The Outcomes of Second Allogeneic Stem Cell Transplantation for Disease Relapse after T Cell Depleted Allogeneic Stem Cell Transplantation: A Single Center Experience-University of Chicago

The outcome of disease relapse after allogeneic stem cell transplantation (allo-SCT) remains very poor. Second SCT has achieved long term survival in select pts. We retrospectively analyzed the outcomes of 65 pts who underwent 2rd SCT for disease relapse at University of Chicago between September 2002 and September 2013. All except 4 pts received T cell depleted (TCD) SCT as 1^st SCT mainly with fludarabine (flu)/clofarabine-melphalan (mel) -alemtuzumab; flu-busulfan-alemtuzumab for MRD or MUD, and flu-mel-ATG for haplo-cord SCT. The majority of pts had AML (n=46) and high risk MDS (n=5). The median age at 2^nd allo-SCT was 47ys (11-73). 33 pts, 21 pts and 11 pts received MRD, MUD and Haplo-Cord SCT respectively for 2^nd SCT. 13 pts (20%) achieved CR before 2^nd SCT. 71% pts received TCD conditioning for 2^nd SCT. 98% (n=64) and 72% (n=47) pts achieved neutrophil and platelet engraftment at a median time of 11 and 18 days, respectively, following the 2^nd SCT. With a median fellow up of 23 (5.5-140) months for survivors after 2^nd SCT, the estimated 1 year PFS was 29.2% and 1 year OS was 33.8%. The day 100 treatment related mortality (TRM) rate was 28%, and the cumulative incidence of aGVHD and cGVHD were 23% and 8%, respectively. Not surprisingly, the majority of pts died from disease relapse (22/47, 47%), followed by infection (11/47, 23%) and GVHD (6/47, 13%). In the univariate analysis, pts with remission duration after 1^st SCT >=12 months or CR status before 2^nd SCT had significantly better PFS (P=0.001 and 0.009) and OS (P=0.001 and 0.013). The differences of 1 year PFS and OS stratified by these two variables were very striking. The 1 years PFS for pts in CR was 62% compared to 21% for pts not in CR; and 1 year PFS for pts with remission duration >=12 months after 1^st SCT was 57% comparing around 14% for pts <12 months. On the other hand, donor type (MRD vs. MUD vs. haplo-cord), conditioning (RIC vs. myeloablative) had no influence on PFS and OS. While age (<=60 vs. >60) had no influence on 1 year PFS (P=0.083), younger pts had better 3 year PFS (P=0.026); Alemtuzumab use (n=37 vs. n=16 without alemtuzumab) in the 2^nd SCT conditioning for related donors significantly worsened 3 years PFS (44% vs. 8%; P=0.027) but not 1 year PFS, and it had no effect on OS. A scoring system using age (<=60 vs. >60), disease status before 2^nd SCT (CR vs. non-CR), and remission duration after 1^st SCT (<6, 6-12 and >=12 months) was generated to attempt to classify the pts into different risk categories. The groups of 0 (n=5), 1-2 (n=34), 3-4 (n=26) could separate the 1 year PFS (80% vs. 32.3% vs. 15.4%) and OS (100% vs. 35.3 vs. 19.2%) nicely. Although the numbers are small, pts with a score of 0 (<=60 yrs, in CR, and >=12 months remission duration after 1^st SCT) had excellent outcomes with 1 year PFS of 80%, and 1 year OS of 100%. In conclusion, 2^nd allo-SCT is a viable option for disease relapse after TCD allo-SCT with acceptable GVHD and good engraftment for those entering transplant in remission and/or remission duration >=12 months after 1^st SCT.