High-dose etoposide and cyclophosphamide in adults and children with primary refractory and multiply relapsed acute leukaemias: The Royal Marsden experience.


Journal

Leukemia research
ISSN: 1873-5835
Titre abrégé: Leuk Res
Pays: England
ID NLM: 7706787

Informations de publication

Date de publication:
10 2019
Historique:
received: 12 06 2019
revised: 11 08 2019
accepted: 12 08 2019
pubmed: 8 9 2019
medline: 27 5 2020
entrez: 8 9 2019
Statut: ppublish

Résumé

For patients with primary refractory and relapsed acute leukaemias allogeneic stem cell transplantation is the only hope for cure, but morphological remission is not always achieved after standard salvage regimens. Here we review the experience with high-dose etoposide and cyclophosphamide (HD-Et/Cy) in relapsed/refractory acute leukaemias at the Royal Marsden Hospital. Twenty-three patients (15 adults, 8 children) with refractory/relapsed acute myeloblastic (n = 18; 78%), lymphoblastic (n = 4; 17%) or biphenotypic (n = 1; 4%) leukaemia who had failed to respond to at least one previous line of chemotherapy received HD-Et/Cy at our institution between 2006 and 2015. Overall response rate was 21.7% (95%CI 4.0-40.0). Median overall survival was 14.8 months (95%CI 9.1-49.1). Eight (35%) patients (7 AML, 1 biphenotypic leukaemia) proceeded to allogeneic transplant after one cycle of HD-Et/Cy: four of them (50%; 3 adults, 1 child) in complete remission and another four children (50%) with aplastic bone marrow with scattered blasts. Among the transplant recipients, three with AML (38%), ie. one adult (responder) and two children with aplastic bone marrow with scattered blasts, became long-term survivors 9.8, 4.4 and 2.5 years post-HD-Et/Cy, respectively. Toxicity profile was comparable to similar regimens with no treatment-related deaths. The most common grade 3-4 toxicity was febrile neutropenia (96%). HD-Et/Cy can salvage patients with refractory/relapsed AML who remain candidates for allogeneic stem cell transplantation after failure of standard salvage regimens and do not have access to clinical trials.

Identifiants

pubmed: 31493701
pii: S0145-2126(19)30162-6
doi: 10.1016/j.leukres.2019.106217
pii:
doi:

Substances chimiques

Biomarkers 0
Etoposide 6PLQ3CP4P3
Cyclophosphamide 8N3DW7272P

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

106217

Informations de copyright

Copyright © 2019 Elsevier Ltd. All rights reserved.

Auteurs

Fernando Carceller (F)

Paediatric Haemato-Oncology Department, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London, SM2 5PT, United Kingdom; Division of Clinical Studies, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, United Kingdom. Electronic address: fernando.carceller@rmh.nhs.uk.

Steffen G Hirsch (SG)

Paediatric Haemato-Oncology Department, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London, SM2 5PT, United Kingdom; Division of Clinical Studies, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, United Kingdom; Hopp Children's Cancer Center (KiTZ) Heidelberg, University Medical Center for Children and Adolescents Angelika Lautenschläger Children's Hospital, Im Neuenheimer Feld 430 D, 69120, Heidelberg, Germany; Institute of Human Genetics, University Hospital Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany. Electronic address: Steffen.Hirsch@med.uni-heidelberg.de.

Komel Khabra (K)

Research Data Management and Statistics Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London, SM2 5PT, United Kingdom; Statistics Department, MRC Clinical Trials Unit, University College London, 90 High Holborn, London, WC1V 6LJ, United Kingdom. Electronic address: k.khabra@ucl.ac.uk.

Toni Petterson (T)

Paediatric Haemato-Oncology Department, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London, SM2 5PT, United Kingdom; Paediatric Haematopoietic Transplant Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London SM2 5PT, United Kingdom; Children's Haematology, Blood and Marrow Transplantation Department, St Mary's Hospital, Imperial College Healthcare NHS Trust, The Bays, S Wharf Rd, Paddington, London W2 1NY, United Kingdom. Electronic address: tonipetterson@nhs.net.

Rubina Malik (R)

Paediatric Haemato-Oncology Department, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London, SM2 5PT, United Kingdom. Electronic address: rubina.malik2@nhs.net.

Pilar Guerra-García (P)

Paediatric Haemato-Oncology Department, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London, SM2 5PT, United Kingdom; Division of Clinical Studies, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, United Kingdom; Paediatric Haemato-Oncology Department, Hospital Universitario 12 de Octubre, Av. de Córdoba, s/n, 28041, Madrid, Spain. Electronic address: pilar.guerra@salud.madrid.org.

Lucas Moreno (L)

Paediatric Haemato-Oncology Department, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London, SM2 5PT, United Kingdom; Division of Clinical Studies, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, United Kingdom; Haemato-Oncology Department, Hospital Vall d'Hebron, Passeig de la Vall d'Hebron, 119, 129, 08035, Barcelona, Spain. Electronic address: lucas.moreno@vhebron.net.

Lynley V Marshall (LV)

Paediatric Haemato-Oncology Department, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London, SM2 5PT, United Kingdom; Division of Clinical Studies, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, United Kingdom. Electronic address: LynleyVanessa.Marshall@icr.ac.uk.

Mary Taj (M)

Paediatric Haemato-Oncology Department, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London, SM2 5PT, United Kingdom; Division of Clinical Studies, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, United Kingdom. Electronic address: Mary.Taj@rmh.nhs.uk.

Ayad Atra (A)

Paediatric Haemato-Oncology Department, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London, SM2 5PT, United Kingdom; Paediatric Haematology-Oncology Unit, The Harley Street Clinic, 35 Weymouth Street, London W1G 8BJ, United Kingdom. Electronic address: ayad.atra@hcaconsultant.co.uk.

Mark Ethell (M)

Paediatric Haematopoietic Transplant Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London SM2 5PT, United Kingdom; Department of Haematology, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London SM2 5PT, United Kingdom. Electronic address: Mark.Ethell@rmh.nhs.uk.

Mike Potter (M)

Paediatric Haematopoietic Transplant Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London SM2 5PT, United Kingdom; Department of Haematology, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London SM2 5PT, United Kingdom. Electronic address: Mike.Potter@rmh.nhs.uk.

Donna Lancaster (D)

Paediatric Haemato-Oncology Department, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London, SM2 5PT, United Kingdom; Division of Clinical Studies, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, United Kingdom. Electronic address: donna.lancaster@nhs.net.

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