ABSTRACT
Chimeric antigen receptor T cell (CAR-T) therapy is becoming the most promising treatment method in children and adolescent with refractory and relapse malignancies.While CAR-T cells exhibit powerful antitumour activity, this therapy has been associated with unique and significant toxicities including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) by triggering immune effector cells, even develop rapid and life-threatening cardiovascular, respiratory and/or neurological dysfunction.The assessment and grading of these adverse events vary widely in different clinical trials and institutions.For integrating the definitions and grading systems for toxicities from immune effector responses, in 2018, the American Bone Marrow Transplantation Society proposed consensus definitions and grading which is objective and easy to apply for CRS and ICANS.It helps clinicians and nurses make early critical care assessment and guide critical care interventions, thereby improving the efficacy and safety of CAR-T therapy.
ABSTRACT
Homoharringtonine (HHT), a plant alkaloid from Cephalotaxus harringtonia, exhibits a unique anticancer mechanism and has been widely used in China to treat patients with acute myeloid leukemia (AML) since the 1970s. Trial SCMC-AML-2009 presented herein was a randomized clinical study designed based on our previous findings that pediatric AML patients younger than two years old may benefit from HHT-containing chemotherapy regimens. Patients randomized to arm A were treated with a standard chemotherapy regimen comprising mainly of anthracyclines and cytarabine (Ara-C), whereas patients in arm B were treated with HHT-containing regimens in which anthracyclines in all but the initial induction therapy were replaced by HHT. From February 2009 to November 2015, 59 patients less than 2 years old with de novo AML (other than acute promyelocytic leukemia) were recruited. A total of 42 patients achieved a morphologic complete remission (CR) after the first course, with similar rates in both arms (70.6% vs.72.0%). At the end of the follow-up period, 40 patients remained in CR and 5 patients underwent hematopoietic stem cell transplantation in CR, which could not be considered as events but censors. The 5-year event-free survival (EFS) was 60.2%±9.6% for arm A and 88.0%±6.5% for arm B (P= 0.024). Patients in arm B experienced shorter durations of leukopenia, neutropenia, and thrombocytopenia and had a lower risk of infection during consolidation chemotherapy with high-dosage Ara-C. Consequently, the homoharringtonine-based regimen achieved excellent EFS and alleviated hematologic toxicity for children aged younger than 2 years with de novo AML compared with the anthracycline-based regimen.
ABSTRACT
Objectives To evaluate the clinical features, treatment scheme and long-term outcomes of stage 1、2 childhood neuroblastoma (NB). Methods The retrospective study included 49 newly diagnosed NB stage 1、2 patients from June 1998 to December 2010. Clinical data and long-term outcomes were analyzed. Results Twenty-four patients with stage 1 NB and twenty patients with stage 2 NB were found among all 237 patients with NB enrolled in this study. The median age at diagnosis was 25 months( 2 week to 9 year old),29 males and 20 females. Thirty-one patients (63.6%) without symptoms were discovered with tumor by physical or imaging examination. Thorax and abdomen were the most common sites of primary tumor (21 and 22 cases, accounting for 42.9% and 44.9% of all patients, respectively). Forty (81.6%) NB patients had favorable pathology classification. One patient was of MYCN amplification status. Urine vanilla mandelic acid was normal in 32 (91.4%) patients, and serum lactate dehydrogenase was less than five times of the normal value in all patients. Ten NB patients were treated ac-cording to the low-risk protocol who received surgery alone.Thirty-nine patients were treated according to intermediate-risk protocol who received both surgery and chemotherapy. All the patients achieved very good partial remission (100%).The medi-an follow-up period was 60 months(22 months to148months). Nine patients were lost after a follow up of 3 months in medi-an. The 2-、3-、5-year event free survival and overall survial of all 49 patients was 100%. Conclusions The prognosis for neu-roblastoma of stage 1、2 in this study was with 100%survival, which provides opportunity for further reduction of dosage and/or duration of episodes in chemotherapy.
ABSTRACT
Objectives To evaluate the long-term outcomes of childhood low-or intermediate-risk neuroblastoma (NB) and their relevant prognostic factors. Methods A total of 70 new cases of low-or intermediate-risk NB diagnosed and treated by NB-99 protocol between 1999 and 2008 were analyzed retrospectively. Results Of these 70 NB patients, fourteen patients were in low-risk group and 56 were in intermediate-risk group. Sixty-seven patients reached complete remission (CR) or very good partial remission and 3 (5%) achieved partial remission. Ten patients relapsed. One patient occured second malignant neo-plasm. No patients died of chemotherapy-related adverse events or infections. The 5 year overall survival rate was 85.9%, event-free survival rate was 81.0%. Bone marrow infiltration, age at diagnosis, stage, lactate dehydrogenase level had a significant effect on prognosis. Conclusion Develop cytogenetic and molecular biology tests and pretreatment risk stratification are im-portant for further improvement of treatment protocol.
ABSTRACT
Objectives To investigate the correlation between single nucleotide polymorphisms (SNP) in interleu-kin-15 (IL-15) and treatment response in childhood acute lymphoblastic leukemia (ALL). Methods Genomic DNA samples extracted from remission bone marrow cells of ALL patients were genotyped by MassArray. Five SNPs (rs10519612, rs10519613, rs17007695, rs17015014 and rs35964658) in IL-15 and their association to minimal residual disease (MRD) status in the end of induction therapy were studied. Results SNP rs17007695 was associated with the early response in children with ALL(P=0.049) and the incidence of positive MRD after induction therapy in CC genotype carriers was 1.8 times more than that in TT genotype carriers. Haplotype analysis of these five SNPs showed that the frequency of haplotype CACGG in MRD positive group was 2.1 times higher than that in MRD negative group (P=0.035). Conclusions IL-15 gene polymorphism was associated with the early treatment response in Han Chinese children with acute lymphoblastic leuke-mia.