ABSTRACT
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.
ABSTRACT
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.