ALLOGENEIC TRANSPLANTATION FOR ADVANCED LEUKEMIA - IMPROVED SHORT-TERM OUTCOME WITH BLOOD STEM-CELL GRAFTS AND TACROLIMUS

We have evaluated the use of blood stem cell. grafts for rapid hematop oietic recovery and tacrolimus (FK506) as GVHD prophylaxis to reduce e arly mortality after allogeneic transplantation. Eighty-five adults wi th advanced leukemia received high-dose thiotepa, busulfan, and cyclop hosphamide as a preparative regimen in a prospective Phase II study, A ll donors were HLA-matched and related, Marrow (BMT) was used for 44 p atients and filgrastim-mobilized blood stem cells (SCT) for 41 patient s, GVHD prophylaxis consisted of cyclosporine (CsA) or FK506: with met hotrexate (MTX) or methylprednisolone (MP). The median time to neutrop hil recovery was earlier after SCT than after BMT (day 10 vs, 17, P<0. 001), but this was due to the selective use of MTX only in the BMT pat ients. The risk, of grades 2-4 GVHD was lower with FK506 than with CsA (16% vs. 45%, P=0.02) and was the same for SCT recipients as for BMT recipients (33% vs. 34%). Regimen-related toxicity was significantly l ower after SCT than after BMT but did not differ between the FK506 and CsA patients, In comparison with those receiving the standard transpl ant (BMT with CsA and MTX), only the SCT recipients using FK506 and RP had a significantly higher survival at day 180 posttransplant (84% vs . 53%, P=0.014), In multivariate analyses, use of FK506 was associated with a lower risk of treatment-related mortality and a higher surviva l at day 180, while the diagnosis of acute lymphoblastic leukemia was associated with a higher risk of treatment-related mortality, These da ta suggest that the use of blood stem cell grafts and FK506 can reduce the early mortality after allogeneic transplantation for advanced leu kemia.