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Summary: Juvenile myelomonocytic leukaemia (JMML) is a rare myeloproliferative neoplasm requiring haematopoietic stem cell transplantation (HSCT) for potential cure. Relapse poses a significant obstacle to JMML HSCT treatment, as the lack of effective minimal residual disease (MRD)‐monitoring methods leads to delayed interventions. This retrospective study utilized the droplet digital PCR (ddPCR) technique, a highly sensitive nucleic acid detection and quantification technique, to monitor MRD in 32 JMML patients. The results demonstrated that ddPCR detected relapse manifestations earlier than traditional methods and uncovered molecular insights into JMML MRD dynamics. The findings emphasized a critical 1‐ to 3‐month window post‐HSCT for detecting molecular relapse, with 66.7% (8/12) of relapses occurring within this period. Slow MRD clearance post‐HSCT was observed, as 65% (13/20) of non‐relapse patients took over 6 months to achieve ddPCR‐MRD negativity. Furthermore, bone marrow ddPCR‐MRD levels at 1‐month post‐HSCT proved to be prognostically significant. Relapsed patients exhibited significantly elevated ddPCR‐MRD levels at this time point (p = 0.026), with a cut‐off of 0.465% effectively stratifying overall survival (p = 0.007), event‐free survival (p = 0.035) and cumulative incidence of relapse (p = 0.035). In conclusion, this study underscored ddPCR's superiority in JMML MRD monitoring post‐HSCT. It provided valuable insights into JMML MRD dynamics, offering guidance for the effective management of JMML. [ABSTRACT FROM AUTHOR]

The standard chemotherapy for acute myeloid leukemia (AML) is usually composed of anthracyclines and cytarabine. We previously reported that homoharringtonine (HHT) was incorporated into regimens for pediatric AML with acceptable efficacy and tolerable toxicity. We treated newly diagnosed AML patients aged 0–18 years on the AML-SCMC-2009 protocol. A total of 102 de novo newly diagnosed AML patients aged 0–18 years were enrolled. All patients were treated with ten courses of chemotherapy including double induction, high dose cytarabine consolidation, and maintenance. The cumulative dose of HHT was 165 mg/m2 and the daunorubicin dose was 120 mg/m2. Complete remission (CR), overall survival (OS) rate, event free survival (EFS) rate, adverse effect response and prognosis factors were retrospectively evaluated to investigate the long-term outcome and safety of this protocol. Eighty-two patients (80.4%) achieved complete remission with the first induction. The 5-year overall survival and event-free survival rates were 65.0% (SE, 4.9%) and 53.3% (SE, 5.2%), respectively. A first induction failure, age older than 2 years, and BCR-ABL translocation were associated with a significantly worse outcome (p < 0.05). No significant drug-related cardiac toxicity was observed. AML-SCMC-2009 protocol which use HHT as backbone drug is efficacious and tolerated. HHT could partially replace anthracycline to be an effective option for childhood AML. [ABSTRACT FROM AUTHOR]

Background: There are many studies about the prognosis and possible predictive factors of mortality for pediatric allogeneic hematopoietic stem cell transplantation (HSCT) recipients requiring pediatric intensive care unit (PICU) treatment, but the related study in China is lacking. This study investigates the data of these special patients in our center.Methods: This retrospective analysis is based on data from bone marrow center and PICU of our hospital. A total of 302 patients received allogeneic HSCT from January 2000 to December 2012, 29 of them were admitted to PICU because of various complications developed after transplantation. We collected the clinical data, identified the reasons why the patients to PICU, analyzed the mortality of these patients in PICU, and the prognostic factors of these patients.Results: The main reasons for admission were: respiratory failure (62.07 %), neurological abnormities (13.79 %), renal failure (13.79 %) and others (10.35 %). Twenty-one cases (72.41 %) died. Compared with survivors, the deaths cases had lower pediatric critical illness score (77 vs. 88, p = 0.004); higher levels of lactic acid and serum urea nitrogen (4.02 vs. 1.19 mmol/L, P = 0.008;11.56 vs. 7.13 m moll /L, P = 0.045); more organs damaged (2.05 vs. 1.38, P = 0.01), and required more supportive treatments (1.52 vs. 0.63, P = 0.02). Univariate analysis identified pediatric critical illness score, use of mechanical ventilation, and the number of supportive treatment as the significant predictors to prognosis. Multivariate analysis by regression showed that pediatric critical illness score was the only independent prognostic factor (P = 0.035).Conclusions: In our study, pediatric allogeneic HSCT recipients who had PICU care had a high rate of mortality. Pediatric critical illness score was the independent prognostic factor for these patients. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the dose and trough concentration ( C min ) of posaconazole delayed-release tablets and injections, and their correlation with efficacy and safety in pediatric patients. Patients younger than 18 years old received posaconazole delayed-release tablets or injections for prophylaxis or treatment of invasive fungal disease (IFD). Blood samples were collected to determine the plasma C min s, and dose regimen adjustments were made if necessary. Clinical data were collected. A total of 210 C min s of 113 pediatric patients were detected. The median C min s were 1.0 and 1.3 mg/L for tablets and injections, respectively ( P < 0.05). The median doses required to achieve the target C min were about 6.0 mg/kg of body weight/day, and no statistical difference was observed between different age groups, formulations, or indications ( P > 0.05). Concomitant treatment of tacrolimus and diarrhea were found to affect C min s of tablets, while age, gender, and BMI were found to be correlated with C min s of injections. IFD breakthrough occurred in 9.2% of patients with a median C min s of 0.74 mg/L for prophylaxis, and infection progression occurred in 43.2% of patients with a median C min s of 0.97 mg/L for treatment, respectively. Transaminitis was the most common adverse event. Posaconazole delayed-release tablets and injections are safe for prophylaxis and treatment of IFD in pediatric patients. An empirical initial dose of 6.0 mg/kg of body weight/day is appropriate for prophylaxis, while a higher dose should be required for the treatment of IFD. It is necessary to adjust the dose regimen according to the results of therapeutic drug monitoring.This study is registered with chictr.gov.cn under identifier ChiCTR2300070008.

Objective: To enrich our national database with data of rare diseases by analyzing molecular diagnosis and hematopoietic stem cell transplantation (HSCT) in children with inherited bone marrow failure syndromes (IBMFS)., Method: Next-generation sequencing (NGS)-based genetic diagnosis panel was applied for the clinical diagnosis and management of IBMFS. Retrospective analysis was performed on clinical and genetic data of 17 consecutive children who received HSCT over a long time interval (November. 2005-June 2015)., Result: Three patients were diagnosed only by clinical manifestation before 2012. After that NGS-based genetic diagnosis panel was used to identify IBMFS-related genes in 12/14.IBMFS patients (except two Diamond-Blackfan anemia (DBA) patients). Two Fanconi anemia (FA) patients were confirmed to be new variations through family-genotype-analysis and 3 families accepted prenatal diagnosis to avoid birth of affected fetuses. Seventeen IBMFS patients (10 FA,5 DBA and 2 dyskeratosis congenital (DKC)) were treated with HSCT from matched sibling donors (n=2), matched unrelated donors (n=8) or mismatched unrelated donors (n=7). The source of stem cells for transplantation included peripheral blood (n=12) and cord blood (n=5). With regard to the conditioning regimens, FA and DKC patients received fludarabine-based reduced intensity conditioning, while DBA patients received classical busulfan-based myeloablative conditioning. Median age at the time of HSCT was 36 months (7-156 months). The number of infused mononuclear cells and CD34⁺ cells was (10.6 ± 6.7) × 10⁸ and (5.9 ± 7.0) × 10⁶ per kilogram of recipient body weight, respectively. The median number of days to neutrophil recovery was 13 days after HSCT (range: 10-19 days). Platelet recovery was faster in the PBSCT group than in the CBT group ((16.3 ± 6.0) days vs. (30.0 ± 17.1) days,t=-2.487,P=0.026). During a median follow-up of 17 months (range: 2-114 months), except one FA patient who was transplanted with HLA-matched unrelated cord blood (CB) died from pneumonia and heart failure because of engraftment failure, other 16 children are alive after the successful HSCT. The failure-free survival rate of the patients three years after HSCT was 94%., Conclusion: NGS-based molecular diagnosis technology and effective HSCT have significantly facilitated the treatment of children with IBMFS in our country, and our national database about this rare disease is to be further exploited.