The Australian Experience with Relapsed Acute Myeloid Leukaemia Post Allogeneic Haematopoietic Stem Cell Transplantation Yields a Simple Prognostic Index for Survival after Relapse

We retrospectively analysed 386 cases of relapsed acute myeloid leukaemia (AML) from 1336 allogeneic haematopoietic stem cell transplants (alloHSCT) performed between 2000-2011, with two aims:  1. To find and validate factors available at time of relapse that would predict for overall survival from relapse (OS). 2. To determine the effect of first salvage therapy and subsequent GVHD on OS.  Aim 1: 349 analysable patients were randomly split into training (n = 233) and validation (n = 116) cohorts. The cohorts were comparable; the only significant difference was more HLA-matched recipients in the validation cohort (P=  .002). Factors predicting inferior OS on univariate analysis were: relapse within 6 months, relapse within 12 months, grade 3-4 acute GVHD prior to relapse, FLT3-ITD mutation, prior induction failure, marrow blasts > 30% at relapse, use of a T cell replete graft, and absence of chronic GVHD prior to relapse. On multivariate analysis, only relapse within 6 months (HR 2.3, P < .001), and grade 3-4 acute GVHD prior to relapse (HR 2.0, P = .004), remained significant. These two factors were combined into a prognostic index and validated; in the validation cohort, patients with 1-2 factors had inferior OS compared to those with 0 factors (HR 2.5, P < .001). This effect remained significant when analysis was limited to the validation cohort patients given salvage (HR 2.3, P = .002). Aim 2: Of 333 analysable patients, 134 patients were not given salvage; their median survival was 33.5 days. 199 patients given salvage had 5y OS of 14%. First salvage therapy was second alloHSCT (ie conditioning plus donor cell infusion) in 55; donor lymphocyte infusion (DLI) (ie donor cell infusion without conditioning) in 16; reinduction chemotherapy (CT) without planned cell infusion in 75; radiotherapy in 8, interferon in 6, and unknown in 7. We defined donor cell therapy (DCT) as second alloHSCT or DLI. Characteristics of patients receiving DCT as first salvage, and patients receiving CT as first salvage, were similar, although CT recipients had shorter median follow-up of survivors (11.2 vs 36.7 months, P = .017). CT as first salvage was inferior to patients receiving DCT as first salvage (5y OS 5% vs 23%, HR 1.8, P < .001). For patients given DCT first, there was no difference in OS between second alloHSCT and DLI (HR 1.1 for second alloHSCT, P = .697). We were unable to demonstrate a benefit in OS for patients with post-relapse GVHD (HR 0.8 for presence of GVHD, P = .405). Our findings underscore the poor prognosis of relapsed AML post alloHSCT and provide useful baseline data for future interventional studies. Patients with relapse beyond 6 months from alloHSCT and without prior grade 3-4 acute GVHD may expect better OS with salvage compared to those with either or both factors. Overall, better outcomes for OS were with DCT as initial treatment.