Homoharringtonine is a safe and effective substitute for anthracyclines in children younger than 2 years old with acute myeloid leukemia
- 20 Downloads
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.
Keywordshomoharringtonine acute myeloid leukemia pediatrics
This work was partially supported by the National Natural Science Foundation of China (No. 81270623), the Science and Technology Commission of Shanghai Municipality (No. 14411950600), and the Public Health 3-Year Project of Shanghai Children’s Medical Center (No. GWIV-25).
- 6.Jin J, Jiang DZ, Mai WY, Meng HT, Qian WB, Tong HY, Huang J, Mao LP, Tong Y, Wang L, Chen ZM, Xu WL. Homoharringtonine in combination with cytarabine and aclarubicin resulted in high complete remission rate after the first induction therapy in patients with de novo acute myeloid leukemia. Leukemia 2006; 20(8): 1361–1367CrossRefGoogle Scholar
- 9.Feldman E, Arlin Z, Ahmed T, Mittelman A, Puccio C, Chun H, Cook P, Baskind P. Homoharringtonine is safe and effective for patients with acute myelogenous leukemia. Leukemia 1992; 6(11): 1185–1188Google Scholar
- 11.Cheson BD, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Löwenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD; International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 2003; 21(24): 4642–4649CrossRefGoogle Scholar
- 16.Gu LF, Zhang WG, Wang FX, Cao XM, Chen YX, He AL, Liu J, Ma XR. Low dose of homoharringtonine and cytarabine combined with granulocyte colony-stimulating factor priming on the outcome of relapsed or refractory acute myeloid leukemia. J Cancer Res Clin Oncol 2011; 137(6): 997–1003CrossRefGoogle Scholar
- 18.Tan CT, Luks E, Bacha DM, Steinherz P, Steinherz L, Mondora A. Phase I trial of homoharringtonine in children with refractory leukemia. Cancer Treat Rep 1987; 71(12): 1245–1248Google Scholar
- 22.de Rooij JD, Branstetter C, Ma J, Li Y, Walsh MP, Cheng J, Obulkasim A, Dang J, Easton J, Verboon LJ, Mulder HL, Zimmermann M, Koss C, Gupta P, Edmonson M, Rusch M, Lim JY, Reinhardt K, Pigazzi M, Song G, Yeoh AE, Shih LY, Liang DC, Halene S, Krause DS, Zhang J, Downing JR, Locatelli F, Reinhardt D, van den Heuvel-Eibrink MM, Zwaan CM, Fornerod M, Gruber TA. Pediatric non-Down syndrome acute megakaryoblastic leukemia is characterized by distinct genomic subsets with varying outcomes. Nat Genet 2017; 49(3): 451–456CrossRefGoogle Scholar
- 23.Hara Y, Shiba N, Ohki K, Tabuchi K, Yamato G, Park MJ, Tomizawa D, Kinoshita A, Shimada A, Arakawa H, Saito AM, Kiyokawa N, Tawa A, Horibe K, Taga T, Adachi S, Taki T, Hayashi Y. Prognostic impact of specific molecular profiles in pediatric acute megakaryoblastic leukemia in non-Down syndrome. Genes Chromosomes Cancer 2017; 56(5): 394–404CrossRefGoogle Scholar
- 25.Rogers AE, Eisenman KM, Dolan SA, Belderson KM, Zauche JR, Tong S, Gralla J, Hilden JM, Wang M, Maloney KW, Dominguez SR. Risk factors for bacteremia and central line-associated blood stream infections in children with acute myelogenous leukemia: a single-institution report. Pediatr Blood Cancer 2017; 64(3): e26254CrossRefGoogle Scholar
- 28.Leung W, Hudson MM, Strickland DK, Phipps S, Srivastava DK, Ribeiro RC, Rubnitz JE, Sandlund JT, Kun LE, Bowman LC, Razzouk BI, Mathew P, Shearer P, Evans WE, Pui CH. Late effects of treatment in survivors of childhood acute myeloid leukemia. J Clin Oncol 2000; 18(18): 3273–3279CrossRefGoogle Scholar
- 29.Temming P, Qureshi A, Hardt J, Leiper AD, Levitt G, Ancliff PJ, Webb DKH. Prevalence and predictors of anthracycline cardiotoxicity in children treated for acute myeloid leukaemia: retrospective cohort study in a single centre in the United Kingdom. Pediatr Blood Cancer 2011; 56(4): 625–630CrossRefGoogle Scholar
- 30.Jarfelt M, Andersen NH, Glosli H, Jahnukainen K, Jónmundsson GK, Malmros J, Nysom K, Hasle H; Nordic Society of Pediatric Hematology and Oncology (NOPHO). Cardiac function in survivors of childhood acute myeloid leukemia treated with chemotherapy only: a NOPHO-AML study. Eur J Haematol 2016; 57(7): 55–62CrossRefGoogle Scholar