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Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are usually associated with poor outcomes, especially in high‐risk AML/MDS. Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is the only curative option for patients suffering from high‐risk AML/MDS. However, many patients relapse after allo‐HSCT. Novel therapy to prevent relapse is urgently needed. Both the BCL‐2 inhibitor venetoclax (VEN) and the hypomethylating agent decitabine (DEC) possess significant antitumor activity effects against AML/MDS. Administration of DEC has been shown to ameliorate graft‐versus‐host disease (GVHD) and boost the graft‐versus‐leukemia (GVL) effect post‐transplantation. We therefore conducted a prospective study (ChiCTR1900025374) to examine the tolerability and efficacy of a maintenance therapy of low‐dose decitabine (LDEC) plus VEN to prevent relapse after allo‐HSCT for high‐risk AML/MDS patients. Twenty patients with high‐risk AML (n = 17) or high‐risk MDS (n = 3) post‐transplantation were recruited. Approximately day 100 post‐transplantation, all patients received LDEC (15 mg/m2 for 3 d) followed by VEN (200 mg) on d 1‐21. The cycle interval was 2 mo, and there was 10 cycles. The primary end points of this study were rates of overall survival (OS) and event‐free survival (EFS). The secondary endpoints included adverse events (AEs), cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), incidences of acute GVHD (aGVHD) and chronic GVHD (cGVHD), and incidences of viral infection after allo‐HSCT. Survival outcomes were assessed using Kaplan‐Meier analysis. The median follow‐up was 598 (149‐1072) d. Two patients relapsed, 1 died, and 1 is still alive after the second transplant. The 2‐y OS and EFS rates were 85.2% and 84.7%, respectively. The median 2‐y EFS time was 525 (149‐1072) d, and 17 patients still had EFS and were alive at the time of this writing. The most common AEs were neutropenia, anemia, thrombocytopenia, neutropenic fever, and fatigue. Grade 2 or 3 AEs were observed in 35% (7/20) and 20% (4/20) of the patients, respectively. No grade >3 AEs were observed. aGVHD (any grade) and cGVHD (limited or extensive) occurred in 55% and 20% of patients, respectively. We conclude that LDEC + VEN can be administered safely after allo‐HSCT with no evidence of an increased incidence of GVHD, and this combination decreases the relapse rate in high‐risk AML/MDS patients. This novel maintenance therapy may be a promising way to prevent relapse in high‐risk AML/MDS patients. The results of the current study suggest that maintenance treatment with LDEC combined with VEN introduced nearly 3 mo after allo‐HSCT is efficacious, with an acceptable toxicity profile and impressive long‐term disease control.

[This corrects the article DOI: 10.3389/fimmu.2023.1128982.].

The best conditioning for hematopoietic stem cell transplantation (HSCT) in acute lymphoblastic leukemia is debated. We analyzed 178 adults undergoing HSCT with total body irradiation (TBI) or chemotherapy conditioning regimens for B-cell leukemia in complete remission 1 (CR1). Both TBI and chemotherapy regimens showed comparable overall survival (OS) and leukemia-free survival (LFS). However, TBI had a trend of reduced relapse (HR 0.56, P  = 0.064) but higher non-relapse mortality (NRM, HR 3.23, P  = 0.072) due to increased grade 3 to 4 graft-versus-host disease (22.8% vs. 8.8%, P  = 0.023). The key factor affecting survival was minimal residual disease (MRD) after three chemotherapy cycles (OS P  = 0.004, LFS P  = 0.006). In MRD-negative patients, both regimens gave similar LFS and cumulative incidence of relapse (CIR) irrespective of whether the transplantation was allogeneic (allo-HSCT) or autologous (auto-HSCT), but the allo-HSCT group had a lower OS due to higher NRM (5.3% vs. 20.6%, P  = 0.020). For MRD-positive patients, TBI was superior in LFS (71.9% vs. 43.9%, P  = 0.017) and relapse rate (18.5% vs. 48.7%, P  = 0.006). Our research indicates the choice between TBI and non-TBI should be based on MRD after three chemotherapy cycles.

Hematopoietic stem cell transplantation (HSCT) is a curative option for children with high-risk acute lymphoblastic leukemia (ALL). This retrospective single-center study analyzed 236 pediatric ALL patients in complete remission who underwent allogeneic HSCT using ex-vivo T cell depletion between 2012 and 2021. The majority received haploidentical grafts ( n  = 202), while the remainder received matched unrelated donor (MUD) grafts ( n  = 34). At four years, event-free survival (EFS) and overall survival (OS) were 57% and 67%, respectively. Total body irradiation (TBI)-based conditioning was associated with significantly lower relapse rates and superior EFS compared to chemotherapy-based regimens. Non-relapse mortality (NRM) was low (9%), with no significant difference between donor types. Pre-transplant minimal residual disease (MRD) positivity and transplantation beyond first complete remission were independently associated with higher relapse and inferior survival. Chronic GVHD incidence was lower in patients receiving abatacept and tocilizumab instead of ATG. These findings confirm the safety and efficacy of ex-vivo T cell-depleted HSCT in pediatric ALL, with outcomes comparable between haploidentical and MUD donors. TBI-based conditioning and MRD negativity remain key prognostic factors for improved outcome.

This study presents the analytical performance of a new Next-Generation Sequencing (NGS) assay designed to detect Human Leukocyte Antigen (HLA) loss. Unlike existing methods, this assay offers increased sensitivity, broader applicability, and does not require prior knowledge of specific HLA mismatches, making it a more versatile tool for post-transplant monitoring. The main goal was to determine whether this assay can reliably identify HLA loss in post-transplant patients and provide clinically actionable information for relapse management. Furthermore, the clinical utility of the assay was assessed in patients undergoing Hematopoietic Stem Cell Transplantation (HSCT) with haploidentical or HLA-mismatched unrelated donors (MMUD). The study included both artificial and clinical samples, which were analyzed using the present assay to examine insertion-deletion (indel) markers located within and adjacent to the HLA region. The results demonstrated that the new assay exhibits excellent correlation with the One Lambda Devyser Chimerism assay in samples without HLA loss, achieving a detection limit of 0.25%. Furthermore, the study showed that the markers employed in the assay can effectively identify the occurrence and location of HLA loss. These findings could potentially influence clinical decision-making, when the donor source of retransplants or Donor Lymphocyte Infusions (DLI) need to be re-considered.

The hyper-IgE syndromes (HIES) are a heterogeneous group of inborn errors of immunity sharing manifestations including increased infection susceptibility, eczema, and raised serum IgE. Since the prototypical HIES description 55 years ago, areas of significant progress have included description of key disease-causing genes and differentiation into clinically distinct entities. The first two patients reported had what is now understood to be HIES from dominant-negative mutations in signal transduction and activator of transcription 3 (STAT3-HIES), conferring a broad immune defect across both innate and acquired arms, as well as defects in skeletal, connective tissue, and vascular function, causing a clinical phenotype including eczema, staphylococcal and fungal skin and pulmonary infection, scoliosis and minimal trauma fractures, and vascular tortuosity and aneurysm. Due to the constitutionally expressed nature of STAT3, initial reports at treatment with allogeneic stem cell transplantation were not positive and treatment has hinged on aggressive antimicrobial prophylaxis and treatment to prevent the development of end-organ disease such as pneumatocele. Research into the pathophysiology of STAT3-HIES has driven understanding of the interface of several signaling pathways, including the JAK-STAT pathways, interleukins 6 and 17, and the role of Th17 lymphocytes, and has been expanded by identification of phenocopies such as mutations in IL6ST and ZNF341. In this review we summarize the published literature on STAT3-HIES, present the diverse clinical manifestations of this syndrome with current management strategies, and update on the uncertain role of stem cell transplantation for this disease. We outline key unanswered questions for further study.

We evaluated anti-spike protein antibody (anti-S) production in 130 hematopoietic stem cell transplant (HSCT) recipients who received the coronavirus disease-2019 vaccine. Sixty-five received allo-HSCT and 65 received auto-HSCT. Disease-specific treatments were being administered to 43.1% of allo-HSCT and 69.2% of auto-HSCT patients. Seropositivity was observed in 87.7% of allo-HSCT and 89.2% in auto-HSCT patients. Anti-S antibody production was significantly impaired in auto-HSCT patients compared with controls (178U/mL [0.4–4990.0] vs. 669 U/mL [40.3–4377.0], p < 0.001), but not in allo-HSCT patients (900 U/mL [0.4–12,893.0] vs. 860 U/mL [40.3–8988.0], P = 0.659). Clinically relevant anti-S antibody levels (> 264 U/mL) were achieved in 59.2% of patients (76.9% in allo-HSCT and 41.5% in auto-HSCT). The main factors influencing the protective level of the antibody response were the CD19 + cell count and serum immunoglobulin G levels, and these were significant in both allo-HSCT and auto-HSCT patients. Other factors included time since HSCT, complete remission status, use of immunosuppressive drugs, and levels of lymphocyte subsets including CD4, CD8 and CD56 positive cells, but these were only significant in allo-HSCT patients. Allo-HSCT patients had a relatively favorable antibody response, while auto-HSCT patients had poorer results.

T lymphoblastic leukemia /lymphoma (T-ALL/LBL) is a rare and highly aggressive neoplasm of lymphoblasts. We evaluated 195 T-ALL/LBL adolescent and adult patients who received ALL-type chemotherapy alone (chemo,n = 72) or in combination with autologous hematopoietic stem cell transplantation(auto-HSCT,n = 23) or allogeneic hematopoietic stem cell transplantation(allo-HSCT,n = 100) from January 2006 to September 2020 in three Chinese medical centers. 167 (85.6%) patients achieved overall response (ORR) with 138 complete response (CR) patients (70.8%) and 29 partial response (PR) patients (14.8%). Until October 1, 2023, no difference was found in 5-year overall survival (5-OS) and 5-year progression free survival(5-PFS) between allo-HSCT and auto-HSCT (5-OS 57.9% vs. 36.7%, P = 0.139, 5-year PFS 49.4% vs. 28.6%, P = 0.078) for patients who achieved CR, for patients who achieved PR, allo-HSCT recipients had higher 5-OS compared with chemo alone recipients (5-OS 23.8% vs. 0, P = 0.042). For patients undergoing allo-HSCT, minimal residual disease (MRD) negative population showed better 5-OS survival compared with MRD positive patients (67.8% vs. 19.6%, p = 0.000). There were no significant differences between early T-cell precursor (ETP), NON-ETP patients with or without expression of one or more myeloid-associated or stem cell-associated (M/S+) markers (NON-ETP with M/S+, NON-ETP without M/S+) groups in allo-HSCT population for 5-OS. (62.9% vs. 54.5% vs.48.4%, P > 0.05). Notch mutations were more common in patients with non-relapsed/refractory disease than relapsed/refractory disease (χ² =4.293, P = 0.038). In conclusion, Allo-HSCT could be an effective consolidation therapy not just for patients with CR, but also for those who achieved PR. The prognosis is significantly improved by obtaining MRD negative prior to allogeneic transplantation.

Introduction:Autologous hematopoietic stem cell transplantation (auto- HSCT) preceded by high-dose chemotherapy is a mainstay in relapsed/refractory lymphoma. The study aimed to compare the efficacy and adverse event profile between BEAM and Benda-EAM (BeEAM) regimens and to evaluate prognostic factors for survival in lymphoma patients undergoing auto-HSCT.Material and methods:We present a single-center retrospective analysis of 82 lymphoma patients (median age 52; IQR 38.2–62.2) who received BEAM (47.6%) or BeEAM (52.4%) followed by auto-HSCT between January 2015 and December 2021.Results:During the post-HSCT period 58% of patients experienced febrile neutropenia (51.3% vs. 64.3% in BEAM and BeEAM, respectively; p = 0.27), 80.5% mucositis (69.2% vs. 90.7%; p = 0.02), 42.5% bacteremia (50% vs. 35.7%; p = 0.26), and 18.8% pneumonia (31.6% vs. 7.1%; p = 0.01). Patients who received bendamustine required more platelet transfusions (p = 0.02). In the multivariate Cox regression model, C-reactive protein level on the first day of hospitalization (hazard ratio – HR = 1.03, 95% CI: 1.01–1.06) and days of agranulocytosis (HR = 1.15, 95% CI: 1.00–1.32) were predictors of poorer overall survival (OS), whereas hemoglobin level at the auto-HSCT was a protective factor in terms of OS (HR = 0.43, 95% CI: 0.23–0.78) and progression-free survival (PFS) (HR = 0.66, 95% CI: 0.45–0.96). The median OS since auto-HSCT was 87 months, while the median PFS was 49 months. No differences in PFS and OS between BEAM and BeEAM regimens were proven.Conclusions:Conditioning with BEAM and BeEAM regimens is associated with comparable post-transplant outcomes. The toxicity of these regimens is comparable; however, BEAM is associated with a higher risk of pneumonia, while BeEAM is associated with a higher risk of mucositis.

Hepatitis-associated aplastic anemia (HAAA) is a rare variant of acquired aplastic anemia characterized with a syndrome of bone marrow failure after hepatitis. We retrospectively analyzed the outcomes of consecutive severe HAAA patients who received immunosuppressive therapy (IST, n = 70), matched-sibling donor hematopoietic stem cell transplantation (MSD-HSCT, n = 26) or haploidentical-donor (HID) HSCT ( n = 11) as the first-line treatment. In the IST group, the hematologic response (HR) rate was 55.71% at 6 months. In contrast, HSCT recipients exhibited significantly more rapid and sustained hematopoiesis (HR 76.92%, 96.15% and 96.15% at 3, 6 and 12months, respectively). The 5-year overall survival (OS) was not different among IST (83.7 ± 4.9%), MSD-HSCT (93.3 ± 6.4%) and HID-HSCT group (80.8 ± 12.3%). Compared with IST, MSD and HID-HSCT demonstrated a trend of superiority in the estimated 5-year failure-free survival rates (93.3 ± 6.4% vs 64.3 ± 6.0%, p = 0.05; 80.8 ± 12.3% vs 64.3 ± 6.0%, p = 0.57). In subsequent stratified analysis on age, we found that HID-HSCT showed its efficacy and safety among young patients. In sum, MSD-HSCT remains first-line treatment choice for HAAA, whereas HID-HSCT represents an alternative treatment choice in addition to IST for young patients (< 40 years) without a matched sibling donor.