Impact of additional cytogenetic aberrations at diagnosis on prognosis of adults patients with Philadelphia chromosome positive acute lymphoblastic leukemia undergoing allogeneic hematopoietic cell transplantation: a retrospective analysis.

Additional chromosomal abnormalities(ACAs) at diagnosis are associated with inferior prognosis in chronic myeloid leukemia. However, the prognostic significance of ACAs in adult patients with Philadelphia Chromosome Positive acute lymphoblastic leukemia (Ph + ALL) receiving TKI-targeted drugs and allogeneic hematopoietic stem cell transplantation(HSCT) is unknown. One hundred thirty-six adult patients with Ph + ALL were included in the study and retrospectively analysed, evaluating the effect of ACAs on outcomes of transplantation. ACAs are observed in 60 cases (44%). ACAs detected in more than 5% of cases were defined as major-route and encompass: +der(22), +der(9), + 8, -7 and complex karyotype. The median follow-up was 26.4 months. In the subgroup analyses of major route ACAs, three-year cumulative incidence of relapse (CIR) and progression-free survival(PFS) are statistically significant in + 8[66.7% vs.23.7%, P = 0.024; 77.8% vs. 23.7%, P = 0.0087], -7[53.8% vs. 23.7%, P = 0.035%; 61.5% vs. 32.9%, P = 0.033], and complex karyotypes[42.9% vs. 23.7%, P = 0.027; 47.6% vs. 23.7%] compared with t(9;22) sole. Additionally, the 3-year CIR for Ph + ALL with + der(22) is 44% vs. 23.7% for t(9;22) sole(P = 0.045). The 3-year overall survival (OS) in the - 7 group is 46.5%, which is statistically significant compared with the other groups(P = 0.001). In multivariate analyses, three years CIR and PFS are statistically significant in + der(22), + 8, -7 and complex karyotype compared with t(9;22) sole(P < 0.05). More importantly, Ph + ALL with - 7 was negatively associated with the rate of 3-year OS(P = 0.012). Thus, ACAs at diagnosis appear to have a significant prognostic impact on transplantation outcomes in patients with Ph + ALL.

Establishment of a humanized mouse model using steady-state peripheral blood-derived hematopoietic stem and progenitor cells facilitates screening of cancer-targeted T-cell repertoires.

Background: Cancer-targeted T-cell receptor T (TCR-T) cells hold promise in treating cancers such as hematological malignancies and breast cancers. However, approaches to obtain cancer-reactive TCR-T cells have been unsuccessful. Methods: Here, we developed a novel strategy to screen for cancer-targeted TCR-T cells using a special humanized mouse model with person-specific immune fingerprints. Rare steady-state circulating hematopoietic stem and progenitor cells were expanded via three-dimensional culture of steady-state peripheral blood mononuclear cells, and then the expanded cells were applied to establish humanized mice. The human immune system was evaluated according to the kinetics of dendritic cells, monocytes, T-cell subsets, and cytokines. To fully stimulate the immune response and to obtain B-cell precursor NAML-6- and triple-negative breast cancer MDA-MB-231-targeted TCR-T cells, we used the inactivated cells above to treat humanized mice twice a day every 7 days. Then, human T cells were processed for TCR ß-chain (TRB) sequencing analysis. After the repertoires had been constructed, features such as the fraction, diversity, and immune signature were investigated. Results: The results demonstrated an increase in diversity and clonality of T cells after treatment. The preferential usage and features of TRBV, TRBJ, and the V-J combination were also changed. The stress also induced highly clonal expansion. Tumor burden and survival analysis demonstrated that stress induction could significantly inhibit the growth of subsequently transfused live tumor cells and prolong the survival of the humanized mice. Conclusions: We constructed a personalized humanized mouse model to screen cancer-targeted TCR-T pools. Our platform provides an effective source of cancer-targeted TCR-T cells and allows for the design of patient-specific engineered T cells. It therefore has the potential to greatly benefit cancer treatment.

Clinical characteristics of membranous nephropathy after allogeneic hematopoietic stem cell transplantation: A real-world multicenter study.

Membranous nephropathy (MN) is a rare complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MN patients may develop nephrotic syndrome or even kidney failure, which greatly affects their quality of life and prognosis. However, current knowledge regarding MN after allo-HSCT is limited. Thus, a multicenter nested case‒control study was conducted. Patients who had been diagnosed with MN after allo-HSCT were retrospectively identified at 8 HSCT centers. A total of 51 patients with MN after allo-HSCT were included. The median age of MN patients after allo-HSCT was 38 years, and the median duration from HSCT to MN was 18 months. The use of HLA-matched donors (P = 0.0102) and peripheral blood as the graft source (P = 0.0060) were identified as independent predisposing risk factors for the onset of MN after allo-HSCT. Compared to those in the control group, the incidence of extensive chronic graft-versus-host disease was greater in the MN patients (P = 0.0002). A total of 31 patients developed nephrotic syndrome. Patients receiving combination treatments of corticosteroids and immunosuppressants appeared to have better outcomes. In conclusion, MN is a rare but occasionally severe complication following HSCT and may require active treatment.

Risk factors and long-term outcomes for human herpesvirus 6 encephalitis in the early period after allogeneic stem cell transplantation.

Human herpesvirus 6 (HHV6) encephalitis is a rare but life-threatening complication for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, reports on susceptibility factors and clinical outcomes are limited. We enrolled HHV6 encephalitis patients following allo-HSCT between 2018 and 2022, then conducted a 1:4 nested case-control cohort study to evaluate risk factors and long-term outcomes. Among 1350 patients, 20 (1.48%) developed HHV6 encephalitis, with a median onset time of 25.5 days after HSCT. Patient age<30 (odds ratio [OR], 3.24, P = 0.016) and NK cell count<115/ul at 21 days (OR, 6.07, P = 0.018) were identified as independent risk factors in multivariate analysis. Moreover, the HHV6 encephalitis group was significantly associated with higher incidence of grade II-IV graft-versus-host disease (aGVHD) (hazard ratio [HR], 5.52, P < 0.001) and transplant-associated microangiopathy (HR,9.86, P < 0.001), and demonstrated a significantly higher non-relapse mortality (NRM) (HR, 5.28, P = 0.004) and a lower overall survival (HR, 4.34, P = 0.001) or progression-free survival (HR, 3.94, P = 0.001) compared to control group. In conclusion, patients <30 years old or with delayed NK cell recovery are more susceptible to HHV6 encephalitis after allo-HSCT, and patients with HHV6 encephalitis after transplantation have poorer clinical outcomes.

Post-transplant de novo anti-HLA donor specific antibodies may contribute to poor graft function after haploidentical haematopoietic stem cell transplantation.

De novo anti-HLA donor-specific antibodies (DSAs) were rarely reported in stem cell transplantation patients. We present a case of 39-year-old acute myelogenous leukaemia patient who developed de novo DSAs only 16 days after transplantation with the highest mean fluorescence intensity (MFI) of 7406.23, which were associated with poor graft function (PGF). We used plasma exchange (PE) and intravenous immunoglobulin (IVIg) to reduce DSA level. A series of treatment including mesenchymal stem cells and donor cell transfusion were used to help recover graft function. On day 130, the patient achieved a successful engraftment.

Guillain-Barr Syndrome Caused by Cytomegalovirus after Multiple Myeloma Treatment.

BACKGROUND: Both humoral and cell-mediated immunity of the patient affected by multiple myeloma (MM) are impaired; thus, infection is the main cause of the onset of symptoms and death caused by MM. Bortezomib is a first-line drug approved for patients with multiple myeloma (MM) and has significantly increased their overall survival. However, bortezomib-induced peripheral neuropathy (PN) remains a significant side effect that has led to its discontinuation in some patients. Guillain-Barre syndrome (GBS) is thought to be related to immune damage, and most patients have cytomegalovirus (CMV), Epstein-Barr virus (EBV), or mycoplasma infection before onset. Cases of GBS secondary to MM are rare. METHODS: We provide a case of GBS caused by cytomegalovirus infection after MM treatment, and briefly review the existing literature. RESULTS: Secondary GBS after MM. This patient received active treatment. The clinical symptoms are gradually improving. CONCLUSIONS: The use of bortezomib has the risk of reactivating the virus. It is more about the reactivation of hep-atitis B virus. Nonetheless, cytomegalovirus and Epstein-Barr virus shall have our attention. Patients with MM need to monitor CMV, regularly, especially during the treatment of bortezomib. At the same time, they also need to closely monitor the symptoms and signs of the nervous system to guard against the occurrence of GBS.

Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia: a multicenter, randomized, open-label, phase 3 trial.

Coinfusion of unrelated cord blood (UCB) units in haploidentical hematopoietic cell transplantation (haplo-HCT) (haplo-cord HCT) for hematopoietic malignancies showed promising results in previous reports, but the efficiency of haplo-cord HCT in acute myeloid leukemia (AML) still lacks sufficient evidence. This multicenter, randomized, phase 3 trial (ClinicalTrials.gov NCT03719534) aimed to assess the efficacy and safety of haplo-cord HCT in AML patients. A total of 268 eligible patients aged 18-60 years, diagnosed with measurable residual disease in AML (excluding acute promyelocytic leukemia), with available haploidentical donors and suitable for allotransplantation, were randomly allocated (1:1) to receive haplo-cord HCT (n = 134) or haplo-HCT (n = 134). The 3-year overall survival (OS) was the primary endpoint in this study. Overall median follow-up was 36.50 months (IQR 24.75-46.50). The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group (80.5%, 95% confidence interval [CI]: 73.7-87.9 vs. 67.8% 95% CI 60.0-76.5, p = 0.013). Favorable progression-free survival (70.3%, 95% CI 62.6-78.8 vs. 57.6%, 95% CI 49.6-67.0, p = 0.012) and cumulative incidence of relapse (12.1%, 95% CI 12.0-12.2 vs. 30.3%, 95% CI 30.1-30.4, p = 0.024) were observed in haplo-cord HCT group. Grade 3-4 adverse events (AEs) within two years posttransplantation in the two groups were similar. Haplo-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery (p = 0.026) and increased T-cell reconstitution in the early period posttransplantation. Haplo-cord HCT can improve OS in AML patients without excessive AEs, which may exert additional benefits for recipients of haplo-HCT.

Psychological and physical side effects during G-CSF mobilization in related donors of allo-HCT.

The psychological side effects of granulocyte colony-stimulating factor mobilization in related donors of allogeneic hematopoietic cell transplantation (allo-HCT) and impacts of psychological/physical side effects on harvest outcomes remain largely unknown. We prospectively analyzed 349 consecutive related peripheral blood stem cell (PBSC) donors for allo-HCT at the First Affiliated Hospital, Zhejiang University, School of Medicine from March 2021 to August 2023. Higher baseline peripheral blood white blood cell counts (p = 0.046), monocyte counts (p < 0.001), platelet counts (p = 0.001), and hemoglobin (p < 0.001) had a positive correlation to CD34+ cell counts in the first leukapheresis, while female donors (male vs. female, p < 0.001) and older age (> 40 vs. < = 40, p = 0.003) were negatively related to CD34+ cell counts. Bone pain was the most observed physical side effect and was more frequent in female donors (p = 0.032). The incidence of fatigue was higher in female donors and older donors (female vs. male, p = 0.016; > 40 vs. < = 40, p = 0.015). Donor depression (pre vs. during mobilization, p < 0.001), anxiety (pre vs. during mobilization, p = 0.043) and insomnia (pre vs. during mobilization, p = 0.011) scores increased during the mobilization period. Donors with higher depression, anxiety and stress scores at admission were more likely to experience nausea. At 1 month after the last leukapheresis, the counts of white blood cell, neutrophil, monocyte and hemoglobin were significant lower than baseline counts, while the platelet counts recovered to baseline. The mobilization and harvest process can increase the depression, anxiety and insomnia scores. Poor psychological status of the donor can aggravate the occurrence of physical side effects.

Lower relapse incidence with haploidentical versus matched sibling or unrelated donor hematopoietic cell transplantation for core-binding factor AML patients in CR2: A study from the Global Committee and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Allogeneic hematopoietic cell transplantation (allo-HCT) is recommended for core-binding factor mutated (CBF) AML patients achieving second complete remission (CR2). However, approximately 20% of patients may relapse after transplant and donor preference remains unclear. We compared in this EBMT global multicenter registry-based analysis the allo-HCT outcomes using either haploidentical (Haplo), matched siblings donors (MSD), or 10/10 matched unrelated donors (MUD). Data from 865 de novo adult CBF AML patients in CR2 receiving allo-HCT in 227 EBMT centers from 2010 to 2022 were analyzed, in which 329 MSD, 374 MUD, and 162 Haplo-HCTs were included. For the entire cohort, 503 (58%) patients were inv(16)/CBFB-MYH11 and 362 patients (42%) were t(8;21)/RUNX1-RUNX1T1 AML. On multivariate analysis, Haplo-HCT was associated with a lower Relapse Incidence (RI) compared to either MSD (hazard ratio [HR] = 0.56, 95% CI 0.32-0.97; p < .05) or MUD (HR = 0.57, 95% CI: 0.33-0.99, p < .05). No significant difference was observed among the 3 types of donors on LFS, OS and GRFS. CBF-AML with t(8;21) was associated with both higher RI (HR = 1.79, 95% CI 1.3-2.47; p < .01) and higher NRM (HR = 1.58, 95% CI 1.1-2.27; p < .01) than CBF-AML with inv(16), which led to worse LFS, OS and GRFS. To conclude, for CBF-AML patients in CR2, Haplo-HCTs were associated with a lower RI compared to MSD and MUD allo-HCTs. There was no difference on LFS, OS or GRFS. CBF AML patients with inv(16) had a better progonosis than those with t(8;21) after allo-HCT in CR2.

Microplastics dampen the self-renewal of hematopoietic stem cells by disrupting the gut microbiota-hypoxanthine-Wnt axis.

Microplastics (MPs) are contaminants ubiquitously found in the global biosphere that enter the body through inhalation or ingestion, posing significant risks to human health. Recent studies emerge that MPs are present in the bone marrow and damage the hematopoietic system. However, it remains largely elusive about the specific mechanisms by which MPs affect hematopoietic stem cells (HSCs) and their clinical relevance in HSC transplantation (HSCT). Here, we established a long-term MPs intake mouse model and found that MPs caused severe damage to the hematopoietic system. Oral gavage administration of MPs or fecal transplantation of microbiota from MPs-treated mice markedly undermined the self-renewal and reconstitution capacities of HSCs. Mechanistically, MPs did not directly kill HSCs but disrupted gut structure and permeability, which eventually ameliorated the abundance of Rikenellaceae and hypoxanthine in the intestine and inactivated the HPRT-Wnt signaling in bone marrow HSCs. Furthermore, administration of Rikenellaceae or hypoxanthine in mice as well as treatment of WNT10A in the culture system substantially rescued the MPs-induced HSC defects. Finally, we validated in a cohort of human patients receiving allogenic HSCT from healthy donors, and revealed that the survival time of patients was negatively correlated with levels of MPs, while positively with the abundance of Rikenellaceae, and hypoxanthine in the HSC donors' feces and blood. Overall, our study unleashes the detrimental roles and mechanisms of MPs in HSCs, which provides potential strategies to prevent hematopoietic damage from MPs and serves as a fundamental critique for selecting suitable donors for HSCT in clinical practice.

Characteristics of Coronavirus Disease in Allogeneic Hematopoietic Stem Cell Transplantation During the Omicron Wave: A Single-Center Study.

Objectives: This study aimed to characterize the clinical characteristics, outcomes, and risk factors for coronavirus disease 2019 (COVID-19) in 492 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) during the Omicron wave. Methods: Data were retrospectively collected from patient charts and the electronic medical record systems at the First Affiliated Hospital of Zhejiang University School of Medicine between December 2022 and January 2023. Results: The median follow-up period of the entire cohort was 62 days. Myeloid malignancies (58.5%) and acute lymphocytic leukemia (30.5%) constituted the most common underlying disease. Among the 492 patients, 415, 67, and 10 exhibited mild, moderate, and severe COVID-19, respectively. The incidence of moderate-to-severe COVID-19 was 15.7%. The 60-day overall survival and complete resolution rates were 98.1% and 80.6%, respectively. The risk factors for moderate-to-severe COVID-19 included corticosteroid use within 3 months before diagnosis, <6 months interval between allo-HSCT and COVID-19 diagnosis, and antithymocyte globulin use for graft-versus-host disease prophylaxis. Conclusions: During the Omicron wave, patients with allo-HSCT demonstrated a low COVID-19-related mortality rate and high moderate-to-severe and prolonged disease incidence. Prevention in the early posttransplantation period is critical for allo-HSCT recipients receiving corticosteroids.

Mendelian Randomisation Analysis of Causal Association between Lifestyle, Health Factors, and Keratoconus.

Keratoconus (KC), a leading cause of vision impairment, has an unclear aetiology. This study used Mendelian randomization (MR) to explore the causal links between various factors (smoking, asthma, Down syndrome, inflammatory bowel disease, atopic dermatitis, and serum 25-hydroxyvitamin D levels) and KC. A two-sample MR design, grounded in genome-wide association study (GWAS) summary statistics, was adopted using data from FinnGen, UK Biobank, and other GWAS-related articles. The inverse-variance weighted (IVW) method was employed, complemented by the Wald ratio method for factors with only one single-nucleotide polymorphism (SNP). Sensitivity and stability were assessed through Cochrane's Q test, the MR-Egger intercept test, MR-PRESSO outlier test, and the leave-one-out analysis. The IVW results for the ORA (Ocular Response Analyzer) biomechanical parameters indicated significant associations between tobacco smoking (CH: p < 0.001; CRF: p = 0.009) and inflammatory bowel disease (CH: p = 0.032; CRF: p = 0.001) and corneal biomechanics. The Wald ratio method showed tobacco smoking was associated with a lower risk of KC (p = 0.024). Conversely, asthma (p = 0.009), atopic dermatitis (p = 0.012), inflammatory bowel disease (p = 0.017), and serum 25-hydroxyvitamin D levels (p = 0.039) were associated with a higher risk of KC by IVW, and the same applied to Down syndrome (p = 0.004) using the Wald ratio. These results underscore the role of corneal biomechanics as potential mediators in KC risk, warranting further investigation using Corvis ST and Brillouin microscopy. The findings emphasise the importance of timely screening for specific populations in KC prevention and management.

Donor-derived Anti-CD19 CAR T cells GC007g for relapsed or refractory B-cell acute lymphoblastic leukemia after allogeneic HSCT: a phase 1 trial.

Background: Although chimeric antigen receptor-modified T cells (CAR T) cell therapy has been widely reported in improving the outcomes of B-cell acute lymphoblastic leukemia (B-ALL), less research about the feasibility and safety of donor-derived CAR T after allogeneic hematopoietic stem cell transplantation (allo-HSCT) was reported. Methods: This phase 1 clinical trial aims to evaluate safety and efficacy of donor-derived anti-CD19 CAR T cells (GC007g) in B-ALL patients who relapsed after allo-HSCT. This trial is registered with ClinicalTrials.gov, NCT04516551. Findings: Between 15 March 2021 and 19 May 2022, fifteen patients were screened, three patients were excluded due to withdraw of consent, donor's reason, and death, respectively. Patients received donor-derived CAR T cells infusions at 6 × 105/kg (n = 3) or 2 × 106/kg (n = 6) dose level. The median time from HSCT to relapse was 185 days (range, 81-2063). The median age of patients was 31 years (range 21-48). Seven patients (77.8%) had BCR-ABL fusion gene. CAR T cells expanded in vivo and the median time to reach Cmax was 9 days (range, 7-11). One patient had hyperbilirubinemia after GC007g infusion which was defined as a dose-limiting toxicity. All patients experienced CRS and hematological adverse events. Three patients had acute graft-versus-host-disease (grade I, n = 1; grade II, n = 1; grade IV, n = 1) and all resolved after treatment. They received CAR T cells from matched sister, haploidentical matched father and sisiter, respectively. At 28 days after infusion, all patients achieved complete remission with/without incomplete hematologic recovery (CRi/CR) with undetectable MRD. At a median follow-up of 475 days (range 322-732), seven patients remained in CR/CRi while two had CD19-negative relapse. The overall response rates (ORR) were 100% (9/9), 88.9% (8/9), and 75% (6/8) at 3 month, 6 month, and 12 month, respectively. The 1-year progression-free and overall survival were 77.8% and 85.7%, respectively. Interpretation: GC007g expanded and induced durable remission in patients with B-ALL relapsed after allo-HSCT, with manageable safety profiles. Funding: Gracell Biotechnologies Inc.

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients With Acute Myeloid Leukemia Harboring KMT2A Rearrangement and Its Prognostic Factors.

KMT2A rearrangement (KMT2A-r) in patients with acute myeloid leukemia (AML) is associated with poor outcomes; the prognostic factors after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain unclear. We investigated 364 adults with AML who underwent allo-HSCT between April 2016 and May 2022, and 45 had KMT2A-r among them. Propensity score analysis with 1:1 matching and the nearest neighbor matching method identified 42 patients in KMT2A-r and non-KMT2A-r cohorts, respectively. The 2-year overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and non-relapsed mortality rates of patients with KMT2A-r (n = 45) were 59.1%, 49.6%, 41.5%, and 8.9%, respectively. Using propensity score matching, the 2-year OS rate of patients with KMT2A-r (n = 42) was lower than that of those without KMT2A-r (n = 42; 56.1% vs 88.1%, P = 0.003). Among patients with KMT2A-r (n = 45), the prognostic advantage was exhibited from transplantation in first complete remission (CR1) and measurable residual disease (MRD) negative, which was reflected in OS, RFS, and CIR (P < 0.001, P < 0.001, and P = 0.002, respectively). Furthermore, patients with AF6 had poorer outcomes than those with AF9, ELL, and other KMT2A-r subtypes (P = 0.032, P = 0.001, and P = 0.001 for OS, RFS, and CIR, respectively). However, no differences were found in the OS, RFS, and CIR between patients with KMT2A-r with and without mutations (all P > 0.05). Univariate and multivariate analyses revealed that achieving CR1 MRD negative before HSCT was a protective factor for OS [hazard ratio (HR) = 0.242, P = 0.007], RFS (HR = 0.350, P = 0.036), and CIR (HR = 0.271, P = 0.021), while AF6 was a risk factor for RFS (HR = 2.985, P = 0.028) and CIR (HR = 4.675, P = 0.004). The prognosis of patients with KMT2A-r AML was poor, particularly those harboring AF6-related translocation; however, it is not associated with the presence of mutations. These patients can benefit from achieving CR1 MRD negative before HSCT.

Graft CD8 T-cell-based risk system predicts survival in antithymocyte globulin-based myeloablative haploidentical peripheral blood stem cell transplantation.

Objective: This study investigated the cellular composition of peripheral blood grafts for anti-thymocyte globulin (ATG)-based myeloablative haploidentical haematopoietic stem cell transplantation (haplo-HSCT). Methods: Clinical characteristics were retrospectively evaluated in a training cohort with ATG-based myeloablative haplo-HSCT between January 2016 and February 2020 and confirmed in a validation cohort between March 2020 and June 2021. Results: A higher dose of graft CD8+ T cells (≥ 0.85 × 108 kg-1) was significantly improved overall survival (OS; hazard ratio [HR], 1.750; P = 0.002) and disease-free survival (DFS; HR, 1.751; P < 0.001) in the training cohort, according to multivariate Cox regression analysis. Higher doses of mononuclear cells (MNCs) demonstrated better OS (HR, 1.517; P = 0.038) and DFS (HR, 1.532; P = 0.027). Older patient age (> 46 years), older donor age (≥ 50 years) and a higher refined disease risk index (rDRI) were also related to OS. A graft CD8+ T-cell risk system based on graft CD8+ T-cell dose, donor age and rDRI was constructed using a nomogram model after LASSO Cox regression analysis. It showed acceptable discrimination, with a C-index of 0.62 and 0.63, respectively. Graft CD8+ T-cell dose was negatively correlated with donor age (P < 0.001) and positively correlated with a higher lymphocyte percentage in the peripheral blood before mobilisation (P < 0.001). Conclusion: A higher CD8+ T-cell dose in peripheral blood-derived grafts improves patients' survival with ATG-based myeloablative haplo-HSCT. Younger donors with higher lymphocyte percentages improved patients' survival with an intermediate rDRI risk.

Prophylactic versus Preemptive modified donor lymphocyte infusion for high-risk acute leukemia after allogeneic hematopoietic stem cell transplantation: a multicenter retrospective study.

Donor lymphocyte infusion (DLI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been widely used in preventing post-transplant relapse. We conducted this study to compare the superiority of prophylactic modified DLI (pro-DLI) and preemptive modified DLI (pre-DLI) in patients with high-risk relapse features acute leukemia. Pro-DLI was performed in 95 patients, whereas the pre-DLI cohort included 176 patients. In the pre-DLI cohort, 42 patients relapsed without chance for pre-DLI while 95 patients remained CR without detectable minimal residual disease (MRD). Thirty-nine patients in the pre-DLI cohort became minimal MRD positive/mixed chimerism and received pre-DLI. Pro-DLI cohort had higher 3-year progression-free-survival (PFS) (63.4%vs.53.0%, P = 0.026) and overall survival (OS) (65.2% vs. 57.0%, P = 0.14) compared to the pre-DLI cohort. The 3-year cumulative incidence of relapse (CIR) was 25.3% in the pro-DLI cohort which was significantly lower than 36.7% in the pre-DLI cohort (P = 0.02). The cumulative incidence of grade III-IV aGVHD, cGVHD and non-relapse mortality were comparable between cohorts. Multivariable analysis demonstrated strong protective effect of pro-DLI on OS (hazard ratio (HR) = 0.63, P = 0.04), PFS (HR = 0.54, P = 0.005) and CIR (HR = 0.50, P = 0.005). In high-risk patients with acute leukemia, early scheduled pro-DLI rather than pre-DLI after detectable MRD would reduce post-transplant relapse and improve long-term survival.

Double filtration plasmapheresis combined with rituximab for donor-specific antibody desensitization in haploidentical haematopoietic stem cell transplantation.

Donor-specific anti-HLA antibodies (DSA) are a major cause of engraftment failure in patients receiving haploidentical haematopoietic stem cell transplantation (Haplo-HSCT). Double filtration plasmapheresis (DFPP) avoids the unnecessary loss of plasma proteins and increases the efficiency of purification. To investigate the effectiveness of the desensitization protocol including DFPP and rituximab, we conducted a nested case-control study. Thirty-three patients who had positive DSA were desensitized by the protocol and 99 patients with negative DSA were randomly matched as control. The median DSA mean fluorescence intensity values before and after DFPP treatment were 7505.88 ± 4424.38 versus 2013.29 ± 4067.22 (p < 0.001). All patients in DSA group achieved haematopoietic reconstitution and the median neutrophils and platelets engraftment times were 13 (10-21) and 13 (10-29) days respectively. Although the cumulative incidence of II-IV aGVHD (41.4% vs. 28.1%) and 3-year moderate to severe cGVHD (16.8% vs. 7.2%) were higher in DSA cohort than in the control, no statistical significance was observed. The 3-year non-relapse mortality and the overall survival were 6.39% and 72.0%, respectively, in the DSA cohort, which were comparable to the negative control. In conclusion, DFPP and rituximab could be effectively used for desensitization and overcome the negative effects of DSA in Haplo-HSCT.