Search Results (212)

Objectives: Allogeneic stem cell transplantation (HSCT) is curative in acute myeloid leukemia (AML) but is limited by relapse and non-relapse mortality (NRM). Metabolomic prognostic value is unclear. We assessed whether plasma metabolite profiles at diagnosis, pre-transplant, and post-transplant are associated with overall survival (OS) and cause-specific mortality. Methods: We retrospectively analyzed plasma metabolites from 63 AML patients undergoing HSCT (263 samples). Results: Higher levels of valine (hazard ratio [HR] 24.454), citrulline (HR 20.478), 5-oxoproline (HR 11.766), and glutamine (HR 8.701) associated with higher NRM, while inosine diphosphate (HR 0.091) and pyridoxamine-5′-phosphate (HR 0.313) associated with lower NRM. For relapse-related mortality (RRM), higher levels of phenylalanine (HR 26.585), leucine/isoleucine (HR 10.755), indolepyruvate (HR 7.676), and creatinine (HR 13.874) were associated with higher RRM, while trans-4-hydroxy-L-proline (HR 0.101) was associated with lower RRM. Higher post-transplant ornithine (HR 0.063), 3-sulfocatechol (HR 0.590), and indole-3-acetate (HR 0.359) were associated with improved OS. Mixed-effects modelling identified lower dehydroascorbate and citrate in relapsed patients, with dehydroascorbate remaining significant after false discovery rate adjustment. Conclusions: Metabolomic profiling nominated candidate metabolites for validation in larger prospective studies and elucidated mechanistic pathways, potentially informing novel interventions or risk-adapted monitoring strategies in HSCT. Full article

Background/Objectives: Children and adolescents undergoing Haematopoietic Stem Cell Transplantation (HSCT) experience complex symptoms, often under-reported by patients and undetected by clinicians, which cause distress. Patient-Reported Outcome Measures (PROMs) offer a way to capture symptom experiences directly from patients, with the potential of supporting effective symptom assessment and management, yet their routine use in paediatric HSCT remains unclear. This systematic review synthesises evidence on PROMs used during inpatient paediatric HSCT care, examining their role in symptom monitoring and clinical decision-making, and identifying gaps to strengthen person-centred, developmentally appropriate care. Methods: We searched the MEDLINE, CINAHL, Embase, APA PsychINFO, and Cochrane Library in October 2024 for studies published in English between 2014 and 2025 describing the use of PROMs during inpatient paediatric (0–18 years) HSCT admission (up to Day +100 post HSCT). In March 2025, prior to data extraction, we added additional studies published by authors of included studies. Two-stage independent screening and data extraction were conducted, and the Quality Assessment with Diverse Studies (QuADS) tool was used to appraise each study. Narrative syntheses informed by Symptom Management Theory were used to compare PROM use, clinical integration, and reported impacts. Results: Seventeen studies met inclusion criteria, describing 20 PROMs used during paediatric HSCT hospitalisation. PROMs captured a wide range of physical and psychological symptoms, with pain and nausea most frequently reported. While PROMs reportedly improve symptom detection and communication, integration into routine paediatric HSCT clinical care was rare; and only two studies systematically used PROMs data to guide symptom management. Evidence of PROMs-driven improvements in HSCT clinical outcomes was scarce, and longitudinal data on symptom trajectories were limited. Conclusions: PROMs are not routinely used to inform clinical practice in paediatric HSCT, and current evidence provides only a partial understanding of symptom trajectories and lived symptom experiences during the paediatric acute transplant admission. To realise the full potential of PROMs in enhancing symptom assessment and management, systematic PROMs integration into clinical workflows is required, supported by electronic health record integration, clinician training, and longitudinal research designs that capture symptom evolution across the transplant continuum. Full article

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has long constituted a cornerstone of post-remission consolidation therapy for adults with high-risk B-cell acute lymphoblastic leukemia (B-ALL), offering potent graft-versus-leukemia activity at the expense of significant treatment-related toxicity (TRT) and non-relapse mortality (NRM). Over the past two decades, however, outcomes following allo-HSCT have improved substantially. This progress has been driven primarily by a marked reduction in NRM, translating into improved overall survival (OS), as consistently documented by large cooperative group analyses and single-center series. Advances in supportive care, infectious prophylaxis, donor selection, and graft-versus-host disease (GvHD) prevention have contributed substantially to this improvement. In parallel, transplant decision-making has been profoundly reshaped by refined disease biology-based risk stratification and the systematic evaluation of measurable residual disease (MRD). Moreover, the advent of highly effective immunotherapeutic approaches—including blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor (CAR) T-cell therapies—has enabled the achievement of deeper molecular remissions prior to transplantation, both in first and subsequent complete remissions. Taken together, these developments have shifted allo-HSCT from a widely applied strategy to a more individualized, risk-adapted therapeutic approach. This review examines how the indications, timing, and objectives of allo-HSCT are evolving in the contemporary treatment landscape of adult B-ALL, with particular emphasis on Philadelphia chromosome–negative, Philadelphia-like, and Philadelphia chromosome–positive disease subsets. Full article

Hematopoietic stem cell transplant (HSCT) is a curative therapy for acute lymphoblastic leukemia (ALL), but its success is limited by chronic graft-versus-host disease (cGvHD) and disease relapse. A central challenge is uncoupling the graft-versus-leukemia (GvL) effect from cGvHD. Early changes in the bone marrow microenvironment following HSCT may offer a predictive window into these divergent outcomes. We conducted a retrospective, single-center, exploratory study on 14 pediatric ALL HSCT patients. Applying single-cell antibody-sequencing (AbSeq) on archived bone marrow aspirates collected 60–100 days post-HSCT, we evaluated immune patterns associated with the development of cGvHD or ALL relapse after day 114. cGvHD after day 114 was associated with upregulation of the endoplasmic reticulum (ER) stress transcription factor XBP1 in transitional B cell and IgM memory B cell populations, a mincle^highPD1⁻ neutrophil population, and exhausted LAG3⁺ effector memory T cells (T_EM). ALL relapse after day 114 was associated with higher CD22, CD24, and ARG1 expression in M(IL-4)-like macrophages and exhausted TIGIT⁺ T_EM. Results from this exploratory study suggest that marrow immune signatures of B cell ER stress preceding later development of cGvHD and macrophage-mediated immune evasion preceding relapse may potentially be early biomarkers for separating GvL from cGvHD in ALL HSCT. Validation with larger cohorts is warranted. Full article

Hematopoietic stem cell transplant (HSCT) recipients are at high risk for opportunistic infections due to profound immunosuppression and graft-versus-host disease (GvHD). Molds and nontuberculous mycobacteria (NTM) pose diagnostic and therapeutic challenges, especially when infections overlap. A 42-year-old woman with prior allogeneic HSCT for acute myeloid leukemia (AML) developed pulmonary infections with Microascus spp. and Mycobacterium chimaera, later complicated by Aspergillus calidoustus and RSV infection. Initial therapy included voriconazole, amphotericin B, and a macrolide-based multidrug regimen for NTM. Modifications were required for drug resistance and hepatotoxicity. Despite partial response, recurrent fungal infection necessitated prolonged antifungal therapy, including adjunctive inhaled amphotericin B and terbinafine. Ultimately, progressive bronchiolitis obliterans prompted bilateral lung transplantation. Explant pathology revealed necrotizing granulomas positive for NTM and Microascus spp. Post-transplant prophylaxis with voriconazole, rifabutin, azithromycin, and inhaled amikacin prevented recurrence, and the patient remained clinically stable at 6-month follow-up. This case illustrates the complexity of managing overlapping mold and NTM infections in HSCT recipients, highlighting the need for individualized, multidisciplinary care. Therapeutic drug monitoring, careful adjustment for drug–drug interactions, and the use of adjunctive inhaled antifungals were critical to achieving a favorable outcome. Full article

Background/Objectives: The emergence of FLT3 inhibitors (FLT3i) has radically transformed the prognostic and therapeutic landscape for FLT3-mutated Acute Myeloid Leukemia, stimulating the need for comprehensive and structured clinical guidance. Methods: We aimed to develop evidence-based recommendations spanning the entire disease continuum of FLT3-mutated AML from leading Italian experts through a modified Delphi consensus process. Results: The panel achieved a high degree of agreement on specific interventions covering diagnostic testing, upfront FLT3i integration, role of allogeneic hematopoietic cell transplantation (allo-HSCT), Minimal Residual Disease (MRD) monitoring, and relapsed/refractory (R/R) strategies. Key recommendations mandate that analysis for both FLT3-ITD and FLT3-TKD mutations is required at diagnosis, with capillary electrophoresis or NGS as preferred methods. All fit patients with FLT3m-AML must receive intensive chemotherapy plus a FLT3i (midostaurin or quizartinib) and be evaluated for allo-HSCT. For unfit patients, the current standard of HMA + venetoclax is considered suboptimal, making the search for alternative strategies imperative. MRD monitoring using available molecular or flow cytometry markers is recommended to assess relapse risk and to optimize the allo-HSCT strategy. In the R/R setting, retesting the FLT3 status is mandatory, and gilteritinib is the standard treatment, serving as a bridge-to-transplant and for post-HSCT maintenance. Conclusions: The integration of FLT3i has shifted FLT3m-AML into a more favorable intermediate prognostic category, enhancing the role of curative strategies like allo-HSCT. This consensus paper provides a structured evidence-based comprehensive guide, translating complex data into clear actionable clinical recommendations that minimize practice variability and ultimately optimize management for this high-risk population. Full article

Introduction: Chronic lymphocytic leukemia (CLL) is a common adult leukemia often treated with fludarabine, cyclophosphamide, and rituximab (FCR). While effective, FCR can lead to therapy-related myeloid neoplasms (t-MN), including aggressive therapy-related acute myeloid leukemia (t-AML). Stem cell transplantation offers the best chance for long-term remission in these cases. Here, we report a rare case of t-AML with plasmacytoid dendritic cells (pDC-AML) developing after FCR treatment for CLL that was successfully treated with haplotransplantation. Case Presentation: A 57-year-old woman with CLL-B was treated with six cycles of FCR, achieving a complete response. Six years later, at age 63, she developed t-AML with a rare morphophenotypic subtype: acute myelomonocytic leukemia with plasmacytoid dendritic cells (pDC-AML) and monosomy 8. Diagnostic challenges included distinguishing this subtype from blastic plasmacytoid dendritic cell neoplasm (BPDCN). She was treated with high-dose cytarabine followed by haploidentical stem cell transplantation from her son. Haploidentical transplantation was prioritized due to the urgent clinical need in a patient with high-risk acute leukemia (therapy-related leukemia secondary to prior chemoimmunotherapy and failure to achieve complete remission following the standard 3 + 7 induction protocol). In this critical setting, the patient’s son was immediately available as an HLA-haploidentical donor. Prior to the performance of the haploidentical stem cell transplant from her son, no HLA-matched unrelated donor (MUD) could be identified. Another viable alternative would have been the utilization of umbilical cord blood-derived stem cells harvested from the patient’s twin granddaughters. She was closely monitored post-transplant for potential complications, including graft-versus-host disease (GVHD), post-transplant lymphoproliferative disorder, and thyroid dysfunction, all of which were ruled out during follow-up. The patient remains in complete remission 15 years after her initial CLL diagnosis and 8 years after the t-AML diagnosis and haplotransplantation. Notably, no residual CLL clone was detected at the time of t-AML development, and a benign polyclonal lymphocytosis observed between 2018 and 2020 spontaneously resolved without intervention. Conclusions: This case illustrates the potential for long-term survival in high-risk patients with therapy-related AML developed after cytotoxic treatment for lymphoid malignancies. Haplotransplantation from a semi-identical Human Leukocyte Antigen (HLA) donor proved to be a viable and effective treatment option despite the patient’s age and dual hematologic malignancies. Full article

In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), emerging evidence suggests that the oral microbiota may serve as a predictive biomarker. We conducted a systematic review to provide a critical overview of oral microbiota research in the allo-HSCT setting. We searched PubMed, Embase, and Web of Science from inception to December 2025 to identify studies assessing the oral microbiota in allo-HSCT settings. We included all articles reporting detailed data on the oral microbiota in this context and conducted a qualitative synthesis. Risk of bias was assessed using the JBI critical appraisal tools. From 8160 initially identified records, 35 studies evaluating the oral microbiota in 1964 allo-HSCT patients were included. Of these, 27 studies (77%) assessed temporal oral microbiota dynamics and reported dysbiosis in the early post-transplantation period, followed by gradual recovery. Additionally, 27 studies (77%) evaluated the prognostic value of the oral microbiota, identifying associations with key clinical outcomes such as oral mucositis, overall survival, and graft-versus-host disease. Finally, substantial methodological heterogeneity was observed across studies, including differences in sampling techniques, sampling timepoints, and analytical strategies. This systematic review highlights the prognostic and therapeutic potential of the oral microbiota in allo-HSCT and underscores the need for standardized methodologies. Full article

Germline genetic testing plays a critical role in diagnosing inherited predispositions and increasingly guides therapeutic and surveillance choices—but becomes technically challenging after allogeneic hematopoietic stem cell transplantation (HSCT), when donor-derived DNA contaminates host tissues. To address this, we compared donor-derived DNA across three accessible tissues—buccal swab, nail, and eyebrow follicles—in recipients after hematopoietic stem cell transplantation using two orthogonal assays (34-SNP next-generation sequencing and a 27-marker short tandem repeat panel) and modeled clinical covariates that influence chimerism. Eyebrow follicles showed consistently low donor DNA (median 1% by NGS; 3% by STR) whereas buccal swabs and nails carried substantially higher donor fractions (+25 and +22 percentage points versus eyebrow, respectively; both p < 0.01). Across methods, STR yielded on average ≈6 percentage points higher donor fractions than NGS at low-level chimerism. Several transplant covariates correlated with chimerism: matched-related donors and a perfect HLA match (10/10) were each associated with lower donor DNA (≈12–14 and 15–20 percentage points, respectively); longer times since hematopoietic stem cell transplantation correlated with lower levels for nail samples, and donor–recipient sex match correlated with higher donor DNA (~7–8 percentage points). Even low-level chimerism can distort germline variant interpretation. We propose a pragmatic protocol for post-hematopoietic stem cell transplantation germline testing that prioritizes eyebrow follicles as the default tissue. An SNP-based quality control assay is used to flag unsafe donor fractions (≥ 5–10%) before comprehensive germline analysis, reducing the risk that chimeric donor DNA distorts germline variant interpretation. Full article

Background and Clinical Significance: Histiocytic sarcoma (HS) is a rare and aggressive form of malignant histiocytosis, often associated with poor prognosis. The diagnosis and management of HS are challenging due to the complexity of its pathogenesis, molecular profile, and the unclear cellular origin of histiocytic neoplasms, compounded by the limited literature on treatment strategies. Case Presentation: We report the case of a young patient with HS localized to the lymph nodes, spleen, and liver, who also presented with hemophagocytic lymphohistiocytosis (HLH) documented on bone marrow biopsy. Initial treatment with CHOEP-21 and ICE-21 chemotherapy resulted in only a partial metabolic response, as evidenced by a Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET)/CT scan. Given the aggressive nature of the disease and the presence of HLH, an allogeneic hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor was performed as consolidation therapy, leading to a progressive complete response without significant toxicity. A suspected relapse at 18 months post-transplant was excluded following a mediastinal lymph node biopsy, which revealed a benign intravascular papillary endothelial hyperplasia (IPEH). Over five years post-diagnosis and more than four years after transplantation, the patient remains in complete remission with full functional recovery. Conclusions: This case highlights the diagnostic and molecular challenges of HS and demonstrates the curative potential of early allogeneic HSCT, even when only partial remission is initially achieved. Full article

Adoptive cellular therapy with donor-derived T cells has always been an attractive strategy after allogeneic hematopoietic stem cell transplantation (allo-HSCT) to reduce the risk of relapse in acute myeloid and lymphoid leukemias. Donor lymphocyte infusion (DLI) is still the best-established option, especially in the preemptive phase when measurable residual disease (MRD) becomes positive and in the prophylactic setting—when MRD is not detectable. However, the clinical benefit of DLI is counterbalanced by the possible onset of graft-versus-host disease (GvHD), which continues to restrict its wide application. To address this challenge, several alternative cell-based strategies have been developed. One of these is represented by cytokine-induced killer (CIK) cells, generated from donor peripheral blood mononuclear cells through stimulation with anti-CD3 antibodies, interferon-γ, and interleukin-2. These cells are characterized by a hybrid phenotype, combining T-cell functions with natural killer-like properties, and exhibit antitumor activity in an MHC-unrestricted manner. CIK cells are generally well tolerated and associated with low toxicity but their efficacy is so far modest. Based on the experience of CAR-T in the treatment of B-cell lymphoid disease, CIK cells have been engineered with chimeric antigen receptors (CAR) developing the CARCIK cells. This novel cellular strategy represents a promising approach in the treatment of acute myeloid and lymphoid leukemia relapsed post-allo-HSCT. This review provides an overview of the current CAR-CIK experiences in the setting of acute leukemias and outlines future directions for their clinical translation. Full article

Background/Objectives: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established therapy for a range of hereditary disorders, including hemoglobinopathies, primary immunodeficiencies, and lysosomal storage diseases. Despite its long-standing use, rapid developments in donor availability, conditioning strategies, and supportive care have significantly broadened and refined its clinical application. This review combines recent evidence to clarify how these advances redefine current indications and therapeutic expectations. Methods: We critically analyze contemporary clinical data with a focus on elements that have undergone meaningful evolution—donor selection algorithms, conditioning intensity, graft manipulation, and post-transplant management. Comparative outcomes across major hereditary disease groups were examined to identify emerging trends in efficacy and safety. Results: The analysis highlights several novel shifts: expanding eligibility due to improved donor options, increasing reliance on reduced-toxicity regimens, and enhanced understanding of the mechanistic basis for hematologic, immunologic, and metabolic correction. These developments collectively improve survival and functional outcomes across diverse hereditary disorders. Conclusions: allo-HSCT remains a key therapeutic strategy for selected hereditary diseases, offering durable hematologic and metabolic correction. The prospective development of gene-addition and genome-editing therapies creates opportunities to complement—or in some cases replace—allo-HSCT, supporting the emergence of more personalized treatment approaches. Full article

Background: Although Enterococcus domination has been extensively evaluated in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT), the prevalence and clinical implications of other dominant genera remain poorly understood. Objective: In this study, we sought to determine the dynamics, predictors and clinical implications of intestinal domination in Brazilian patients undergoing allo-HSCT. Methods: In a prospective study of four Brazilian centers, fecal specimens were collected longitudinally prior to allo-HSCT until six months post-transplantation. To identify intestinal domination, we performed 16S rRNA gene sequencing using the Illumina platform. We then evaluated the impact of intestinal domination on overall survival and acute Graft-versus-Host-Disease (aGvHD) incidence. Finally, to identify predictors of intestinal domination, we performed a logistic regression model. Results: A total of 192 fecal specimens were collected from 69 patients. No significant changes in alpha or beta diversity were observed over the course of allo-HSCT. Among the 192 specimens, 131 (68%) presented intestinal domination. The top four dominant genera were Bacteroides, Akkermansia, Phascolarctobacterium, and Escherichia-Shigella. No significant associations were found between domination by these genera and either overall survival or aGvHD incidence. Furthermore, no patient-level characteristics, including age, sex, underlying disease, conditioning regimen, or stem cell source, reliably predicted intestinal domination. Conclusions: Our findings reveal a unique intestinal domination fingerprint in Brazilian patients and highlight the importance of geographic context in interpreting microbiota–outcome associations in allo-HSCT settings. Full article

Background: Pediatric non-Down Syndrome Acute Megakaryoblastic Leukemia (non-DS-AMKL) is a rare subtype of Acute Myeloid Leukemia (AML) arising from primitive megakaryocytes and is associated with poor outcomes. Given its high incidence of relapse, this subpopulation of children is frequently referred for allogeneic hematopoietic stem cell transplant (allo-HSCT) in first complete remission (CR1). Objectives: The objective of this study was to describe the clinical outcomes of non-DS-AMKL pediatric patients in a large, single-institution cohort. Methods: A retrospective review of the medical records of thirty-six patients diagnosed with non-DS-AMKL treated at Texas Children’s Hospital from 2000 to 2022 was conducted. Results: Twenty-nine patients were included in the analysis, with cohorts defined by intention to treat. Twelve patients received chemotherapy only during upfront therapy, and seventeen received upfront HSCT. The 5-year overall survival (OS) and disease-free survival (DFS) for the entire cohort were 19.1% and 24.1%, respectively, with a median survival of 17.4 months. A higher percentage of patients in the chemotherapy-only group had relapsed/refractory disease at death (chemotherapy only, n = 9; HSCT, n = 8). However, 5-year OS and DFS were similar for both groups (OS = 18.8% vs. 31.3%, p = 0.58; DFS = 37.6% vs. 22.2%, p = 0.51). Relapse was the leading cause of death (5-year cumulative incidence of relapse (CIR) 0.78). Treatment with allo-HSCT did not improve outcomes due to the high CIR, even after HSCT in CR1. Conclusions: These dismal outcomes highlight the need for development and incorporation of novel targeted agents into upfront therapy or in the post-HSCT setting for patients with this challenging disease. Full article

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy, typically presenting with systemic symptoms and mediastinal involvement. Leukemia cutis (LC) and renal infiltration are rare, especially at disease onset. A 27-year-old man presented with a solitary scalp lesion without systemic symptoms or hematologic abnormalities. Histopathology revealed a blastoid lymphoid infiltrate with a T-ALL immunophenotype. Two weeks later, laboratory tests showed leukocytosis, lymphocytosis, and renal dysfunction. Imaging revealed a large mediastinal mass, scalp soft tissue involvement, and bilateral renal infiltration. Bone marrow biopsy confirmed T-ALL with a mature phenotype. FISH identified TRAD:NKX2 rearrangement and CDKN2AB deletion. The patient received three cycles of pediatric-inspired chemotherapy, achieving complete molecular remission and resolution of extramedullary disease. He subsequently underwent allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-matched sibling. Post-transplant complications included febrile neutropenia and mucositis. On day +100, he remained in minimal residual disease (MRD)-negative remission. This case illustrates a rare presentation of T-ALL with isolated skin involvement and renal infiltration at diagnosis, highlighting the importance of early biopsy and immunophenotyping of atypical skin lesions. Intensive chemotherapy followed by HSCT represents a viable strategy for young adults with high-risk T-ALL and extramedullary disease. Full article