Search Results (159)

T-cell lymphomas (TCLs) are generally associated with a poorer prognosis compared to B-cell lymphomas, and allogeneic hematopoietic cell transplantation (allo-HCT) is often considered for eligible patients. One of the primary reasons for the inferior outcomes in TCLs has been the lack of effective novel agents for many years, resulting in a continued reliance on traditional cytotoxic chemotherapy regimens. However, over the past decade, several novel agents with promising efficacy against TCLs have been developed. Notably, many of these agents not only exert direct anti-tumor effects but also modulate host immune function, raising clinical questions regarding the optimal integration of these agents with allo-HCT. In this review, we aim to summarize how the use of novel agents that are approved for the treatment of TCLs—such as mogamulizumab, brentuximab vedotin, lenalidomide, histone deacetylase inhibitors, enhancer of zeste homolog inhibitors, and immune checkpoint inhibitors—before or after allo-HCT may impact transplantation outcomes in patients with TCLs. Full article

The therapeutic landscape of adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is undergoing a paradigm shift, driven by the development of immunotherapy-based “chemo-free” and “chemo-light’ regimens. These strategies aim to achieve high efficacy with reduced toxicity, particularly in older adults who may not tolerate intensive chemotherapy. In Philadelphia chromosome-positive (Ph+) BCP-ALL, the incorporation of ABL tyrosine kinase inhibitors (TKIs) with blinatumomab (CD3/CD19 bispecific T-cell engager) has shown remarkable efficacy, with some studies reporting molecular response rates in the range of 90–100% and long-term survival exceeding 80% without the need for intensive chemotherapy or allogeneic hematopoietic cell transplantation (allo-HCT). In Philadelphia-negative (Ph−) BCP- ALL, an immunotherapy-based combination of blinatumomab and inotuzumab ozogamicin (anti-CD22 antibody-drug conjugate) has demonstrated high rates of complete remission and measurable residual disease (MRD) negativity, with manageable toxicity. While chimeric antigen receptor (CAR) T-cell therapy remains a transformative option for relapsed/refractory B-ALL, its integration into frontline treatment is still under investigation. Ongoing trials are evaluating the optimal sequencing and combinations of these agents and their potential to obviate the need for chemotherapy and/or allo-HCT in selected patients. As evidence continues to accumulate, chemo-free and chemo-light regimens, incorporating minimal chemotherapy with targeted agents to balance efficacy and reduced toxicity, are poised to redefine the standard of care for adults BCP-ALL, offering the possibility of durable remissions with reduced treatment-related morbidity. Full article

Background: Acute leukemia (AL) is the most prevalent pediatric malignancy and is frequently associated with systemic iron dysregulation, often leading to iron overload. This study aimed to characterize the regulatory mechanisms of iron metabolism in children with AL, considering treatment stages and associated clinical parameters. Methods: A total of 149 children were stratified into four groups: newly diagnosed AL (n = 43), patients post-chemotherapy (n = 55), patients following hematopoietic cell transplantation (HCT; n = 32), and healthy controls (n = 19). Serum concentrations of matriptase-2 (TMPRSS6), neogenin-1 (NEO1), and soluble hemojuvelin (sHJV) were quantified using ELISA. Results: Compared to healthy children, significantly higher serum concentrations of TMPRSS6 and NEO1 were found in patients post-chemotherapy and post-HCT, while sHJV levels were markedly decreased. Higher TMPRSS6 and NEO1 levels and lower sHJV were associated with increased ferritin levels and greater numbers of transfused packed red blood cell (PRBC) units. sHJV negatively correlated with TMPRSS6, NEO1, ferritin, C-reactive protein (CRP), and PRBC transfusions. TMPRSS6 and NEO1 showed a positive correlation. Among the analyzed biomarkers, Kaplan–Meier analysis revealed no statistically significant associations with overall survival (OS) or event-free survival (EFS) within the chemotherapy and HCT subgroups. Conclusions: AL in pediatric patients is associated with profound disruptions of systemic iron homeostasis. Our investigation identified notable perturbations in TMPRSS6, NEO1, and sHJV, suggesting that these proteins could contribute mechanistically to the pathophysiological alterations underlying iron dysregulation observed in pediatric AL. Full article

Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease (SOS/VOD) is a severe complication of hematopoietic cell transplantation (HCT). Furthermore, emerging evidence suggests the potential role of complement activation and endothelial injury in SOS/VOD pathogenesis. In this study, we aimed to identify potential distinct pathogenic genetic variants between SOS/VOD and other endothelial injury syndromes following HCT, such as transplant-associated thrombotic microangiopathy (TA-TMA). For this aim, genomic DNA from 30 SOS/VOD patients and 30 controls with TA-TMA was analyzed. Using Next-Generation Sequencing (NGS), variants in complement-related genes (CFH, CFI, CFB, CFD, C3, CD55, C5, CD46, and thrombomodulin/THBD) and ADAMTS13 were examined. Out of 426 detected variants, 20 were classified as pathogenic. In SOS/VOD patients, variants were identified in ADAMTS13 (4), CFH (3), C3 (2), and CFB (1) genes. One of the variants has been recognized as the strongest genetic predictor of ADAMTS13 activity. Controls exhibited more variants in complement-related genes, particularly CFH, CFI, and C3. The genetic differences between SOS/VOD and TA-TMA highlight different pathogenic mechanisms, offering the potential for targeted risk assessment and therapy in HCT recipients. Full article

Cancer patients use cannabis for medicinal purposes; however, few studies have examined hematology patients’ use of cannabis and no research to our knowledge has investigated the use of cannabis amongst hematology patients before and after hematopoietic stem cell transplant (HCT). The purpose of this longitudinal survey study was to assess aspects of cannabis use in patients who underwent HCT. Eligible patients (N = 30) completed two surveys before and 90 days following their HCT. The surveys inquired about several aspects of cannabis (e.g., rate of use, beliefs and attitudes, access to information) and physical and psychological outcomes (e.g., anxiety, comorbidities, graft-versus-host-disease). Rates of cannabis use decreased following HCT (n = 14, 46% to n = 11, 40%). Conversations on cannabis that were initiated by an oncology health care provider increased post-transplant (n = 3, 10% to n = 11, 37%). This coincided with fewer who were smoking cannabis as a primary consumption method (n = 5, 38 to n = 2, 18) and an increase in the use of pharmaceutical cannabinoid products (n = 4, 13% to n = 6, 21%) as well as oils and topicals. Of the total sample, 63% (n = 17) experienced post-treatment complications and 33% (n = 10) developed GVHD, six of whom where recent cannabis users. This study provided insight into cannabis use amongst HCT patients and warrants further research with this population, including more exploration of the relationship between GVHD and cannabis. Full article

Allogeneic hematopoietic cell transplantation (alloHCT) is the sole curative therapy for myelodysplastic syndrome (MDS). While alloHCT clearly confers a significant survival advantage in high-risk MDS, it is less clear how the disease burden and impact of conditioning intensity impact survival. This review addresses critical issues surrounding this topic, emphasizing the unique cell biology of MDS and the evolving concepts of conditioning intensity compared to other diseases, including acute myeloid leukemia (AML). The review is structured around three interconnected themes. First, it clarifies the varying interpretations of conditioning intensity. Second, it examines the interplay between disease burden at transplant and conditioning intensity in determining outcomes, including a comparative analysis with acute myeloid leukemia (AML) to highlight similarities and differences. Third, it explores the relationship between conditioning regimen intensity and immune reconstitution, particularly focusing on the graft-versus-tumor (GvT) effect and its potential modulation by conditioning intensity. Understanding the stem cell target of conditioning regimens is emphasized, as the persistence of the underlying MDS stem cell necessitates a thorough understanding of this concept for improved therapeutic strategies. Full article

Background: Pseudomonas aeruginosa (PSA) infections are associated with a high recurrence rate and high mortality in immuno-compromised patients. There are limited studies regarding pediatric hematopoietic cell transplantation recipients. Aim: The nationwide multicenter study was conducted to analyze the epidemiology of PSA infections in children treated with chemotherapy (PHO, pediatric hematology and oncology) or undergoing hematopoietic allogeneic or autologous cell transplantation (HCT) in the period 2014–2023. Methods: We retrospectively analyzed the clinical and microbiological data of children who underwent anticancer therapy or hematopoietic cell transplantation in 17 Polish PHO centers and six pediatric HCT centers. The data were collected in two-year intervals. Results: During the 10-year study period, a total of 1629 HCTs (both autologous and allogeneic) and 9614 children newly diagnosed with neoplasms were analyzed. The cumulative incidence of PSA infection was similar in both groups (6.71% in PHO vs. 6.32% in HCT, p = 0.624). The total number of PSA bloodstream infections was comparable in the PHO and HCT groups (31.9% vs. 26.2%; p = 0.223). In both analyzed groups, the antipseudomonal drugs of choice were as follows: meropenem, ceftazidime, and tazobactam/piperaciline in combination with other antibiotics. In the HCT group, high rates of meropenem (20.4%) and tazobactam/piperaciline (18.4%) non-susceptibility were observed. This led to colistin therapy in 5.3% of patients. There was no difference in the median antibiotic therapy time in both groups; however, the survival rates from PSA infection were significantly lower in the HCT group (89.3% vs. 96.0%, p = 0.004). Conclusions: Although the risk of infection and the occurrence of resistant bacterial strains in HCT patients were comparable with those in PHO patients, the outcome of PSA infections was better in the PHO setting. Full article

Background: Allogeneic hematopoietic cell transplant (alloHCT) is a curative option for relapsed/refractory B-cell lymphomas (BCLs), but its role in the evolving field of cellular therapy is increasingly unclear as recent advances in transplant procedures have improved outcomes. Methods: This retrospective, single-center study included 55 BCL patients (large B-cell lymphoma—LBCL; indolent BCL; and mantle cell lymphoma—MCL) treated with alloHCT from 2015 to 2023 at Hôpital Maisonneuve-Rosemont. Primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included NRM and GVHD incidence. Results: A total of 55 patients were included (25 LBCLs, 16 indolent BCLs, 14 MCLs), and 76% of LBCLs were of indolent origin (Richter transformation, transformed follicular lymphoma). After a median follow-up of 6.1, 5.8 and 2.4 years for LBCLs, indolent BCLs and MCLs, their 5-year PFS and OS were 57.2% (IC 95%: 34.2–74.7) and 62.8% (IC 95%: 37.9–80.0), 81.2% (IC 95%: 52.5–93.5) and 93.8% (IC 95%: 63.2–99.1), and 39.0% (IC 95%: 14.3–63.3) and 68.1% (IC 95%: 35.4–86.8), respectively. The 5-year NRM was 16.9% (IC 95%: 8.2–28.3) with a relapse incidence of 23.4%. Overall/grade 3–4 acute GVHD occurred in 43.6% and 18.1% of patients. At 3 years, overall/moderate or severe chronic GVHD incidence was 49% and 34.5%. Conclusions: AlloHCT remains a potentially curative option and should be considered for fit patients with chemosensitive FL or LBCLs of indolent origin and a low comorbidity index. Full article

Background: Hematopoietic cell transplantation (HCT) remains the only curative therapy for pediatric myelodysplastic syndrome (MDS) in all but rare cases. While HCT outcomes for pediatric MDS are similar across the largest registry and single-center trials, factors identified as contributing to inferior outcomes vary from study to study. We performed an analysis to provide more clarity on the prognostic implications of disease characteristics, including blast burden and cytogenetic abnormalities, in the current era. Methods: We conducted a retrospective analysis of 36 consecutive children (<18 years of age at HCT) who underwent allogeneic HCT for MDS between June 2000 and October 2019 at the Fred Hutchinson Cancer Center. Results: Overall survival (OS) was 77% (95% CI 64–92%) and relapse-free survival (RFS) was 71% (95% CI 57–88%) at 2 years post-HCT. Patients with <5% blasts by morphology in the bone marrow at the time of HCT showed superior 2-year OS at 87% (95% CI 74–100%) as compared to 54% (95% CI 32–93%) in patients with ≥5% blasts, consistent with an HR of 4.6 (CI 1.14–18.7, p = 0.03). The inferior outcomes in patients with ≥5% blasts were due to increased relapse incidence (HR 7.6, CI 1.5–39.3) with no difference in NRM or acute GVHD. Conclusions: OS and RFS were comparable to what has been observed in other large, single-center studies (OS 77%, RFS 71% at 2 years) and compared favorably to outcomes from the largest multi-center retrospective analyses. Full article

Background: T-prolymphocytic leukemia (T-PLL) is a rare lymphoid neoplasm with particularly poor prognosis. Although it is no longer recognized as a distinct entity by the World Health Organization (WHO), B-prolymphocytic leukemia (B-PLL) comprises conditions with unfavorable outcomes. Both diseases most frequently affect patients in the seventh decade of their lives. Allogeneic hematopoietic stem cell transplantation (alloHSCT) significantly improves outcomes for selected PLL cases, as shown by several, mostly retrospective, analyses. Methods: In this article, we provide a review of existing PLL analyses, followed by a summary of cases treated at our center. We describe outcomes of six T-PLL and three B-PLL cases receiving alloHSCT at our institution between 2015 and 2022. Results: Despite a post-transplant 4-year cumulative relapse incidence of 61% in our T-PLL series, the median OS was 78 months, because relapse therapy was remarkably successful. All B-PLL patients are alive and relapse-free, with a median follow-up of 54 (range of 11–74) months. A poor pre-transplant Karnofsky performance status (KPS) (≤ 80%) and an HCT comorbidity index (HCT-CI) of ≥3 were significantly associated with post-transplant mortality. Conclusions: The comparatively favorable outcomes in our case series underline the increasing value of alloHSCT in PLL in the current era, as it offers a prospect of cure in selected patients with otherwise very poor prognosis. Full article

A 5-year-old boy affected by chronic granulomatous disease (CGD) underwent two allogeneic hematopoietic cell transplants (HCT) from the same unrelated donor. The first HCT was complicated by prolonged fever and primary graft failure. While fully aplastic, the patient developed a disseminated infection by Scedosporium apiospermum involving the knee and parasternal skin (day +34 and +40 post-HCT). The patient was treated with voriconazole and granulocyte transfusions followed by a second HCT 80 days after the first HCT. At day +105, the patient developed fever, headache, and altered level of consciousness associated with multiple bilateral cerebral abscesses at magnetic resonance imaging. The serum B-D-glucan test was positive. Micafungin was added to voriconazole. Despite an initial clinical improvement, the patient developed hydrocephalus. Scedosporium apiospermum was cultured from cerebrospinal fluid. Liposomal amphotericin B, instead of micafungin, was combined with voriconazole as salvage therapy. Unfortunately, the patient developed uncal herniation and died at day +193 from HCT. This case shows that the prognosis of scedosporiosis remains poor despite adequate antifungal treatment. Noteworthy, the B-D-Glucan test is confirmed useful as a non-invasive marker for early diagnosis and may help the differential diagnosis of mycoses. Full article

Background/Objectives: This study evaluated infectious complications and immune reconstitution in 253 adults undergoing peripheral blood allogeneic hematopoietic cell transplantation (allo-HCT) with post-transplant cyclophosphamide (PTCY)-based GVHD prophylaxis. Methods: Patients received grafts from HLA-matched donors (47.4%), mismatched unrelated donors (MMUD, 33.2%), or haploidentical donors (19.4%). Results: The estimated 2-year non-relapse mortality (NRM) was 11.8%, 26.4%, and 22.4%, respectively (p = 0.0528). The cumulative incidence (Cum.Inc) of acute and chronic GVHD, immunosuppression duration, and post-transplant outcomes were similar across donor types. The day +30 Cum.Inc of bacterial bloodstream infections (BSI) tended to be higher in HLA-matched transplants (49.2%, p = 0.073), while HHV-6 reactivation showed a trend toward higher frequency in haploidentical transplants (22.4%, p = 0.068). Cytomegalovirus (CMV) reactivation occurred between days +30 and +100, with the highest Cum.Inc in MMUD (59.5%, p = 0.033). BK virus-associated hemorrhagic cystitis showed a trend toward higher incidence in MMUD (22.3%, p = 0.056). Respiratory and fungal infections were most frequent in the first 100 days, with comparable rates across donor types. By day +180, most patients achieved immune reconstitution, with normalization of CD4+ T cells, CD8+ T cells, and IgG levels, independent of donor type. Conclusions: Patients undergoing allo-HCT with PTCY-based prophylaxis experience a high infectious density rate early post-transplant, which decreases after 6 months as immune reconstitution progresses, regardless of donor type. Full article

The treatment of B-cell acute lymphoblastic leukemia (B-ALL) in adults remains a significant therapeutic challenge. While advances in chemotherapy and targeted and immunotherapies have improved overall survival, relapsed or refractory (r/r) adult ALL is associated with poor outcomes. CD19-directed chimeric antigen receptor (CAR) T-cell therapy has emerged as a transformative option, achieving high remission rates even in heavily pretreated patients. However, relapse is common. Allogeneic hematopoietic stem cell transplantation (allo-HCT), a traditional cornerstone of remission consolidation, may improve long-term outcomes but carries risks of transplant-related mortality (TRM) and morbidity. Most evidence for HCT after CAR T therapy comes from retrospective analyses of subgroups from CAR T cell trials, with small sample sizes and inconsistent data on transplant procedures and outcomes. Despite these limitations, consolidative allo-HCT appears to prolong relapse-free survival (RFS). While overall survival (OS) benefits are in question, extended remission duration has been observed. Nonrelapse mortality (including TRM), ranging from 2.4 to 35%, underscores the need for careful patient selection. Emerging real-world data affirm these findings but highlight the importance of individualized decisions based on disease and treatment history. This review examines current evidence on the sequential use of CD19-directed CAR T-cell therapy and allo-HCT in adults with r/r B-ALL. Full article

Background: Graft versus host disease (GVHD) and the graft versus tumor (GVT) effect after allogeneic hematopoietic cell transplantation (allo-HCT) result from complex interactions between the donor immune system and the recipient environment. High-temporal longitudinal monitoring might be necessary to identify triggering events of GVHD and GVT and to intercept these events before their occurrence. But it would require an overall considerable amount of blood by venipuncture, which is unfeasible in such a fragile population. Methods: In this study, we implemented a targeted multiplex microfluidics q-PCR-based transcriptional fingerprint assay (TFA) on 50 µL of blood collected by a simple fingerstick to evaluate post-allo-HCT systemic immune perturbations associated with the development of GVHD. Fluctuations of a panel of 264 genes were measured in 31 allo-HCT patients by frequent (weekly or biweekly) analysis of 50 µL serial blood samples. Cross-sectional and longitudinal analyses correlated with detailed clinical annotations were performed. Results: Signatures of neutrophil activation and interferon (IFN) characterized the onset of acute GVHD, while an ongoing cytotoxic response was modulated in chronic mild GVHD and protein-synthesis and B-cell-related signatures characterized late acute/overlap GVHD. An unexpected erythroid signature distinguished patients with acute and mild chronic GVHD. Conclusions: Our micro-invasive approach unveiled the molecular heterogeneity of GVHD and identified hierarchically important biological processes conducive to different forms of GVHD. These findings increase our understanding of GVHD and reveal potentially targetable alterations. This approach might be implemented clinically to intercept GVHD before its occurrence and to modulate therapeutic interventions accordingly. Full article

Allogeneic hematopoietic cell transplantation (HCT) remains an important curative-intent treatment for many patients with acute myeloid leukemia (AML), but AML recurrence after allografting is common. Many factors associated with relapse after allogeneic HCT have been identified over the years. Central among these is measurable (“minimal”) residual disease (MRD) as detected by multiparameter flow cytometry, quantitative polymerase chain reaction, and/or next-generation sequencing. Demonstration of a strong, independent prognostic role of pre- and early post-HCT MRD has raised hopes MRD could also serve as a predictive biomarker to inform treatment decision-making, with emerging data indicating the potential value to guide candidacy assessment for allografting as a post-remission treatment strategy, the selection of conditioning intensity, use of small molecule inhibitors as post-HCT maintenance therapy, and preemptive infusion of donor lymphocytes. Monitoring for leukemia recurrence after HCT and surrogacy for treatment response are other considerations for the clinical use of MRD data. In this review, we will outline the current landscape of MRD as a biomarker for patients with AML undergoing HCT and discuss areas of uncertainty and ongoing research. Full article