Combination chemotherapy plus dasatinib leads to comparable overall survival and relapse-free survival rates as allogeneic hematopoietic stem cell transplantation in Philadelphia positive acute lymphoblastic leukemia.


Journal

Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310

Informations de publication

Date de publication:
06 2019
Historique:
received: 15 11 2018
revised: 14 02 2019
accepted: 26 03 2019
pubmed: 25 4 2019
medline: 7 7 2020
entrez: 25 4 2019
Statut: ppublish

Résumé

The Philadelphia chromosome is associated with a poor prognosis in acute lymphoblastic leukemia (ALL). While hematopoietic stem cell transplantation (HSCT) has been regarded as a favorable treatment option in adult Philadelphia-positive (Ph+) ALL, its benefit is less clear in the era of newer generation tyrosine kinase inhibitors (TKIs) like dasatinib. This was a retrospective study that analyzed the outcomes of adult patients with Ph+ ALL treated with either combination chemotherapy plus dasatinib or combination chemotherapy plus dasatinib followed by allogeneic HSCT. A total of 70 patients were included; 30 (42.9%) underwent allogeneic HSCT while 40 (57.1%) received only chemotherapy plus dasatinib. In comparing overall survival (OS) rates, results between the 2 groups were similar with a 1-year OS of 93.3% versus 100% (P = 0.20), 2-year OS of 89.8% versus 86.2% (P = 0.72), and 3-year OS of 76% versus 71.3% (P = 0.56) in the transplant versus nontransplant groups, respectively. The 3-year relapse-free survival (RFS) rates were also similar at 70.5% in the transplant group and 80.1% in the nontransplant group (P = 0.94). Subgroup analyses were performed for patients with specific poor prognostic factors (higher white blood count, older age, positive minimal residual disease status), but results again showed no significant survival difference between transplant and nontransplant patients. While HSCT has historically led to a survival advantage in Ph+ ALL, the results of our study demonstrate that it may have a less beneficial role in the era of newer generation TKIs such as dasatinib.

Sections du résumé

BACKGROUND
The Philadelphia chromosome is associated with a poor prognosis in acute lymphoblastic leukemia (ALL). While hematopoietic stem cell transplantation (HSCT) has been regarded as a favorable treatment option in adult Philadelphia-positive (Ph+) ALL, its benefit is less clear in the era of newer generation tyrosine kinase inhibitors (TKIs) like dasatinib.
METHODS
This was a retrospective study that analyzed the outcomes of adult patients with Ph+ ALL treated with either combination chemotherapy plus dasatinib or combination chemotherapy plus dasatinib followed by allogeneic HSCT.
RESULTS
A total of 70 patients were included; 30 (42.9%) underwent allogeneic HSCT while 40 (57.1%) received only chemotherapy plus dasatinib. In comparing overall survival (OS) rates, results between the 2 groups were similar with a 1-year OS of 93.3% versus 100% (P = 0.20), 2-year OS of 89.8% versus 86.2% (P = 0.72), and 3-year OS of 76% versus 71.3% (P = 0.56) in the transplant versus nontransplant groups, respectively. The 3-year relapse-free survival (RFS) rates were also similar at 70.5% in the transplant group and 80.1% in the nontransplant group (P = 0.94). Subgroup analyses were performed for patients with specific poor prognostic factors (higher white blood count, older age, positive minimal residual disease status), but results again showed no significant survival difference between transplant and nontransplant patients.
CONCLUSIONS
While HSCT has historically led to a survival advantage in Ph+ ALL, the results of our study demonstrate that it may have a less beneficial role in the era of newer generation TKIs such as dasatinib.

Identifiants

pubmed: 31016870
doi: 10.1002/cam4.2153
pmc: PMC6558592
doi:

Substances chimiques

Dasatinib RBZ1571X5H

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2832-2839

Informations de copyright

© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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Auteurs

Jeremy Chang (J)

Los Angeles County - University of Southern California, Los Angeles, California.

Dan Douer (D)

Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, Norris Cancer Center, Los Angeles, California.

Ibrahim Aldoss (I)

City of Hope, Duarte, California.

Golnaz Vahdani (G)

Los Angeles County - University of Southern California, Los Angeles, California.

Ah-Reum Jeong (AR)

Los Angeles County - University of Southern California, Los Angeles, California.

Zunera Ghaznavi (Z)

Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, Norris Cancer Center, Los Angeles, California.

Sherry Zhang (S)

Harbor-UCLA Medical Center, Torrance, California.

George Yaghmour (G)

Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, Norris Cancer Center, Los Angeles, California.

Kum-Ja Lee (KJ)

University of Southern California School of Pharmacy, Los Angeles, California.

Ashley Weissman (A)

University of Southern California School of Pharmacy, Los Angeles, California.

Mojtaba Akhtari (M)

Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, Norris Cancer Center, Los Angeles, California.

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