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.
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Combined Modality Therapy
/ adverse effects
Dasatinib
/ administration & dosage
Female
Graft vs Host Disease
/ etiology
Hematopoietic Stem Cell Transplantation
/ adverse effects
Humans
In Situ Hybridization, Fluorescence
Male
Middle Aged
Neoplasm, Residual
/ diagnosis
Philadelphia Chromosome
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ diagnosis
Prognosis
Retrospective Studies
Transplantation, Homologous
Treatment Outcome
Young Adult
Dasatinib
Philadelphia chromosome
acute lymphoblastic leukemia
stem cell transplantation
survival
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
06 2019
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
2832-2839Informations de copyright
© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Références
Blood. 2001 Mar 15;97(6):1572-7
pubmed: 11238093
J Clin Oncol. 2014 Mar 20;32(9):905-11
pubmed: 24516026
Hematology Am Soc Hematol Educ Program. 2006;:133-41
pubmed: 17124052
Blood. 1988 Jan;71(1):123-31
pubmed: 3422030
J Clin Oncol. 2006 Jan 20;24(3):460-6
pubmed: 16344315
Am J Hematol. 2010 Mar;85(3):164-70
pubmed: 20131302
Cancer. 2015 Dec 1;121(23):4158-64
pubmed: 26308885
Blood. 2007 Oct 1;110(7):2309-15
pubmed: 17496201
Blood. 2007 Apr 15;109(8):3189-97
pubmed: 17170120
Blood. 2008 Aug 15;112(4):1005-12
pubmed: 18477770
Biol Blood Marrow Transplant. 2013 Jan;19(1):150-5
pubmed: 22960387
Blood. 2009 May 7;113(19):4489-96
pubmed: 19244158
Blood. 2004 Jun 15;103(12):4396-407
pubmed: 14551133
Leukemia. 2014 Jul;28(7):1467-71
pubmed: 24441288
Cancer Med. 2019 Jun;8(6):2832-2839
pubmed: 31016870
Lancet Oncol. 2015 Nov;16(15):1547-1555
pubmed: 26432046
Blood. 2005 Dec 1;106(12):3760-7
pubmed: 16105981
Hematology Am Soc Hematol Educ Program. 2010;2010:7-12
pubmed: 21239764
Leukemia. 2011 Jan;25(1):41-7
pubmed: 20944676
Leuk Lymphoma. 2008 Jan;49(1):19-26
pubmed: 18203007
Blood. 2008 Aug 1;112(3):918-9
pubmed: 18650471
J Clin Oncol. 2018 Aug 1;36(22):2306-2314
pubmed: 29812996
J Clin Oncol. 2010 Aug 1;28(22):3644-52
pubmed: 20606084
J Clin Oncol. 2004 Oct 15;22(20):4075-86
pubmed: 15353542
Hematology Am Soc Hematol Educ Program. 2008;:366-73
pubmed: 19074112
Bone Marrow Transplant. 2003 May;31(10):909-18
pubmed: 12748668
Cancer. 2016 Dec 1;122(23):3650-3656
pubmed: 27479888
N Engl J Med. 2006 Jun 15;354(24):2531-41
pubmed: 16775234
J Clin Oncol. 2009 Nov 1;27(31):5175-81
pubmed: 19805687
Blood Adv. 2016 Dec 27;1(3):250-259
pubmed: 29046900