Ruxolitinib-based regimen in children with primary hemophagocytic lymphohistiocytosis.

Primary hemophagocytic lymphohistiocytosis (pHLH) is a rare immune disorder and hematopoietic stem cell transplan- tation (HSCT) is the only potentially curative treatment. Given the high pre-HSCT mortality of pHLH patients reported in the HLH-2004 study (17%), more regimens to effectively control the disease and form a bridge with HSCT are needed. We conducted a retrospective study of pHLH children treated by ruxolitinib (RUX)-based regimen. Generally, patients received RUX until HSCT or unacceptable toxic side-effect. Methylprednisolone and etoposide were added sequentially when the disease was suboptimally controlled. The primary end point was 1-year overall survival. Twenty-one pHLH patients (12 previously treated and 9 previously untreated) were included with a median follow-up of 1.4 years. At last follow-up, 17 (81.0%) patients were alive with a 1-year overall survival of 90.5% (95% confidence interval: 84.1-96.9). Within the first 8 weeks, all patients had an objective response, of which 19 (90.5%) achieved complete response (CR) and two (9.5%) achieved partial response (PR) as a best response. Seventeen (81.0%) patients received HSCT, of which 13 (76.5%) had CR, three (17.6%) had PR and one (5.9%) had disease reactivation at the time of HSCT. Fifteen (88.2) patients were alive post- HSCT. Notably, eight (38.1%) patients received zero doses of etoposide, suggesting the potential of RUX-based regimen to reduce chemotherapy intensity. Patients tolerated RUX-based regimen well and the most frequently observed adverse events were hematologic adverse events. Overall, RUX-based regimen was effective and safe and could be used as a bridge to HSCT for pHLH children.

Allogeneic hematopoietic stem cell transplantation for pediatric acute lymphoblastic leukemia.

This study was aimed to explore the prognosis of allogenic hematopoietic stem cell transplantation (allo-HSCT) in pediatric patients with acute lymphoblastic leukemia (ALL). This retrospective case series study included children with ALL who underwent allo-HSCT at Beijing Children's Hospital of Capital Medical University, Beijing, China, between January 2009 and December 2019. The outcomes included 5-year overall survival (OS) and event-free survival (EFS). A total of 75 children (52 males) were included. The median age at presentation was 5.30 years, and the median time from diagnosis to transplantation was 1.64 years. There were 15 human leukocyte antigen (HLA)-matched and 60 HLA-semi-matched transplants, 73 complete remissions (CR), and 2 MRD-positive transplants. The median follow-up time was 41 months. Out of 75 patients, 51 children survived, and 24 died/given up at the terminal stage. The 5-year OS and EFS rates were 67.77% and 57.30%, respectively, whereas the 5-year recurrence rate was 35.69%. Acute and chronic graft versus host diseases occurred in 40 and 28 cases, respectively. Children with MLL gene fusion had higher survival rates compared to other subgroups. Haplo-HSCT is not inferior to HLA-matched transplant. The children with MLL rearrangement had an acceptable 5-year OS, while complications and relapse should be monitored.

Analysis of BK Virus Infection in Children After Hematopoietic Cell Transplantation: A Retrospective Single-Center Study.

BACKGROUND: BK virus (BKV) is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic stem cell transplantation (HSCT). Viruses can be found in urine and serum of immunocompromised patients. OBJECTIVE: This study aimed to evaluate the incidence, clinical course, and risk factors for BKV infection in children undergoing HSCT. METHODS: Retrospectively analyzed children who underwent HSCT at Beijing Children's Hospital, Capital Medical University from June 2020 to June 2022. Data related to the clinical manifestations, engraftment, and prognosis were extracted from medical records. Patients were divided into the case group and the control group, according to the BKV infection or not after HSCT. RESULTS: A total of 149 patients were enrolled in this study, and 61 (40.9%) patients developed BKV infection after HSCT. Among the 61 patients, BKV load was detected in all patients in urine samples and 22 patients in blood samples. The median value of BKV DNA copies in urine and plasma were 9.50×107 (5.37×102 to 6.84×109) copies/mL and 2.97×103 (9.96×102 to 3.58×108) copies/mL, respectively. The median time from beginning of the conditioning regimen to BKV infection was 23 (0 to 273) days, and the first positive time of urinary BKV was earlier than that of blood (13.5 d [0.0 to 123.0 d] vs. 30.5 d [7.0 to 165.0 d], P=0.003). Among the patients with BKV infection, 36 (59.0%) patients met the diagnosis of hemorrhagic cystitis (HC), and the incidence was higher than that in the control group (P<0.001). Similarly, 15 (24.6%) patients developed renal function damage in the case group and the proportion was higher than that in the control group. The median follow-up was 5.67 (0.03 to 24.90) months, and there was no significant difference in 1-year overall survival rate between the case group and the control group (84.2%±5.7% vs. 95.3%±2.3%, P=0.688), but the incidence of TA-TMA/VOD (31.1%) and diffuse alveolar hemorrhage (9.8%) in the case group was higher than that in the control group (P=0.002 and 0.038, respectively). Multivariate analysis showed that age above 5 years old (OR=9.039, 95% CI: 3.561-24.333, P<0.001) and use of MMF (OR=2.708, 95% CI: 1.041-7.044, P<0.05) were independent risk factors for BKV infection after HSCT. CONCLUSION: Among children after HSCT, the incidence of BKV infection was high and BKV infection was associated with an increased incidence of TA-TMA/VOD and diffuse alveolar hemorrhage. Patients older than 5 years of age at the time of HSCT and treated with MMF were more likely to develop BKV infection.

Haploidentical hematopoietic stem cell transplantation as a first-line treatment for paediatric severe aplastic anemia: a single-center research.

MRD-HSCT is the first-line therapy for children with SAA, while it is not easy to find a compatible donor due to the Chinese one-child policy. IST has a high recurrence rate, a risk of clonal transformation. Thus, Haplo-HSCT, as a first-line treatment, has gradually attracted clinicians' attention. To evaluate the efficacy of Haplo-HSCT in children with SAA, we performed a retrospective study (2006.06-2021.01) of 210 patients with AA who received HSCT or IST in Beijing Children's Hospital. The OS and FFS rates were analyzed to evaluate the efficacy of Haplo-HSCT and IST. We found that from 2006 to 2021, 3- and 5-year cumulative survival rates were both 85.3% in the first-line Haplo group, 98.1% and 96.8% in the first-line IST group, both 85.7% in the ATG group (P = 0.866), both 100% in the ATG + TPO group (P = 0.016), and 99.1% and 97.2% in the ATG + eltrombopag group (P = 0.056). 3- and 5-year cumulative FFS rates were both 85.3% in the first-line Haplo-HSCT group and 67.5% and 66.2% in the first-line IST group (P = 0.033). Therefore, we believe that Haplo-HSCT can be a first-line treatment for paediatric SAA.

Busulfan for Allogeneic Hematopoietic Stem Cell Transplantation in Children with Severe Aplastic Anemia: A Retrospective Study.

INTRODUCTION: This retrospective study aimed to compare a range of conditioning regimens in children with severe aplastic anemia (SAA) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the Seventh Medical Center of PLA General Hospital between January 2008 and June 2017. METHODS: Patients were categorized into the Bu (Bu + Flu + Cy + ATG-F regimen) and control (Flu + Cy + ATG-F) groups, with a median follow-up time after HSCT of 3.5 (range, 3.1-6.2) and 3.7 (3.2-5.9) years in the Bu and control groups, respectively. RESULTS: No differences were observed between the two groups regarding the median time of peripheral blood neutrophil and platelet engraftment (p = 0.538 and p = 0.491); the 28-day engraftment rates of neutrophils were similar (p = 0.199), although higher for platelets with Bu (p = 0.044). Additionally, graft failure was 0% and 20.0% in the Bu and control groups, respectively (p = 0.004). In both groups, the incidence of grades III-IV (or grades II-IV) acute graft-versus-host disease (GVHD) and chronic GVHD was not significantly different (p > 0.05). Moreover, the 3-year overall survival and failure-free survival did not show significant differences (p = 0.670 and p = 0.908). DISCUSSION: In children with SAA undergoing allo-HSCT, conditioning regimen with Bu + Flu + Cy + ATG-F is capable of enhancing the myeloablation effect, promoting donor hematopoietic stem cell engraftment, and reducing the graft failure rate. Furthermore, it does not increase the incidence of complications, including GVHD.

Efficacy of hematopoietic stem cell transplantation in the treatment of children with non-severe aplastic anemia.

BACKGROUND: Non-severe aplastic anemia is more likely to develop into severe aplastic anemia, and there is no widely accepted treatment plan at present. Hematopoietic stem cell transplantation might be a new therapeutic strategy. METHODS: Retrospectively analyzed 32 patients with non-severe aplastic anemia who underwent hematopoietic stem cell transplantation from September 2007 to September 2020, and the 5-year estimated overall survival rate and the incidence of graft-versus-host disease were analyzed to evaluate the efficacy and safety of hematopoietic stem cell transplantation in the treatment of pediatric non-severe aplastic anemia. RESULTS: Thirty-two patients who underwent transplantation, 29 patients (90.6%) survived, 3 patients (9.4%) died. The incidence of acute graft-versus-host disease was 51.6% (16/31), including 15 cases (48.4%) of grade I-II and 1 case (3.2%) of grade III-IV. The incidence of chronic graft-versus-host disease was 38.7% (12/31). The 5-year overall survival rate was 91.8%. CONCLUSIONS: Hematopoietic stem cell transplantation is a practicable, safe, and effective treatment option for non-severe aplastic anemia pediatric patients who are suitable for transplant.

Immune Reconstitution in Pediatric Aplastic Anemia after Allogeneic Hematopoietic Stem-cell Transplantation.

Background: Previous studies had revealed that immune reconstitution (IR) after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) affected the clinical prognosis of patients. However, few studies were based on pediatric patients and patients with aplastic anemia (AA). The purpose of this research was to analyze IR of pediatric AA after HSCT and further explore its clinical prognostic value. Methods: The whole of 61 pediatric patients with AA who underwent HSCT were enrolled. Lymphocyte subsets count in peripheral blood, CD4+/CD8+ T cell ratio, and serum concentration of immunoglobulins were detected using flow cytometry at regular intervals after HSCT. Results: Innate immunity recovered faster than adaptive immunity, T lymphocytes recovered faster than B lymphocytes. The number of transfused CD34+ cells and the implantation time of ANC significantly affected the early rapid IR of CD3+ T cells. The degree of HLA site coincidence significantly affected the early rapid IR of CD19+ B cells. The number of transfused MNC and CD34+ cells significantly affected the early rapid IR of CD56+ NK cells. The overall survival (OS) and failure-free survival (FFS) of CD56+ NK cells in early rapid IR group were higher than those in non-IR group. The CD3+ T cell early rapid IR group and CD8+ T cell early rapid IR group had higher OS than the non-IR group. Conclusion: Early rapid IR after HSCT is a good predictor of clinical prognosis in children with AA. This study provides a reasonable prediction for early rapid IR, which may improve clinical outcomes of children.

Haploidentical Hematopoietic Stem Cell Transplantation for XIAP Deficiency: a Single-Center Report.

PURPOSE: X-linked inhibitor of apoptosis (XIAP) deficiency caused by mutations in the XIAP/BIRC4 gene is a rare inherited primary immunodeficiency also known as X-linked lymphoproliferative syndrome type 2 (XLP2). Hematopoietic stem cell transplantation (HSCT) is currently the only curative strategy available. However, few studies of haploidentical HSCT have been published regarding the outcomes in patients with this syndrome. METHODS: We evaluated the XIAP gene analysis and clinical characteristics of four Chinese patients with XIAP who underwent haploidentical HSCT. RESULTS: The mutations in the two of four patients had not yet been reported in the literature. All of the patients had recurrent hemophagocytic lymphohistiocytosis but did not have a good matched donor and underwent haploidentical HSCT at BCH in China between September 2016 and December 2018. All four patients received antithymocyte globulin with fludarabine-based regimens. Two patients underwent reduced intensity conditioning (RIC), and the other two received modified myeloablative conditioning (MAC) regimens. Three of the four patients survived. Three patients experienced complications with mixed chimerism. One of the four patients who underwent RIC had early graft loss and then developed grade IV acute graft-versus-host disease (GVHD) after donor lymphocyte infusion with bone marrow. The two patients who received MAC survived with no or mild GVHD, even though one of them developed hepatic veno-occlusive disease in the early stage of transplantation. CONCLUSIONS: Haploidentical HSCT may be a treatment option for patients with XIAP deficiency who lack a good matched donor. More studies are needed to determine whether modified MAC with reduced toxicity is more suitable for haploidentical transplantation.

Treatment of pediatric primary hemophagocytic lymphohistiocytosis with the HLH-94/2004 regimens and hematopoietic stem cell transplantation in China.

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.

Insensitive to PTH of CD8+ T cells regulate bone marrow mesenchymal stromal cell in aplastic anemia patients.

Aplastic anemia (AA) is a rare disorder characterized by the suppression of bone marrow function resulting in progressive pancytopenia. The pathogenesis of AA is complex and involves an abnormal hematopoietic microenvironment, hematopoietic stem cell/progenitor cell deficiencies, and immunity disorders. However, the underlying mechanism of the disease is still not fully uncovered. In this research, we collected both donor and patient samples and found suppressed proliferation, abnormal differentiation as well as increased apoptosis of patient mesenchymal stem cells (MSCs). Considering the close relationship of parathyroid hormone (PTH) and MSCs differentiation, further studies showed that although patients maintained normal serum PTH level, their CD8+ T cells possessed lower PTH receptors. The insensitive to PTH of patients' CD8+ T cells finally lead to reduced expression of key Wnt factors. In all, bone marrow CD8+ T cells may play an important role in inducing MSCs adipogenesis and osteogenesis imbalancement.

Eltrombopag for Delayed Platelet Recovery and Secondary Thrombocytopenia Following Allogeneic Stem Cell Transplantation in Children.

The delay in platelet recovery after hematopoietic stem cell transplantation (HSCT) is closely related to the overall survival rate of transplanted children. The use of platelet-producing agents such as eltrombopag and romiplostim has made great progress in treating diseases such as immune thrombocytopenia and aplastic anemia. However, the use of such drugs in patients with thrombocytopenia after transplantation, especially in children, is rare. This study aimed to report eltrombopag treatment for 3 children with primary platelet engraftment failure and secondary thrombocytopenia after allogeneic HSCT. Of these patients, 2 had platelets stabilized at ≥50×10/L after eltrombopag treatment and subsequent withdrawal of eltrombopag. All 3 patients showed no clear adverse reactions. The results indicated a wide application prospect of eltrombopag treatment in children with thrombocytopenia after allogeneic HSCT.

Hematopoietic stem cell transplantation without in vivo T-cell depletion for pediatric aplastic anemia: A single-center experience.

For young patients, HLA-MRD HSCT is the first-line treatment of SAA. However, due to China's birth control policy, few patients could find suitable sibling donors and HLA-MUD. More and more transplantation centers have used Haplo-D as the donor source for young adult and pediatric patients. However, studies with larger amount of pediatric patients are rare. We retrospectively analyzed the data of children with AA who were treated with allogeneic HSCT and compared the therapeutic efficacy of Haplo-HSCT and MRD/MUD group. A total of 62 patients were enrolled. Implantation was successfully performed in 58 patients. There was no significant difference in the time for reconstruction of hematopoietic function between patients in the two groups. Thirty-two had grade I-IV aGVHD with incidence of 51.61%. The incidence of aGVHD was 79.41% for patients in the Haplo-HSCT, significantly higher than that of 17.86% for patients in the MRD/MUD group (P < .01). However, the incidence of cGVHD was not significantly different between patients in the two groups (26.47% vs 10.71%, P = .09), the incidence of CMV infection was 28.57% and 52.94% for patients in the MRD/MUD and Haplo group, respectively, showing no significant difference (P = .053). The incidence of EBV infection was 47.06% for patients in the Haplo group and 28.57% for patients in the MRD/MUD group, showing no significant difference (P = .11). However, the 3- and 5-year cumulative OS and FFS rates showed statistically significant difference in the two groups, P = .012 and .045, respectively. Compared to Haplo-HSCT, MRD/MUD is more economic. In this study, we achieved good Haplo transplantation results. The incidences of cGVHD and CMV/EBV were not significantly different between Haplo group and MRD/MUD group. Although OS and FFS of the Haplo group were not as good as those of the MRD/MUD group, it is still acceptable as an alternative treatment under emergency.

Clinical outcomes of unrelated cord blood transplantation in children with malignant and non-malignant diseases: Multicenter experience in China.

This multicenter retrospective study included 184 children with malignant and non-malignant diseases who underwent UCBT between January 1998 and August 2012. The malignant disease group included 101 children with ALL, AML, CML, JMML, and MDS, and the non-malignant disease group included 83 children with PID, ß-thalassemia, IMD BMF, and HLH. The median duration to neutrophil and platelet engraftment was 16 and 35 days in the malignant disease group vs 15 and 38 days in the non-malignant disease group. The cumulative incidence of grade II-IV aGVHD and cGVHD was 25.6% and 13.5% in the malignant disease group vs 19.7% and 11.1% in the non-malignant disease group, respectively. The median duration and cumulative incidence of neutrophil and platelet engraftment, and the cumulative incidence of grade II-IV aGVHD and cGVHD were similar between the two groups. Of the 184 pediatric patients, 114 patients survived during a median follow-up period of 14 months (range 4-138). The 5-year OS and DFS were not statistically different between the two groups (56.3% and 46.1% in malignant disease group vs 68.5% and 52.8% in non-malignant disease group). The above results indicate that UCB is a viable source for HSCT for children with malignant or non-malignant diseases, especially in urgent cases.

Allogeneic Hematopoietic Stem Cell Transplantation in Thirty-Four Pediatric Cases of Mucopolysaccharidosis-A Ten-Year Report from the China Children Transplant Group.

We investigated the efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) in pediatric patients with mucopolysaccharidosis (MPS). A retrospective analysis of transplantation data from 34 cases of MPS from the China Children Transplant Group, treated between December 2004 and September 2015, was conducted. Among the 34 cases, 12 cases were type I, 12 were type II, 4 were type IV, 4 were type VI, and 2 were of an unknown type. The median age at transplantation was 3.75 years (range, 1 to 7 years); the median follow-up time was 14 months (range, 2 to 119 months). Eleven patients underwent unrelated cord blood transplantation and 23 underwent peripheral blood stem cell transplantation (4 cases with an HLA-matched sibling donor, 2 cases with an HLA-mismatched related donor, and 17 cases with an unrelated donor). A busulfan-based myeloablative regimen was used as a conditioning regimen. The estimated overall survival at 3 years was 84.8% ± 6.3% and 91.2% of the patients (31 of 34) achieved full donor chimerism. Twenty-seven children were evaluable and all but 1 (carrier sibling donor; enzyme level improved but failed to reach normal) achieved normal enzyme level after transplantation. The incidence of grades II to IV acute graft-versus-host disease (aGVHD) was 41.1% (14 of 34), wherein the incidence of grades III and IV aGVHD was 11.8% (4 of 34). The incidence of moderate-to-severe chronic graft-versus-host disease was 5.9% (2 of 34). There was a significant difference in the survival rate between children who received transplantation before 2009 and those after 2009 (55.6% versus 95.7%, P = .002); the survival rate was lower in patients with pneumonia before transplantation than in those with no active infection before transplantation (66.7% versus 95.5%, P = .019), and no significant differences in survival rates were observed among children with different disease types, ages at transplantation, donor/graft source, and conditioning regimens. After transplantation, upper-airway obstruction, hepatosplenomegaly, and corneal clouding were significantly improved; hearing and motor function were improved to a certain extent; valvular heart disease was improved in some patients but progressed in others; and short stature and speech skills showed little improvement. AlloHSCT may save the lives of patients with MPS I, II, IV or VI and could improve quality of life. Pretransplantation pneumonia affects transplantation outcomes. Advances in transplantation protocols and techniques help to improve patient prognosis. Well-matched unrelated donors can also be an ideal donor source. Standardized follow-up and a multidisciplinary team contribute to accurate evaluation of long-term post-transplantation outcome and further improve the quality of life of MPS patients.

Reliability and validity of the Chinese mandarin version of PedsQL™ 3.0 transplant module.

BACKGROUND: Long-term health-related quality of life (HRQoL) of pediatric patients after hematopoietic stem cell transplantation (HSCT) is increasingly studied worldwide. However, few studies have been performed in China, where no uniform scale is available; the PedsQL™ Cancer Module 3.0 Chinese Mandarin version has been used to evaluate HRQoL of patients after HSCT in China. This study aimed to assess the reliability and validity of the Chinese Mandarin version of PedsQL™ 3.0 Transplant Module. METHODS: Patients between 2 and 18 years old, who underwent HSCT from January 2006 to June 2014, were recruited in Beijing Children's Hospital affiliated to Capital Medical University, the First Affiliated Hospital of Southern Medical University and Beijing Daopei Hospital. 207 parent reports and 182 child self-reports of the PedsQL™ 3.0 Transplant Module Chinese Mandarin version were assigned, of which 362 were returned. RESULTS: No missing item response was observed in the returned reports. Cronbach's alpha coefficient exceeded 0.7 in total scale and every dimension. The intraclass correlation coefficient exceeded 0.8 in all dimensions of child self-reports and parent reports. Spearman's rank correlation coefficients of items and their respective dimensions were 0.6-0.94 in parent reports, and 0.62-0.93 in child self-reports, while a weak association was found between the items and other dimensions. Exploratory factor analysis indicated a good extraction effect, and construct validity of the scale was >60 %. CONCLUSIONS: The Chinese Mandarin version of PedsQL™ 3.0 Transplant Module has good feasibility, reliability and validity. Its use may help improve the HRQoL of children after HSCT in China.

Pediatric hematopoietic stem cell transplantation in China: Data and trends during 1998-2012.

The success of treating a wide variety of pediatric diseases with HSCT, hematologic malignancies in particular, has resulted in an increased number of long-term survivors. This study is the first large-scale, multicentre report that describes the evolution of pediatric HSCTs in China during the period of 1998-2012. Of all 1052 patients, 266 cases were treated with autologous HSCs and 786 used allogeneic HSCs. The disease indications for HSCTs mainly included leukemias, lymphoma, solid tumors, and non-malignant disorders. The total number of HSCTs, especially unrelated donor transplants, appeared to be increasing year by year. For patients with neuroblastoma, the therapeutic efficacy seemed to be poor, with a five-yr OS and DFS rate of 34.5 ± 14.3% and 20.7 ± 9.6%, respectively. In contrast, the survival of patients with SAA was prominently improved, and their five-yr OS and DFS rates were 82.8 ± 4% and 80.7 ± 4.1%, respectively. Patients who received cord blood transplants had a lower incidence of acute GVHD than that of PB and/or BM transplants from unrelated donors. This report offers us a valuable resource for evaluating the changes in HSCTs in China over the past 14 yr.

Efficacy and safety of human umbilical cord derived mesenchymal stem cell therapy in children with severe aplastic anemia following allogeneic hematopoietic stem cell transplantation: a retrospective case series of 37 patients.

The treatment of pediatric severe aplastic anemia (SAA) with allogeneic hematopoietic stem cell transplantation (allo-HSCT), presents major challenges including the risks of graft failure, septic complications, and graft-versus-host disease (GVHD). Additive infusions of human umbilical cord derived mesenchymal stem cell (hUC-MSC) may be administered to improve patient survival. We retrospectively examined 37 pediatric patients with SAA who received allo-HSCT and subsequent infusions of hUC-MSC suspension at a dose of 1.0 × 10(6 )/kg. The times and doses of hUC-MSC infusions were increased in patients with severe GVHD. All patients received hUC-MSC infusions. The median time to post-transplantation neutrophil count of greater than 0.5 × 10(9 )/L was 14 days (range, 11-20 days) and time to post-transplantation platelet count of greater than 20 × 10(9 )/L was 19 days (14-29 days). The overall frequency of acute GVHD (aGVHD) was 45.9% (17/37). These aGVHD episodes occurred at a median time of post-transplantation 47 days (15-83 days). The frequency of chronic GVHD (cGVHD) was 18.9% (7/37); cGVHD developed from aGVHD in 10.8% (4/37) of patients. The GVHD-associated mortality rate was 18.9% (7/37) and aGVHD-specific mortality rate was 8.1% (3/37). The median overall survival time was 35 months (9-67 months) and the three-year overall survival rate was 74.2% (28/37). Seven patients died of GVHD, one patient died of a severe invasive fungal infection, and one patient died of renal failure. In conclusion, post-transplantation hUC-MSC infusions seemed to be safely infused in children with SAA who have previously received allo-HSCT.

Practice guideline on ovarian tissue cryopreservation and transplantation in the prevention and treatment of iatrogenic premature ovarian insufficiency.

Premature ovarian insufficiency (POI) refers to the decline of ovarian function before the age of 40. POI causes a reduction in or loss of female fertility, accompanied by different degrees of menopausal symptoms, which increases the risk of chronic diseases related to early menopause and seriously affects patients' quality of life and health. It is conservatively estimated that at least one million prepubertal girls and women of reproductive age in China are at risk of iatrogenic POI caused by radiotherapy and chemotherapy every year. With the development of medical technology and the breakthrough of scientific and technological advances, preventing and treating iatrogenic POI have become possible. International and national guidelines consider cryopreserved ovarian tissue transplantation to be the most promising method of preserving the ovarian function and fertility of prepubertal girls and women of reproductive age who cannot delay radiotherapy and chemotherapy. In order to guide the clinical application of ovarian tissue cryopreservation and transplantation technology in China, the Guideline Working Group finally included 14 scientific questions and 18 recommendations through a questionnaire survey, field investigation, and consultation of a large number of Chinese and English literature databases in order to provide a reference for colleagues in clinical practice.

[Visual function of seven children with malignant osteopetrosis after hematopoietic stem cell transplantation].

OBJECTIVE: To detect long-term ocular alteration of children with malignant osteopetrosis after hematopoietic stem cell transplantation. METHODS: Children diagnosed as osteopetrosis from 5 months to 31 months underwent hematopoietic stem cell transplantation. Computed tomography of optic canal, FVEP, ERG and fundus examination were applied to assess the visual function. RESULTS: Bone marrow transplantation was successful. Peripheral blood test, splenohepatomegalia and osteosclerosis improved gradually. The mean optic canal diameters of right eyes before transplantation was (1.7 ± 0.4)mm. The mean optic canal diameters of right eyes was (3.2 ± 0.7)mm after transplantation. The mean optic canal diameters of left eyes before transplantation was (1.9 ± 0.5)mm . The mean optic canal diameters of left eyes was (3.1 ± 0.8)mm after transplantation. The difference between above two groups was statistically significant(t = -5.204, -4.211;P < 0.05). P2 latency period of FVEP prolonged in 7 cases before transplantation. Mean P2 latency period of FVEP decreased 21.13 ms in 5 cases after transplantation. Mean P2 latency period of FVEP prolonged 22.25 ms in 2 cases after transplantation. Under light adaptation and dark adaptation, ERG amplitude depressed obviously in 2 cases. Two cases with optic nerve atrophy did not change after transplantation. CONCLUSIONS: Hematopoietic stem cell transplantation is an effective way to deal with malignant osteopetrosis. Successful transplantation has been shown to arrest visual deterioration in some cases.

Homoharringtonine-Based Induction Therapy Reduces the Recurrence Rate of Pediatric Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment for acute myeloid leukemia (AML). Pediatric patients with AML who relapse after HSCT have an extremely poor prognosis. We performed a retrospective study of pediatric patients diagnosed with AML from August 2015 to October 2019 who were treated with HSCT. Kaplan-Meier analyses were used to evaluate overall survival (OS), event-free survival (EFS), and cumulative recurrence rate (CRR). Cox regression analysis was used to determine the association between the baseline characteristics and relapse. A total of 37 pediatric patients met the inclusion criteria. Twenty-eight (75.7%) patients survived, and 9 (24.3%) patients died. The OS rates of AML patients treated with HSCT were 89.2% ± 5.1%, 75.7% ± 7.1%, and 75.7% ± 7.1% at 1, 3, and 5 years, respectively, and the CRRs were 11.4% ± 5.4%, 24.7% ± 7.7%, and 33.1% ± 10.4% at 1, 3, and 5 years after HSCT, respectively; four of nine children who relapsed after transplantation died. Induction with etoposide rather than homoharringtonine and fungal infections could be high-risk factors for recurrence after transplantation. The association between homoharringtonine-based induction therapy and a low recurrence rate persisted after adjusting for age, sex, risk stratification, fusion genes, and fungal infections. This study clarifies the clinical features and poor prognosis of post-transplant relapse in pediatric AML and indicates the urgent need for effective therapy for patients who relapse after HSCT.