Venous thromboembolism in children with acute lymphoblastic leukemia in China:a report from the Chinese Children’s Cancer Group-ALL-2015

Venous thromboembolism(VTE)is a complication in children with acute lymphoblastic leukemia(ALL).The Chinese Children’s Cancer Group-ALL-2015 protocol was carried out in China,and epidemiology,clinical characteristics,and risk factors associated with VTE were analyzed.We collected data on VTE in a multiinstitutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019.First,VTE occurred in 159(2.08%)patients,including 90(56.6%)during induction therapy and 108(67.92%)in the upper extremities.T-ALL had a 1.74-fold increased risk of VTE(95%CI 1.08–2.8,P=0.022).Septicemia,as an adverse event of ALL treatment,can significantly promote the occurrence of VTE(P<0.001).Catheter-related thrombosis(CRT)accounted for 75.47%(n=120);and,symptomatic VTE,58.49%(n=93),which was more common in patients aged 12–18 years(P=0.023),non-CRT patients(P<0.001),or patients with cerebral thrombosis(P<0.001).Of the patients with VTE treated with anticoagulation therapy(n=147),4.08%(n=6)had bleeding.The VTE recurrence rate was 5.03%(n=8).Patients with VTE treated by non-ultrasoundguided venous cannulation(P=0.02),with residual thrombus(P=0.006),or with short anticoagulation period(P=0.026)had high recurrence rates.Thus,preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.

Homoharringtonine is a safe and effective substitute for anthracyclines in children younger than 2 years old with acute myeloid leukemia

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 HHTcontaining 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.

Early T-cell precursor leukemia:a subtype of high risk childhood acute lymphoblastic leukemia

Acute lymphoblastic leukemia includes T-cell acute lymphoblastic leukemia(T-ALL)and B-cell acute lymphoblastic leukemia(B-ALL).In children,T-ALL usually has a worse prognosis than B-ALL,although childhood T-ALL prognoses have improved remarkably.The varying outcomes among T-ALL cases suggest that an unrecognized biological heterogeneity may contribute to chemo-resistance.Deep exploration of T-lymphocyte development in recent years has found a subgroup of patients with a phenotype that resembles early T-cell precursor,which confers a much poorer prognosis than any other form of T-ALL.This novel subtype of T-ALL was called early T-cell precursor acute lymphoblastic leukemia(ETP-ALL).Flow cytometry data from T-ALL patients enrolled in Shanghai Children’s Medical Center between July 2002 and October 2010 were assessed according to Dr.Campana’s protocol.Among total 89 T-ALL cases,74 cases had enough immunophenotype data available to differentiate between ETP(CD1a^(-),CD8^(-),CD5^(dim),at least one marker of stem cell or myeloid lineage)and non-ETP.From these 74 subjects,12 ETP-ALL cases(16.2%)were identified.The event-free survival(EFS)rate at 66.8 months was 11.1%±10.1% for ETP-ALL and 57.6%±5.6% for non-ETP-ALL(P=0.003).The overall survival rates were 13.3%±11.0% for ETP-ALL and 64.7%±6.3% for non-ETP-ALL(P=0.002).Our findings demonstrate that early T-cell precursor leukemia is a very high-risk subtype of acute lymphoblastic leukemia with poor prognosis.