Physicians Poster Sessions EBMT 2009 Acute leukaemia P433 A survey on the outcomes following allogeneic haematopoietic stem cell transplantation for adult P432 patients with acute lymphoblastic leukaemia in fi rst Leukaemia-free survival of AML patients conditioned with relapse: a retrospective study on behalf of the ALWP FBM or other RIC protocols prior to allogeneic stem cell from the EBMT transplantation S. Santarone, M. Labopin, P. Di Bartolomeo, R. Arnold, R. Marks, M. Labopin, H. Bertz, T. de Witte, V. Rocha, J. Finke J. Finke, H.J. Kolb, C. Cordonnier, M. Baccarani, A. Fassas, on behalf of the Acute and Chronic Leukemia Working Parties M. Michallet, G. Ehninger, B. Samey, V. Rocha on behalf of the ALWP EBMT Conditioning with reduced intensity protocols (RIC) prior to allogeneic stem cell transplantation (SCT) has been proven The outcome after HSCT for adult patients with ALL is largely successful in the treatment of hematologic malignancies in dependent on disease status at the time of transplantation. patients with higher age or comorbidities, formerly regarded as Indication of allogeneic HSCT in patients with active disease at uneligible for treatment with SCT and standard conditioning. transplant is controversial. This retrospective study was aimed Nevertheless, control of advanced or active myeloid disease to analyze the results of HSCT in adult patients with ALL receiv- relies more on the dose intensity of the conditioning protocol ing HLA-identical or matched unrelated donor (MUD) myeloab- than on the graft versus leukemia effect and is hampered in lative HSCT while being in fi rst relapse of their disease between regimens with minimal intensity. Recently we described a 1990 and 2006. The primary and secondary endpoints of this conditioning protocol with reduced toxicity including fl udarab- study were the 3-year overall survival (OS) and the remission ine, melphalan and BCNU (FBM group), with particular activ- rate following HSCT. The EBMT registry received reports of 532 ity against advanced diseases with an acceptable rate of non patients (332 HLA-identical sibling and 200 MUD transplants). relapse mortality (Blood, 2008, 112: 415). Here we retrospec- Their median age was 29 years (16-65). There were 333 males tively compared FBM treated AML patients with patients treated and 199 females. The ALL immunological distribution at diag- with various TBI-, busulfan- or melphalan- containing RIC pro- nosis was: B-lineage 253, T-lineage 114, other 42, missing 123. tocols registered within the EBMT (RIC group). The two groups Sixty two patients were affected by Philadelphia chromosome differed signifi cantly not only in size (FBM group=130pt., RIC positive ALL. The median number of white blood cells at diagno- group=625pt.) but also in AML characteristics (sAML pt. in sis was 26x109/L (0.4-746). The median intervals from diagnosis FBM=47%, in RIC=88%), status at SCT (active disease/upfront to fi rst complete remission (CR1), from CR1 to relapse, and from SCT: 83% v. 17%), median patient age (63y v. 56y), and use CR1 to HSCT were 45, 140, 193 days respectively. The median of unrelated donors (67% v. 31%). Nevertheless, the 2-year blasts in the bone marrow (BM) at transplant was 8,5% (0-93). leukemia free survival (LFS) of AML patients in remission (CR1/ Total body irradiation (TBI) was used as conditioning regimen CR2) at SCT did not differ signifi cantly between the two groups in 400 out of 532 patients. Most patients (308, 58%) obtained a (FBM=32%(±10%) v. RIC=49%(±3%), p= 0,14). Patients with CR following HSCT. The 3-yr OS for all patients was 19+2%. In active disease at SCT (FBM=107pt., RIC=109pt.) differed in univariate analysis, 3 factors were signifi cantly associated with the use of unrelated donors (FBM=71% v. RIC= 36%). 2-year a better 3-yr OS: type of donor (HLA-identical sibling vs MUD, LFS in patients with active AML transplanted from a HLA iden- 21+3% vs 17+3%, p=0.03; no circulating blasts at transplant tical sibling was 30%(±5%) in the FBM group and 17%(±5%, (28+6% vs 14+5%, p=0,01) and lower number of BM blasts p=0.12) in the RIC group. Results for 2-year LFS with unrelated (<8% vs >8%, 33+6% vs 12+4%, p=0,004). There was no sig- donors were 38%(±6%) and 35%(±8%, p=0.41), respectively. nifi cant impact of other potential prognostic variables studied. Defi nitive conclusions between AML patients treated with FBM In multivariate analysis, performed for 102 patients with enough or other RIC protocols are diffi cult to make by this analysis information, there were 2 factors signifi cantly associated with due to the signifi cant heterogeneity of the two study groups. a decreased 3-yr OS: higher number of blasts in the BM >8% Anyway, despite the increased patient age in the FBM group (hazard ratio 0,49, 95% CI 0,31 to 0,76, p=0.002) and older treatment outcomes were comparable with a trend of better patients >29yr (HR 0,6, 95% CI 0,38 to 0,94, p=0.03). Our study LFS in AML patients with active disease and related donors. confi rms that HSCT is an effective salvage regimen for patients These data once more emphasize the fact that RIC protocols with ALL in fi rst relapse, mainly for young patients with lower show substantial differences in cytotoxicity and the choice of tumor burden. Half of patients achieve the CR after HSCT and the appropriate conditioning regimen should not only be guided a small but signifi cant proportion of them can benefi t in terms of by patient factors like age or comorbidities but also by charac- 3-yr overall survival either from related or unrelated donor. The teristics of the underlying malignant disease. number of blasts in BM has an important impact on OS. S85 P434 analysis of 48 adults with high risk Ph negative ALL undergoing Fludarabine and PK-targeted intravenous busulfan before T- cell depleted (TCD) URD-HSCT in CR1 reported to the Brit- allografting for adult acute lymphoid leukaemia ish Society of Blood and Marrow Transplantation Registry from S. Santarone, M. Alsina, E. Ayala, T. Field, M. Kharfan-Dabaja, 1993 to 2005. Median follow-up of survivors was 56.3 months L. Ochoa, L. Perez, J. Perkins, J. Raychaudhuri, D. Sullivan, (range 18-160). Median age was 26.2 years (range 15.9-50). H. Fernandez, C. Anasetti Sixty seven percent of transplants were matched at 10 of 10 Department of Blood and Marrow Transplantation Moffi tt Cancer loci and 33% were mis-matched (27% at one allele only and 6% Center (Tampa, US) at two). TCD was carried out by in-vivo Campath administration in all recipients with additional ex-vivo TCD in 21% of patients. Remission consolidation with allogeneic blood or marrow The estimated actuarial overall survival (OS), disease free sur- transplantation improves survival of young patients with acute vival (DFS) and non relapse mortality (NRM) were 61%, 54% lymphoid leukemia (ALL), but the potential benefi t of transplan- and 13% at 5 years respectively. The overall incidence of Grade tation in older patients is offset by regimen toxicity and non- II-IV and III-IV acute GVHD was 26% and 8% respectively. The relapse mortality. Busulfan (BU) is not thought to be an effective actuarial estimate of extensive chronic GVHD was 25% at drug for ALL, presumably because of intrinsic resistance of ALL 5 years. Adverse cytogenetics at diagnosis was the only factor to alkylating agents, or perhaps because of the large variability associated with poorer 5 year DFS (41 vs 61%). T-cell depleted in BU pharmacokinetics and erratic drug exposure. Here we URD HSCT can result in good OS and low NRM for adults with report results of treatment with a PK-targeted intravenous BU high risk ALL in CR1 and merits prospective evaluation. regimen in 35 adults with ALL. Patient age was 19-55 (median 38) years, 21 were treated in fi rst complete remission (CR1), 4 in CR1 following primary induction failure (PIF), 9 in CR2, P436 and 1 in CR3. Treatment was with 4 consecutive daily doses High-resolution genome-wide analysis of copy number of fl udarabine (FLU) 40 mg/m2, followed by i.v. BU, given on abnormalities in adult acute myeloid leukaemia using days 1 and 2 at 130-145 mg/m2 daily over 4 hours with PK- single nucleotide polymorphism arrays identifi ed poor sampling and mass spectrometry assay. On days 3 and 4 risk pts candidate to allo-BMT BU dose was adjusted to target an average area under the I. Iacobucci (1), E. Ottaviani (1), F. Salmi (1), A. Astolfi (2), concentration curve of 5300+530 mMol*min/L for each of the N. Testoni (1), S. Luatti (1), C. Papayannidis (1), P. Giannoulia (1), four days. Donors were siblings (19), or unrelated (16). Grafts P. Paolini (1), PP. Piccaluga (1), D. Cilloni (3), F. Messa (3), were T-replete, fi lgrastim-mobilized hematopoietic blood cells. F. Arruga (3), C. Dell’Agnola (4), S. Cingarlini (4), D. Russo (5), Graft-versus-host disease (GVHD) prophylaxis was tacrolimus M. Baccarani (1), G. Martinelli (1) plus methotrexate or mycophenolate mofetil. Mortality from (1)Dpt. of Hematology/Oncology Seràgnoli (Bologna, IT); all non-relapse causes was 6% at 100 days, and 9% at one (2)Pediatric Oncology and Hematology “L. Seràgnoli” (Bologna, year. Causes of death were GvHD in 2 patients and infection IT); (3)Hematology (Orbassano, Turin, IT); (4)Policlinico GB in 1. Eight patients had leukemia relapse between day 20 and Rossi (Verona, IT); (5)Chair of Hematology and Unit of Blood 426 (median, day 82) post-transplant.