cell transplantations: Outcomes from an adult Italian population.

AIM: To describe oral cavity changes in patients who underwent a hematopoietic stem cell transplantation (HSCT). METHODS AND RESULTS: A group of 32 patients was studied after a mean period of 48.8 months (±11.22) from HSCT; oral, dental, and periodontal status were collected and compared with those of healthy matched controls. Unstimulated whole salivary flow (UWS) and salivary pH were also measured. A validated questionnaire (EORTC QLQH&N-35) was used for reported quality of life. Fifty-nine percent of patients were affected by chronic graft-versus-host disease (cGVHD). Dental health and periodontal status were statistically worse than in controls (P = .003 and P = .008, respectively). Regarding the HSCT group, UWS was statistically lower, and EORTC QLQH&N-35 significantly higher than those reported in controls (P = .000 for both). There was no statistical correlation between hypo-salivation and conditioning, presence of cGVHD, type of medication used before and after transplantation, and time of follow-up. A reduction in salivary pH has been noted only for patients with erosive oral lesions. CONCLUSION: The oral cavity of HSCT patients appeared to undergo substantial modifications and the quality of life was deeply compromised.

Frequency and risk factors for thrombosis in acute myeloid leukemia and high-risk myelodysplastic syndromes treated with intensive chemotherapy: a two centers observational study.

The frequency of thrombosis in AML has been evaluated only in a few studies and no validated predictive model is currently available. Recently, DIC score was shown to identify patients at higher thrombotic risk. We aimed to evaluate the frequency of thromboembolism in AML patients treated with intensive chemotherapy and to assess the ability of genetic and clinical factors to predict the thrombotic risk. We performed a retrospective observational study including 222 newly diagnosed adult AML (210) and high-risk MDS (12), treated with intensive chemotherapy between January 2013 and February 2020. With a median follow-up of 44 months, we observed 50 thrombotic events (90% were venous, VTE). The prevalence of thrombosis was 22.1% and the 6-months cumulative incidence of thrombosis was 10%. The median time to thrombosis was 84 days and 52% of the events occurred within 100 days from AML diagnosis. Khorana and DIC score failed to stratify patients according to their thrombotic risk. Only history of a thrombotic event (p = 0.043), particularly VTE (p = 0.0053), platelet count above 100 × 109/L at diagnosis (p = 0.036) and active smoking (p = 0.025) significantly and independently increased the risk of thrombosis, the latter particularly of arterial events. AML genetic profile did not affect thrombosis occurrence. Results were confirmed considering only thromboses occurring within day 100 from diagnosis. DIC score at diagnosis, but not thrombosis, was independently associated with reduced survival (p = 0.004). Previous VTE, platelet count above 100 × 109/L and active smoking were the only factors associate with increased thrombotic risk in AML patients treated intensively, but further studies are needed to validate these results.

Risk Factors for Early Cytomegalovirus Reactivation and Impact of Early Cytomegalovirus Reactivation on Clinical Outcomes after T Cell-Replete Haploidentical Transplantation with Post-Transplantation Cyclophosphamide.

Risk factors for cytomegalovirus (CMV) reactivation and the impact of CMV reactivation on patient outcomes have been extensively investigated after matched related or unrelated donor transplantation, but little is known in the setting of haploidentical stem cell transplantation (Haplo-SCT) with post-transplantation cyclophosphamide (PT-Cy), in which recipients are considered more severely immunocompromised. We retrospectively analyzed a cohort of 554 consecutive patients undergoing Haplo-SCT with PT-Cy at 3 different centers. Early CMV reactivation (occurring within the first 120 days post-transplantation) occurred in 242 patients, for an estimated cumulative incidence of 44%. Among those patients, 74 (30%) had recurrent CMV and 20 (8%) had CMV disease. On multivariable analysis, positive recipient CMV serostatus (hazard ratio [HR] >2.5; P < .001), disease histology (lymphoid versus myeloid: HR, 0.66; P = .003) and increasing recipient age (HR, 1.01; P = .015) were independent predictors of CMV reactivation. At a 4-month landmark analysis, CMV reactivation was associated with higher 1-year and 5-year cumulative incidence of nonrelapse mortality (NRM) relative to patients without reactivation: 13% versus 5% and 22% versus 9%, respectively (P < .001). On multivariable analysis, CMV reactivation was an independent negative predictor of NRM (HR, 2.69; P < .001) and was close to statistically significant for overall survival (HR, 1.38; P = .062). Our results suggest that CMV reactivation plays an important role at determining NRM. Because patient CMV serostatus is the main predictor of CMV reactivation, it should be considered when evaluating strategies for preventing CMV reactivation. 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

GITMO Registry Study on Allogeneic Transplantation in Patients Aged ≥60 Years from 2000 to 2017: Improvements and Criticisms.

Today, allogeneic stem cell transplantation (allo-SCT) can be offered to patients up to age 70 to 72 years and represents one of the most effective curative treatments for many hematologic malignancies. The primary objective of the study was to collect data from the allo-SCTs performed in Italy between 2000 and 2017 in patients aged ≥60 years to evaluate the changes in safety and efficacy outcomes, as well as their distribution and characteristics over time. The Italian Group for Bone Marrow Transplantation, Hematopoietic Stem Cells and Cell Therapy (GITMO) AlloEld study (ClinicalTrials.gov identifier NCT04469985) is a retrospective analysis of allo-SCTs performed at 30 Italian transplantation centers in older patients (age ≥60 years) between 2000 and 2017 (n = 1996). For the purpose of this analysis, patients were grouped into 3 time periods: time A, 2000 to 2005 (n = 256; 12%); time B, 2006 to 2011 (n = 584; 29%); and time C, 2012 to 2017 (n = 1156; 59%). After a median follow-up of 5.6 years, the 5-year nonrelapse mortality (NRM) remained stable (time A, 32.8%; time B, 36.2%; and time C, 35.0%; P = .5), overall survival improved (time A, 28.4%; time B, 31.8%; and time C, 37.3%; P = .012), and the cumulative incidence of relapse was reduced (time A, 45.3%; time B, 38.2%; time C, 30.0%; P < .0001). The 2-year incidence of extensive chronic graft-versus-host disease was reduced significantly (time A, 17.2%; time B, 15.8%; time C, 12.2%; P = .004). Considering times A and B together (2000 to 2011), the 2-year NRM was positively correlated with the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score; NRM was 25.2% in patients with an HCT-CI score of 0, 33.9% in those with a score of 1 or 2, and 36.1% in those with a score of 3 (P < .001). However, after 2012, the HCT-CI score was not significantly predictive of NRM. This study shows that the transplantation procedure in elderly patients became more effective over time. Relapse incidence remains the major problem, and strategies to prevent it are currently under investigation (eg, post-transplantation maintenance). The selection of patients aged ≥60 could be improved by combining HCT-CI and frailty assessment to better predict NRM.

Letermovir Prophylaxis for Cytomegalovirus Infection in Allogeneic Stem Cell Transplantation: A Real-World Experience.

Despite effective treatments, cytomegalovirus (CMV) continues to have a significant impact on morbidity and mortality in allogeneic stem cell transplant (allo-SCT) recipients. This multicenter, retrospective, cohort study aimed to evaluate the reproducibility of the safety and efficacy of commercially available letermovir for CMV prophylaxis in a real-world setting. Endpoints were rates of clinically significant CMV infection (CSCI), defined as CMV disease or CMV viremia reactivation within day +100-+168. 204 adult CMV-seropositive allo-SCT recipients from 17 Italian centres (median age 52 years) were treated with LET 240 mg/day between day 0 and day +28. Overall, 28.9% of patients underwent a haploidentical, 32.4% a matched related, and 27.5% a matched unrelated donor (MUD) transplant. 65.7% were considered at high risk of CSCI and 65.2% had a CMV seropositive donor. Low to mild severe adverse events were observed in 40.7% of patients during treatment [gastrointestinal toxicity (36.3%) and skin rash (10.3%)]. Cumulative incidence of CSCI at day +100 and day +168 was 5.4% and 18.1%, respectively, whereas the Kaplan-Meier event rate was 5.8% (95% CI: 2.4-9.1) and 23.3% (95% CI: 16.3-29.7), respectively. Overall mortality was 6.4% at day +100 and 7.3% at day +168. This real-world experience confirms the efficacy and safety of CMV.