Reduced Intensity (RI) Allogeneic Hematopoietic Cell Transplantation (HCT) Improves Outcomes for Older (≥ 60 Yrs) Patients (Pts) with Acute Myeloid Leukemia (AML).

The current paradigm of cytarabine-based induction chemotherapy followed by repetitive cycles of similar consolidation has yielded 2-year disease-free survival (DFS) of no more than 20% in older pts (≥60 yrs) who achieve remission. Induction failure (IF) is also high in this population (20–35%), depending on cytogenetic risk. Regimen-related toxicities have been a barrier to allogeneic HCT in older pts. RI conditioning provides a means to harness graft vs. leukemia in this group. Between 2/2000 and 3/1/2007, 46 pts ≥ 60 yrs (median 63 yr, range 60–71) received RI HCT from either related (26) or unrelated (20) HLA matched donors. In 23 pts, RI HCT was used as consolidation of remission (CR¹ [19 pts] + CR² [4 pts]) while 23 had active disease, including 10 IF. Karyotype was favorable in 9%, intermediate in 48% and poor in 41%. The median % marrow blasts for non-remission pts was 31% (6–80%) and peripheral blood blast was 5% (0–78%). The majority (41 pts) received fludarabine (FLU)/melphalan (MEL) for conditioning. Four pts received FLU with either 200G total body irradiation (TBI) (3 pts) or busulfan (1 pt) and one received TBI alone. Graft vs. host disease (GVHD) prophylaxis was based on either cyclosporine/mycophenolate mofetil alone or with methotrexate (MTX) (20/10) or tacrolimus/sirolimus +/− MTX (2/14 pts). The graft source was peripheral blood in 43 pts and marrow in 3 pts. Engraftment occurred at a median of 15 days (0–27 days) in 98% of recipients; graft failure occurred in one sibling HCT. Donor engraftment based on DNA analysis ranged from 30–100% at 4–6 wks post-HCT (median 100%) in the 33 analyzed pts. Mortality at day 100 was 10.8%. Acute GVHD (Grade 2–4) occurred in 61% of recipients and chronic GVHD has occurred in 23/33 evaluable pts. With a median follow-up of 24.5 months (m) for surviving pts (4–83 m), 25/46 (64.5%) pts are alive. For remission pts, the 2 yr DFS is 65% (CI 51–76%). For pts who received RI HCT as “salvage”, 34% are DF at 2 yrs. (CI 27–41%). Relapse rates were 11% for remission pts and 60% for non-remission pts. Deaths post HCT were attributed to relapse in 12 pts and treatment related mortality due to GVHD (6 pts) or infection (3 pts).

Conclusion: DFS can be improved for older patients with the use of RI HCT as remission consolidation. RIC also provides a meaningful salvage option for pts with IF or early relapse. Evaluation of donor options including both siblings and unrelated donors should be considered during induction for patients with good performance status.