Safety and efficacy of peripheral blood stem cells collection in healthy children and pediatric patients with thalassemia major weighing 20 kg or less.

BACKGROUND: Peripheral blood stem cell (PBSC) collection in children poses challenges due to their small size, low body weight (BW), and unique pediatric physiology, especially among children weighing 20 kg (kg) or less. METHODS: PBSC collection data of both healthy children and patients with thalassemia major (TM) weighing 20 kg or less between January 2013 and December 2020 were reviewed. Moreover, PBSCs characteristics along with various aspects of efficiency and safety between healthy donors and patients with TM were compared. RESULTS: A total of 262 PBSC procedures were performed on 255 children. Of these, 91 procedures were carried out on 85 allogeneic healthy donors, and 171 auto-backup collections were performed on 170 patients with TM to ensure PBSC availability and prevent transplantation failure. A minimum pre-apheresis hemoglobin (HGB) level of 60 g/L was discovered to be safe and feasible in patients with TM. The median CD34+ cell dose in the PBSC product during the initial apheresis procedure was higher in healthy donors compared to patients with TM (7.29 ± 5.28 × 106 cells/kg vs5.88 ± 4.23 × 106 cells/kg, P = .043). The total CD34+ cells/kg recipient weight exhibited a positive correlation with pre-apheresis monocyte counts, but a negative correlation with donor weight. Apheresis significantly reduced hematocrit and platelet counts in the allogeneic group compared to the autologous group. Patients with TM experienced a higher occurrence of bone pain related to granulocyte colony-stimulating factor treatment. Notably, no serious complications related to PBSCs mobilization, central venous catheter placement, or the apheresis procedure were observed in either group. CONCLUSIONS: PBSCs collection was both safe and effective in healthy children and pediatric patients with TM weighing 20 kg or less.

The Effect of Iron Overload on the Mobilization of Peripheral Blood Hematopoietic Stem Cells in Pediatric Patients with Thalassemia Major.

INTRODUCTION: The purpose of this study was to examine the effect of iron overload on the mobilization of peripheral blood stem cells (PBSCs) in pediatric patients with ß-thalassemia major (TM). METHODS: We retrospectively reviewed the records of 226 patients with TM from whom PBSCs were collected. Iron overload was based on serum ferritin level, and liver and cardiac iron overload was measured by magnetic resonance imaging (MRI) T2*. RESULTS: The mean age of the TM patients was 7.35 ± 3.41 years. Of the patients, only 171 received MRI. Of the 171 patients, 35 had normal liver iron levels, 39 mild liver iron overload, 90 intermediate liver iron overload, and 7 severe liver iron overload. The intermediate + severe group was associated with significantly higher age and BMI and lower leukapheresis product white blood cell count and CD34+ cell levels (all, p < 0.05). CONCLUSION: Leukapheresis indices were similar between patients with different degrees of iron overload according to the ferritin level and cardiac iron overload, in which the later might be due to the small number of patients with cardiac overload. In patients with TM, the intermediate and severe liver iron overload was associated with poorer mobilization of PBSCs.

Applying Rituximab During the Conditioning Regimen Prevents Epstein-Barr Virus Infection Following Allogeneic Hematopoietic Stem Cell Transplant in a Children's Cohort: A Retrospective Case-Control Study.

INTRODUCTION: Since hematopoietic stem cell transplant (HSCT) is an important therapy for malignant and non-malignant pediatric diseases, improving transplant-related mortality remains a challenge. Currently, rituximab, a monoclonal antibody of anti-CD20, is widely used for several post-HSCT complications. However, few studies have focused on the application of rituximab before HSCT. METHODS: We conducted a retrospective case-control study from January 2019 to July 2021 to determine this effect in a single center. Forty-eight patients were included in the rituximab group, with a one-to-one ratio matched to the control group. RESULTS: Both the occurrence rate and cumulative incidence rate of Epstein-Barr virus (EBV) infection were significantly lower in the rituximab group than in the without-rituximab group (10.4% vs. 33.3%, p = 0.014 and 12.2% vs. 39.3% p = 0.0026, respectively). Furthermore, without the application of rituximab was identified as a risk factor for post-HSCT EBV infection via both univariate [hazard ratio (HR) = 4.17, 95%CI (1.52-11.43), p = 0.005] and multivariate analyses [HR = 4.65, 95%CI (1.66-13.0), p = 0.003]. Although the overall survival (OS) probability of the rituximab group was comparable to the without-rituximab group, a markedly improved OS of the rituximab group was found in the malignant disease subgroup (78.9% vs. 42.1%, p = 0.032). The outcomes of graft-versus-host disease, neutrophil and platelet engraftment, other viral infections, and the reconstitution of lymphocytes showed no significant differences between the two groups. CONCLUSIONS: The administration of rituximab before HSCT may prevent EBV infection following HSCT.

Features of cytomegalovirus infection and evaluation of cytomegalovirus-specific T cells therapy in children's patients following allogeneic hematopoietic stem cell transplantation: A retrospective single-center study.

Cytomegalovirus (CMV) infection remains a critical cause of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), despite improvement by pre-emptive antivirus treatment. CMV-specific cytotoxic T lymphocytes (CMV-CTL) are universally used and proven well-tolerance after allo-HSCT in adult clinical trials. However, it is not comprehensively evaluated in children's patients. Herein, we conducted a retrospective study to determine the risk factors of CMV infection and evaluation of CMV-CTL in children patients who underwent allo-HSCT. As result, a significantly poor 5-year overall survival was found in the CMV infection group (87.3 vs. 94.6%, p=0.01). Haploidentical HSCT (haplo-HSCT) was identified as an independent risk factor for CMV infection through both univariate and multivariate analyses (p<0.001, p=0.027, respectively). Furthermore, the cumulative incidence of CMV infection was statistically higher in the haplo-HSCT group compared to the HLA-matched donor group (44.2% vs. 21.6%, p<0.001). Finally, the overall response rate of CMV-CTL was 89.7% (26/29 patients) in CMV infection after allo-HSCT. We concluded that CMV infection following allo-HSCT correlated with increased mortality in children's patients, and haplo-HSCT was an independent risk factor for CMV infection. Adoptive CMV-CTL cell therapy was safe and effective in pediatric patients with CMV infection.

Mechanisms of Cell Adhesion Molecules in Endocrine-Related Cancers: A Concise Outlook.

Chemotherapy is a critical treatment for endocrine-related cancers; however, chemoresistance and disease recurrence remain a challenge. The interplay between cancer cells and the tumor microenvironment via cell adhesion molecules (CAMs) promotes drug resistance, known as cell adhesion-mediated drug resistance (CAM-DR). CAMs are cell surface molecules that facilitate cell-to-cell or cell-to-extracellular matrix binding. CAMs exert an adhesion effect and trigger intracellular signaling that regulates cancer cell stemness maintenance, survival, proliferation, metastasis, epithelial-mesenchymal transition, and drug resistance. To understand these mechanisms, this review focuses on the role of CD44, cadherins, selectins, and integrins in CAM-DR in endocrine-related cancers.

Encouraging the outcomes of children with beta-thalassaemia major who underwent fresh cord blood transplantation from an HLA-matched sibling donor.

BACKGROUND: Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is currently the only curative treatment for thalassaemia major (TM). Cord blood (CB) from a sibling has different characteristics from marrow and has potential advantages and disadvantages as a stem cell source. METHODS: We retrospectively analyzed 68 children with beta-thalassaemia major (ß-TM) who underwent fresh cord blood transplantation (F-CBT) from an HLA-matched sibling donor (MSD) between June 2010 and July 2018 in the Department of Pediatrics, Nanfang Hospital and Haematology-Oncology, Shenzhen Children's Hospital. RESULTS: The median infused doses of total nucleated cells (TNCs) and CD34 + cells were 8.51×107/kg and 3.16×105/kg, respectively. The median time to neutrophil and platelet engraftment were, respectively, 27 and 31 days. The cumulative probabilities of acute and chronic graft-versus-host disease (GVHD) were very low after F-CBT (7.8% and 0.0%, respectively). Of the 68 paediatric patients, 67 patients survived during a median follow-up period of 61 months. The estimated 5-year probability of overall survival (OS) and disease-free survival (DFS) were 98.5% and 87.9%, respectively. Three patients experienced graft rejection (GR) (4.5%), and we identified CD34 + cell dose as a significant risk factor for graft failure (p = 0.036) in stratify analysis. CONCLUSIONS: The above results indicate that patients with ß-TM have excellent outcomes after F-CBT from an HLA-MSD.

[Prognostic significance and risk factors of minimal residual disease ≥1% on 19th day of induction chemotherapy in children with acute lymphoblastic leukemia].

OBJECTIVE: To assess the prognostic value of minimal residual disease on 19th day of induction chemotherapy (D19 MRD) and the risk factors of D19 MRD ≥ 1% in children with acute lymphoblastic leukemia (ALL) treated following the Chinese Children's Cancer Group ALL protocol. METHODS: We retrospectively analyzed the data of 243 children with ALL diagnosed between January 1, 2015 and December 31, 2018 in the Department of Pediatrics of Nanfang Hospital (Guangzhou China). Kaplan Meier-survival analysis was performed to compare the survival time between the patients with D19 MRD < 1% and those with D19 MRD ≥ 1%; logistic regression analyisis and Chi-square test were used to identify the risk factors of D19 MRD ≥ 1%. RESULTS: Compared with those with D19 MRD ≥ 1%, the children with D19 MRD < 1% had significantly better 3-year overall survival (100% vs 90.2%, P=0.004) and event-free survival (97.6% vs 71.6%, P < 0.001). Univariate analysis showed that the odds ratio (OR) for mediastinal invasion, T-cell immunophenotype, TEL/AML1 fusion gene and the presence of blasts in peripheral blood on the 5th day were 4.47 (95%CI: 0.275-72.968, P=0.034), 5.250 (95%CI: 1.950-14.133, P=0.02), 0.330 (95%CI: 0.112-0.970, P=0.036) and 4.407 (95%CI: 1.782-10.895, P=0.01), respectively. The initial risk stratification (P < 0.001), white blood cell grades (P=0.018) and its counts (P=0.027), and the number of blasts on the 5th day (P < 0.001) were significantly different between the two groups. Multivariate analysis showed that initial risk stratification as intermediate and high risks (OR=2.889, 95% CI: 1.193-6.996) and the presence of blasts in peripheral blood on the 5th day (OR=4.477, 95% CI: 1.692-11.843) were independent risk factors for poor early treatment response. CONCLUSIONS: D19 MRD ≥ 1% is a predictor of poor prognosis in children with ALL. Mediastinal invasion, T-cell immunophenotype and the presence of blasts in peripheral blood on the 5th day are all risk factors for poor early treatment response, while TEL/AML1 fusion gene is a protective factor; the initial risk stratification as intermediate to high risk and the presence of blasts in peripheral blood on the 5th day are independent risk factors for poor early treatment response of the patients.

Transplant Outcomes in Beta-Thalassemia Major Patients Receiving Combined Granulocyte Colony-Stimulating Factor-Primed Bone Marrow and Cord Blood Graft Compared to Granulocyte Colony-Stimulating Factor-Primed Bone Marrow Alone.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for thalassemia majorTM. Graft rejection (GR) and graft-versus-host disease (GVHD) are the primary obstacles to a successful outcome. METHODS: We conducted a retrospective study of HSCT in 29 children (median age at transplantation: 6 years) with Beta-thalassemia (ß-TM) after the combined infusion of granulocyte colony-stimulating factor-primed bone marrow (G-BM) and cord blood (CB) from the human leukocyte antigen (HLA)-identical sibling donors. We also compared the outcomes of the co-transplanted children with those of children with ß-TM who received G-BM alone from an HLA-identical sibling donor (n = 26). RESULTS: Compared to the G-BM transplant (G-BMT) recipients, those who received a co-transplant had a lower incidence of grade ≥II acute (17.24 vs. 30.7%, p = 0.047) and limited chronic (0 vs.15.4%, p = 0.022) GVHD as well as a lower incidence of GR (0 vs. 7.7%, p = 0.132). Neutrophil recovery time was faster in the co-transplant group (18.5 vs. 21 days, p = 0.04). All the patients were monitored until December 31, 2016; the median follow-up time was 74 months, and the 5-year thalassemia-free survival rate was 89.7% in the co-transplant group and 84.6% in the G-BMT-alone group (p = 0.590). CONCLUSIONS: A combined CB and G-BM graft from an HLA-identical sibling donor is an effective treatment option for TM in children, with less acute and chronic GVHD.