Older age (e.g. > 55–60 yrs) is a commonly cited indication for reduced-intensity conditioning regimens (RIC) in the treatment of myeloid leukemias. These diseases, however, may benefit from the highest possible dose intensity that can be safely delivered. Here we analyze our experience treating patients (pts) older than 55 yrs. with intravenous (IV) busulfan (Bu)-based preparative regimens.

Methods: Fifty-six pts older than age 55 yrs. with MDS (n=13), AML (n=33), or CML/myeloproliferative disorder (n=10) were transplanted from 6/1997 to 12/2004 on two consecutive protocols. Conditioning were IV fludarabine (Flu) 40 mg/m2 and IV Bu 130 mg/m2 over 3 hr (days -6 till -3) given once daily (BuFlu; n=36), and IV Bu 0.8 mg/kg over 2 hr every 6 hr for 16 doses (days -7 till -4), followed by Cyclophosphamide (Cy) 60 mg/kg on days -3 and -2 (IV BuCy2; n=20). Pts with an unrelated (UD) or mismatched donor received ATG. Graft-versus-host disease (GVHD) prophylaxis was based on tacrolimus and mini-methotrexate.

Results: Median age was 58.4 yrs (55–66.8); 14 pts were older than 60 yrs. Most pts were not in complete remission (CR) at BMT (n=38, 68%, with similar distribution in pts older and younger than age 60). Donors were HLA-compatible siblings (SIBS) in 59% (n=33) and UD in 41% (n=23). UD were used in 5 pts >59 yrs (36%) and in 18 < 60 yrs (43%). Stem cell source was bone marrow (n=23) or peripheral blood (n=33). All but one pt had documentation of donor cell engraftment. Median follow-up of surviving pts (June 2005) was 15 mos (range, 4–49; n=23). Grade II-IV acute (a) and chronic (c) GVHD rates were as follows (pts <60 vs >59 yrs): 38% vs 64% and 45% vs 54%, respectively. 100-day treatment-related mortality (TRM) was 11% (due to graft rejection (n=1), toxicity (n=2); pulmonary hemorrhage with fungal pneumonia (n=1) and aGVHD (n=2). All early 100-day TRM pts were < 60 yrs. Overall, 17 pts relapsed and 33 pts have died. One-year TRM: 29%, n=16 (due to GVHD, n=7, infections, n=4; rejection, n=1; unknown causes, n=1; toxicity, n=2, bleeding, n=1). Only 2 pts > 59 yrs are alive, while the others died of cGVHD (n=5) and disease relapse (n=7).

Conclusion: In this older population of predominantly relapsed pts with myeloid leukemias, major cause of treatment failure was not the preparative regimen employed, but GVHD and disease relapse. An association between intensity of the regimen, age and GVHD cannot be ruled out in this analysis. These results would suggest that age per se should not be used as the main reason for selecting a reduced intensity regimen in patients up to at least age 60 with myeloid leukemias.

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Topics:
bone marrow transplantation, busulfan, conditioning (psychology), leukemia, myeloid, older adult, brachial plexus neuritis, graft-versus-host disease, toxic effect, complete remission, cyclophosphamide
2005, The American Society of Hematology
2005
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