Second- and third-generation tyrosine kinase inhibitors for Philadelphia-positive adult acute lymphoblastic leukemia relapsing post allogeneic stem cell transplantation-a registry study on behalf of the EBMT Acute Leukemia Working Party.


Journal

Bone marrow transplantation
ISSN: 1476-5365
Titre abrégé: Bone Marrow Transplant
Pays: England
ID NLM: 8702459

Informations de publication

Date de publication:
05 2021
Historique:
received: 17 07 2020
accepted: 23 11 2020
revised: 09 11 2020
pubmed: 10 12 2020
medline: 10 7 2021
entrez: 9 12 2020
Statut: ppublish

Résumé

Second- and third-generation tyrosine kinase inhibitors (TKI) play an important role in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, data on feasibility and efficacy of using these drugs for persisting or relapsed Ph + ALL after allogeneic stem cell transplantation (alloSCT) are scarce. Based on the EBMT Acute Leukemia Working Party registry, we evaluated the use of second-/third-generation TKI in 140 patients with Ph + ALL, suffering from measurable residual disease (MRD, n = 6), molecular relapse (MRel, n = 23), or hematological relapse (HRel, n = 111) following alloSCT. Treatment included dasatinib in 104, nilotinib in 18, or ponatinib in 18 patients. Forty-nine patients received TKI monotherapy, while 91 received additional treatment. Toxicity of second-/third-generation TKI post alloSCT was comparable to pretransplant use and could be managed with dose reduction or temporary discontinuation. Response rates were 71% (overall) and 61% (following TKI monotherapy). For the entire cohort, 2- and 5-year overall survival (OS) was 49% and 33%, respectively. OS was comparable among patients treated for persisting MRD/MRel and HRel. Among patients treated with TKI monotherapy, 2- and 5-year OS was 38% and 33%, respectively. The data underscore that second-/third-generation TKI are important compounds for the management of active Ph + ALL post alloSCT.

Identifiants

pubmed: 33293597
doi: 10.1038/s41409-020-01173-x
pii: 10.1038/s41409-020-01173-x
doi:

Substances chimiques

Protein Kinase Inhibitors 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1190-1199

Références

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Auteurs

Klaus Hirschbühl (K)

Department Hematology and Oncology, Medical Faculty, University of Augsburg, Augsburg, Germany.

Myriam Labopin (M)

Service d'Hématologie et de Thérapie cellulaire, Hôpital Saint Antoine, ALWP Office (EBMT), Paris, France.

Mohamed Houhou (M)

Service d'Hématologie et de Thérapie cellulaire, Hôpital Saint Antoine, ALWP Office (EBMT), Paris, France.

Ludovic Gabellier (L)

Département d'Hématologie Clinique, CHU Lapeyronie, Montpellier, France.

Hélène Labussière-Wallet (H)

Centre Hospitalier Lyon Sud, Service Hematologie, Lyon, France.

Bruno Lioure (B)

Nouvel Hopital Civil, Strasbourg, France.

Dietrich Beelen (D)

Department of Bone Marrow Transplantation, University Hospital Essen, Essen, Germany.

Jan Cornelissen (J)

Department of Hematology, Erasmus MC Cancer Institute University Medical Center Rotterdam, Rotterdam, The Netherlands.

Gerald Wulf (G)

Abteilung Hämatologie und Onkologie, Universitätsklinikum Göttingen, Göttingen, Germany.

Pavel Jindra (P)

Department of Hematology/Oncology, Charles University Hospital, Pilsen, Czech Republic.

Hervé Tilly (H)

Department of Hematology, Centre Henri Becquerel, Rouen, France.

Jakob Passweg (J)

Department of Hematology, University Hospital of Basel, Basel, Switzerland.

Riita Niittyvuopio (R)

HUCH Comprehensive Cancer Center, Stem Cell Transplantation Unit, Helsinki, Finland.

Gesine Bug (G)

Universitätsklinikum Frankfurt, Medizinische Klinik II, Frankfurt, Germany.

Christoph Schmid (C)

Department Hematology and Oncology, Medical Faculty, University of Augsburg, Augsburg, Germany. christoph.schmid@uk-augsburg.de.

Arnon Nagler (A)

Department of Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer and Tel-Aviv University, Tel Aviv, Israel.

Sebastian Giebel (S)

Department of Bone Marrow Transplantation and Oncology/Hematology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.

Mohamad Mohty (M)

Service d'Hématologie et de Thérapie cellulaire, Hôpital Saint Antoine, ALWP Office (EBMT), Paris, France.

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