The use of nonmyeloablative regimens in patients (pts) not suitable for allogeneic HSCT because of poor performance status or advanced age has become an area of intense clinical research in the last few years. The optimum low intensity approach which maximizes engraftment and GVL while minimizing transplant related complications is yet to be defined. From April 1999 to May 2000 we treated 11 pts with fludarabine (25mg/m2x 3days) and cyclophosphamide (750mg/m2x3days) followed by HSCT from a G-CSF stimulated HLA identical sibling donor. As GVHD prophylaxis 8 pts received cyclosporin (CSA) and mini dose methotrexate, 2 pts CSA and mycophenolate mofetyl and 1 pt CSA and prednisone. CSA was given until T+60 then tappered off if no GVHD occured. Pts with persistent mixed donor/recipient chimerism or those with disease progression received escalation doses of DLL There were 4 females and 7 males with a median age of 57 years (range 39 to 67). Underlying diseases included: Secondary MDS (1), AML (3), Myeloma (1), CML (3), Amyloid (1 ), NHL (1) and CMMoL ( 1 ). Four pts had previous transplants ( 1 auto, 3 allo).Only one pt was in CR at time of therapy. A median of 5xl06/Kg CD34+ cells and 2xl08/Kg CD3+ cells were infused. Ten pts engrafted. Two pts died before day 28, one from disseminated aspergillus infection the other with presumed engraftment syndrome. Donor engraftment on day 30 was as follows (range[medianj): peripheral blood (80-95%); bone marrow (80-95%). The median time to ANC>0.5xlO'/L was 11 days (range 6 to 13) and to a platlet>20x 109/L was 14 days (range 6 to 18). Six pts experienced grade III-IV acute GVHD. DLI were given 10 two pts for disease progression. Four pts (36%) died before T+IOU . Two pts died after T+100, one with disease progression and another from GVHD. Five pts are alive at T+15, T+13, T+l 1, T+5 and T+3 months. Four (36%) pts are in CR ( one after receiving DLI for cytogenetic relapse). Conclusion: These data confirm that engraftment of allogeneic peripheral blood can be achieved with a low intensity regimen and that remissions occur in some pts with advanced hematological malignancies. GVHD remains a serious complication of this approach.
|Original language||English (US)|
|Issue number||11 PART II|
|State||Published - Dec 1 2000|
All Science Journal Classification (ASJC) codes
- Cell Biology