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Upfront umbilical cord blood transplantation versus immunosuppressive therapy for pediatric patients with idiopathic severe aplastic anemia
Zhao, X., Lv, W., Song, K., Yao, W., Li, C., Tang, B., Wan, X., Geng, L., Sun, G., Qiang, P., et al
Transplantation and cellular therapy. 2024
Abstract
BACKGROUND Umbilical cord blood transplantation (UCBT) has been rarely reported as a first-line treatment for idiopathic severe aplastic anemia (SAA) patients lacking HLA-matched sibling donors (MSD). OBJECTIVE Our study aimed to compare the clinical outcomes of pediatric SAA patients who received UCBT and immunosuppressive therapy (IST) upfront. STUDY DESIGN A retrospective analysis was performed on 43 consecutive patients who received frontline IST (n = 17) or UCBT (n = 26) between July 2017 and April 2022. RESULTS The 3-year overall survival (OS) was comparable between the UCBT and IST groups (96.2% vs. 100%, P = 0.419), while the 3-year event-free survival (EFS) was significantly better in the former than in the latter (88.5% vs. 58.8%, P = 0.048). In the UCBT group, 24 patients achieved successful engraftment, 2 patients developed severe acute graft-versus-host disease (aGVHD), no extensive chronic GVHD (cGVHD), and a high GVHD-free, failure-free survival (GFFS) of 84.6% at 3 years. After one year of treatment, 12 patients in the IST group responded, while 5 patients did not achieve remission and 2 patients had disease relapse. At both 3 and 6 months after treatment, the proportion of transfusion-independent patients was higher in the UCBT group than in the IST group. Faster immune recovery and earlier transfusion independence further reduced the risk of infection and bleeding, thereby improving health-related quality of life in the UCBT-treated group. CONCLUSION Our results suggested that UCBT as upfront therapy may be an effective and safe option for pediatric SAA patients, with favorable outcomes in experienced centers.
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Matched related transplantation versus immunosuppressive therapy plus eltrombopag for first-line treatment of severe aplastic anemia: a multicenter, prospective study
Liu, L., Lei, M., Fu, R., Han, B., Zhao, X., Liu, R., Zhang, Y., Jiao, W., Miao, M., Zhang, F., et al
Journal of hematology & oncology. 2022;15(1):105
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Editor's Choice
Abstract
This study prospectively compared the efficacy and safety between matched related donor-hematopoietic stem cell transplantation (MRD-HSCT) (n = 108) and immunosuppressive therapy (IST) plus eltrombopag (EPAG) (IST + EPAG) (n = 104) to determine whether MRD-HSCT was still superior as a front-line treatment for patients with severe aplastic anemia (SAA). Compared with IST + EPAG group, patients in the MRD-HSCT achieved faster transfusion independence, absolute neutrophil count ≥ 1.0 × 10(9)/L (P < 0.05), as well as high percentage of normal blood routine at 6-month (86.5% vs. 23.7%, P < 0.001). In the MRD-HSCT and IST + EPAG groups, 3-year overall survival (OS) was 84.2 ± 3.5% and 89.7 ± 3.1% (P = 0.164), whereas 3-year failure-free survival (FFS) was 81.4 ± 4.0% and 59.1 ± 4.9% (P = 0.002), respectively. Subgroup analysis indicated that the FFS of the MRD-HSCT was superior to that of the IST + EPAG among patients aged < 40 years old (81.0 ± 4.6% vs. 63.7 ± 6.5%, P = 0.033), and among patients with vSAA (86.1 ± 5.9% vs. 54.9 ± 7.9%, P = 0.003), while the 3-year OS of the IST + EPAG was higher than that of the MRD-HSCT among the patient aged ≥ 40 years old (100.0 ± 0.0% vs. 77.8 ± 9.8%, P = 0.036). Multivariate analysis showed that first-line MRD-HSCT treatment was associated favorably with normal blood results at 6-month and FFS (P < 0.05). These outcomes suggest that MRD-HSCT remains the preferred first-line option for SAA patients aged < 40 years old or with vSAA even in the era of EPAG.
PICO Summary
Population
Adults with severe aplastic anaemia (n=212)
Intervention
Matched related donor stem cell transplantation (MRD-HSCT, n=108)
Comparison
Immunosuppressive therapy plus eltrombopag (IST + EPAG, n=104)
Outcome
Compared with IST + EPAG group, patients in the MRD-HSCT achieved faster transfusion independence, absolute neutrophil count ≥ 1.0 × 10(9)/L, as well as high percentage of normal blood routine at 6-month (86.5% vs. 23.7%). In the MRD-HSCT and IST + EPAG groups, 3-year overall survival (OS) was 84.2 ± 3.5% and 89.7 ± 3.1%, whereas 3-year failure-free survival (FFS) was 81.4 ± 4.0% and 59.1 ± 4.9%, respectively. Subgroup analysis indicated that the FFS of the MRD-HSCT was superior to that of the IST + EPAG among patients aged < 40 years old (81.0 ± 4.6% vs. 63.7 ± 6.5%), and among patients with vSAA (86.1 ± 5.9% vs. 54.9 ± 7.9%), while the 3-year OS of the IST + EPAG was higher than that of the MRD-HSCT among the patient aged ≥ 40 years old (100.0 ± 0.0% vs. 77.8 ± 9.8%). Multivariate analysis showed that first-line MRD-HSCT treatment was associated favorably with normal blood results at 6-month and FFS.
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Inefficacy of Immunosuppressive Therapy for Severe Aplastic Anemia Progressing From Non-SAA: Improved Outcome After Allogeneic Hematopoietic Stem Cell Transplantation
Liu, L., Zhao, X., Miao, M., Zhang, Y., Jiao, W., Lei, M., Zhou, H., Wang, Q., Cai, Y., Zhao, L., et al
Frontiers in oncology. 2021;11:739561
Abstract
BACKGROUND AND AIMS This study aimed at comparing the efficacy and safety of severe aplastic anemia (SAA) cases that had met the criteria for SAA at the time of diagnosis (group A) with SAA that had progressed from non-SAA (NSAA) (group B), both undergoing first-line immunosuppressive therapy (IST). Additionally, group B was compared with SAA that had progressed from NSAA and who had been treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT) (group C). METHODS We retrospectively compared 608 consecutive patients in group A (n = 232), group B (n = 229) and group C (n = 147) between June 2002 and December 2019. Six months after treatment, the rate of overall response and the fraction of patients who had achieved normal blood values, treatment-related mortality (TRM), secondary clonal disease, 5-year overall survival (OS) and failure-free survival (FFS) were indirectly compared between group A and group B, group B and group C. RESULTS Six months after treatment, the rate of overall response and the fraction of patients who had achieved normal blood values in group A was higher than in group B (65.24% vs. 40.54%, P < 0.0001; 23.33% vs. 2.25%, P < 0.0001); the same was true for group C (92.50% vs. 2.25%, P < 0.0001). The rate of relapse in group B was higher than in group C (P < 0.0001), but there were no differences in TRM and secondary clonal disease (P > 0.05). There were no differences in estimated 5-year OS between groups A and B (83.8% ± 2.6% vs. 85.8% ± 2.6%, P = 0.837), or between B and C (85.8% ± 2.6% vs. 77.9% ± 3.4%, P = 0.051). The estimated 5-year FFS in groups A and C was higher than for group B (57.1% ± 3.3% vs. 39.7% ± 3.4%, P < 0.001; 76.7% ± 3.5% vs. 39.7% ± 3.4%, P < 0.0001). CONCLUSION These results indicate that IST is less effective in SAA progressing from non-SAA but allo-HSCT can improve outcomes.
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Unmanipulated haploidentical hematopoietic stem cell transplantation for children with myelodysplastic syndrome
Suo, P., Wang, S., Xue, Y., Cheng, Y., Kong, J., Yan, C., Zhao, X., Chen, Y., Han, W., Xu, L., et al
Pediatric transplantation. 2020;:e13864
Abstract
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders and is rare in children. Allogeneic hematopoietic stem cell transplantation (HSCT) is commonly used in children with MDS with excess blasts and in patients with refractory cytopenia of childhood (RCC) associated with monosomy 7, complex karyotype, severe neutropenia, or transfusion dependence. We recruited 27 children with MDS who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT). At transplantation, 10 patients had RCC, 12 patients had advanced MDS (RAEB and RAEB-T), and 5 patients had myelodysplasia-related acute myeloid leukemia (MDR-AML). All patients received granulocyte colony-stimulating factor (G-CSF)-mobilized bone marrow cells and peripheral blood stem cells. At a median follow-up of 24.1 months (range: 2.0-74.5 months) after HSCT, the estimated probabilities of 3-year disease-free survival (DFS) and overall survival (OS) were both 81.9% (95% CI, 66.8-100.0%). The estimated 3-year incidences of relapse (CIR) and non-relapse mortality (NRM) were both 7.4% (95% CI, 1.2%-21.4%). The 100-day cumulative incidence of grade II-IV aGVHD was 52.6% (95% CI, 42.9-62.3%), while that of grade III-IV aGVHD was 11.1% (95% CI, 5.1-17.1%). The 3-year cumulative incidences of overall and extensive cGVHD were 42.3% (95% CI, 19.8%-57.5%) and 21.1% (95% CI, 2.5%-63.2%), respectively. Univariate analysis showed that chronic GVHD significantly affected OS and DFS. Haploidentical HSCT may be an effective treatment option with easier donor availability for pediatric patients with MDS.
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Pre-transplant cytoreductive therapy can improve overall survival of patients with MDS-AML but not MDS-EB2 receiving HLA-matched sibling donor peripheral blood stem cell transplantation
Wang, Q., Zhao, X., Liu, Z., Zhao, X., Zhang, G., Yao, J., Zheng, X., Zhang, L., Shen, Y., He, Y., et al
American journal of cancer research. 2020;10(4):1218-1228
Abstract
To evaluate whether cytoreductive therapy is needed for myelodysplastic syndromes (MDS) patients with excess blasts type 2 (MDS-EB2) and acute myeloid leukemia derived from MDS (MDS-AML) before HLA-matched sibling donor peripheral blood stem cell transplantation (MSD-PBSCT), we retrospectively analyzed 80 cases of MDS-EB2 and MDS-AML patients who received MSD-PBSCT between February 2006 and December 2019 in our hospital. The 3-years overall survival (OS) rate and disease-free survival (DFS) rate were (59.1+/-5.8)% and (52.5+/-5.7)%, respectively. The 3-years non-relapse mortality (NRM) rate and relapse rate (RR) were (22.4+/-0.2)% and (25.4+/-0.2)%, respectively. Univariate analysis showed that, hematopoietic cell transplantation comorbidity index (HCT-CI) ≥ 2, poor/very poor karyotype and occurrence of grade III-IV acute graft-versus-host disease (aGVHD) are risk factors for OS. Patients received pre-transplant cytoreductive therapy (PCT) and obtained complete remission (CR) had significantly higher OS rate than those who failed to achieve CR (non-CR group) and those who did not receive PCT (non-PCT group) [(80.0+/-8.3)% versus (38.1+/-10.6)% versus (56.1+/-9.3)%, P=0.010]. PCT significantly increased the OS rate [(62.2+/-10.0)% versus (20.0+/-17.9)%, P=0.013] for MDS-AML patients but not for MDS-EB2 patients [(59.2+/-11.1)% versus (62.9+/-10.1)%, P=0.991]. Our findings suggest reducing tumor burden by cytoreductive therapy to obtain CR before transplant improves OS. For MDS-AML patients, PCT is beneficial, while for MDS-EB2 patients, PCT is not necessary.
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Treatment of pediatric primary hemophagocytic lymphohistiocytosis with the HLH-94/2004 regimens and hematopoietic stem cell transplantation in China
Ma, H., Zhang, R., Zhang, L., Wei, A., Zhao, X., Yang, Y., Liu, W., Li, Z., Qin, M., Wang, T.
Annals of hematology. 2020
Abstract
We aimed to clarify the clinical characteristics, prognostic factors, and effectiveness of the HLH-94/2004 regimens and hematopoietic stem cell transplantation (HSCT) in pediatric patients with primary hemophagocytic lymphohistiocytosis (pHLH) in China. A retrospective analysis was performed on 38 patients with pHLH at Beijing Children's Hospital. PRF1 (34.2%) and UNC13D (31.6%) were the most common mutations in the pHLH. Thirty-eight patients were treated with the HLH-94/2004 regimens after diagnosis. Twenty-six patients (72.2%) responded to first-line treatment (complete response: 55.5%, partial response: 16.7%). The median survival time was 23 months. The overall survival (OS) rate at 3 years was 74.7%. There was no significant difference in the response rate (72% vs. 63.6%, P?=?0.703) or 3-year OS (83.6% vs. 66.7%, P?=?0.443) between the patients treated with the HLH-94 regimen and those treated with the HLH-2004 regimen. The incidences of all side effects in patients treated with the HLH-94 or HLH-2004 regimen were 32.0% and 18.2%, respectively (P?=?0.394). Among 15 patients treated with HSCT, neither the preconditioning regimen nor the donor type affected patient prognosis (P?=?0.205 and P?=?0.161, respectively). The disease status (remission or nonremission) before preconditioning did not affect prognosis or the incidence of GVHD. Furthermore, a higher bilirubin level (=?30 µmol/L) was correlated with a poorer prognosis in pHLH patients (P?=?0.026). The effectiveness rates of the HLH-94 and HLH-2004 regimens, chemotherapy, and HSCT were similar in pHLH patients. A bilirubin level =?30 µmol/L might be an adverse prognostic factor in pHLH.