Long-Term Remission After Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia Patients with Active Disease

Between 1994 and 2011 343 adult patients with acute myeloid leukemia (AML) underwent allogeneic stem cell transplantation (SCT). 244 pts were transplanted in CR 1, CR 2 or CR 3 and 99 pts were transplanted with active disease. 56/99 pts were male, 43/99 pts were female. Median age was 50 years (17 – 70). 65 pts had primary AML, 22 pts secondary AML after MDS and 12 pts had therapy related (t-AML). 45/99 pts had induction failure (primary refractory), in 3/99 pts AML was untreated (Fanconi, SCID, active NHL), 39/99 pts were transplanted for AML in first relapse and 12/99 pts were transplanted for AML in second relapse. Median blast count in the bone marrow before conditioning was 20 % (5 – 90). 21 pts had extramedullary leukemia, mainly meningeosis and skin involvement. Karyotype was intermediate in 60 pts and high risk in 33 pts. In 5 pts karyotype analysis was not done, in 1 patient favourable. Induction failure was defined as blast persistence after two cycles of chemotherapy including high dose ARAC. Pts transplanted in first relapse had an untreated relapse (n = 15) or had received another chemotherapy. Pts with meningeosis had received intrathecal therapy. Donors for SCT were HLA identical siblings in 35/99 pts or unrelated donors in 64/99 pts. Conditioning regimen was myeloablative (MAC) (12 Gy TBI + CY) in 42 pts (since 1995), reduced intensity conditioning (RIC) (FLU/ BU/ATG) in 42 pts (since 1998) and FLAMSA-RIC in 15 pts (since 2007).

Results: After allogeneic SCT 4/99 pts had progression of leukemia, 95/99 went in remission. 24/99 pts are alive, 4 with AML and 20 pts in CCR. Median remission duration of the 20 pts in CCR is 47 months (0.5 - 130). 75/99 pts are dead. Causes of death are leukemia in 48/75 and TRM in 27/75 pts, mainly gvhd and infection. Probability of survival at 60 months, 90 months and 120 months for the whole group is 0.26, 0.19 and 0.08, respectively. The stage of disease at conditioning had no significant influence. Probability of survival at 60 months and 90 months for primary refractory pts was 0.3 and 0.22, in first relapse 0.26 und 0.13 and in second relapse 0.19 and 0.19. The conditioning regimen was not randomized and showed a trend for better survival in RIC vs. MAC vs. FLAMSA RIC, at 60 months 0.42 vs. 0.17 vs. 0.1 (at 30 months), at 90 months 0.25 vs. 0.14.

In conclusion: After induction failure or after first relapse SCT is the only curative therapy. About 25 % of the pts can enjoy a long lasting remission (at 5 years). The high relapse rate and high TRM rate has to be improved by preemptive DLI therapy and better supportive care.