title: Prognostic factors and outcomes of unrelated bone marrow transplantation for Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) pre-treated with tyrosine kinase inhibitors.
abstract: BACKGROUND
  The treatment and prognosis of Acute Lymphoblastic Leukemia (ALL), including Philadelphia chromosome positive ALL (Ph+ALL), a poor prognostic factor, has changed with the introduction of tyrosine kinase inhibitors (TKIs). Nevertheless, allogeneic hematopoietic cell transplantation (allo-HCT) is still recommended as the first-line curative treatment. To date, no study has investigated the prognostic factors and outcomes of unrelated bone marrow transplantation (u-BMT) for Ph+ALL following pre-transplant treatment with a TKI-containing regimen.
  
  
  METHODS
  We retrospectively evaluated 15 transplantations of 14 patients with Ph+ALL pre-treated with a TKI-containing regimen at our institute. The 14 patients comprised 11 males and 3 females, with a median age of 50 years (range: 19-64). We performed univariate and multivariate analyses of risk factors that contributed to overall survival (OS) or leukemia-free survival (LFS).
  
  
  RESULTS
  Three-year OS of the patients with molecular complete remission (MCR) and with non-MCR at transplantation were 89% and 40% (p = 0.006), respectively, and three-year LFS rates were 79% and 0% (p = 0.001), respectively. Univariate analysis revealed that first hematological complete remission (HCR1) and MCR at transplant were significantly related to better OS and LFS. Multivariate analysis showed that MCR at transplant was significantly associated with better OS and LFS.
  
  
  CONCLUSIONS
  In agreement with a previous study that included other stem cell sources, u-BMT was deemed feasible for the treatment of Ph+ALL. Analysis of a larger cohort is required to clarify the prognostic factors that affect transplant outcome in Ph+ALL since the introduction of TKIs.
authors.affiliation: Department of Hematology, Osaka City University, Graduate School of Medicine, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Yoshimura
authors.forename: Takahiko
authors.initials: T
authors.lastname: Nakane
authors.forename: Asao
authors.initials: A
authors.lastname: Hirose
authors.forename: Hideo
authors.initials: H
authors.lastname: Koh
authors.forename: Mika
authors.initials: M
authors.lastname: Nakamae
authors.forename: Mizuki
authors.initials: M
authors.lastname: Aimoto
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Nishimoto
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Terada
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Nakamae
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hino
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000009:adverse effects; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases