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In this retrospective EBMT study, the outcome of MDS pts after bone marrow HLA matched unrelated donor transplantation (BMmUrD, n=144) was compared to the one after bone marrow (BMsib, n=240) or PBPC (PBsib, n=184) HLA identical sibling transplantation (HIS, n=424), with myeloablative conditionings, from 1994 to 2004. There were 191 RA/RARS, 183 RAEB, and 194 RAEB-T with no history of MPD/acute leukemia. BMmUrD pts were younger at SCT (p<.001), and more frequently received TBI and anti-T cell serotherapy during conditioning (p<.001). Cytogenetics was available for 461 pts (unfavorable, n=127), and IPSS for 469 pts (int2+high IPSS, n=180). T-cell depletion (TCD) was performed for 27%, 41%, and 38% of the BMsib, PBsib, and BMmUrD grafts (p=.014). The median follow-up after BMsib, PBsib, and BMmUrD SCT was 60, 36, and 29 mo. The 3-year TRM after BMsib, PBsib, and BMmUrD SCT was 37%, 34%, and 46% (p<.08). In a Gray multivariate model, the use of BMmUrD was associated with an increased 3-year TRM. The impact of this covariate was mainly observed during the first 100 days after SCT, and in pts with either advanced stage MDS, favorable/intermediate cytogenetics, or who received TBI-based conditionings or TCD grafts. The 3-year relapse incidence (RI) was 24%, 22%, and 19% for the BMsib, PBsib, and BMmUrD groups, and excluding TCD: 24%, 15%, and 13% (p=.03). In non-TCD transplants (n=337), RI was significantly decreased in BMmUrD pts (p=.025) when adjusted for other significant covariates. However, this result was associated with an increased incidence of the competing risk in BMmUrD, i.e., TRM. For instance, in advanced stage MDS, RI was 37%, 35%, and 8% in the BMsib, PBsib, and BMmUrD groups, but the TRM was 35%, 30%, and 63%, respectively. The 3-year survival with BMsib, PBsib, and BMmUrD was 43%, 48%, and 39% (p<.07); 44%, 52%, and 45% without TCD (p=NS); and 40%, 40%, 29% with TCD (p=.055). Considering the overall group of pts and adjusting for age, advanced stage MDS, and unfavorable cytogenetics, the use of BMmUrD was adversely affecting the outcome (RR, 1.17; 95%CI, 1.06–1.29; p=.001, n=513 pts - Cox predicted survivals: 44%, 53%, 35% for BMsib, PBsib, BMmUrD). Without TCD, the outcome of BMmUrD was similar to the one of BMsib (RR, 1.12; 95%CI, 0.99–1.27; p=.08 - Cox predicted survivals: 46%, 59%, 43% for BMsib, PBsib, and BMmUrD). Finally, replacing cytogenetics by the IPSS in the model, Int-2/High IPSS pts had a Cox predicted survival of 41%, 51%, and 51% in the BMsib, PBsib, and the BMmUrD groups (p=NS, n=108 pts), whereas Low/Int-1 IPSS pts had a worse outcome with BMmUrD (RR, 1.29; 95%CI, 1.09–1.53; p=.003 - Cox predicted survivals, 53%, 62%, 32%). Finally, the 3-year DFS for the BMsib, PBsib, and BMmUrD groups was 39%, 44%, and 36% (p=.07); and 41%, 49%, and 43% without TCD. In conclusion, BMmUrD is associated with an increased early TRM, a lower RI, and a survival that can be similar to, or even better than the one after BMsib in some subgroups of pts, especially if using unmanipulated grafts. We confirm our previous results showing an improved outcome in high-risk MDS with the use of PBPC as a stem cell source for HIS transplantation.

Allogeneic stem-cell transplantation (alloSCT) is the most powerful antileukemic post-remission strategy in patients with acute myeloid leukemia (AML), and has shown its capability of increase leukemia-free survival and survival in earlier phases of the disease. However, the possible role of alloSCT in AML patients not in CR is mostly unknown, and deserves specific investigation. For this purpose, a survey within the EBMT registry including patients who underwent an undepleted alloSCT from an HLA-identical sibling for advanced AML (not in CR) was performed. We have analyzed 977 adults patients with AML submitted to alloSCT for a primary refractory disease (REF, n=346), first relapse (REL1, n=506) or second relapse (REL2, n=125) from 1990 to 2002 in EBMT centers. Median age was 40 (16 – 73) and 55% of patients were male. FAB classification was: M1/M2, 44%; M4/M5, 33%; M6, 5%; M0, 4%; M3, 3%; M7, 3%. Median time from diagnosis to alloSCT was 136, 219 and 403 days for REF, REL1, and REL2 subgroups, respectively. Bone marrow was the source of stem cells in a higher proportion of patients with relapsed disease as compared to refractory AML (59% for REL1 + REL2 vs 41% for REF, p<0001). Conditioning regimen included TBI in 56% of cases. No significant differences among subgroups (REF/REL1/REL2) were observed in terms of donor-recipient’s CMV status and TBI usage. After a median follow-up of 22 months, the main estimates of the outcome at 2 years are depicted in the following table: Group Refractory 1st relapse 2nd relapse * All the results are expressed in % ±SE Relapse incidence 57 ±6 51 ±4 54 ±8 Transplant-related mortality 25 ±5 26 ±4 31 ±6 Overall survival 25 ±3 26 ±2 24 ±2 Leukemia-free survival 18 ±2 23 ±2 16 ±3 In conclusion, although the overall outcome of HLA-identical sibling allotransplant for patients with non-CR AML is poor, a small fraction of patients, of approximately 20%, seems to benefit from the procedure in this otherwise incurable disease. A further analysis is addressed to the recognition of favorable prognostic factors in order to identify subgroups of patients with advanced AML who are candidates to allogeneic transplantation.