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.

Seasonal differential expression of KiSS-1/GPR54 in the striped hamsters(Cricetulus barabensis)among different tissues

Kisspeptins and G protein coupled receptor(GPR54)play significant roles in regulating reproductive activity among seasonally reproductive animals;however,the mechanisms of KiSS-1 and GPR54 gene affecting the seasonal reproduction in striped hamster are still unknown.In this study,real-time quantitative polymerase chain reaction was employed to examine the expression profiles of KiSS-1 and GPR54 in the hypothalamus,ovaries,testes,uterus and epididymis of striped hamsters across 4 different seasons.Our results showed that,across different seasons,the KiSS-1 expression mode of male striped hamsters and the GPR54 expression mode of female striped hamsters were consistent with the seasonal photoperiod in the hypothalamus.Meanwhile,across different seasons,the expression profile of KiSS-1 in the testes and the GPR54 expression profile of male striped hamsters in the hypothalamus were consistent with the intensity of their seasonal reproductive activity.Among different tissues,the expression trend for GPR54 is consistent across 4 seasons,while that for KiSS-1 is tissue-dependent.The expression trend for GPR54 across 4 seasons is the same regardless of gender,while that for KiSS-1 is dramatically different and sex-dependent across different seasons.These results suggest that the expressions of KiSS-1 and GPR54 in the striped hamsters were regulated by complicated mechanisms,and the regulatory mechanisms in the striped hamsters are seasonal-dependent and sex-dependent.This research will provide a theoretical basis for studying how KiSS-1 and GPR54 affect seasonal reproduction and the mechanisms behind their influence.