Ph+ ALL patients in first complete remission have similar survival after reduced intensity and myeloablative allogeneic transplantation: Impact of tyrosine kinase inhibitor and minimal residual disease

V. Bachanova, D. I. Marks, M. J. Zhang, H. Wang, M. De Lima, M. D. Aljurf, M. Arellano, A. S. Artz, U. Bacher, J. Y. Cahn, Y. B. Chen, E. A. Copelan, W. R. Drobyski, R. P. Gale, J. P. Greer, V. Gupta, G. A. Hale, P. Kebriaei, H. M. Lazarus, I. D. LewisV. A. Lewis, J. L. Liesveld, M. R. Litzow, A. W. Loren, A. M. Miller, M. Norkin, B. Oran, J. Pidala, J. M. Rowe, B. N. Savani, W. Saber, R. Vij, E. K. Waller, P. H. Wiernik, D. J. Weisdorf

Research output: Contribution to journalArticle

60 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)658-665
Number of pages8
JournalLeukemia
Volume28
Issue number3
DOIs
StatePublished - Mar 2014

Keywords

  • Acute lymphoblastic leukemia
  • Allograft
  • Minimal residual disease
  • Philadelphia chromosome
  • Reduced intensity conditioning
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Bachanova, V., Marks, D. I., Zhang, M. J., Wang, H., De Lima, M., Aljurf, M. D., Arellano, M., Artz, A. S., Bacher, U., Cahn, J. Y., Chen, Y. B., Copelan, E. A., Drobyski, W. R., Gale, R. P., Greer, J. P., Gupta, V., Hale, G. A., Kebriaei, P., Lazarus, H. M., ... Weisdorf, D. J. (2014). Ph+ ALL patients in first complete remission have similar survival after reduced intensity and myeloablative allogeneic transplantation: Impact of tyrosine kinase inhibitor and minimal residual disease. Leukemia, 28(3), 658-665. https://doi.org/10.1038/leu.2013.253