Long-Term Follow-Up and Impact of Comorbidity before Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Relapsed or Refractory Acute Myeloid Leukemia-Lessons Learned from the Prospective BRIDGE Trial

Biol Blood Marrow Transplant. 2017 Sep;23(9):1491-1497. doi: 10.1016/j.bbmt.2017.05.014. Epub 2017 May 17.


In patients with relapsed or refractory (r/r) acute myeloid leukemia (AML), allogeneic hematopoietic stem cell transplantation (HSCT) is considered to be the only treatment providing long-term disease control. The BRIDGE trial studied the safety and efficacy of a clofarabine-based salvage therapy before HSCT in patients with r/r AML. Here, we report the long-term follow-up of this phase II multicenter trial and exploratory analyses on the impact of comorbidity on outcome. Eighty-four patients with a median age of 61 years (range, 40 to 75) were enrolled. Patients were scheduled for at least 1 cycle of salvage therapy with CLARA (clofarabine 30 mg/m2; cytarabine 1 g/m2, days 1 to 5). Chemo-responsive patients with a donor received HSCT after first CLARA. The conditioning regimen consisted of clofarabine 30 mg/m2, day -6 to -3, and melphalan 140 mg/m2 day -2. The Eastern Cooperative Oncology Group (ECOG) score, the hematopoietic cell transplantation-specific comorbidity index (HCT-CI), and the Cumulative Illness Rating Scale were obtained at study enrollment as well as before HSCT. Sixty-seven percent of the patients received HSCT within the trial. After a median follow up of 40 months, the estimated 3-year overall survival (OS) for all enrolled patients and those with HSCT within the trial was 40% and 55%, respectively. Relapse-free survival for patients who underwent transplantation with a complete remission afterwards (n = 50) was 48%, calculated from the day of transplantation. In multivariate analysis, both the HCT-CI and ECOG score had a statistically significant impact on OS with a hazard ratio of 1.22 (P = .025)and 1.72 (P = .001), respectively. Using a clofarabine-based salvage therapy combined with early allogeneic HSCT, we were able to achieve good long-term results for patients with r/r AML. In this cohort, both the HCT-CI and the ECOG scores gave prognostic information on OS, showing the feasibility and clinical relevance of comorbidity evaluation at the time of diagnosis of r/r AML patients.

Keywords: Acute myeloid leukemia; Clofarabine; Comorbidity; Hematopoietic stem cell transplantation.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adenine Nucleotides / therapeutic use
  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / therapeutic use
  • Arabinonucleosides / therapeutic use
  • Cardiovascular Diseases / immunology
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / pathology
  • Cardiovascular Diseases / therapy*
  • Clofarabine
  • Comorbidity
  • Cytarabine / therapeutic use
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Kidney Diseases / immunology
  • Kidney Diseases / mortality
  • Kidney Diseases / pathology
  • Kidney Diseases / therapy*
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy*
  • Lung Diseases / immunology
  • Lung Diseases / mortality
  • Lung Diseases / pathology
  • Lung Diseases / therapy*
  • Male
  • Melphalan / therapeutic use
  • Middle Aged
  • Prognosis
  • Recurrence
  • Salvage Therapy / methods*
  • Survival Analysis
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous


  • Adenine Nucleotides
  • Antimetabolites, Antineoplastic
  • Arabinonucleosides
  • Cytarabine
  • Clofarabine
  • Melphalan