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 journalArticlepeer-review

101 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

Bibliographical note

Funding Information:
This work was supported in part by Novartis providing the grant to CIBMTR for supplemental data collection. The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24 CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement U10 HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two grants N00014-12-1-0142 and N00014-13-1-0039 from the Office of Naval Research; and grants from Allos Therapeutics, Inc.; Amgen, Inc. Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd; Genentech, Inc.; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; the Leukemia and Lymphoma Society; the Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; TerumoBCT; Teva Neuroscience, Inc.; THERAKOS, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense or any other agency of the US Government.

Keywords

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

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this