What Happens Next? - Outcomes after Relapse Following Allogeneic Haematopoietic Stem Cell Transplant for Acute Leukemia in Adults

Background: Relapse after allogeneic stem cell transplant (allo-HSCT) for acute leukaemia (AL) remains a major challenge. Despite advances in allo-HSCT reducing risk of morbidity and mortality, relapse has not altered significantly. We performed a single institution review of relapse following allo-HSCT in patients with AL examining salvage therapy and characteristics of long term survivors.

Methods: All adult patients who proceeded to an allo-HSCT for AL from 1998-2012 (n=100) were reviewed. 24 relapsed following allo-HSCT and a detailed review of salvage treatments and outcomes was made. Probability of overall survival (POS) and 95% confidence interval (CI) were calculated by actuarial method.

Results: The 5 year POS of the 100 patients with AL proceeding to allo-HSCT was 71 % (CI 61-80%). Of 24 relapsing after allo-HSCT, 17 had initial diagnosis AML, and 7 ALL. The AML group median age was 49y (range 22-65), 53% male. Ten patients received sibling donors, 6 unrelated donors and 1 patient a related haplo-identical donor. Relapses were mostly systemic (14) and extra medullary (EM) 3 of the 17 cases. Median time to relapse was 13 months (3-57). Salvage treatments were: second allo-HSCT +/- chemotherapy (chemo) (n=5); donor lymphocyte infusion (DLI) +/- chemo (n=5); chemo +/- withdrawal of immunosuppression (WI) (n=4); or palliative/supportive care (n=3). Ten patients (57%) achieved complete response (CR), and CR was maintained by 8 patients (47%), with a median follow up 34 months (range 8-66). All deaths (n=9) were due to disease. All 3 patients with EM relapse are in ongoing remission.

In the ALL group (n=7) median age was 22y (range 19-52), 57% of male. 3 were sibling donor transplants, 3 unrelated and 1 patient received a double cord. Relapse was systemic in 5 patients, and EM in 2. Median time to relapse was 13 months (range 3-57). Salvage treatments comprised: chemo +/- WI (n=3), second allo-HSCT +/- salvage chemo (n=2), DLI +/- salvage chemo (n=1), with 1 patient receiving novel monoclonal antibody therapy.  Three patients achieved a CR, however, all died, 2 of disease progression. Two patients remain alive in PR with ongoing salvage treatment to be determined.

Conclusions: Despite advances in allo-HSCT, long term survival outcomes for patients with ALL who relapse after allo-HSCT remain poor. However, in contrast, for patients with AML who relapse, durable long-term remissions can be achieved with salvage therapy (with and without second allo-HSCT) with almost half of our patients (47%) in ongoing CR at a median of 34 months (range 8-66). As shown in other studies EM relapse, may be salvaged with good long term results.