Hematopoietic Cell Transplants (HCT) from HLA-Matched Related (MRD) and Unrelated (URD) Donors for Patients with Hematologic Malignancies Using Low-Dose TBI Conditioning.

Nonmyeloablative conditioning regimens for allogeneic HCT were introduced to reduce the non-relapse mortality and as a therapeutic modality to patients (pts) who otherwise would not be considered candidates for HCT. Here, we present data on 727 pts with hematologic malignancies who received either MRD (n=426) or URD (n=301) HCT using a nonmyeloablative regimen consisting of 2 Gy TBI with or without fludarabine (30 mg/m²/day x 3 days) given before HCT. Mycophenolate mofetil and cyclosporine or, more recently, tacrolimus were administered after HCT for both host and donor cell immunosuppression. Ninety-eight percent of pts received unmodified G-CSF-mobilized peripheral blood cells and 2% received marrow (all URD). Transplants were done between 12/97 and 02/05 on multi-institutional studies with a median follow-up of 2.6 (range 0.3–6.9) years amongst survivors. Pts were ineligible for myeloablative conditioning due to advanced age or co-morbidities. Median pt age was 54 (range 5–74) years (MRD 55; URD 54). Diagnoses included ALL (n=26), AML (n=118), CLL (n=70), CML (n=49), HD (n=45), MDS/MPD (n=120), MM (n=155), and NHL (n=144). Forty-nine percent of pts had aggressive advanced stage diseases (MRD 39%, URD 62%) and 22% had failed previous high-dose autologous or allogeneic HCT (MRD 17%; URD 30%). Sustained engraftment occurred in 93% of pts (MRD 96%; URD 90%). Acute GVHD grades II-IV and III-IV occurred in 51% and 13% of pts, respectively (MRD: 44% and 13%; URD: 60% and 13%). Forty-five percent of pts had chronic extensive GVHD (MRD 46%; URD 43%). Overall, the 3-year Kaplan-Meier estimate of relapse-related mortality was 28% (MRD 26%; URD 30%), and non-relapse mortality was 23% (MRD 20%; URD 27%). The rates of 3-year overall and progression-free survivals were 46% and 36%, respectively (MRD 51%, 38%; URD 39%, 31%). Among pts with measurable disease at HCT (65%), the 3-year overall survival was 49% (MRD 50%; URD 45%). The best outcomes were seen in pts with B-cell malignancies, including MM, CLL and NHL, and with early stage myeloid malignancies. In pts who had failed a previous transplant, 3-year overall survival was 39% (MRD 37%; URD 41%). In summary, nonmyeloablative regimens allowed engraftment of allogeneic hematopoietic cells and the development of graft versus tumor effects. Encouraging outcomes were achieved using nonmyeloablative conditioning for both MRD and URD HCT in pts who otherwise were not eligible for myeloablative conditioning regimens, including those who had failed a myeloablative HCT.