title: Pretransplantation use of the second-generation tyrosine kinase inhibitors has no negative impact on the HCT outcome.
abstract: BACKGROUND
  Allogeneic hematopoietic cell transplantation (HCT) was a standard therapy in chronic phase (CP) chronic myeloid leukemia (CML). As a result of the effective therapy with tyrosine kinase inhibitors (TKI), HCT was shifted to defined clinical situations. We present the results of observational prospective analysis of 28 CML patients undergoing HCT after exposure to, at least, two lines of TKI (including dasatinib and/or nilotinib), with respect to response, overall survival (OS), treatment toxicity, graft versus host disease (GVHD), and progression/relapse incidence.
  
  
  RESULTS
  All the patients but one engrafted with median time 19 days. OS for patients in CP1 and CP2/accelerated phase (AcP) were 92.9 and 85.7 %, respectively. Six patients allotransplanted in blast crisis (BC) CML died early after HCT. Eighteen patients achieved deep molecular remission (MR(4.5) or MR(4.0)). Relapse incidence was 29.6 %. Median time to progression (TTP) differs significantly depending on the CML phase prior to HCT, the best response achieved after HCT and development of chronic GvHD. NRM yielded the values 7.1, 12.5, and 50 % in CP1, CP2/AcP, and BC, respectively. Fatal outcome, due to veno-occlusive disease (VOD), was observed in two (7 %) patients. In five (17.9 %) patients, mild or moderate VOD was observed with no negative impact of preceding therapy with TKI2. Acute GvHD was diagnosed in 25.9 % of patients, while chronic GvHD developed in 42.9 % of individuals.
  
  
  CONCLUSIONS
  Pretransplantation therapy with TKI2 in CP CML is safe and reasonable. In BC, the optimal approach before HCT is to reduce the leukemic burden and achieve subsequent CP.
authors.affiliation: Department of Hematology and Transplantology, Medical University of Gdansk, Debinki 7, 80-952, Gdansk, Poland. babajaga@gumed.edu.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Piekarska
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Szamarzewskiego 84, 60-569, Poznan, Poland.
authors.forename: Lidia
authors.initials: L
authors.lastname: Gil
authors.affiliation: Department of Hematology and Transplantology, Medical University of Gdansk, Debinki 7, 80-952, Gdansk, Poland.
authors.forename: Witold
authors.initials: W
authors.lastname: Prejzner
authors.affiliation: Department of Endocrinology and Internal Diseases, Medical University of Gdansk, Debinki 7, 80-952, Gdansk, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Wiśniewski
authors.affiliation: Department of Hematology and Transplantology, Medical University of Gdansk, Debinki 7, 80-952, Gdansk, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Leszczyńska
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Szamarzewskiego 84, 60-569, Poznan, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Gniot
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Szamarzewskiego 84, 60-569, Poznan, Poland.
authors.forename: Mieczysław
authors.initials: M
authors.lastname: Komarnicki
authors.affiliation: Department of Hematology and Transplantology, Medical University of Gdansk, Debinki 7, 80-952, Gdansk, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hellmann
mesh_terms: D000328:Adult; D000368:Aged; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D000069439:Dasatinib / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015466:Leukemia, Myeloid, Chronic-Phase / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use; D012008:Recurrence; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C498826:nilotinib; D000069439:Dasatinib
keywords: Allogeneic hematopoietic cell transplantation; Chronic myeloid leukemia; Dasatinib; Nilotinib; Second-generation tyrosine kinase inhibitors