Campath-1H-Containing Reduced Intensity Regimen Followed by Unrelated Allogeneic Stem Cell Transplantation in Patients with Advanced Hematologic Malignancies.

Abstract

BACKGROUND: Graft versus host disease (GVHD) remains a major cause of mortality after unrelated transplants. Reduced intensity conditioning regimens (RIC) followed by allogeneic stem cell transplantation (SCT) with in vivo T-cell depletion using Campath-1H have been shown to decrease the incidence of GVHD. We report our experience with such an approach in 19 patients (pts) with advanced hematologic malignacies who undergone unrelated SCT.PATIENTS AND METHODS: Between October 2001 and June 2003, 19 pts with a median age of 56 years (range 18–70) not eligible for ablative SCT received Campath-1H 20 mg/m2, fludarabine 25 mg/m2 × 5 days and either cyclophosphamide 1 g/m2 × 2 days (n=16pts), melphalan 140mg/m2 (1 pt) or busulfan 0.8 mg/m2 × 8 doses (n=2pts) followed by G-CSF stimulated peripheral blood (n=13) or unmanipulated bone marrow (n=6). GVHD prophylaxis consisted of cyclosporin at least until T+60 and mycophenolate mofetil through T+30. DLI was allowed for residual disease/progressive disease or mixed chimerism after T+ 60, in the absence of acute GVHD. Seven pts had a previous autologous transplant. Ten pts had myeloid diseases (AML=6, CML Ph negative=1, CML accelerated phase =1, therapy related MDS=1, myelofibrosis=1); 9 pts lymphoid (HD=3, NHD=5, PLL=1); Only 5 pts were in CR at transplant. Six pts received bone marrow witha median CD34+ cells infused of 3.7 × 106/Kg, and 13 pts received peripheral blood with a median of 4.5 × 106/Kg CD34+ cells infused.RESULTS:19 pts achieved ANC>0.5 × 106/L within a median of 12 days (range 8–16); 2 pts rejected the graft and 1 had autologous reconstitutuion; 10/19 pts achieved sustained platelet engraftment at a median of 16 days (range7–27). 2/17 pts with sustained engraftment developed acute GVHD (grade IV T+30 and grade III T+53); 7/14 at risk pts had CMV reactivation; TRM at T+100 was 16% (disease progression in 2 and GVHD in 1). Nine pts received DLI (5 for mixed chimerism and 4 pts for persistent/progressive disease). After DLI, 5 pts had GVHD limited to skin. None of the pts receiving DLI for persistent/progressive disease responded. Response to transplant was as follows: CR in 3/6 AML pts, CR in 1/1 pt with myelofibrosis, CR in 3/3 HD pts, CR in 3/5 NHL pts. Five pts (26%) remain alive in CR at T+ 36, 42, 50, 56 and 66 months. Causes of death include disease progression/relapse in 7 pts, CMV disease in 1 pt, sepsis in 2 pts, GVHD in 3 pts (2 underwent a second transplant), other malignancy in 1 pt.CONCLUSION: These results confirm that unrelated SCT with in vivo T -cell depletion using Campath-1H is well tolerated. This approach is associated with low TRM even in pts with advanced disease, and some can achieve long-term disease control. Disease progression/relapse remains a major impediment to this approach.