Objective:To investigate the clinical characteristics and prognosis of children with acute promyelocytic leukemia (APL) complicated with thrombosis.Methods:The clinical profiles of four APL patients complicated with thrombosis treated at the First Affiliated Hospital of Zhengzhou University between January 2012 and December 2019 were reviewed. Literature search and review covered the China national knowledge infrastructure, Wanfang database, China biology medicine disc and PubMed using the key words of "acute promyelocytic leukemia" and "thrombosis" up to June 2020.Results:Four patients included one male and three females with an age range of 4-13 years. In two patients, thrombosis occurred intracranially, both patients presented with seizure and hemiplegia. In one patient, thrombosis occurred in spleen, the patient presented with severe abdominal pain. In the last patient, thrombosis occurred in liver, the patient presented with abdominal pain, distension and ascites. Thrombosis occurred during the course of retinoic acid treatment in three patients, it occurred before the initiation of the treatment in one patient. Thrombosis was confirmed by imaging examination in all four patients. After thrombolytic and anticoagulation treatment, the vessels were recanalized and the symptoms were alleviated in 3 cases, the fourth patient died of hepatic venous thrombosis. Literature search identified no similar reports in Chinese journals, 11 case reports were found in English journals. In these 15 patients, 9 were male and 6 females with an age range of 3-16 years. Thrombus located in brain in 6 cases, in lower limbs for 3 cases, in liver for 3 cases, in spleen in 2 cases and in coronary artery for 1 case. In 10 cases thrombosis occurred before the induce treatment and in 5 cases occurred during the induction treatment. After surgery, thrombolytic and anticoagulation treatment vascular recanalization was observed in 10 patients, and in those patients, the symptoms were relieved, death occurred in 5 patients, including three patients with hepatic venous thrombosis.Conclusions:Thrombosis may occur before or during the treatment for APL. Both arterial and venous thrombosis may occur in patients with APL. Imaging examination is a reliable method for its diagnosis. After treatment, most patients had good prognosis with recanalization of blood vessels, but the mortality rate was high for patients with hepatic venous thrombosis.

Objective:To explore the clinical efficacy and safety of Ruxolitinib, a Janus kinase inhibitor, in combination with Methylprednisolone as a bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT) for relapsed/refractory Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) in pediatric patients.Methods:The clinical data of 4 patients with relapsed/refractory EBV-AHS treated with Ruxolitinib in combination with Methylprednisolone as a bridge to allo-HSCT at the Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University from August 2018 to February 2020 were retrospectively analyzed, and the disease characteristics, diagnosis and treatment process, clinical experience and related research progress were analyzed and summarized.Results:Among 4 patients with relapsed/refractory EBV-AHS, 2 patients were treated with low-dose Ruxolitinb in combination with Methylprednisolone for 6-10 weeks after partial remission.The disease did not progress, and they survived after being bridged to allo-HSCT.One patient was treated with large-dose Ruxolitinib in combination with Methylprednisolone due to the intolerance to chemotherapy, with the biochemical indicators of hemophagocytic syndrome significantly improved, and then the bridging to allo-HSCT was performed 2 months ago and this patient survived.One patient with EBV-AHS relapsed was relieved by chemotherapy again, then was given maintenance therapy with Ruxolitinib and Methylprednisolone, but the condition still progressed and the treatment was ineffective.This patient underwent allo-HSCT for salvage treatment more than 1 year ago and survived.Except that 1 patient developed mild anemia, the other 3 patients had no significant Ruxolitinib-related toxicities.Conclusions:Ruxolitinib in combination with Methylprednisolone can be safely employed as a salvage treatment for pediatric patients with relapsed/refractory EBV-AHS and a bridge to allo-HSCT, which has favorable safety, efficacy and tolerance in clinical practice.

Objective:To summarize the clinical features, treatments and prognoses of aggressive natural killer cell leukemia (ANKL) in children.Methods:Clinical data and follow-up results were retrospectively reviewed for one hospitalized case of ANKL in June 2019.Through a literature search, the relevant items were retrieved from the databases of China National Knowledge Infrastructure, WanFang and PubMed using the Chinese and English keywords of "aggressive natural killer cell leukemia" and "children" up to December 2021.Results:This 8-year-old girl was diagnosed with ANKL by flow cytometric immunophenotype and immunohistochemical stain.Fever was the initial manifestation accompanied by sallow complexion, fatigue, enlargement of liver, spleen and lymph node and hematopenia of three lines.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed after chemotherapy.As of April 2022, the child stayed in a disease-free survival state after follow-ups for over 2 years.The literature search finally yielded 7 eligible Chinese and 10 English reports with a total of 17 pediatric ANKLs.In this group, there were fever (n=15), rash (n=1), perineal mass (n=1) and diarrhea, vomiting and other digestive tract symptoms (n=1). Six cases were misdiagnosed during an early stage of disease.4 cases received chemotherapy alone, 3 cases received chemotherapy regimen for acute lymphoblastic leukemia, 1 child died and one death occurred after received chemotherapy regimen of "cisplatin + vincristine + doxorubicin + ifosfamide". Allo-HSCT was performed in 5 patients after remission with chemotherapy and one child died from multiple organ failure at 9 months after allo-HSCT.Nine cases gave up treatment.Conclusions:ANKL has a rapid disease progression, diverse clinical manifestations, easy misdiagnosis and poor prognosis.For suspected ANKL cases, clinicians perform multiple bone perforations at multiple sites and immunophenotype by flow cytometry as soon as possible to confirm the diagnosis.Currently allo-HSCT offers a long-term survival of ANKL patients.

Objective:To investigate the genotypic and hematological characteristics of β-thalassemia patients and carriers from Henan Province of China.Methods:Clinical data of the patients and carriers were collected. Results of routine blood test, hemoglobin electrophoresis and genetic testing were retrospectively analyzed.Results:Of the 83 β-thalassemia patients and carriers, there were 46 females and 37 males, and their mean age was 27.37 ± 14.71, ranging from 5 months to 83 years. A total of 13 types of β-thalassemia alleles (86 alleles in total) were detected, with the most common three including IVS-Ⅱ-654(C>T) (33.72%), CD41-42(-TTCT) (26.74%) and CD17(A>T) (18.60%). Five rare alleles, including CD8-9(+ G), IVS-Ⅱ-1(G>A), CD42(T>G), and start codons ATG>AGG and ATG>ACG were identified. Among these, HBB: c. 128T>G(CD42T>G) was previously unreported in China. Fifteen β-thalassemia genotypes were detected, which included 12 simple heterozygote genotypes (80 cases, 96.40%), 2 double heterozygote genotypes (2 cases, 2.40%) and 1 homozygote genotype (1 case, 1.20%). The main manifestations were mild microcytic hypochromic anemia and raised HbA2. Compared with those with a β + /β N genotype, carriers with a β 0/β N genotype have lower mean corpuscular volume (MCV) and mean corpusular hemoglobin (MCH) but higher HbA2 ( P<0.05). Conclusion:β-thalassemia is not rare in Henan Province and its characteristics are different from those in high incidence areas, which deserves close attention. The newly discovered HBB: c. 128T>G (CD42T>G) has enriched the spectrum of β-thalassemia mutations in China. Above results will also facilitate genetic counseling and prenatal diagnosis of β-thalassemia in Henan Province.