Ph+ ALL patients in first complete remission have similar survival after reduced intensity and myeloablative allogeneic transplantation: impact of tyrosine ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-03

AUTHORS

Veronika Bachanova, David I. Marks, Mei-Jie Zhang, Hailin Wang, Marcos de Lima, Mahmoud D. Aljurf, Martha Arellano, Andrew S. Artz, Ulrike Bacher, Jean-Yves Cahn, Yi-Bin Chen, Edward A. Copelan, William R. Drobyski, Robert Peter Gale, John P Greer, Vikas Gupta, Gregory A. Hale, Partow Kebriaei, Hillard M. Lazarus, Ian D. Lewis, Victor A. Lewis, Jane L. Liesveld, Mark R. Litzow, Alison W. Loren, Alan M. Miller, Maxim Norkin, Betul Oran, Joseph Pidala, Jacob M. Rowe, Bipin N. Savani, Wael Saber, Ravi Vij, Edmund K. Waller, Peter H. Wiernik, Daniel J. Weisdorf

ABSTRACT

The efficacy of reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) for Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is uncertain. We analyzed 197 adults with Ph+ ALL in first complete remission; 67 patients receiving RIC were matched with 130 receiving myeloablative conditioning (MAC) for age, donor type and HCT year. Over 75% received pre-HCT tyrosine kinase inhibitors (TKIs), mostly imatinib; 39% (RIC) and 49% (MAC) were minimal residual disease (MRD)(neg) pre-HCT. At a median 4.5 years follow-up, 1-year transplant-related mortality (TRM) was lower in RIC (13%) than MAC (36%; P=0.001) while the 3-year relapse rate was 49% in RIC and 28% in MAC (P=0.058). Overall survival (OS) was similar (RIC 39% (95% confidence interval (CI) 27-52) vs 35% (95% CI 27-44); P=0.62). Patients MRD(pos) pre-HCT had higher risk of relapse with RIC vs MAC (hazard ratio (HR) 1.97; P=0.026). However, patients receiving pre-HCT TKI in combination with MRD negativity pre-RIC HCT had superior OS (55%) compared with a similar MRD population after MAC (33%; P=0.0042). In multivariate analysis, RIC lowered TRM (HR 0.6; P=0.057), but absence of pre-HCT TKI (HR 1.88; P=0.018), RIC (HR 1.891; P=0.054) and pre-HCT MRD(pos) (HR 1.6; P=0.070) increased relapse risk. RIC is a valid alternative strategy for Ph+ ALL patients ineligible for MAC and MRD(neg) status is preferred pre-HCT. More... »

PAGES

658

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/leu.2013.253

DOI

http://dx.doi.org/10.1038/leu.2013.253

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1021658729

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23989431


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65 schema:description The efficacy of reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) for Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is uncertain. We analyzed 197 adults with Ph+ ALL in first complete remission; 67 patients receiving RIC were matched with 130 receiving myeloablative conditioning (MAC) for age, donor type and HCT year. Over 75% received pre-HCT tyrosine kinase inhibitors (TKIs), mostly imatinib; 39% (RIC) and 49% (MAC) were minimal residual disease (MRD)(neg) pre-HCT. At a median 4.5 years follow-up, 1-year transplant-related mortality (TRM) was lower in RIC (13%) than MAC (36%; P=0.001) while the 3-year relapse rate was 49% in RIC and 28% in MAC (P=0.058). Overall survival (OS) was similar (RIC 39% (95% confidence interval (CI) 27-52) vs 35% (95% CI 27-44); P=0.62). Patients MRD(pos) pre-HCT had higher risk of relapse with RIC vs MAC (hazard ratio (HR) 1.97; P=0.026). However, patients receiving pre-HCT TKI in combination with MRD negativity pre-RIC HCT had superior OS (55%) compared with a similar MRD population after MAC (33%; P=0.0042). In multivariate analysis, RIC lowered TRM (HR 0.6; P=0.057), but absence of pre-HCT TKI (HR 1.88; P=0.018), RIC (HR 1.891; P=0.054) and pre-HCT MRD(pos) (HR 1.6; P=0.070) increased relapse risk. RIC is a valid alternative strategy for Ph+ ALL patients ineligible for MAC and MRD(neg) status is preferred pre-HCT.
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