Although myeloablative conditioning (MAC) before haploidentical donor transplant (HIDT)
with post-transplant cyclophosphamide is being increasingly used, the optimal preparative
regimen remains unclear. In our initial trial, the feasibility of HIDT following a
MAC preparative regimen using fludarabine and 12 Gy of total-body irradiation was
demonstrated in 30 patients. We now present long-term outcome results, including an
additional 52 patients, now with 47 months (16 to 96) median follow-up. Median patient
age was 42 (19 to 61) years. The most common diagnoses were acute myelogenous leukemia
(51%) and acute lymphoblastic leukemia (33%), and 39% had a high/very high disease
risk index (DRI). Engraftment was universal with no cases of primary or secondary
graft failure. Grade 3 to 4 acute graft-versus-host disease (GVHD) and moderate to
severe chronic GVHD occurred in 17% and 23%, respectively. Nonrelapse mortality (NRM)
was 7% at 1 year and 13% at 4 years. Estimated 4-year overall survival (OS), disease-free
survival, and cumulative incidence of relapse (CIR) were 67%, 60%, and 27%, respectively.
CIR was significantly higher in patients with high/very high- versus low/intermediate-risk
DRI (38% versus 20%, P= .032), which led to inferior 4-year OS (50% versus 77%, P = .001).
Median time to systemic immunosuppressive therapy (IST) discontinuation was 7.8 months,
with 84% of patients off IST at 2 years post-transplant. Current GHVD-free, relapse-free
survival (CGRFS) at 2, 3, and 4 years was 60%, 57%, and 60%, respectively. This approach
to MAC HIDT results in universal engraftment; low rates of NRM, infection, and clinically
significant GVHD; and relatively rapid IST discontinuation, resulting in high rates
of CGRFS and survival.