OBJECTIVES: To investigate the prognostic value of molecular minimal residual disease (Mol-MRD) monitored before and after allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric acute myeloid leukemia (AML). METHODS: Clinical data of 71 pediatric AML patients who underwent HSCT between August 2016 and December 2023 were analyzed. Mol-MRD levels were dynamically monitored in MRD-positive patients, and survival outcomes were evaluated. RESULTS: No significant difference in the 3-year overall survival (OS) rate was observed between patients with pre-HSCT Mol-MRD ≥0.01% and <0.01% (77.3% ± 8.9% vs 80.4% ± 7.9%, P=0.705). However, patients with pre-HSCT Mol-MRD <1.75% had a significantly higher 3-year OS rate than those with Mol-MRD ≥1.75% (86.6% ± 5.6% vs 44.4% ± 16.6%, P=0.020). The median Mol-MRD level in long-term survivors was significantly lower than in non-survivors [0.61% (range: 0.04%-51.58%)] vs 10.60% (range: 1.90%-19.75%), P=0.035]. Concurrent flow cytometry-based MRD positivity was significantly higher in non-survivors (80% vs 24%, P=0.039). There was no significant difference in the 3-year overall survival rate between patients with Mol-MRD ≥0.01% and those with <0.01% at 30 days post-HSCT (P=0.527). For children with Mol-MRD <0.22% at 30 days post-HSCT, the 3-year overall survival rate was 80.4% ± 5.9%, showing no significant difference compared to those with molecular negativity (87.0% ± 7.0%) (P=0.523). CONCLUSIONS Patients with pre-HSCT Mol-MRD <1.75% or post-HSCT Mol-MRD <0.22% may achieve long-term survival outcomes comparable to Mol-MRD-negative cases through HSCT and targeted interventions.
Humans ; Hematopoietic Stem Cell Transplantation ; Neoplasm, Residual ; Leukemia, Myeloid, Acute/genetics* ; Child ; Male ; Female ; Child, Preschool ; Prognosis ; Adolescent ; Infant ; Transplantation, Homologous

OBJECTIVE: To analyze the factors associated with mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with severe aplastic anemia (SAA). METHODS: The clinical data of 90 children with SAA who received allo-HSCT in the Department of Hematology, Wuhan Children's Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from August 2016 to July 2023 were collected. The clinical features and causes of death were analyzed retrospectively. Cox proportional hazards model was used to screen the risk factors of death. RESULTS: Only 9 children died with a median time of 6.3(2.6, 8.3) months among the 90 children with SAA after allo-HSCT. Among the 5 deaths due to infection, 3 were pulmonary infection, including 2 cases of cytomegalovirus pneumonia. One case developed septic shock due to gastrointestinal infection. One case experienced graft failure, which was complicated by bloodstream infection, and developed septic shock. Three cases died of transplantation-associated thrombotic microangiopathy (TA-TMA). One case died of gastrointestinal graft-versus-host disease (GVHD). The results of multivariate analysis showed that post-transplant +60 d PLT≤30×10⁹/L (HR=7.478, 95%CI : 1.177-47.527, P =0.033), aGVHD Ⅲ-Ⅳ (HR=7.991, 95%CI : 1.086-58.810, P =0.041), and TA-TMA occurrence (HR=13.699, 95%CI : 2.146-87.457, P =0.006) were independent risk factors for post-transplant mortality. CONCLUSION Allo-HSCT is an effective therapy for SAA in children. Post-transplant +60 d PLT≤30×10⁹/L, aGVHD Ⅲ-Ⅳ, and TA-TMA occurrence are independently associated with post-transplant mortality, which may be helpful for early detection of potential high-risk children and optimization of clinical diagnostic and treatment strategies.
Humans ; Anemia, Aplastic/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Risk Factors ; Retrospective Studies ; Child ; Transplantation, Homologous ; Male ; Female ; Graft vs Host Disease ; Child, Preschool ; Proportional Hazards Models ; Adolescent ; Infant

OBJECTIVE: To investigate the clinical features and risk factors associated with cutaneous chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. METHODS: A retrospective analysis was conducted on the clinical data of children who underwent allo-HSCT in the Wuhan Children's Hospital from August 1, 2016, to December 31, 2023, and were regularly followed up for 1 year or more. The differences in clinical features between children with and without cutaneous cGVHD were compared, and the risk factors affecting the occurrence of cutaneous cGVHD were analyzed. RESULTS: During the study period, 296 children received allo-HSCT. Until December 31, 2024, follow-up showed that 20 children (6.8%) developed cutaneous cGVHD, which manifested as cutaneous lichenification, hyperpigmentation, keratosis pilaris, sclerotic changes, and hair or nail involvement. According to their skin lesion area and degree of grading, 5 cases were mild, 10 cases were moderate, and 5 cases were severe. Multivariate logistic regression analysis revealed that female donors and previous acute GVHD were risk factors for the development of cutaneous cGVHD after allo-HSCT. All 20 children were treated with glucocorticoid ± calcineurin inhibitors (tacrolimus/cyclosporine) as first-line therapeutic agents. Only 1 child improved after first-line treatment. The remaining 19 children treated with a second-line regimen of combination interventions based on individualized status, including 10 children who could not tolerate hormonotherapy or first-line treatment, and showed no significant improvement after 3 months, as well as 9 children with multi-organ cGVHD. After comprehensive second-line treatment, 17 children showed improvement in cutaneous symptoms. There were 3 deaths, including 1 due to primary disease recurrence and 2 due to pulmonary infections. CONCLUSION The skin is the first manifestation and most common organ involved in cGVHD in children. Cutaneous cGVHD severely affects the daily activities of transplanted children and requires prolonged immunosuppressive therapy, but has a favorable prognosis. First-line treatments for adults are not applicable to children who usually require a combination treatment with multiple drugs.
Humans ; Graft vs Host Disease/etiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Retrospective Studies ; Risk Factors ; Female ; Child ; Skin Diseases/etiology* ; Chronic Disease ; Transplantation, Homologous ; Male ; Child, Preschool ; Adolescent

Objective:To investigate the safety and efficacy of mitoxantrone liposome in the treatment of children with high-risk acute myeloid leukemia(AML).Methods:The children with high-risk AML who received the mitoxantrone liposome regimen at Wuhan Children's Hospital from January 2022 to February 2023 were collected as the observation group,and the children with high-risk AML who received idarubicin regimen were enrolled as controls,and their clinical data were analyzed.Time to bone marrow recovery,the complete remission rate of bone marrow cytology,the clearance rate of minimal residual disease,and treatment-related adverse reactions were compared between the two groups.Results:The patients treated with mitoxantrone liposome showed shorter time to recovery of leukocytes(17 vs 21 day),granulocytes(18 vs 24 day),platelets(17 vs 24 day),and hemoglobin(20 vs 26 day)compared with those treated with idarubicin,there were statistical differences(P＜0.05).The effective rate and MRD turning negative rate in the observation group were 90.9％and 72.7％,respectively,while those in the control group were 94.1％and 76.4％,with no statistical difference(P＞0.05).The overall response rate of the two groups of patients was similar.Conclusion:The efficacy of mitoxantrone liposome is not inferior to that of idarubicin in children with high-risk AML,but mitoxantrone liposome allows a significantly shorter duration of bone marrow suppression and the safety is better.

Objective:To investigate the prognostic value of minimal residual disease(MRD)detected by multi-parameter flow cytometry(MFC)in pediatric patients with acute myeloid leukemia(AML)after induction chemotherapy.Methods:A retrospective study was conducted on 97 pediatric patients initially diagnosed with AML at Wuhan Children's Hospital from August 2015 to December 2022.The study analyzed the results of MRD detection using MFC after the first and second cycles of induction chemotherapy,and its association with prognosis were analyzed.Results:Following the first cycle of induction treatment,57 of the 97 patients tested positive for MRD(MRD1+,58.8％).Subsequently,19 patients remained MRD positive(MRD2+,19.6％)after the second cycle of induction treatment.Kaplan-Meier survival analysis showed that the estimated 3-year overall survival(OS)rate of the 37(64.9％)MRD1+patients who underwent transplantation was significantly higher than that of the 20(35.1％)MRD1+patients who did not undergo transplantation(84.6％vs 40.0％,P=0.0001).Among the 35 MRD1+MRD2-patients,the 3-year OS rate of the 25 children who underwent transplantation was higher than that of the 10 children who did not undergo transplantation(87.2％vs 70.0％,P=0.3229).The 3-year OS rate of the 19 MRD1+MRD2+patients was lower than that of the 35 MRD1+MRD2-patients(57.4％vs 81.8％,P=0.059).In the 19 MRD2+patients,the 3-year OS rate of the 12 children who underwent transplantation was significantly higher than that of the 7 children who did not undergo transplantation(80.8％vs 14.3％,P=0.0007).There was no significant difference in 3-year OS between the 12 MRD1+MRD2+patients and 25 MRD1+MRD2-patients,both treated with transplantation(80.8％vs 87.2％,P=0.8868).In those not treated with transplantation,the 7 MRD1+MRD2+patients had a significantly lower 3-year OS compared with the 10 MRD1+MRD2-patients(14.3％vs 70.7％,P=0.0114).Further multivariate analysis indicated that MRD2 positivity and transplantation were both independent prognostic factors(P=0.031,0.000),while MRD1 positivity was not significantly associated with the overall prognosis of 97 patients(P=0.902).Conclusion:MRD positivity following the second cycle of induction chemotherapy is an independent risk factor for unfavorable outcomes in children with AML.MRD2 positivity indicates a poorer prognosis and can help to identify the candidates requiring transplantation.MRD2 positivity is not a contraindication for transplantation in pediatric patients,and early transplantation significantly improves the prognosis of high-risk patients.

This study aimed to investigate the effect of iron overload on the transplant outcomes of pediatric patients with severe aplastic anemia (SAA) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). A retrospective analysis was conducted on the clinical data of 74 children with SAA who received allo-HSCT at the Hematology Department of Wuhan Children’s Hospital between January 2018 and August 2022. Children with iron overload (serum ferritin >1 000 μg/L) before transplantation had a longer disease course, received more red blood cell transfusions, and had a higher number of CD34 + cells infused. Moreover, iron overload significantly delayed the reconstitution of regulatory T cells after transplantation, increasing the incidence of hemorrhagic cystitis and grade Ⅲ-Ⅳ acute graft-versus-host disease after transplantation. However, iron overload did not significantly affect the overall survival and failure-free survival rates of the children.

OBJECTIVE: To analyze the gene mutation profile in children with acute lymphocyte leukemia (ALL) and to explore its prognostic significance. METHODS: Clinical data of 249 primary pediatric ALL patients diagnosed and treated in the Department of Hematological Oncology of Wuhan Children's Hospital from January 2018 to December 2021 were analyzed retrospectively. Next-generation sequencing (NGS) was used to obtain gene mutation data and analyze the correlation between it and the prognosis of children with ALL. RESULTS: 227 (91.2%) were B-ALL, 22 (8.8%) were T-ALL among the 249 cases, and 178 (71.5%) were found to have gene mutations, of which 85 (34.1%) had ≥3 gene mutations. NRAS(23.7%), KRAS (22.9%),FLT3(11.2%), PTPN11(8.8%), CREBBP (7.2%), NOTCH1(6.4%) were the most frequently mutated genes, the mutations of KRAS, FLT3, PTPN11, CREBBP were mainly found in B-ALL, the mutations of NOTCH1 and FBXW7 were mainly found in T-ALL. The gene mutation incidence of T-ALL was significantly higher than that of B-ALL (χ²= 5.573，P＜0.05) and were more likely to have co-mutations (P＜0.05). The predicted 4-year EFS rate (47.9% vs 88.5%, P＜0.001) and OS rate (53.8% vs 94.1%, P＜0.001) in children with tp53 mutations were significantly lower than those of patients without tp53 mutations. Patients with NOTCH1 mutations had higher initial white blood cell count （128.64×10⁹/L vs 8.23×10⁹/L，P＜0.001）, and children with NOTCH1 mutations had a lower 4-year EFS rate than those of without mutations (71.5% vs 87.2%, P＝0.037). CONCLUSION Genetic mutations are prevalent in childhood ALL and mutations in tp53 and NOTCH1 are strong predictors of adverse outcomes in childhood ALL, with NGS contributing to the discovery of genetic mutations and timely adjustment of treatment regimens.
Child ; Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Cell Cycle Proteins/genetics* ; Proto-Oncogene Proteins p21(ras)/genetics* ; Retrospective Studies ; Ubiquitin-Protein Ligases/genetics* ; Prognosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Mutation ; Lymphocytes

OBJECTIVE: To investigate the clinical features and outcomes of infants (<1 year old) with acute lymphoblastic leukemia (IALL). METHODS: The clinical manifestations, laboratory examination results, treatment and prognosis of 18 infants diagnosed with ALL at our department between January 1, 2014 and August 31, 2022 were retrospectively analyzed. RESULTS: Among the 18 cases of IALL, there were 10 males and 8 females. The median age of patients was 6.5 months old (3 months-11 months old). The median white blood cell count (WBC) was 33.63×10⁹/L ［(3.92-470)×10⁹/L］ at initial diagnosis, including 2 patients with WBC≥300×10⁹/L. Flow cytometric immunophenotyping showed a B-lineage infant ALL in all the 18 patients. Eight of the 18 children had abnormal chromosome karyotype analysis. Fusion gene detection showed 12 KMT2A-rearrangement of 18 patients. 15 patients underwent leukemia related mutation gene screening, among which KRAS, NRAS and FLT3 were the most common mutation genes. 4 patients underwent allogeneic hematopoietic stem cell transplantation and two survived. 14 patients received chemotherapy only and ten survived. The 3-year OS rate was (65.5±11.5)%, while the EFS rate was (46.9±12.3)%. CONCLUSION B-cell ALL and KMT2A rearrangement are prevalent in IALL. The therapeutic effect of IALL with standard childhood ALL protocal is similer to international infant specific protocal.
Male ; Child ; Infant ; Female ; Humans ; Retrospective Studies ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Prognosis ; Hematopoietic Stem Cell Transplantation ; Mutation

OBJECTIVE: To analyze the clinical effects of CCLG-AML-2015 protocol on newly diagnosed children with acute myeloid leukemia (AML). METHODS: The clinical data of 60 newly diagnosed AML children in the Department of Hematology and Oncology, Wuhan Children's Hospital from August 2015 to September 2019 were summarized, the effect of chemotherapy using the CCLG-AML-2015 regimen (hereinafter referred to as the 2015 regimen) were retrospectively analyzed. 42 children with AML treated by the AML-2006 regimen (hereinafter referred to as the 2006 regimen) from February 2010 to July 2015 were used as control group. RESULTS: There were no statistical differences between the 2015 regimen group and the 2006 regimen group in sex, age at first diagnosis, and risk stratification (P>0.05). The complete remission rate of bone marrow cytology after induction of 1 course of chemotherapy (84.7% vs 73.1%, P=0.155), and minimal residual disease detection (MRD) negative (42.3% vs 41.4%, P=0.928) in the 2015 regimen group were not statistically different than those in the 2006 regimen group. The bone marrow cytology CR (98.1% vs 80.6%, P=0.004) and MRD negative (83.3% vs 52.8%, P=0.002) in the 2015 regimen group after 2 courses of induction were higher than those in the 2006 regimen group. The 5-year overall survival (OS) rate in the 2015 regimen group (62.3%±6.4% vs 20.6%±6.4%, P=0.001), the 5-year disease-free survival (EFS) rate (61.0%±6.4% vs 21.0% ±6.4% , P=0.001) were better than those in the 2006 regimen group. The 5-year OS and EFS of high-risk transplant patients in the 2015 regimen group were significantly better than those of high-risk non-transplant patients (OS: 86.6%±9.0% vs 26.7%±11.4%, P=0.000; EFS: 86.6%±9% vs 26.7%±11.4%, P=0.000). CONCLUSION The 2015 regimen can increase the CR rate after 2 courses of induction compared with the 2006 regimen. High-risk children receiving hematopoietic stem cell transplantation can significantly improve the prognosis.
Child ; Disease-Free Survival ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Prognosis ; Remission Induction ; Retrospective Studies

OBJECTIVE: To observe the clinical characteristics, treatment and prognosis of intestinal acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children and futher evaluate the occurring risk factors. METHODS: The clinical data of 136 patients undergoing allo-HSCT in Wuhan Children's Hospital Affiliated to Tongji Medical College from August 2016 to August 2020 were retrospectively analyzed, clinical characteristics of children with intestinal aGVHD were observed. The risk factors of intestinal aGVHD were assessed by logistic regression while cumulative survival were analyzed by Kaplan-Meier method. RESULTS: Among 136 patients intestinal aGVHD occurred in 24 (17.6%) cases, with 4 cases of grade II, 20 cases of grade III-IV, and the median occurrence time was 28(10-63) days. The clinical manifestations were diarrhea with intermittent abdominal pain, 17 cases with nausea and vomiting, 11 cases with fresh bloody stool, and 8 cases with skin rash before intestinal aGVHD. The average time for treatment was 33(11-100) days. 18 cases received electronic colonoscopy and histopathology examination. 20 out of 24 cases achieved remission after treatment, and the total effective rate was 83.3%. Finally, 9 out of 24 cases died during the follow-up time. Survival analysis showed that the cumulative survival rate of patients with intestinal aGVHD (15/24, 62.5%) were significantly lower than those without intestinal aGVHD (101/112, 90.2%) (Log-rank test, P=0.001). Univariate analysis showed that recipient age, sex, primary disease, donor age, donor sex, donor-recipient blood type, conditioning regimen, prophylaxis of GVHD, dosage of ATG, engraft time of blood platelet and neutrophils, and number of MNC/CD34+ were not risk factors for intestinal aGVHD (P>0.05). Only the type of HSCT (χ2=16.020, P=0.001) and matched degree of HLA (χ2=15.502, P=0.001) had statistical significance with intestinal aGVHD (P<0.05). Multivariate analysis showed that only HLA-mismatched unrelated donor was the risk factor for intestinal aGVHD for children (P=0.014，OR=16，95%CI 1.735-147.543). CONCLUSION Intestinal aGVHD is a risk factor for cumulative survial of patients who received allo-HSCT in children and HLA-mismatched unrelated donor is its independent risk factor.
Acute Disease ; Child ; Graft vs Host Disease/prevention & control* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Retrospective Studies ; Risk Factors ; Tissue Donors