Second Allogeneic Stem-Cell Transplantation (SCT) From a Different Donor for the Treatment of Relapsed AML and MDS After a Previous Allogeneic SCT

Allogeneic SCT is curative therapy for patients (pts) with AML and MDS. However, relapsed disease continues to be the most common reason for treatment failure. Treatment options range from supportive care alone to chemotherapy and donor lymphocyte infusion (DLI) and up to a second SCT from the same or a different donor. However, the most effective therapy is controversial and treatment results are often poor. Over the last 6 years our policy was to offer a second SCT from a different donor to pts who had a second donor available and were in relatively good medical status, most often after an attempt for remission induction with intensive chemotherapy. There were 129 relapses of AML/MDS after SCT during this period, and 26 pts (20%) were able to proceed to a second SCT from a different donor. The median age at second SCT was 51 years (19-78). 20 pts were initially given SCT from a matched sibling, 12 were re-transplanted from a second sibling and 8 from an unrelated donor.  Six pts were initially transplanted from an unrelated donor and re-transplanted from a different unrelated donor.  The initial conditioning regimen was myeloablative (MAC, n=10), reduced-toxicity (RTC, n=12) or reduced-intensity (n=4). The second regimen was most often fludarabine and treosulfan (FT, n=15) for those not previously given treosulfan, including all previously MAC recipients. Other regimens were fludarabine/ busulfan (n=7) or FLAMSA (n=4). The median time from the first SCT to relapse was 12 months (2 months – 9 years), 7 within 6 months. The median time from first relapse to second SCT was 3 months (range, 1-41 months).  10 pts were in remission at second SCT with prior therapy, 9 were chemo-refractory  and 7 were re-transplanted with no attempts of re-induction. The median follow-up of surviving pts is 14 months (range, 2-77). 24 pts engrafted in a median of 13 days (range, 9-26). 2 pts died early from infections and 2 from GVHD and the 2-year cumulative incidence of NRM was 16% (95%CI, 6-38). 13 pts relapsed after second SCT, 2-year cumulative incidence 52% (95%CI, 34-77), 10 of them died.  The estimated 2-year OS is 37% (95%CI, 14-60) and the 2-year disease-free survival is 33% (95%CI, 13-53). Pts re-transplanted in chemo-sensitive or untreated relapse had a better outcome than those with chemo-refractory relapse, 2 year OS 49% and 17%, respectively (p=0.05). Pts given FT for second SCT also fared better than the other regimens, 2-year OS 65% and 18%, respectively (p=0.01). 3 of 7 pts with relapse less than 6 months after SCT are long-term survivors after second SCT.  In conclusion, a second SCT from a different donor is feasible in a subset of pts with AML and MDS relapsing after SCT. Toxicity with the new RTC regimens, such as treosulfan-based is acceptable. This is a promising option for pts able to be successfully re-induced or re-transplanted early with a pre-identified second donor. These observations merit further confirmation in larger studies.