PS1564 HAPLOIDENTICAL TRANSPLANTATION FOR ACUTE MYELOID LEUKEMIA PATIENTS WITH DETECTABLE DISEASE AT TRANSPLANT
Authors: Srour S.A. , Saliba R. , Popat U. , Oran B. , Mehta R. , Kebriaei P. , Bashir Q. , Olson A. , Chen J. , Hosing C. , Khouri I. , Qazilbash M. , Shpall E. , Champlin R. , Ciurea S. 
Published: June 2019

Background:

Patients with acute myeloid leukemia (AML) with minimal residual disease (MRD) and not in complete remission (CR) have inferior outcomes after HLA‐matched allogeneic stem cell transplantation (SCT). Haploidentical SCT (HSCT) is being increasingly used worldwide as an alternative donor source for patients who lack an HLA matched donor. The impact of MRD and disease status at transplant on HSCT outcomes for patients with AML are unknown.

Aims:

To determine the impact of pre‐transplant disease status on AML outcomes after HSCT.

Methods:

All consecutive patients with AML who underwent HSCT with post‐transplantation cyclophosphamide (PTCy)‐based graft‐versus‐host‐disease (GVHD) prophylaxis between 02/2009–10/2018 were included. MRD status was measured using flow cytometry and/or presence of cytogenetic/molecular abnormalities at time of SCT. Primary endpoints: progression‐free survival (PFS) and overall survival (OS). Secondary endpoints: cumulative incidence of relapse (CIR) and nonrelapse mortality (NRM). Kaplan‐Meier estimates, Cox proportional hazards and competing risks regression were used.

Results:

A total of 143 patients with a median age of 52 (18–72) were identified. Patients received conditioning with fludarabine 160 mg/m2, melphalan 100 or 140 mg/m2 and 2GyTBI, as previously described by our group (Gaballa S. Cancer. 2016). With a median follow up of 29 months, the median PFS and OS of all patients were 10 and 18 months, respectively. The 2‐year PFS and OS were 41% and 47%, respectively. Compared to patients in CR at transplant, those with active disease (n = 29) and CR with incomplete count recovery/hyoplastic marrow [CRi] (n = 39) have worse 2‐year PFS hazard ratios (HR) of 3.5 (95% CI: 2.05–6.1; p < 0.001) and 2.3 (95% CI: 1.3–3.9; p = 0.002), respectively (Figure). Likewise, patients with active disease (HR 3.7, 95% CI: 2.1–6.6; p < 0.001) and CRi (HR 2.1, 95% CI: 1.2–3.8; p = 0.01) had inferior 2‐year OS. Patients with active disease and CRi at transplant have statistically significant worse CIR, but comparable NRM compared to patients in CR. The median PFS and OS for patients in CR at transplant were not reached, compared to 4.3 and 6.5 months, respectively, for those with active disease and 7.1 and 10.3 months, respectively, for those with CRi.

When we subgrouped patients in CR by MRD status at transplant, there was no statistically significant differences between MRD+ve (n = 24) and MRD–ve (n = 41) in both 2‐year PFS (HR 1.85, 95% CI: 0.9–4.0; p = 0.1) and OS (HR 2.1, 95% CI: 0.9–4.8; p = 0.08). In multivariable analysis, only age was predictive for outcomes (Figure). For ≤50 years, MRD status has no influence on outcomes with 2‐year PFS and OS of 65% and 76% and 2‐year OS of 89% and 76% for those with MRD+ve and MRD–ve, respectively (p = NS). Patients older than 50 year and with MRD+ve disease had the worst outcomes with 2‐year PFS and OS of 29% (p = 0.005) and 26% (p = 0.002), respectively.

Summary/Conclusion:

Our findings suggest that patients with MRD+ve have excellent outcomes with HSCT and melphalan‐based conditioning with PTCy‐based GVHD prophylaxis, especially in younger patients. Proceeding to a HSCT in patients with MRD+ve disease does not appear to compromise transplant outcomes and are better than reported outcomes with HLA matched donor transplants. Haploidentical grafts might be a preferred donor source for MRD+ve AML patients who frequently may need to proceed urgently to transplant.

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