The development of multidrug resistance (MDR) to chemotherapy remains a major trouble in the treatment of tumors,and the mechanisms of MDR are complicated.The classic mechanisms involve the overexpression of multidrug resistance-associated protein,inhibition of cell apoptosis,abnormality of enzyme system and gene repair.Studies in recent years have shown that the mechanisms of MDR are also closely related with tumor stem cells,tumor microenvironment and abnormality of signal transduction pathways.

Objective:To raise awareness of acute myeloid leukemia (AML) combined with lymphoblastic lymphoma (LBL) in children.Methods:The clinical characteristics, diagnostic methods, treatment plans and prognosis of a child with AML combined with LBL who was admitted to the First Affiliated Hospital of Zhengzhou University in April 2016 were retrospectively analyzed, and the relevant literature was reviewed.Results:The patient was an 11-year-old boy with fever, abnormal hemogram and cervical lymph node enlargement as clinical manifestations. A biopsy of the cervical lymph node was performed and the patient was diagnosed as T-lymphoblastic lymphoma (T-LBL). After the bone marrow morphology, immunology, cytogenetics and molecular biology (MICM) classification examination, the diagnosis was AML. The patient met the diagnostic criteria of two diseases at the same time, and thus he was confirmed as AML combined with T-LBL. AML chemotherapy regimens were given, and the patient achieved complete remission and disease-free survived.Conclusions:AML with LBL is extremely rare in children. The diagnosis mainly depends on MICM classification examination of bone marrow and pathological examination of lymph nodes. There is currently no standard treatment scheme, and the prognosis is extremely poor. AML chemotherapy followed by bridging hematopoietic stem cell transplantation is the best treatment option for these patients.

OBJECTIVETo explore significance of serum soluble CD163(sCD163) and soluble CD25(sCD25) in diagnosis and guiding treatment of children with hemophagocytic lymphohistiocytosis (HLH).

METHODData of 42 cases of children with HLH, 32 cases of non-HLH children with infection presented to First Affiliated Hospital of Zhengzhou University pediatric clinic and ward were collected from December 2013 to December 2014. Twenty-four healthy children were enrolled into a normal control group in the same period.Peripheral venous blood specimens (3 ml) were taken from the children with HLH after fasting before treatment, two weeks after treatment and eight weeks after treatment.Peripheral venous blood specimens (3 ml) were also taken from children of non-HLH infected group and normal control group after fasting at the initial visit. Serum sCD163 and sCD25 levels in the peripheral blood in three groups were determined by ELISA. According to cause of disease, children with HLH were divided into infection-related HLH, tumor-related HLH, primary HLH and others; relationship between serum sCD163 and sCD25 level and cause of disease was analyzed.

RESULTSerum sCD163 of HLH group ((6 094 ± 2 769) µg/L) and serum sCD163 of non-HLH infection group ((2 174 ± 950) µg/L) were significantly higher than that of normal control group ((777 ± 256) µg/L), F=71.396, P<0.05), and the differences among groups were statistically significant (P<0.05); serum sCD25 of HLH group ((41 963 ± 31 821) ng/L) and serum sCD25 of non-HLH infection group ((6 700 ± 4 105) ng/L) were significantly higher than that of normal control group ((2 440 ± 1 870) ng/L, F=37.513, P<0.05).There was no statistically significant difference between the non-HLH infection group with the normal control group (P>0.05), and the difference between the remaining groups was statistically significant (P<0.05). And serum sCD163 and sCD25 level of HLH group had a positive linear correlation, and Pearson correlation coefficient r=0.742 (t=7.000, P<0.05). The difference of serum sCD163 and sCD25 level among the different cause of disease in HLH group was significant (P<0.05).Pairwise comparison showed that serum sCD163 and sCD25 level of tumor-associated HLH group significantly increased as compared with infection-associated HLH group (P<0.05), but the difference was not statistically significant between the other groups (all P>0.05). Serum sCD163 and sCD25 level of HLH group before treatment, 2 weeks and 8 weeks after treatment showed a statistically significant tendency of decrease (P<0.05). Seen from the ROC curve, when sCD163 cut-off point was 2 359.08 µg/L, the diagnostic sensitivity was 83.3%, and specificity was 83.9%.When sCD25 cut-off point was 14 901.024 ng/L, the diagnosis sensitivity was 76.2%, and specificity was 98.2%.

CONCLUSIONSerum sCD163 and sCD25 levels may be used for diagnosis of HLH.Dynamically monitoring of serum sCD163 and sCD25 level can help to determine deterioration of HLH and guide treatment.

Antigens, CD ; blood ; Antigens, Differentiation, Myelomonocytic ; blood ; Case-Control Studies ; Child ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-2 Receptor alpha Subunit ; blood ; Lymphohistiocytosis, Hemophagocytic ; blood ; diagnosis ; therapy ; ROC Curve ; Receptors, Cell Surface ; blood ; Sensitivity and Specificity

Objective:To investigate the clinical characteristics, diagnosis and treatment and prognosis of children with leukemia secondary to malignant solid tumor.Methods:From January 2012 to January 2022, a total of 2 275 children under 15 years of age with malignant solid tumor were admitted to the First Affiliated Hospital of Zhengzhou University.Six children diagnosed with secondary leukemia after follow-up to August 1, 2022 were selected as the study objects.Their clinical data were retrospectively analyzed and the literature was reviewed.Results:(1)A total of 2 275 children with malignant solid tumors included 1 369 males and 906 females.There were 6 children with secondary leukemia, with an incidence rate of 0.26%, including 4 males and 2 females.The age of onset of solid tumor was 5.5(2.8, 9.7)years, and the age of secondary leukemia was(9.1±3.9)years, and the interval between them was(26.2±17.3)months.(2)Malignant solid tumor types: according to the time of secondary leukemia, there were hip malignant rhabdomyoma in 1 case, intracranial medulloblastoma in 2 cases, intracranial and pelvic malignant germinoma in 1 case respectively, and pancreatic blastoma in 1 case.Intracranial lesion biopsy was performed in 1 case, and tumor resection was performed in the other 5 cases.Three patients with intracranial tumors underwent local tumor bed, whole brain and spinal radiotherapy.All the 6 children received chemotherapy, and the main chemotherapy drugs were doxorubicin, vincristine, cyclophosphamide, platinum, ifosfamide, etoposide, bleomycin, temozolomide, etc.Complete remission was achieved in 3 cases, partial remission in 1 case, stable disease in 1 case, and disease progression in 1 case.(3)The secondary leukemia types were as follows: acute myeloid leukemia(AML)M5 in 3 cases, M1 in 1 case, M2 in 1 case, and acute B-lymphoblastic leukemia(B-ALL)in 1 case.All six cases refused hematopoietic stem cell transplantation(HSCT).One case with B-ALL gave up after receiving hydroxyurea and dexamethasone.Five cases with AML received chemotherapy according to the AML-2006 Protocol of Hematology Group of Pediatrics Society of Chinese Medical Association.The outcome of the disease was as follows: 2 cases died early, 4 cases achieved complete remission after 1 ~ 2 courses of chemotherapy, among which 2 cases did not continue treatment after 3 courses of chemotherapy due to pulmonary infection, deep mycosis, osteomyelitis, etc, and then recurred and died.By the end of follow-up, 2 cases survived and continued treatment, of which 1 case relapsed.After the diagnosis of secondary leukemia, the 1-year overall survival rate of the 6 cases was(33±26)%.Conclusion:Leukemia secondary to malignant solid tumors in children is rare and mostly occurs in older children.The pathogenesis is related to genotoxic injury caused by exposure to chemotherapy or radiotherapy, and the prognosis is unfavourable.HSCT after chemotherapy combined with immunotherapy is the best treatment strategy.

OBJECTIVE To investigate the efficacy and adverse reaction of CD 19-targeted chimeric antigen receptor T cells （CAR-T）in the treatment of relapsed/refractory diffuse large B -cell lymphoma （R/R DLBCL ），so as to provide an evidence -based basis for more reasonable and efficient application of CAR -T. METHODS Retrieved from PubMed ，Embase，Cochrane， ClinicalTrials.gov，CNKI，Wanfang，VIP database ，the literature about CD 19 targeted CAR -T in the treatment of R/R DLBCL that were published from the inception to April 2022 were screened . Taking objective remission rate （ORR），complete remission rate （CRR）and incidence of adverse reactions as outcome indicators ，subgroup analysis was performed according to the costimulatory factor of CAR -T and the different types of research . R 4.1.2 software was used for meta -analysis，sensitivity analysis and publication bias analysis . RESULTS A total of 11 pieces of literature were screened ，involving 1 466 patients. The ORR of CD -19 targeted CAR -T cells in the treatment of R/R DLBCL was 72.1%（95% CI：62.3%-81.9%），the CRR was 50.8%（95% CI：41.1%- 60.5%），the incidence of cytokine release syndrome （CRS）was 77.5%（95% CI：65.6%-89.4%），the incidence of neurotoxicity was 41.4%（95% CI：26.8%-56.1%）. Results of subgroup analysis showed that the incidence of ORR ，CRR，CRS and neurotoxicity in costimulatory factor CD 28 subgroup were higher than those in 4-1BB subgroup . The incidence of ORR ，CRR，CRS and neurotoxicity in the observational experimental subgroup were higher than those in the intervention experimental subgroup . CONCLUSIONS CD19 targeted CAR -T has high ORR and CRR for R/R DLBCL ，as well as higher incidence of adverse reactions. Co-stimulatory factor CD 28 has higher ORR ，CRR， CRS incidence and neurotoxicity incidence than 4-1BB.

OBJECTIVE To systematically evaluate the efficacy and safety of eltrombopag combined with immunosuppressive therapy （IST） for severe aplastic anemia （SAA）， and to provide evidence-based basis for clinical treatment of SAA. METHODS Retrieved from PubMed， Embase， Cochrane Library， ClinicalTrials.gov， VIP， CNKI and Wanfang data， randomized controlled trials （RCTs） and cohort studies about eltrombopag combined with IST （trial group） versus IST alone （control group） were collected from the inception to May 2023. After data extraction and quality evaluation （Cochrane manual 5.1.0） of included studies， meta-analysis， subgroup analysis， sensitivity analysis and publication bias analysis were performed by using RevMan 5.4 software. RESULTS A total of 12 studies were screened， including 1 344 patients. Compared with control group， objective remission rate （ORR） （RR＝1.34， 95%CI was 1.06-1.69， P＝0.01） and complete response rate （CRR） （RR＝1.88， 95%CI was 1.31-2.71， P＝ 0.000 6） at 3 months， ORR （RR＝1.33，95%CI was 1.23-1.43， P＜0.000 01） and CRR （RR＝1.88，95%CI was 1.57-2.25，P＜0.000 01） at 6 months were significantly increased in trial group. There was no statistically significant difference between the two groups in ORR （RR＝0.99， 95%CI was 0.82-1.18， P＝0.88） and CRR （RR＝1.02， 95%CI was 0.78-1.34， P＝0.87） at 12 months， two-year overall survival （OS） rate （HR＝0.61， 95%CI was 0.31-1.22， P＝0.17）， two-year event-free survival （EFS） rate （HR＝0.81， 95%CI was 0.61-1.07， P＝0.14）， clone evolution rate（RR＝1.01， 95%CI was 0.51-2.00， P＝ 0.98） or the incidence of adverse drug reactions such as liver/renal insufficiency， rash （P＞0.05）. Results of subgroup analysis showed that ORR and CRR of trial group at 6 months were higher than those of the control group in RCT and the cohort study subgroups （P＜0.05）. There was no statistically significant difference in the two-year OS rate， two-year EFS rate or clone evolution rate between trial group and control group in the two subgroups （P＞0.05）. The results of sensitivity analysis and publication bias analysis showed that the results of this study were robust and the possibility of publication bias was small. CONCLUSIONS The addition of eltrombopag in the IST regimen of SAA can improve the early hematological remission rate of patients， has no significant impact on short-term survival， and will not increase the occurrence of adverse drug reactions and clonal evolution.