Risk factors and prognosis of poor graft function after allogeneic hematopoietic stem cell transplantation in pediatric: a retrospective study

Objective: To analyze the risk factors and outcomes of poor graft function (PGF) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with transfusion dependent thalassemia (TDT). Methods: A retrospective cohort study was conducted in 118 pediatric TDT patients who underwent allo-HSCT at the First Affiliated Hospital of Guangxi Medical University from June 30, 2018 to December 31, 2022. Based on PGF diagnostic criteria, patients were categorized into PGF and good graft function (GGF) groups. Clinical features, including pre-transplant baseline characteristics and post-transplant complications, were compared between groups. Inter-group comparisons were conducted by χ² test or Fisher exact test, as appropriate for the data type and distribution. Multivariate Logistic regression identified PGF risk factors, and model performance was assessed by receiver operating characteristic (ROC) curve analysis. Survival analysis was conducted using the Kaplan-Meier method with Log-Rank testing. Results: Among 118 patients, there were 69 males (58.5%) and 49 females (41.5%). Fifteen cases (12.7%) developed PGF while 103 cases (87.3%) achieved GGF. Compared to the GGF group, the PGF group had significantly higher rates of age ≥10 years at transplant, interval from diagnosis to transplant ≥6.7 years, human leukocyte antigen (HLA) mismatch, ABO mismatch, post-transplant BK virus infection, and hemorrhagic cystitis (all P<0.05). Multivariate analysis identified independent risk factors for PGF: age ≥10 years (OR=27.20, 95%CI 2.11-350.91), diagnosis-to-transplant interval ≥6.7 years (OR=23.23, 95%CI 1.39-388.23), post-transplant cytomegalovirus (CMV) infection (OR=57.83, 95%CI 3.01-1 111.71), post-transplant and BK virus infection (OR=67.73, 95%CI 2.56-1 794.52). The ROC curve showed an area under curve of 0.92 (95%CI 0.86-0.97, P<0.001). The 4-year overall survival rate was significantly lower in the PGF group compared to the GGF group ((53.3±12.9)%vs.(90.2±2.9)%,χ2=16.49,P<0.001). Conclusions: Risk factors for PGF in TDT children after allo-HSCT include age ≥10 years at transplantation, time from diagnosis to transplantation ≥6.7 years, post-transplant CMV infection and post-transplant BK virus infection. The PGF patients after allo-HSCT exhibit significantly poorer overall survival compared to those with GGF.

Longitudinal Blood Count Analysis Reveals That Poor Graft Function after Pediatric Hematopoietic Cell Transplantation Is a Common Complication Associated with Poor Outcome

CMV Infection after Transplant from Cord Blood Compared to Other Alternative Donors: The Importance of Donor-Negative CMV Serostatus

Outcome of relapsed/refractory acute promyelocytic leukaemia in children, adolescents and young adult patients - a 25-year Italian experience.

Impact of anti-HLA antibodies on allogeneic hematopoietic stem cell transplantation outcomes after reduced-intensity conditioning regimens

Late-Onset Hemorrhagic Cystitis in Children after Hematopoietic Stem Cell Transplantation for Thalassemia and Sickle Cell Anemia: A Prospective Evaluation of Polyoma (BK) Virus Infection and Treatment with Cidofovir

To analyze the risk factors of primary poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid malignancies and the impact of primary PGF on survival. The clinical data of 146 patients with myeloid malignancies who underwent allo-HSCT in our hospital from January 2015 to December 2021 were retrospectively studied. Some relevant clinical parameters which may affect the development of primary PGF after allo-HSCT were selected for univariate and multivariate analysis, as well as performed survival analysis. A total of 9 patients (6.16%) were diagnosed with primary PGF, and their medium age was 37(28-53) years old. Among them, 1 case underwent matched sibling donor HSCT, 1 case underwent matched unrelated donor HSCT, and 7 cases underwent HLA-haploidentical related donor HSCT. Moreover, 5 cases were diagnosed as cytomegalovirus (CMV) infection, and 3 cases as Epstein-Barr virus (EBV) infection. Univariate and multivariate analysis showed that CD34+ cell dose <5×106/kg and pre-transplant C-reactive protein (CRP) >10 mg/L were independent risk factors for occurrence of the primary PGF after allo-HSCT in patients with myeloid malignancies. The 3-year overall survival (OS) rate of primary PGF group was 52.5%, which was significantly lower than 82.8% of good graft function group (P < 0.05). Making sure pre-transplant CRP≤10 mg/L and CD34+ cell dose ≥5×106/kg in the graft may have an effect on preventing the occurrence of primary PGF after allo-HSCT. The occurrence of primary PGF may affect the OS rate of transplant patients, and early prevention and treatment are required.

Pretransplant Predictors and Posttransplant Sequels of Acute Kidney Injury after Allogeneic Stem Cell Transplantation

To compare the bone marrow microenvironment between healthy children and adults and investigate the association between the posttransplant bone marrow microenvironment and PGF in pediatric HSCT recipients.This retrospective study involved pediatric patients who underwent allogeneic-HSCT at Beijing Children's Hospital and Baoding Children's Hospital between January 2021 and June 2024. Bone marrow samples were collected before HSCT and between Days 14 and 90 post-HSCT to measure the percentages of endothelial progenitor cells (EPCs) and hematopoietic stem cells (CD34 + HSCs), as well as reactive oxygen species (ROS) levels. Selected donors were enrolled as controls, and their bone marrow samples were similarly assessed for those parameters.One hundred forty pediatric patients and 48 bone marrow donors were included in this study. Subsequent analysis revealed that adult donors had a significantly lower proportion of HSCs compared with the 0-6-year donors subgroup (0.865% (0.03, 2.21) vs. 3.38% (1.38, 5.23); U = 3.93, P < 0.001) and significantly higher HSC-ROS levels (1,979 (1,039, 5,166) vs. 977 (453, 1,597); U = 3.11, P = 0.002). The good graft function (GGF) group had a significantly greater proportion of EPCs compared with the poor graft function (PGF) group (0.106% (0.03-0.69) vs. 0.047%(0.015-0.09), U = 3.184, P = 0.001). Receiver operating characteristic (ROC) analysis revealed that an EPC proportion threshold > 0.071% in the bone marrow at 14-90 days post-transplantation predicted GGF outcomes (AUC = 0.874; 95% CI: 0.743-1.000).These findings suggest that compared with their adult counterparts, pediatric bone marrow niches possess superior hematopoietic regenerative capacity and reduced oxidative stress and that a lower proportion of EPCs is responsible for defective hematopoiesis in PGF pediatric patients.

To explore the risk factors of cytomegalovirus (CMV) and refractory CMV infection (RCI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their influences on survival. A total of 246 patients who received allo-HSCT from 2015 to 2020 were divided into CMV group (n=67) and non-CMV group (n=179) according to whether they had CMV infection. Patients with CMV infection were further divided into RCI group (n=18) and non-RCI group (n=49) according to whether they had RCI. The risk factors of CMV infection and RCI were analyzed, and the diagnostic significance of Logistics regression model was verified by ROC curve. The differences of overall survival (OS) and progression-free survival (PFS) between groups and the risk factors affecting OS were analyzed. For patients with CMV infection, the median time of the first CMV infection was 48(7-183) days after allo-HSCT, and the median duration was 21 (7-158) days. Older age, EB viremia and gradeⅡ-Ⅳacute graft-versus-host disease (aGVHD) significantly increased the risk of CMV infection (P=0.032, <0.001 and 0.037, respectively). Risk factors for RCI were EB viremia and the peak value of CMV-DNA at diagnosis≥1×104 copies/ml (P=0.039 and 0.006, respectively). White blood cell (WBC)≥4×109/L at 14 days after transplantation was a protective factor for CMV infection and RCI (P=0.013 and 0.014, respectively). The OS rate in CMV group was significantly lower than that in non-CMV group (P=0.033), and also significantly lower in RCI group than that in non-RCI group (P=0.043). Hematopoietic reconstruction was a favorable factor for OS (P<0.001), whereas CMV-DNA≥1.0×104 copies/ml within 60 days after transplantation was a risk factor for OS (P=0.005). The late recovery of WBC and the combination of EB viremia after transplantation are common risk factors for CMV infection and RCI. CMV-DNA load of 1×104 copies/ml is an important threshold, higher than which is associated with higher RCI and lower OS risk.

Incidence, Risk Factors, and Outcomes of Primary Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation

Predictive factors for outcomes after reduced intensity conditioning hematopoietic stem cell transplantation for hematological malignancies: a 10-year retrospective analysis from the Société Française de Greffe de Moelle et de Thérapie Cellulaire

Risk Factors of BK Virus Cystitis in Haematopoietic Stem Cell Transplantation-a Retrospective Monocentric Study

Red Blood Cell Transfusion Dependence and Outcome after Allogeneic Peripheral Blood Stem Cell Transplantation in Patients with de Novo Myelodysplastic Syndrome (MDS)

Cytomegalovirus prevention strategies and the risk of BK polyomavirus viremia and nephropathy.