Konference: 2015 57th ASH Annual Meeting - účast ČR
Téma: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Transplant Toxicities: Poster
Číslo abstraktu: 3105
Autoři: Florent Malard; MD Myriam Labopin, MS; MD Gernot Stuhler; MD Johanna Tischer; MD Joerg Thomas Bittenbring; Prof. Dr. med. Arnold Ganser; MD Nicolaus Kröger; MD Donald W. Bunjes, PhD; Dr. Christoph Schmid; prof. MUDr. Jiří Mayer, CSc.; MD Mauricette Michallet, Ph.D.; Prof. MD Michael Hallek; MD Bipin N. Savani; MD Mohamad Mohty, PhD; MD Arnon Nagler, MSc.
Patients and methods. In the current study we analyzed transplantation outcomes in a cohort of 411 adults AML patients in CR at time of transplant, treated between 2002 and 2013. Patients received a “sequential” conditioning regimen based on Fludarabine 30 mg/m2/d, high-dose aracytine 1-2 g/m2/d, amsacrine 100 mg/m2/d for 5 days and after a 3 days rest, total body irradiation (TBI) 4Gy, cyclophosphamide 50-120 mg/kg, and antithymocyte globulin (ATG) for 2 to 3 days (TBI group, n=269 [65%]). In 142 (35%) patients, TBI was substituted by IV Busulfan 3.2 mg/kg/d for 2 days, or orally equivalent dose (Bu group). 323 patients (79%) had de-novo AML and 88 (21%) had a secondary AML (with prior myelodysplastic syndrome). At time of transplant, 300 (73%) patients were in CR1 and 111 (27%) in CR2. Cytogenetic study in de novo AML was favorable in 19 patients (6%), intermediate in 102 (32%) and poor in 41 (13%). Cytogenetic data were missing in 161 (50%). 104 (25%) patients received matched related donors (MRD) and 307 (75%) unrelated donor (URD) HCT. Majority of patients (94%) received mobilized peripheral blood stem cells graft.
Results. Median follow-up of surviving patients was 28 months and median age at transplant was 54 years (18-76). ANC>500/μL was achieved at a median of 17 (range, 9–74) days after HCT. Sixteen patients (4%) failed to engraft. Two year cumulative incidence of relapse (RI) and non-relapse mortality (NRM) were 22% (95%CI, 18–26%) and 22% (95%CI, 18–27%), respectively. The Kaplan-Meier estimate of overall (OS) and leukemia-free survival (LFS) at 2 years were 59% (95%CI, 54–65%) and 56% (95%CI, 50–61%), respectively. Acute GVHD (grade II-IV) occurred in 109 (28%) patients. The 2-year cumulative incidence of chronic GVHD was 31% (95%CI, 26-36), extensive in 17% (95%CI, 12-21). Two years RI, NRM, LFS and OS in TBI vs. Bu patients were 21.8% vs 21.7% (p=0.69), 29.4% vs 18.3% (p=0.008), 48.8% vs 59.6% (p=0.045) and 51.2% vs 64.0% (p=0.013), respectively. In multivariate analysis adjusted for variable with different distribution between Bu and TBI groups, the type of conditioning (TBI vs Bu) has no impact on RI, NRM, LFS and OS. Age over 55 at transplant was an independent adverse prognostic factor in multivariate analysis for NRM (hazard ratio (HR: 1.61, 95% CI: 1.00-2.61, p=0.05)), LFS (HR: 1.39, 95% CI: 1.00-1.92, p=0.05) and OS (HR: 1.55, 95% CI: 1.11-2.18, p=0.01). Being treated in an experienced center (defined as having including 10 or more transplants in the study) was associated with a significant lower RI (HR: 0.84, 95% CI: 0.75-0.93, p=0.001) and better LFS (HR: 0.91, 95% CI: 0.84-0.98, p=0.01) and OS (HR: 0.91, 95% CI: 0.84-0.98, p=0.02). Finally, transplantation from an URD was associated with a significant increase in NRM (HR: 2.11, 95% CI: 1.14-3.91, p=0.02). Of note, CR1 vs. CR2 and de novo vs. secondary AML had no impact on patients’ outcome.
Conclusions. These results in a rather large cohort of patients with AML suggest that a FLAMSA “sequential” regimen provided an efficient disease control in high-risk AML patients including in CR2 and secondary AML. Furthermore Busulfan and TBI based FLAMSA “sequential” regimens provide a similar outcome. These results should be confirmed in a multicenter well design randomized study.
Disclosures: Off Label Use: off-label drug use: antithymocyte globulin (ATG) for allo-SCT conditioning. Tischer:Sanofi-Aventis: Other: advisory board . Schmid: Neovii: Consultancy ; Janssen Cilag: Other: Travel grand . Mayer:Cell Therapeutics: Other: Grants, personal fees . Hallek: GSK, Genentech: Membership on an entity’s Board of Directors or advisory committees , Research Funding ; Mundipharma: Honoraria , Other: Speakers Bureau and/or Advisory Boards , Research Funding ; Boehringher Ingelheim: Honoraria , Other: Speakers Bureau and/or Advisory Boards ; Pharmacyclics: Honoraria , Other: Speakers Bureau and/or Advisory Boards , Research Funding ; Celgene:Honoraria , Other: Speakers Bureau and/or Advisory Boards , Research Funding ; Gilead: Honoraria , Other: Speakers Bureau and/or Advisory Boards , Research Funding ; Roche: Honoraria , Other: Speakers Bureau and/or Advisory Boards , Research Funding ; Janssen: Honoraria , Other: Speakers Bureau and/or Advisory Boards , Research Funding ; AbbVie: Honoraria , Other: Speakers Bureau and/or Advisory Boards , Research Funding
Datum přednesení příspěvku: 6. 12. 2015