OBJECTIVE: Alloimmunization against red blood cell (RBC) antigen is an important concern in myelodysplastic syndromes (MDSs) patients with chronic transfusion, causing potential risk for hemolytic reaction and limited supply of compatible blood. However, there is little data addressing RBC alloimmunization in this patient cohort among the Chinese population. This study aims to evaluate the incidence, specificity of antibodies, and RBC units transfused before antibody formation and its significance in a population of patients consistently receiving RhD-matched RBC units.
METHODS: We retrospectively reviewed the transfusion and clinical information of all transfused patients with MDS enrolled in our hospital from 2012 to 2022. The cumulative incidence of alloimmunization was analyzed by a Kaplan-Meier plot. Alloimmunization incidence was compared based on different transfused RBC units using the log-rank test.
RESULTS: A total of 103 patients with MDS were included in this study; alloantibody formed in 8 (7.8%) patients. Before reaching 32 RBC units, 87.5% of the alloimmunized patients had developed their alloantibodies. All but 1 of the alloantibodies developed were antibodies to Rh antigens. The RBC transfusion intensity and frequency were significantly higher following alloimmunization in the alloimmunized patients (P = .008, P = .008, respectively).
CONCLUSIONS: The antibodies detected mostly involve the Rh system among MDS patients in China. The alloimmunization tended to occur early prior to reaching 32 RBC units in patients with MDS. Rh antigen matching should be considered early in the patient\'s transfusion history and completed before receiving 32 RBC units.

BACKGROUND: Myelodysplastic syndrome (MDS) is a complicated hematopoietic malignancy characterized by bone marrow (BM) dysplasia with symptoms like anemia, neutropenia, or thrombocytopenia. MDS exhibits considerable heterogeneity in prognosis, with approximately 30% of patients progressing to acute myeloid leukemia (AML). Single cell RNA-sequencing (scRNA-seq) is a new and powerful technique to profile disease landscapes. However, the current available scRNA-seq datasets for MDS are only focused on CD34+ hematopoietic progenitor cells. We argue that using entire BM cell for MDS studies probably will be more informative for understanding the pathophysiology of MDS.
METHODS: Five MDS patients and four healthy donors were enrolled in the study. Unsorted cells from BM aspiration were collected for scRNA-seq analysis to profile overall alteration in hematopoiesis.
RESULTS: Standard scRNA-seq analysis of unsorted BM cells successfully profiles deficient hematopoiesis in all five MDS patients, with three classified as high-risk and two as low-risk. While no significant increase in mutation burden was observed, high-risk MDS patients exhibited T-cell activation and abnormal myelogenesis at the stages between hematopoietic stem and progenitor cells (HSPC) and granulocyte-macrophage progenitors (GMP). Transcriptional factor analysis on the aberrant myelogenesis suggests that the epigenetic regulator chromatin structural protein-encoding gene HMGA1 is highly activated in the high-risk MDS group and moderately activated in the low-risk MDS group. Perturbation of HMGA1 by CellOracle simulated deficient hematopoiesis in mouse Lineage-negative (Lin-) BM cells. Projecting MDS and AML cells on a BM cell reference by our newly developed MarcoPolo pipeline intuitively visualizes a connection for myeloid leukemia development and abnormalities of hematopoietic hierarchy, indicating that it is technically feasible to integrate all diseased bone marrow cells on a common reference map even when the size of the cohort reaches to 1,000 patients or more.
CONCLUSIONS: Through scRNA-seq analysis on unsorted cells from BM aspiration samples of MDS patients, this study systematically profiled the development abnormalities in hematopoiesis, heterogeneity of risk, and T-cell microenvironment at the single cell level.

UNASSIGNED: Immune imbalance appears to have a critical role in tumor growth according to emerging research. Peripheral lymphocyte subsets are considered to reflect the systemic immune response and clinical prognosis. The prognostic value of lymphocyte subpopulations in myelodysplastic syndrome (MDS) patients remains unclear.
UNASSIGNED: A total of 94 MDS patients were enrolled for the study. X-tile software was performed to determine the prognostic significance of various lymphocyte subpopulations, CD3, CD4, CD8, CD4/CD8 ratio, natural killer cell (NK) and CD19. Among them, the appropriate threshold of NK percent could be found only. Patients were divided into the high NK percent group and the low NK percent group. The prognostic significance was determined by univariate and multivariate Cox hazard models.
UNASSIGNED: MDS patients with lower NK level had significantly shorter overall survival (OS). Based on univariate analysis, male gender (P = 0.030), lower HB (<10 g/dl, P = 0.029), higher BM blast (>5%, P < 0.0001), higher-risk IPSS-R cytogenetic (P = 0.032) and lower NK percent (P < 0.0001) were significantly associated with shorter OS. Multivariate Cox proportional hazards regression analysis indicated that low NK was also independent adverse prognostic factor for OS in MDS.
UNASSIGNED: Decreased NK level predicts poor prognosis independent of the IPSS-R and provide a novel evaluation factor for MDS patients.

BACKGROUND: Serious illness conversations may help patients avoid unwanted treatments. We previously piloted the telehealth Serious Illness Care Program (SICP) for older adults with acute myeloid leukemia and myelodysplastic syndrome.
OBJECTIVE: In this study, we aimed to understand the experience of the telehealth SICP from the clinician\'s perspective.
METHODS: We studied 10 clinicians who delivered the telehealth SICP to 20 older adults with acute myeloid leukemia or myelodysplastic syndrome. Quantitative outcomes included confidence and acceptability. Confidence was measured using a 22-item survey (range 1-7; a higher score is better). Acceptability was measured using an 11-item survey (5-point Likert scale). Hypothesis testing was performed at α=.10 (2-tailed) due to the pilot nature and small sample size. Clinicians participated in audio-recorded qualitative interviews at the end of the study to discuss their experience.
RESULTS: A total of 8 clinicians completed the confidence measure and 7 clinicians completed the acceptability measure. We found a statistically significant increase in overall confidence (mean increase of 0.5, SD 0.6; P=.03). The largest increase in confidence was in helping families with reconciliation and goodbye (mean 1.4, SD 1.5; P=.04). The majority of clinicians agreed that the format was simple (6/7, 86%) and easy to use (6/7, 86%). Clinicians felt that the telehealth SICP was effective in understanding their patients\' values about end-of-life care (7/7, 100%). A total of three qualitative themes emerged: (1) the telehealth SICP deepened relationships and renewed trust; (2) each telehealth SICP visit felt unique and personal in a positive way; and (3) uninterrupted, unrushed time optimized the visit experience.
CONCLUSIONS: The telehealth SICP increased confidence in having serious illness conversations while deepening patient-clinician relationships.
BACKGROUND: ClinicalTrials.gov NCT04745676; https://www.clinicaltrials.gov/study/NCT04745676.

BACKGROUND: The definitive establishment of a causal relationship between gut microbiota and myelodysplastic syndrome (MDS) has not been achieved. Furthermore, the involvement of immune cells in mediating the connection between gut microbiota and MDS is presently unclear.
METHODS: To elucidate the bidirectional correlation between gut microbiota and MDS, as well as to investigate the mediating role of immune cells, a bidirectional two-sample, two-step Mendelian randomization (MR) study was conducted. Summary statistics were obtained from genome-wide association studies (GWAS), including MDS (456,348 individuals), gut microbiota (18,340 individuals), and 731 immune cells signatures (3757 individuals).
RESULTS: Genetically predicted eight gut microbiota traits were significantly associated with MDS risk, but not vice versa. Through biological annotation of host-microbiome shared genes, we found that immune regulation may mediate the impact of gut microbiota on MDS. Subsequently, twenty-three immunophenotypes that exhibited significant associations with MDS risk and five of these immunophenotypes were under the causal influence of gut microbiota. Importantly, the causal effects of gut microbiota on MDS were significantly mediated by five immunophenotypes, including CD4 +T cell %leukocyte, CD127 on CD45RA - CD4 not regulatory T cell, CD45 on CD33 + HLA DR + WHR, CD33 on basophil, and Monocyte AC.
CONCLUSIONS: Gut microbiota was causally associated with MDS risk, and five specific immunophenotypes served as potential causal mediators of the effect of gut microbiota on MDS. Understanding the causality among gut microbiota, immune cells and MDS is critical in identifying potential targets for diagnosis and treatment.

This longitudinal study was based on the outcomes of Donor Lymphocyte Infusion (DLI) for falling peripheral blood (PB) CD34+ and CD3+ donor chimerism (DC).
From 2012 to 2018, data was collected from the BMT database and electronic medical records (EMR). The primary objective was to compare the indication for DLI based on falling PB CD34+ or CD3+ DC in patients post allo-SCT for AML and MDS and their overall survival (OS).
18/70 patients met the inclusion criteria. Indications for DLI were i) falling PB CD34+ DC ≤ 80 % with morphological relapse, ii) falling PB CD34+ DC ≤ 80 % without morphological relapse and iii) falling PB CD3+ DC ≤ 80 % without falling PB CD34+ DC. Log rank analysis showed falling PB CD34+ DC and morphological relapse had significantly lower OS. Linear regression demonstrated better OS post DLI if there was PB CD34+ and CD3+ chimerism response at 30 days (p = 0.029), GVHD (p = 0.032) and tapering immunosuppression at the time of falling DC (p = 0.042).
DLI for PB CD34+ DC values ≤ 80 % and morphological relapse had the lowest OS. In this study, full DC was achieved after DLI even with a PB CD3+DC value as low as 13 %, provided the PB CD34+ DC remained > 80 %. Further research is vital in CD34+ DC as a biomarker for disease relapse and loss of engraftment.

Cytomegalovirus (CMV) reactivation is a prominent complication associated with adverse outcomes in allogeneic hematopoietic stem cell transplantation (HSCT). However, CMV reactivation after allogeneic HSCT may be associated with a lower incidence of relapse in some hematological malignancies. This study analyzed the Japanese registry data from 1082 patients with myelodysplastic syndrome (MDS) who underwent their first allogeneic HSCT and survived for 100 days after transplantation without graft failure or disease relapse to investigate this association. Patients who received cord blood transplants, demonstrated in vivo T cell depletion, underwent prophylactic anti-CMV treatment, or diagnosed with secondary MDS were excluded. CMV reactivation measured by pp65 antigenemia within 100 days after allogeneic HSCT was observed in 57.5% of patients, with a median time of 46 days from transplant. The 5-yr overall survival and cumulative incidence of relapse (CIR) in the cohort were 60.5% and 15.6%, respectively. The 5-yr CIR showed no significant difference between patients with and without CMV reactivation (14.4% versus 17.2%; P = .185). Interestingly, CMV reactivation within 100 days was significantly associated with a lower 5-yr CIR (7.6% versus 16.4%; P = .002) in patients with <5% myeloblasts in the bone marrow (BM) just before HSCT. Furthermore, this relevancy confirmed even when excluding patients with Grade II to IV acute GVHD (Hazard ratio: 0.38; 95% confidential intervals: 0.18-0.801; P = .011). Our findings indicate a correlation between early CMV reactivation and MDS relapse, based on the proportion of myeloblasts in the BM. These results may contribute to the development of effective CMV prophylaxis post-HSCT.

OBJECTIVE: Studies on intestinal Behçet\'s disease (BD) complicated by myelodysplastic syndrome (MDS) are rare, and no established therapeutic guidelines exist. This study aimed to evaluate the clinical presentation and outcomes of patients with intestinal BD complicated by MDS (intestinal BD-MDS) and suggest a treatment strategy.
METHODS: Data from patients with intestinal BD-MDS from four referral centers in Korea who were diagnosed between December 2000 and December 2022 were retrospectively analyzed. Clinical features and prognosis of intestinal BD-MDS compared with age-, sex-matched intestinal BD without MDS were investigated.
RESULTS: Thirty-five patients with intestinal BD-MDS were included, and 24 (70.6%) had trisomy 8. Among the 35 patients, 23 (65.7%) were female, and the median age at diagnosis for intestinal BD was 46.0 years (range, 37.0-56.0 years). Medical treatments only benefited eight of the 32 patients, and half of the patients underwent surgery due to complications. Compared to 70 matched patients with intestinal BD alone, patients with intestinal BD-MDS underwent surgery more frequently (51.4% vs. 24.3%; p=0.010), showed a poorer response to medical and/or surgical treatment (75.0% vs. 11.4%; p<0.001), and had a higher mortality (28.6% vs. 0%; p<0.001). Seven out of 35 patients with intestinal BD-MDS underwent hematopoietic stem cell transplantation (HSCT), and four out of the seven patients had a poor response to medical treatment prior to HSCT, resulting in complete remission of both diseases.
CONCLUSIONS: Patients with intestinal BD-MDS frequently have refractory diseases with high mortalities. HSCT can be an effective treatment modality for medically refractory patients with intestinal BD-MDS.

Treosulfan has shown promise in allogeneic hematopoietic cell transplantation (HCT) for its myeloablative properties and low toxicity. In this single-center retrospective propensity score-matched cohort study we compared treosulfan- and busulfan-based conditioning in allogeneic HCT for patients with myelodysplastic syndrome (MDS). This study included 138 adults who underwent allogeneic HCT for MDS or chronic myelomonocytic leukemia at Princess Margaret Hospital, Toronto, from 2015 to 2022. Using propensity score matching, we compared transplant outcomes between 2 well-matched cohorts who received conditioning with either fludarabine-treosulfan (FT) (n = 46) or fludarabine-busulfan with total body irradiation (FBT200) (n = 92). A scoring system based on patient age, Karnofsky performance score, and hematopoietic cell transplant comorbidity index was used to assign patients based on fitness to low-dose (30 g/m2) or high-dose (42 g/m2) treosulfan: 32 (69.6%) received high-dose treosulfan. The racial composition of the 2 groups was similar, with 27.2% and 21.7% of FBT200 and FT recipients, respectively, identifying as non-Caucasian (P = .61). Primary outcomes were analyzed at a median follow-up of 747 days. Of all participants, 116 (84.0%) received graft-versus-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCY) and antithymocyte globulin (ATG). Patients who received FT had a superior 2-year overall survival (OS) compared to those who received FBT200: 66.9% (95% confidence interval (CI): 46.1 to 81.2) versus 44.5% (95% CI: 34 to 54.4), hazard ratio (HR): 0.43, 95% CI: 0.22 to 0.84 (P = .013). In multivariate analysis (MVA), only the use of fresh grafts (P = .02) and FT (P = .01) were associated with improved OS. FT was associated with superior 2-year relapse-free survival (RFS) compared to FBT200: 63.1% (95% CI: 42.6 to 77.9) versus 39.1% (95% CI: 29.1 to 49.1), HR: 0.44 (95% CI: 0.24 to 0.81), P = .008. In MVA, the use of fresh grafts (P = .03) and FT (P = .009) were associated with improved RFS. Recipients of FT demonstrated superior 2-year graft-versus-host disease relapse-free survival (GRFS) compared to those who received FBT200: 57.4% (95% CI: 37.8 to 72.8) versus 35.1% (95% CI: 25.5 to 45). In MVA, only FT was associated with superior GRFS (P = .02). FT recipients exhibited markedly superior 1-year event-free survival compared to recipients of FBT200 in univariate analysis (40.3% (95% CI: 25.9 to 54.2) versus 9.2% (95% CI: 4.4 to 16.3), HR: 0.47 (95% CI: 0.30 to 0.72), P < .001) and MVA (P = .004). FT was associated with lower 1-year nonrelapse mortality compared to FBT200 in univariate analysis (9.9% (95% CI: 3.0 to 21.8) versus 29.7% (95% CI: 20.6 to 39.3), HR: 0.41 (95% CI: 0.17 to 0.96), P = .04) and MVA (P = .04). Our study utilized propensity score matching to demonstrate superiority of treosulfan- over busulfan-based conditioning in stem cell transplantation of patients with MDS and is the first to evaluate the performance of treosulfan-based conditioning in combination with ATG and PTCY. As such, it contributes to the increasing body of evidence supporting the safety of treosulfan, even at the dose of 42 g/m2.

Since HMAs were recommended for treatments in AML and MDS, we wondered whether HMAs could provide similar benefit to AML and intermediate/high-risk MDS under the direction of next-generation sequencing. Here we retrospectively analyzed the prognosis of 176 AML and 128 intermediate/high-risk MDS patients treated with HMAs or non-HMA regimens. For AML, HMAs regimen was related to better CR rate compared with non-HMA regimen in elder cohort, while the situation was the opposite in younger cohort. In consolidation phase, EMM (+) patients could benefit from HMAs regimen. Relapsed AML patients receiving HMAs regimen rather than non-HMA regimen had better post-relapse survival. Multivariate analysis identified HMA regimen as an independent prognostic factor for OS in EMM (+) cohort. For intermediate/high-risk MDS patients not undergoing HSCT, however, HMA regimen showed no survival advantage in EMM (+) cohort and was conversely associated with shorter survival in EMM (-) cohort compared with non-HMA regimen. And among those undergoing HSCT, HMA prior to HSCT predicted poor prognosis compared with upfront HSCT regardless of the existence of EMMs. Therefore, HMAs had better therapeutic value in AML rather than in intermediate/high-risk MDS based on EMMs.