Clofarabine, cytarabine, and mitoxantrone in refractory/relapsed acute myeloid leukemia : High response rates and effective bridge to allogeneic hematopoietic stem cell transplantation

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

View graph of relations

Author(s)

  • Harinder Gill
  • Rita Yim
  • Herbert H. Pang
  • Paul Lee
  • Thomas S. Y. Chan
  • Yu-Yan Hwang
  • Garret M. K. Leung
  • Ho-Wan Ip
  • Rock Y. Y. Leung
  • Sze-Fai Yip
  • Bonnie Kho
  • Harold K. K. Lee
  • Vivien Mak
  • Chi-Chung Chan
  • June S. M. Lau
  • Chi-Kuen Lau
  • Shek-Yin Lin
  • Raymond S. M. Wong
  • Wa Li
  • Edmond S. K. Ma
  • Gianni Panagiotou
  • Joycelyn P. Y. Sim
  • Albert K. W. Lie
  • Yok-Lam Kwong

Detail(s)

Original languageEnglish
Pages (from-to)3371-3382
Journal / PublicationCancer Medicine
Volume9
Issue number10
Online published18 Mar 2020
Publication statusPublished - May 2020

Abstract

Clofarabine is active in refractory/relapsed acute myeloid leukemia (AML). In this phase 2 study, we treated 18- to 65-year-old AML patients refractory to first-line 3 + 7 daunorubicin/cytarabine induction or relapsing after 3 + 7 induction and high-dose cytarabine consolidation, with clofarabine (30 mg/m2/d, Days 1-5), cytarabine (750 mg/m2/d, Days 1-5), and mitoxantrone (12 mg/m2/d, Days 3-5) (CLAM). Patients achieving remission received up to two consolidation cycles of 50% CLAM, with eligible cases bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT). The mutational profile of a 69-gene panel was evaluated. Twenty-six men and 26 women at a median age of 46 (22-65) years were treated. The overall response rate after the first cycle of CLAM was 90.4% (complete remission, CR: 69.2%; CR with incomplete hematologic recovery, CRi: 21.2%). Twenty-two CR/CRi patients underwent allo-HSCT. The 2-year overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) were 65.8%, 45.7%, and 40.2%, respectively. Multivariate analyses showed that superior OS was associated with CR after CLAM (P =.005) and allo-HSCT (P =.005), and superior RFS and EFS were associated with allo-HSCT (P <.001). Remarkably, CR after CLAM and allo-HSCT resulted in 2-year OS of 84.3% and 90%, respectively. Karyotypic aberrations and genetic mutations did not influence responses or survivals. Grade 3/4 neutropenia/thrombocytopenia and grade 3 febrile neutropenia occurred in all cases. Other nonhematologic toxicities were mild and uncommon. There was no treatment-related mortality and the performance of allo-HSCT was not compromised. Clofarabine, cytarabine, and mitoxantrone was highly effective and safe in refractory/relapsed AML. This study was registered at ClinicalTrials.gov (NCT02686593).

Research Area(s)

  • acute myeloid leukemia, adult, clofarabine, cytarabine, mitoxantrone, refractory, relapsed

Bibliographic Note

© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Citation Format(s)

Clofarabine, cytarabine, and mitoxantrone in refractory/relapsed acute myeloid leukemia : High response rates and effective bridge to allogeneic hematopoietic stem cell transplantation. / Gill, Harinder; Yim, Rita; Pang, Herbert H.; Lee, Paul; Chan, Thomas S. Y.; Hwang, Yu-Yan; Leung, Garret M. K.; Ip, Ho-Wan; Leung, Rock Y. Y.; Yip, Sze-Fai; Kho, Bonnie; Lee, Harold K. K.; Mak, Vivien; Chan, Chi-Chung; Lau, June S. M.; Lau, Chi-Kuen; Lin, Shek-Yin; Wong, Raymond S. M.; Li, Wa; Ma, Edmond S. K.; Li, Jun; Panagiotou, Gianni; Sim, Joycelyn P. Y.; Lie, Albert K. W.; Kwong, Yok-Lam.

In: Cancer Medicine, Vol. 9, No. 10, 05.2020, p. 3371-3382.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal