To elucidate the effect of BCOR mutation (BCORmut) on clinical outcomes, we included a total of 899 consecutive AML patients in a single-center during July 2016 to December 2021. Fifty cases (5.6%) had BCOR mutations, which co-occurred with mutations of RUNX1, DNMT3A, IDH2, BCORL1, STAG2, SF3B1 and U2AF1, but were exclusive with KIT and CEBPA mutations. BCORmut was also found to be exclusive with t(8;21)(q22;q22.1) AML in all patients and MLL rearrangements in the European Leukemia Net (ELN) adverse group. In those receiving intensive chemotherapy regimens, BCORmut was associated with lower complete remission (CR) rates and worse prognosis. Subgroup analysis showed that BCORmut mainly conferred a poor prognosis in the intermediate and adverse groups of the ELN2017 risk. These results suggest that BCOR mutation is an independent prognostic parameter in AML, implying BCOR mutation as a novel marker for chemorefractory disease and inferior prognosis.

BACKGROUND: Droplet digital PCR (ddPCR) is widely applied to monitor measurable residual disease (MRD). However, there are limited studies on the feasibility of ddPCR-MRD monitoring after allogeneic hematopoietic stem cell transplantation (allo-HSCT), especially targeting multiple molecular markers simultaneously.
METHODS: Our study collected samples from patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) in complete remission after allo-HSCT between January 2018 and August 2021 to evaluate whether posttransplant ddPCR-MRD monitoring can identify patients at high risk of relapse.
RESULTS: Of 152 patients, 58 (38.2%) were MRD positive by ddPCR within 4 months posttransplant, with a median variant allele frequency of 0.198%. The detectable DTA mutations (DNMT3A, TET2, and ASXL1 mutations) after allo-HSCT were not associated with an increased risk of relapse. After excluding DTA mutations, patients with ddPCR-MRD positivity had a significantly higher cumulative incidence of relapse (CIR, 38.7% vs. 9.7%, P < 0.001) and lower rates of relapse-free survival (RFS, 55.5% vs. 83.7%, P < 0.001) and overall survival (OS, 60.5% vs. 90.5%, P < 0.001). In multivariate analysis, ddPCR-MRD positivity of non-DTA genes was an independent adverse predictor for CIR (hazard ratio [HR], 4.02; P < 0.001), RFS (HR, 2.92; P = 0.002) and OS (HR, 3.12; P = 0.007). Moreover, the combination of ddPCR with multiparameter flow cytometry (MFC) can further accurately identify patients at high risk of relapse (F+/M+, HR, 22.44; P < 0.001, F+/M-, HR, 12.46; P < 0.001 and F-/M+, HR, 4.51; P = 0.003).
CONCLUSIONS: ddPCR-MRD is a feasible approach to predict relapse after allo-HSCT in AML/MDS patients with non-DTA genes and is more accurate when combined with MFC.
BACKGROUND: ClinicalTrials.gov identifier: NCT06000306. Registered 17 August 2023 -Retrospectively registered ( https://clinicaltrials.gov/study/NCT06000306?term=NCT06000306&rank=1 ).

OBJECTIVE: The primary objective of this observational study was to perform an exhaustive description concerning patients receiving extracorporeal photopheresis (ECP) as second line treatment after steroid resistance for either acute or chronic GVHD following allo-HCT, secondary objectives were to evaluate the efficacy and long-term outcomes.
METHODS: A total of 106 patients were included, 65 (61%) males and 41 (39%) females with a median age at transplantation of 52 years (range: 20-67). ECP was initiated after transplantation either for acute GVHD [N = 25 (24%), 12 grade III and 13 grade IV] affecting skin alone (N = 5), gut alone (N = 12), gut and liver (N = 8), or chronic GVHD [N = 81 (76%), 15 (14%) limited and 66 (62%) extensive].
RESULTS: Among the 25 patients treated for acute GHVD, 67% were responders and among the 81 patients with chronic GVHD, 78% were responders. Patients with acute GVHD had a median OS of 6 months with a survival probability at 2 years of 35% [95%CI: 14-56]. Patients with chronic GVHD had a median OS of 72 months with a survival probability at 2 years of 68% [95%CI: 56-78]. There was a significant difference in terms of survival for patients responding to ECP compared to non-responders in both acute and chronic GVHD forms. Acute GVHD grade III-IV, negatively impacted on OS (HR=7.77, 95%CI: 1.7-34), p = 0.007 and on disease relapse HR= 5.88, 95%CI: 1.7-20, p = 0.005.
CONCLUSIONS: We demonstrated that ECP is an effective treatment for GVHD in a good proportion of patients with high overall response rate.

暂无摘要。

Bloodstream infections (BSIs) are the most common infectious complication in patients who receive allogeneic hematopoietic stem-cell transplants (allo-HSCTs). Polymorphonuclear neutrophils (PMNs) are quantified to monitor the susceptibility to BSIs; however, their degree of activation is not. We previously identified a population of primed PMNs (pPMNs) with distinct markers of activation representing approximately 10% of PMNs in circulation. In this study, we investigate whether susceptibility to BSIs is related to the proportion of pPMNs rather than strictly PMN counts.
In this prospective observational study, we used flow cytometry to assess pPMNs in blood and oral rinse samples collected from patients receiving an allo-HSCT over the course of their treatment. We used the proportion of pPMNs in the blood on day 5 post-transplant to categorize patients into a high- or a low-pPMN group (>10% or <10% pPMNs). These groups were then used as a predictor of BSIs.
A total of 76 patients were enrolled in the study with 36 in the high-pPMN group and 40 in the low-pPMN group. Patients in the low-pPMN group had lower expression of PMN activation and recruitment markers and displayed a delay in PMN repopulation of the oral cavity after the transplant. These patients were more susceptible to BSIs compared with patients in the high-pPMN group with an odds ratio of 6.5 (95% confidence interval, 2.110-25.07; P = .002).
In patients who receive an allo-HSCT, having <10% pPMNs early in the post-transplant phase can be an independent predictor of BSI in allo-HSCT patients.

Haematopoietic stem cell reinjection may be a curative option for poor graft function after haematopoietic stem cell transplantation; however, literature supporting its use remains limited. We conducted a multicentre retrospective study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy, including 55 patients. We demonstrated response rates of nearly 40% and two-year survival of more than 60% in the context of an otherwise deadly complication and we observed that the timing of injection and the degree of cytopenia are strongly associated with outcomes. This study shows the feasibility of the procedure informing on its epidemiology, outcomes and prognostic factors, setting the stage for future guidelines.

BACKGROUND: Fludarabine followed by fractionated total body irradiation (Flu/FTBI) as conditioning was well-studied in allo-HSCT. Cyclophosphamide as pre-FTBI (Cy/FTBI) and post-FTBI (FTBI/Cy) has also shown acceptable outcomes, although data are limited. However, unlike FTBI/Cy, no studies have examined FTBI followed by fludarabine (FTBI/Flu). Due to logistics, we have used FTBI/Flu or FTBI/Cy with appropriate stem cell infusion timing.
OBJECTIVE: Report outcomes using FTBI/Flu and FTBI/Cy conditioning.
METHODS: Retrospective chart review.
METHODS: Single institution: academic hospital/county hospital.
METHODS: Patients (18-99 years, M/F) with hematologic malignancies diagnosed 1/2015-2/2021 who underwent allo-HSCT at our institution.
METHODS: Primary: OS and EFS since time of transplant, stratified between FTBI/Flu and FTBI/Cy. Secondary: Patient/treatment characteristics, GVHD, and (non-) relapse-related mortality ((N)RM) rates. P≤0.05 was considered significant.
RESULTS: In 26 patients, median age was 47.5 years, 65% males, 65% Hispanic, 50% with ALL, and 42.3% with AML. Pre-transplant, 65.4% of patients were at CR1, and 23.1% were at CR2/3. Disease risk index (DRI) was intermediate for 73.1% and high for 23.1%. MSD was administered to 26.9%, MUD to 38.5%, and haploidentical stem cells to 34.6%. FTBI/flu conditioning was administered to 84.6% and FTBI/Cy to 15.4%. Post-transplant GVHD prophylaxis was cytoxan/tacrolimus/mycophenolate in 80.8% and tacrolimus/methotrexate in 19.2%. Since transplant, in the overall population, 3-year (3y) OS was 81% (15.4% had NRM) and 3y-EFS was 72.5% (7.7% had relapse). FTBI/Flu 2y-OS was 77.5% and FTBI/Cy 2y-OS was 100% (p=0.38). FTBI/Flu 2y-EFS was 77.5% and FTBI/Cy 2y-EFS was 50% (p=0.24). Any grade/any type acute GVHD occurred in 77.3% of FTBI/Flu patients vs. 50% of FTBI/Cy patients (p=0.29), with 15.4% of FTBI/Flu patients experiencing G3 acute gut GVHD vs 0% of FTBI/Cy patients (p=0.99). Any grade/any type of chronic GVHD occurred in 27.3% of FTBI/Flu patients vs. 50% of FTBI/Cy patients (p=0.56); however, 50% of FTBI/Flu patients experienced G3 chronic gut GVHD vs. 0% of FTBI/Cy patients(p=0.99).
CONCLUSIONS: Given most of our patients had intermediate/high DRI, the OS and EFS using both flipped conditioning regimens were generally similar and appreciable. However, more any type/grade, acute GVHD and G3 acute/chronic gut GVHD cases were identified in the FTBI/Flu population, although not significant.

Allo-HSCT with CCR5Δ32/Δ32 donor cells is the only curative HIV-1 intervention. We investigated the impact of allo-HSCT on the viral reservoir in PBMCs and post-mortem tissue in two patients. IciS-05 and IciS-11 both received a CCR5Δ32/Δ32 allo-HSCT. Before allo-HSCT, ultrasensitive HIV-1 RNA quantification; HIV-1-DNA quantification; co-receptor tropism analysis; deep-sequencing and viral characterization in PBMCs and bone marrow; and post-allo-HSCT, ultrasensitive RNA and HIV-1-DNA quantification were performed. Proviral quantification, deep sequencing, and viral characterization were done in post-mortem tissue samples. Both patients harbored subtype B CCR5-tropic HIV-1 as determined genotypically and functionally by virus culture. Pre-allo-HSCT, HIV-1-DNA could be detected in both patients in bone marrow, PBMCs, and T-cell subsets. Chimerism correlated with detectable HIV-1-DNA LTR copies in cells and tissues. Post-mortem analysis of IciS-05 revealed proviral DNA in all tissue biopsies, but not in PBMCs. In patient IciS-11, who was transplanted twice, no HIV-1-DNA could be detected in PBMCs at the time of death, whereas HIV-1-DNA was detectable in the lymph node. In conclusion, shortly after CCR5Δ32/Δ32, allo-HSCT HIV-1-DNA became undetectable in PBMCs. However, HIV-1-DNA variants identical to those present before transplantation persisted in post-mortem-obtained tissues, indicating that these tissues play an important role as viral reservoirs.

OBJECTIVE: To evaluate the utilization of scleral lenses and prosthetic replacement of the ocular surface ecosystem devices (SL/PDs) in the management of ocular graft-versus-host disease (oGVHD).
METHODS: A survey of 15 questions was sent via email to 6032 subjects registered with the Blood and Marrow Transplant Information Network. The survey reviewed transplant history, graft-versus-host disease history, as well as oGVHD symptoms and onset. Additional questions surveyed treatments used for oGVHD, as well as the degree of ocular symptom control and experience with SL/PDs. A total of 306 respondents met the eligibility requirements to be part of the analyzed cohort.
RESULTS: The mean number of symptoms reported from the analyzed cohort was 4.79 ± 2.44, median (IQR) of 5.0 (3.0 to 7.0), with the most common symptom being gritty, dry eyes (87%). The mean number of treatments utilized across the analyzed cohort was 3.21 ± 2.55, median (IQR) of 2.5 (1.0 to 5.0), with the most common treatment being artificial tears (86%). Wearing scleral lenses resulted in a mean of 5.42 ± 1.86, median (IQR) of 6.0 (4.0 to 7.0) symptoms improving, with improved dryness/grittiness of the eyes (94%), improved eye pain (92%) and improved quality of life (89%) being the most commonly improved symptoms. Fifty-six percent of those wearing scleral lenses wished the lenses had been recommended sooner. The most common reason patients cited for not wearing scleral lenses was that they had never heard of them (63%).
CONCLUSIONS: SL/PDs help to control the symptoms of oGVHD. With their use, clinicians are able to improve the quality of life of this patient population. Despite the known benefits, SL/PDs still remain underutilized in oGVHD care. A majority of current SL/PD wearers wish that they had been recommended sooner as a treatment option. SL/PDs should be considered a component of comprehensive oGVHD management.

OBJECTIVE: To explore whether dual-lumen power injectable peripherally inserted central catheters (PICCs) could be effectively and safely applied in allogeneic hematopoietic stem cell transplantation (allo-HSCT) and for serum cyclosporine level monitoring.
BACKGROUND: Compared to conventional central venous access devices, PICC provides a feasible route not only for fluid infusion, but also for blood sample collection in patients undergoing oncological treatments.
METHODS: A prospective observational study was conducted according to the STROBE guidelines.
METHODS: We prospectively evaluated the applications and complications of power injectable PICCs in 52 consecutive allo-HSCT recipients. We also compared the cyclosporine levels in 188 paired blood samples, simultaneously obtained via power injectable PICCs and percutaneous venous puncture, to investigate whether power injectable PICC is a feasible route for cyclosporine concentration monitoring in allo-HSCT.
RESULTS: The median PICC placement duration was 29 days. The insertion-site blood oozing and central line-associated bloodstream infection rates were 36.5% (19/52) and 26.9% (14/52), respectively, indicating the feasibility of these PICCs for various applications in allo-HSCT. No power injectable PICC-related thrombotic adverse events were identified; 90.4% (47/52) of cases with power injectable PICC removal occurred because of lack of medical utility, suggesting that power injectable PICC-related complications were manageable. However, cyclosporine levels in samples obtained via these PICCs were significantly higher than those in samples obtained via percutaneous venous puncture (261.5 ± 139.2 vs. 232.4 ± 253.6 ng/ml; p = 0.019 [set 1]; 254.8 ± 89.3 vs. 225.1 ± 233.3 ng/ml; p<0.001 [set 2]; 283.6 ± 103.9 vs. 238.0 ± 254.7 ng/ml; p = 0.006 [set 3]; 291.0 ± 94.9 vs. 266.0 ± 274.7 ng/ml; p = 0.016 [set 4]).
CONCLUSIONS: The power injectable PICC is a feasible venous access device for allo-HSCT.
CONCLUSIONS: The dual-lumen power injectable PICCs provided a reliable access for blood sample collection, decreasing the number of blind percutaneous venous punctures in allo-HSCT. However, its application in cyclosporine level monitoring needs further investigation.