Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Apr 26;6(8):2688-2694.
doi: 10.1182/bloodadvances.2021005753.

Clofarabine with topotecan, vinorelbine, and thiotepa reinduction regimen for children and young adults with relapsed AML

Kavitha Ramaswamy  1 , Peter G Steinherz  1 , Anurag K Agrawal  2 , Christopher J Forlenza  1 , Audrey Mauguen  3 , Mikhail Roshal  4 , Tanya Trippett  1 , Nancy A Kernan  1 , Maria Luisa Sulis  1 , Neerav Shukla  1
Affiliations

Clofarabine with topotecan, vinorelbine, and thiotepa reinduction regimen for children and young adults with relapsed AML

Kavitha Ramaswamy et al. Blood Adv. .

Abstract

Effective reinduction regimens are needed for children with relapsed and refractory acute myeloid leukemia (AML), as outcomes remain poor. Therapeutic options are limited in this heavily pretreated patient population, many of whom have reached lifetime recommended doses of anthracycline chemotherapy. The development of effective non-anthracycline-based salvage regimens is crucial to these patients who are at significant risk of life-threatening cardiotoxicity. We previously reported results of a phase 2 trial of a clofarabine-based regimen with topotecan, vinorelbine, and thiotepa (TVTC) in patients with relapsed acute leukemias. Here we report on an expanded bicenter cohort of 33 patients, <25 years of age, with relapsed/refractory AML treated with up to 2 cycles of the TVTC reinduction regimen from 2007 to 2018. The overall response rate, defined as complete remission or complete remission with partial recovery of platelet count, was 71.4% (95% confidence interval [CI], 41.9-91.6) for those patients in first relapse (n = 14) and 47.4% (95% CI, 24.4-71.1) for patients in second or greater relapse or with refractory disease. Responses were seen across multiple high-risk cytogenetic and molecular subtypes, with 84% of responders successfully bridged to allogeneic stem cell transplantation. The 5-year overall survival for patients in first relapse was 46.2% (95% CI, 19.1-73.3) and 50.0% (95% CI, 26.9-73.1) for patients who responded to TVTC. For pediatric and young adult patients with relapsed/refractory AML, TVTC reinduction compares favorably with currently used salvage regimens and warrants further exploration.

PubMed Disclaimer

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Outcomes of relapsed/refractory patients with AML treated with TVTC. (A) Five-year OS of patients in Group A vs Group B. (B) Five-year OS according to response to TVTC. (C) Five-year OS of responders who proceeded to allogeneic HSCT (n = 16).
See this image and copyright information in PMC

References

    1. Rubnitz JE, Inaba H, Dahl G, et al. Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: results of the AML02 multicentre trial. Lancet Oncol. 2010;11(6):543-552. - PMC - PubMed
    1. Gibson BE, Webb DK, Howman AJ, De Graaf SS, Harrison CJ, Wheatley K; United Kingdom Childhood Leukaemia Working Group and the Dutch Childhood Oncology Group . Results of a randomized trial in children with acute myeloid leukaemia: medical research council AML12 trial. Br J Haematol. 2011;155(3):366-376. - PubMed
    1. Gamis AS, Alonzo TA, Meshinchi S, et al. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014;32(27):3021-3032. - PMC - PubMed
    1. Creutzig U, Zimmermann M, Bourquin JP, et al. Randomized trial comparing liposomal daunorubicin with idarubicin as induction for pediatric acute myeloid leukemia: results from Study AML-BFM 2004. Blood. 2013;122(1):37-43. - PubMed
    1. Wells RJ, Adams MT, Alonzo TA, et al. ; Children’s Cancer Group Study 2951 . Mitoxantrone and cytarabine induction, high-dose cytarabine, and etoposide intensification for pediatric patients with relapsed or refractory acute myeloid leukemia: Children’s Cancer Group Study 2951. J Clin Oncol. 2003;21(15):2940-2947. - PubMed

Publication types