Search Results (191)

Background/Objectives: Myelofibrosis (MF) is a clonal myeloproliferative neoplasm driven by dysregulated JAK-STAT signaling, characterized by progressive marrow fibrosis, splenomegaly, constitutional symptoms, and increased risk of leukemic transformation. Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains the only potentially curative intervention. In Italy, allo-HCTs for myeloproliferative neoplasms (MPN, i.e., myelofibrosis, polycythaemia vera, and essential thrombocythaemia combined) increased by 163% from 2015 to 2025; MF-specific procedure counts were not separately available in this registry export, so this figure should not be read as MF-specific, with MPN accounting for 8% of all allogeneic procedures (n = 171) in 2025, showing a 29.5% year-on-year increase from 2024. Concurrently, the demographic profile shifted, with individuals aged 60 and over representing 38% of all recipients, surpassing other age groups for the first time in 2025. Results: This review synthesizes current evidence on transplant indications and timing, pre-transplant management, donor selection, and conditioning regimen optimization, emphasizing the emerging role of treosulfan-based and dual-alkylator platforms, including the thiotepa–treosulfan–fludarabine (TTF) regimen. Post-transplant molecular MRD monitoring and relapse management are also discussed. Three-year overall survival in myelofibrosis ranges from about 59% to 67%, depending on donor type, with outcomes improving due to better patient selection, optimized conditioning, and supportive care. Conclusions: Prospective randomized trials are urgently needed to validate optimal conditioning intensity, the role of novel JAK inhibitors in the peri-transplant period, and MRD-guided pre-emptive strategies. Full article

Background/Objectives: Patients receiving allogeneic hematopoietic stem cell transplantation (alloHCT) for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are at high risk for severe disease and treatment-related complications and toxicities. Pharmacogenetic studies suggest that genetic variants can alter the response to several drugs critical to alloHCT outcomes, including tacrolimus and cyclophosphamide, potentially impacting toxicity and treatment outcomes. Methods: To assess the frequency of pharmacogenetic variants in AML/ALL patients undergoing alloHCT, we used a validated 11-gene pharmacogenetic panel in an exploratory descriptive study. We retrospectively genotyped 142 AML/ALL patients including two atypical chronic myeloid leukemia (aCML) patients, ≥18 years, who underwent alloHCT at our center between January 2020 and June 2024. Results obtained from 470 individuals in the Lifelines NEXT population cohort were used as controls. Results: Almost all patients carried at least one pharmacogenetic variant (97.2%), with a mean of 3.2 (standard deviation = 1.5) variants per patient. Variants known to influence tacrolimus metabolism (CYP3A4 and CYP3A5) were present in 26.8% of patients. Variants known to influence cyclophosphamide metabolism (CYP2B6, CYP2C9, CYP2C19) were present in 81.7% of patients. Variant frequencies did not significantly differ from controls. Conclusions: Actionable pharmacogenetic variants are highly prevalent in alloHCT-recipients. Future studies should investigate whether genotype-guided drug selection and dosing could improve outcomes in alloHCT recipients. Full article

Background/Objectives: Cytomegalovirus (CMV) reactivation is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. Letermovir is used to prevent infections, but it is not available in many countries. Ganciclovir and valganciclovir carry a risk of bone marrow suppression. Foscarnet is frequently used as a bone marrow-sparing alternative; however, its clinical utility is constrained by nephrotoxicity. In this study, we aimed to evaluate the efficacy and renal safety of foscarnet and to identify factors associated with acute kidney injury (AKI) occurring during foscarnet treatment. Methods: This real-world, retrospective, single-center cohort study included 40 adult allo-HCT recipients treated with foscarnet for CMV reactivation between May 2022 and February 2025. Results: CMV polymerase chain reaction (PCR) negativity was achieved in 90% of patients, with a median time to PCR negativity of 10 (4–28) days. AKI occurred in 42.5% of patients, and 12.5% required hemodialysis. Foscarnet treatment was associated with a significant increase in serum creatinine levels and significant reductions in potassium, calcium, and magnesium concentrations (p < 0.05 for all). In univariable logistic regression analysis, myeloablative conditioning was associated with higher odds of AKI (OR 10.29, 95% CI 1.15–91.63; p = 0.037), while male sex showed numerically higher odds that did not reach conventional statistical significance (OR 4.28, 95% CI 0.96–19.01; p = 0.056). Conclusions: Among allo-HCT recipients treated with foscarnet, virological clearance was frequently observed, while AKI and electrolyte disturbances were common. These findings suggest that close renal and electrolyte monitoring may be warranted. However, given the retrospective, single-center design, small sample size, and absence of a comparator group, the findings should be interpreted cautiously and confirmed in larger prospective comparative studies. Full article

Nutritional deterioration in adults with acute myeloid leukemia (AML) may be present at diagnosis and may evolve rapidly during intensive chemotherapy, lower-intensity treatment, and allogeneic hematopoietic cell transplantation (allo-HCT). This structured narrative review critically examines nutritional screening and diagnostic instruments, anthropometry and body composition, laboratory-derived composite indices, and objective physical-function measures. PubMed was searched for publications from 1 January 2015 through 13 July 2026; Google Scholar and reference lists were used foradditional citation searching. Of 292 records screened, 52 full-text reports were assessed and 34 empirical studies were included. Methodological limitations were appraised with the 2018 Mixed Methods Appraisal Tool. Evidence was heterogeneous and predominantly observational. PG-SGA and NRS-2002 identified nutritional risk and nutrition-impact symptoms, but their classifications were not interchangeable with GLIM diagnosis, body-composition phenotyping, or prognostic indices. BMI alone did not capture muscle depletion. CT, quantitative CT, BIA-derived phase angle, skeletal muscle indices, and repeated anthropometry detected clinically relevant changes, although thresholds varied and fluid shifts may bias BIA. Albumin-based indices, including CONUT, sCONUT, NRI, GNRI, PNI, and the C-reactive protein/albumin ratio, were associated with outcomes in several retrospective cohorts, but largely reflect inflammation, disease burden, and treatment effects as well as nutrition; no head-to-head evidence establishes superiority. SPPB, gait speed, walking tests, chair stands, and grip strength provided prognostic information in selected older and transplant cohorts, including patients treated with hypomethylating agents plus venetoclax. The evidence supports repeated, multimodal assessment, while remaining insufficient to prove that any single tool or tool-guided intervention improves survival. Future studies require standardized definitions, sex-stratified validation, contemporary treatment cohorts, and trials integrating nutrition, symptom control, and exercise. Full article

Hypomethylating agents (HMAs) are the cornerstone in the treatment of higher-risk myelodysplastic syndromes (MDSs), particularly for patients who are not candidates for allogeneic hematopoietic cell transplant (allo-HCT). Despite demonstrated efficacy in improving hematologic outcomes, the clinical management of HMA-associated myelosuppression remains a challenge. This review discusses the use of azacitidine and oral decitabine-cedazuridine (DEC-C) for MDS management in the Canadian context, with a focus on optimizing therapy to mitigate myelosuppression and prevent early HMA discontinuation due to toxicity. Close monitoring of complete blood counts is critical to early detection of myelosuppression and management of treatment-related cytopenias. In the real-world setting, specific HMA dose adjustments are used based on patient risk factors for myelosuppression or treatment-related complications. Supportive care strategies, including the use of growth factors and antimicrobials, can complement monitoring and dose modifications for HMA-related myelosuppression management, although their use is variable. This review summarizes current evidence and real-world management approaches for HMA-induced myelosuppression, with the aim of improving outcomes for patients undergoing treatment for MDS. Full article

Background: Pediatric hematopoietic cell transplantation (HCT) conveys significant risk of mortality, morbidity, impaired quality of life, and multifactorial distress. One potential strategy for improving experience and relieving suffering is proactive specialty palliative care (SPC) utilization. However, SPC is not routinely incorporated into pediatric HCT. One barrier to SPC integration is unknown pediatric HCT provider perceptions of SPC services, particularly among providers with lived experience working within a collaborative HCT-SPC partnership. Objective: This single-institution pilot study aimed to (1) describe an approach to standardized, proactive pediatric HCT-SPC clinical partnership, and (2) quantify acceptability, appropriateness, and satisfaction regarding the program among pediatric HCT providers. Methods: Survey methods were used to assess attitudes among HCT providers who had worked with the SPC clinical partnership for at least three months. Core survey metrics were the validated Acceptability of Intervention Measure and Intervention Appropriateness Measure. Additional survey items were adapted from the Perceptions of Palliative Care Instrument. Results: Respondents reported high mean scores for acceptability (4.96) and appropriateness (4.93) on a 5-point scale. Overall satisfaction with SPC integration averaged 8.72 (SD 1.13) on a 10-point scale. Satisfaction scores for each individual service provided by SPC were similarly high. No significant differences in responses were found based on provider type, prior SPC training, or years in practice. Conclusions: In this single-institution pilot study, pediatric HCT providers with lived experience working in an environment with standardized SPC collaboration view SPC as highly acceptable, appropriate, and beneficial for their patients, supporting the feasibility and value of proactive SPC integration in pediatric HCT care. Full article

Relapse remains the leading cause of treatment failure following hematopoietic cell transplantation (HCT) for hematologic malignancies. Circulating tumor DNA (ctDNA) has emerged as a promising minimally invasive biomarker for measurable residual disease (MRD) assessment and early relapse detection; however, the prognostic significance of ctDNA in the post-transplant setting has not been comprehensively synthesized. We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines and registered the protocol in PROSPERO (CRD420261392100). PubMed, Embase, Web of Science, EBSCO, Cochrane CENTRAL, and supplementary sources were searched through November 2025. Eligible studies evaluated tumor-specific ctDNA or tumor-informed/tumor-associated cfDNA in patients undergoing allogeneic or autologous HCT for hematologic malignancies. Random-effects meta-analyses were performed for relapse/progression, overall survival (OS), and relapse-free/progression-free survival (RFS/PFS). Studies evaluating total cfDNA quantity, methylation-based cfDNA profiling, cfRNA, or chimerism-only monitoring were synthesized narratively. Ten observational cohort studies comprising 883 patients met inclusion criteria. Across acute leukemias, lymphomas, multiple myeloma, and myelodysplastic syndromes, ctDNA/cfDNA positivity was consistently associated with adverse outcomes. The pooled hazard ratio (HR) for relapse or disease progression was 12.57 (95% CI: 4.59–34.46; p < 0.001), while pooled HRs were 7.45 (95% CI: 4.11–13.48; p < 0.001) for OS and 4.46 (95% CI: 2.22–8.97; p < 0.001) for RFS/PFS. Although statistical heterogeneity was low, interpretation was limited by the relatively small number of studies contributing to each pooled endpoint. Narrative evidence additionally suggested that broader circulating nucleic acid approaches may provide complementary information regarding graft-versus-host disease, infection, and other post-transplant complications. Tumor-specific ctDNA positivity is consistently associated with increased relapse risk and inferior survival outcomes following HCT. These findings support further investigation of ctDNA-based MRD monitoring as a promising non-invasive biomarker for post-transplant molecular surveillance and risk stratification. However, prospective multicenter validation studies, assay standardization, and ctDNA-guided interventional trials remain necessary before routine clinical implementation can be recommended. Full article

Background: Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only curative therapy for myelofibrosis (MF), but its use is limited by substantial transplant related morbidity and mortality, particularly in older or comorbid patients. Treosulfan has emerged as a less toxic alternative to busulfan, with potential advantages in myeloablative and reduced intensity conditioning. Methods: We conducted a comprehensive, multi-database literature search (PubMed, Scopus/EMBASE, Cochrane Library, Web of Science, and grey literature) for studies published between 2000 and 2025 evaluating treosulfan-based conditioning in MF patients undergoing allo-HCT. Data on patient characteristics, conditioning regimens, engraftment, graft-versus-host disease (GVHD), and survival outcomes were synthesized. Results: Eight studies including more than 800 patients were analyzed. Treosulfan was most commonly combined with fludarabine, with or without additional agents. Engraftment rates were consistently high at 94 to 100%, with low non-relapse mortality (NRM) and favorable progression-free survival (PFS). An EBMT registry study demonstrated superior survival and significantly lower NRM compared with busulfan based regimens. Benefits were observed across older patients, alternative donors, and second transplants. Higher treosulfan doses were associated with increased toxicity in some cohorts. Conclusions: Treosulfan based conditioning offers an effective and better tolerated option for MF transplantation. Prospective trials are needed to refine dosing and patient selection. Full article

Background: Cyclosporine A (CsA) is a cornerstone in graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic cell transplantation (allo-HCT), and a higher starting dose of 5 vs. 3 mg/kg reduces the risk of acute GVHD. Since hypertension is a relevant side effect of CsA, data on whether a higher CsA starting dose affects the incidence of hypertension are warranted. Methods: In this monocentric cohort study, 367 patients with no preexisting hypertension and treated with a CsA-containing GVHD prophylaxis were included: 230 (63%) with a CsA starting dose of 3 mg/kg and 137 (37%) with 5 mg/kg. The primary outcome was the incidence of early new-onset hypertension during the engraftment period. Potential risk factors for early new-onset hypertension were assessed using uni- and multivariable Cox regression models. Results: Overall, the cumulative incidence of early new-onset hypertension was 67% (246/367), but the incidence rate for early new-onset hypertension in the higher CsA group was lower (CsA 5 vs. 3 mg/kg: 57 vs. 67 per 1,000 patient-days; p = 0.414). In the multivariable analysis, risk factors for early new-onset hypertension were advanced patient age, obesity and prior autologous HCT, while a higher CsA starting dose was not associated with increased early new-onset hypertension (adjusted hazard ratio, 0.90; 95% CI, 0.67–1.21). Conclusions: A higher CSA starting dose of 5 vs. 3 mg/kg did not increase the risk of hypertension. Since previous analyses demonstrated a reduction in GVHD with a higher CsA starting dose of 5 mg/kg, current findings further support the safety of a higher CsA starting dose. Full article

Graft-versus-host disease (GVHD) remains the most severe complications following allogeneic hematopoietic cell transplantation (allo-HCT). Mesenchymal stromal cells (MSCs) have shown therapeutic potential in GVHD due to their immunomodulatory properties. However, their clinical application is constrained by safety concerns, including ectopic engraftment, microvascular obstruction, rejected by host, and potential tumor-supportive effects. Increasing evidence suggests that MSC-derived exosomes (MSC-Exos), as cell-free mediators, retain many of the beneficial effects of MSCs while exhibiting improved safety and stability profiles. MSC-Exos carry diverse bioactive cargo, including nucleic acids, lipids, and proteins, and can modulate immune responses, promote tissue repair, and restore barrier integrity. In this review, we place particular emphasis on both immunoregulation and tissue barrier protection as dual mechanisms underlying MSC-Exos efficacy in GVHD. We further discuss emerging preclinical and clinical evidence, as well as key challenges in translation. Full article

Background: Chimerism analysis is a key tool for monitoring donor-cell engraftment and the risk of relapse and graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (allo-HCT). The advantage of lineage-specific chimerism assessment, and its dynamics in patients receiving post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis, remains unclear. Objective: This review summarizes the current state of the art on chimerism analysis in patients with myeloid neoplasms undergoing allo-HCT with PTCy, with emphasis on lineage-specific testing and modern methodologies. Methods: A structured literature review was conducted to assess chimerism dynamics in whole blood (WB), bone marrow, and peripheral blood (PB) subpopulations, including T-cells, CD34⁺, myeloid, B, and NK (natural killer) cells, and their association with clinical outcomes following PTCy. Results: Lineage-specific PB chimerism, particularly in T-cells, myeloid lineage and CD34⁺ cells, is more sensitive than WB chimerism for predicting relapse. Declining donor myeloid chimerism or persistent myeloid mixed donor chimerism (MDC) may precede hematologic relapse and provide an early signal of graft instability or ineffective graft-versus-leukemia activity. T-cell MDC has been associated with an increased risk of relapse and a lower risk of GVHD, although persistent T-cell MDC in some patients may instead indicate immune tolerance. Declining CD34⁺ donor chimerism correlates with a higher risk of relapse and inferior survival outcomes and may therefore complement measurable residual disease testing. Data regarding B-cell and NK-cell chimerism remain inconsistent, likely influenced by delayed immune reconstitution. Compared to anti-thymocyte globulin, PTCy may promote higher donor T-cell chimerism, though findings across studies are variable. Next-generation sequencing (NGS) enables more sensitive detection of microchimerism and relapse prediction. Conclusions: Chimerism analysis, particularly when lineage-specific and NGS-based, offers valuable prognostic insight in allo-HCT with PTCy. Further prospective studies are needed to standardize testing and guide personalized post-HCT strategies. Full article

Graft-versus-host disease (GVHD) is one of the principal complications seen in the recipients of allogenic hematopoietic stem cell transplantation (allo-HSCT), and persists as a leading cause of post-transplant morbidity and mortality. Increasing evidence highlights the crucial influence of the gut microbiome (GM) on transplant outcomes. Microbial dysbiosis, characterized by reduced bacterial diversity and pathogenic overgrowth, is strongly associated with higher rates of complications and mortality. Patients with lower microbial diversity exhibit poorer overall survival (OS) and an increased incidence of acute GVHD (aGVHD). Conversely, restoration of beneficial commensal communities has been shown to enhance immune homeostasis, mitigate GVHD severity, and decrease infection risk. Emerging therapeutic strategies now focus on modulating the intestinal microbiome through dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation (FMT). It has been demonstrated that bacterial metabolites, such as short-chain fatty acids (SCFAs) from the diet, especially a diet rich in fibers, reduce the occurrence/severity of GVHD by inducing regulatory T cells (Tregs), which release anti-inflammatory cytokines and regulate the host immune system. Hence, the implementation of dietary fibers (DFs) could increase beneficial commensals, Treg induction, and improve outcomes such as GVHD and OS in recipients of allo-HCT. Hereupon, this review addresses how a fiber-rich diet modulates GM composition, reinforces epithelial barrier integrity, and improves the efficacy of Treg-based immunotherapy by stabilizing their regulatory phenotype and increasing their functional persistence, ultimately leading to a reduction in GI complications associated with GVHD. Unlike prior reviews that primarily cover the microbiome–GVHD axis or Treg therapies in isolation, this review emphasizes fermentable dietary fibers as a mechanistically grounded, clinically actionable strategy to support Treg stability and persistence via microbiota-derived metabolites. We integrate mechanistic evidence with emerging clinical feasibility data and ongoing trials of prebiotic supplementation in allogeneic HSCT. Full article

Allogeneic hematopoietic cell transplantation (HCT) has been used for decades to treat certain malignant and non-malignant hematological conditions, but challenges remain. Increased understanding of disease mechanisms and recent developments in genome editing have enabled alternative strategies utilizing gene-edited autologous HCT and many of these have progressed to the clinic. We present here a comprehensive review of clinical trials of gene-edited autologous hematopoietic stem cells for the treatment of hemoglobinopathies and immunodeficiencies. Searches of major international clinical trial registries were carried out using specific key words. In total, 44 interventional clinical trials investigating gene-edited autologous stem cell therapies were identified, with CASGEVY (exagamglogene autotemcel) being the only product approved to date. Hemoglobinopathies were the most common indication (n = 37) followed by immunodeficiencies (n = 4), with single trials in HIV-1 infection, pyruvate kinase deficiency and limb–girdle muscular dystrophy. Gene-editing strategies fall into three categories: disruption of the BCL11A erythroid enhancer, editing of the γ-globin promoter and direct correction or disruption of disease-relevant genes. CD34⁺ hematopoietic stem and progenitor cells are the most common cell types edited, and CRISPR-Cas9 is the most widely used gene-editing modality. While results are encouraging, efficient intracellular delivery of gene-editing tools, editing efficiencies and off-target editing remain challenges for the field. Full article

Invasive infections caused by Magnusiomyces spp. are rare, but are associated with severe complications in hematopoietic cell transplantation (HCT) recipients and hospital outbreaks. Following a Magnusiomyces clavatus outbreak in our HCT unit, a prospective targeted screening protocol was implemented, which included pharyngeal and rectal swabs cultured on yeast-selective media with prolonged incubation. Clinical and microbiological data were analyzed, and whole-genome sequencing (WGS) was performed on the available isolates. During the study period (September 2022–July 2023), five colonizations and five invasive breakthrough Magnusiomyces infections were identified. Despite prompt initiation of antifungal treatment, 4/5 patients (80%) died. WGS demonstrated clonal relatedness among four M. clavatus isolates, supporting clonal transmission, although no environmental sources were identified. An enhanced two-phase screening strategy involving 71 patients showed limited benefit, identifying only one additional colonization case compared to routine surveillance cultures. A retrospective review (2007–2021) identified 58 Magnusiomyces spp. episodes, with only 10% occurring in patients with hematological malignancies. Our study describes a prolonged clonal outbreak confined to an HCT unit and provides a detailed evaluation of a targeted screening approach in this setting, highlighting the challenges of early identification and prediction of invasive infections. Further studies are needed to define the optimal surveillance and prevention strategies. Full article

Background/Objectives: Smoking is linked to an increased risk of pulmonary complications and adverse outcomes following allogeneic hematopoietic cell transplantation (Allo-HCT). Unfortunately, data is rarely correlated with the incidence of GVHD and does not show whether smoking has a negative impact independent from underlying pulmonary comorbidities. Methods: We retrospectively analyzed 407 patients who underwent Allo-HCT between January 2019 and May 2021 and evaluated the impact of smoking history and pre-transplant pulmonary comorbidities on the risk of outcomes including graft-versus-host disease (GVHD), overall survival (OS), and non-relapse mortality (NRM). Results: Patients were divided into the following groups: Group A: smokers with pre-transplant pulmonary comorbidity, 40 pts (9.8%); Group B: non-smokers with pre-transplant pulmonary comorbidity, 71 pts (17.4%); Group C: smokers without pre-transplant pulmonary comorbidity, 105 pts (25.8%); and Group D: non-smokers without pre-transplant pulmonary comorbidity, 191 pts (46.9%). Smokers were also grouped by their smoking history (<10 pack-years (59 pts), 11 to 25 pack-years (50 pts), and >25 pack-years (35 pts)) and by smoking recency: Recent (until Allo-HCT), Former (quit > 1 year ago), and Remote smokers (quit > 10 years ago). Our results showed that Group A demonstrated increased chronic lung GVHD compared to the other groups (p = 0.01). The 3-year OS was lowest in Group A at 45.0%, compared to 70.4%, 62.4%, and 69.4% (p = 0.006), and the NRM was highest at 37.5%, compared to 15.5%, 18.2%, and 14.7% in Groups B, C, and D, respectively (p = 0.001). Smoking recency and higher pack-year dose were associated with worse outcomes. Conclusions: Our study demonstrated the negative synergistic effect of smoking history and pre-transplant pulmonary comorbidities on the incidence of lung GVHD, OS, and NRM. Full article