Objective:To examine the clinical experience and efficacy of unrelated cord blood transplantation (UCBT) in the treatment of recurrent refractory Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in children.Methods:The clinical data of a patient with recurrent refractory EBV-HLH and intestinal perforation who was treated by UCBT in Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University in September 2015 and finally cured were retrospectively analyzed.Meanwhile, literature was reviewed.Results:The patient, male, 1 year and 6 months, was admitted to the hospital with " fever for 15 days, rash for 9 days" as the main complaint, mainly manifested as high fever, large liver, spleen, lymph nodes, rapidly progressing pancytopenia, liver function damage, phagocytic blood cells on bone marrow smear, diagnosed as EBV-HLH in September 2015.The patient received chemotherapy according to the HLH-2004 protocol developed by the International Association of Cell Societies.During the treatment, he suffered two recurrence during the maintenance period, and a second-line rescue treatment was adopted, namely, " Pegaspargase, Doxorubicin liposome, Etoposide and Methylprednisolone" (L-DEP regimen) chemotherapy.The complete relief of diagnostic indexes for hemophagocytic lymphohistiocytosis was evaluated after chemotherapy.The patient developed sudden intestinal perforation and underwent emergency surgical surgery, enteroenterostomy.After the condition was stabilized, the patient was pretreated with the " Fludarabine+ Busulfan+ Cyclophosphamide" (Flu+ BU+ CY) therapy and then treated with UCBT, with intravenous nutritional support provided during the entire process.Neutrophil and platelet implantation was implemented on day 13 and day 35 after transplantation, respectively.The chimeric rate was 100%, and the implantation was a success.Hepatic veno-occlusive disease, fungal pneumonia and skin graft-versus-host disease (GVHD) Ⅱ occurred on the 15 th day, 22 nd day and 26 th day after transplantation, respectively.The corresponding symptoms improved after treatment.On day 49 after transplantation, phase Ⅱ " enterostomy fistula" was performed.The patient was followed up to 70 months after transplantation, and generally in good condition.His symptoms relieved, and no chronic GVHD and other comorbidities occurred. Conclusions:Allogeneic hematopoietic stem cell transplantation is the only possible effective means of treating relapsed refractory EBV-HLH in children.In the absence of a suitable sibling or unrelated donor, unrelated cord blood stem cells can be used as a graft source.Enterostomy after intestinal perforation is not contraindicated for transplantation.

Objective:To investigate the safety and efficacy of Belintoumab on the treatment of children with acute B-lymphoblastic leukemia (B-ALL).Methods:The clinical data of 10 children with CD 19+ B-ALL who were admitted to the Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University from September 2021 to May 2022 and treated with Belintoumab were analyzed retrospectively. Results:Among the 10 cases, there were 6 recurrent cases, 3 cases with persistent minimal residual disease (MRD) positive after an initial treatment, and 1 case complicated with invasive candidiasis.Before treatment, bone marrow blasts ≥0.25, and that ranged 0.05-<0.25 were detected in 2 cases and 1 case, respectively.Seven cases had a complete remission (CR) of bone marrow, 6 of which were MRD positive and 1 case was MRD negative.After treatment with Belintoumab, the CR rate was 66.7% (2/3). The overall MRD negative rate was 88.9% (8/9), and the negative rate in previously MRD positive children was 100% (6/6). The median follow-up time was 4.1 (1.6-10.0) months after the application of Belintoumab.The overall survival (OS) rate was 70.0% (7/10). Eight MRD negative children received hematopoietic stem cell transplantation, and the OS rate was 75% (6/8). Survived children did not relapse until the last follow-up visit.Fever (90%, 9/10) was the most common adverse events, followed by neutropenia (90%, 9/10). One case (10%, 1/10) of neurotoxicity was seizures (grade 2) and one case (10%, 1/10) suffered cytokine release syndrome (grade 2), which did not influence the therapeutic efficacy of Belintoumab after symptomatic treatment.Conclusions:Belintoumab is safe and effective on the treatment of children with recurrent/refractory CD 19+ B-ALL, and those with MRD positive who have achieved CR in bone marrow have a higher rate of turning negative.Belintoumab can also be used as a bridge scheme for CD 19+ B-ALL children who cannot tolerate chemotherapy.

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.