Lowered-intensity preparative regimen for allogeneic stem cell transplantation delays acute graft-versus-host disease but does not improve outcome for advanced hematologic malignancy.

Reduced conditioning intensity has extended the option of allogeneic hematopoietic stem cell transplantation to patients who cannot tolerate fully myeloablative regimens. However, relapse and graft-versus-host disease (GVHD) continue to be major causes of morbidity and mortality. We prospectively tested whether a moderate reduction of the intensity of the preparative regimen would lead to significant reduction in regimen-related toxicity without compromising tumor control in a cohort of 44 patients ineligible for conventional hematopoietic stem cell transplantation. Patients were conditioned with fludarabine, busulfan, mycophenolate, and total lymphoid irradiation. Tacrolimus and methotrexate were given as prophylaxis for GVHD. Donors were 5 of 6 or 6 of 6 matched family members. The median age was 61 years. Eleven patients had comorbid conditions that precluded conventional myeloablative transplantation. Fatal regimen-related organ toxicity occurred in 3 patients. The cumulative incidence of grade 2 to 4 or grade 3 to 4 acute GVHD by day 100 was 38% (95% confidence interval [CI] = 25%, 55%) and 20% (95% CI = 10%, 39%), respectively, with a median time to onset of 66 days. For the entire cohort, 1-year overall survival, disease-free survival, and relapse rates were 54% (95% CI = 41%, 71%), 47% (95% CI = 35%, 65%), and 37% (95% CI = 19%, 51%), respectively. Outcomes differed based on stage of disease at time of transplantation, advanced (n = 19) versus nonadvanced (n = 25). Median survival times were 138 days and 685 days for subjects with advanced and nonadvanced disease, respectively (P =.005). After adjusting for age and comorbidity, disease stage continued to be significantly associated with overall survival (P =.005). In conclusion, a moderate reduction in conditioning dose intensity resulted in delayed onset of acute GVHD (compared with historical controls). A reduction in conditioning intensity is associated with poor survival for patients with advanced-stage disease, highlighting the importance of the conditioning regimen for tumor control.

Levine JE ，Uberti JP ，Ayash L ，Reynolds C ，Ferrara JL ，Silver SM ，Braun T ，Yanik G ，Hutchinson R ，Ratanatharathorn V ... -  《BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION》

Allogeneic stem cell transplantation after a fludarabine/busulfan-based reduced-intensity conditioning in patients with myelodysplastic syndrome or secondary acute myeloid leukemia.

Kröger N ，Bornhäuser M ，Ehninger G ，Schwerdtfeger R ，Biersack H ，Sayer HG ，Wandt H ，Schäfer-Eckardt K ，Beyer J ，Kiehl M ，Zander AR ，German Cooperative Transplant Study Group ... -  《ANNALS OF HEMATOLOGY》

Impact of postgrafting immunosuppressive regimens on nonrelapse mortality and survival after nonmyeloablative allogeneic hematopoietic stem cell transplant using the fludarabine and low-dose total-body irradiation 200-cGy.

Koh LP ，Chen CS ，Tai BC ，Hwang WY ，Tan LK ，Ng HY ，Linn YC ，Koh MB ，Goh YT ，Tan B ，Lim S ，Lee YM ，Tan KW ，Liu TC ，Ng HJ ，Loh YS ，Mow BM ，Tan DC ，Tan PH ... -  《BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION》

Alloreactivity as therapeutic principle in the treatment of hematologic malignancies. Studies of clinical and immunologic aspects of allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning.

Petersen SL 《-》

A fludarabine-based dose-reduced conditioning regimen followed by allogeneic stem cell transplantation from related or unrelated donors in patients with myelodysplastic syndrome.

Kröger N ，Schetelig J ，Zabelina T ，Krüger W ，Renges H ，Stute N ，Schrum J ，Kabisch H ，Siegert W ，Zander AR ... -  《BONE MARROW TRANSPLANTATION》