Busulfan-cyclophosphamide versus cyclophosphamide-busulfan as conditioning regimen before allogeneic hematopoietic cell transplantation: a prospective randomized trial.
Claire SeydouxMichael MedingerSabine GerullJoerg HalterDominik HeimYves ChalandonStavroula Masouridi LevratUrs SchanzGayathri NairMarc AnsariPatrick SimonJakob R PasswegNathan CantoniPublished in: Annals of hematology (2020)
Busulfan and cyclophosphamide (BuCy) is a frequently used myeloablative conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT). Theoretical considerations and pharmacological data indicate that application of busulfan prior to subsequent cyclophosphamide (BuCy) may trigger liver toxicity. Reversing the order of application to cyclophosphamide-busulfan (CyBu) might be preferable, a hypothesis supported by animal data and retrospective studies. We performed a prospective randomized trial to determine impact of order of application of Bu and Cy before allo-HCT in 70 patients with hematological malignancy, 33 patients received BuCy and 37 CyBu for conditioning. In the short term, there were minimal differences in liver toxicity favoring CyBu over BuCy, significant only for alanine amino transferase at day 30 (p = 0.03). With longer follow-up at 4 years, non-relapse mortality (6% versus 27%, p = 0.05) was lower and survival (63% versus 43%, p = 0.06) was higher with CyBu compared to BuCy. Other outcomes, such as engraftment (p = 0.21), acute and chronic graft-versus-host disease (p = 0.40; 0.36), and relapse (p = 0.79), were similar in both groups. We prospectively show evidence that the order of application of Cy and Bu in myeloablative conditioning in allo-HCT patients has impact on outcome.
Keyphrases
- stem cell transplantation
- high dose
- allogeneic hematopoietic stem cell transplantation
- low dose
- end stage renal disease
- ejection fraction
- newly diagnosed
- bone marrow
- machine learning
- prognostic factors
- cardiovascular disease
- intensive care unit
- acute lymphoblastic leukemia
- liver failure
- acute myeloid leukemia
- hematopoietic stem cell
- patient reported outcomes
- cell death
- big data
- coronary artery disease
- signaling pathway
- cell cycle arrest
- weight loss
- data analysis
- respiratory failure
- cell proliferation
- patient reported
- pi k akt