Outcomes among Patients with Recurrent High-Risk Hematologic Malignancy after Nonmyeloablative Versus Myeloablative Allogeneic Hematopoietic Cell Transplantation.
Authors: Mielcarek Marco , Martin Paul J. , Maloney David G. , Storb Rainer , Sandmaier Brenda M. 
Published: October 2019

Recurrence of high risk hematologic malignancy after allogeneic hematopoietic cell transplantation (HCT) indicates the persistence of malignant cells that are resistant to the conditioning regimen given before HCT and the immunologic effects of donor cells after HCT. Early recurrence of high-risk hematologic malignancy after myeloablative conditioning is associated with a very poor prognosis. Given the minimal exposure to cytotoxic therapy during and the lower burden of regimen-related toxicity after nonmyeloablative preparative regimens, we hypothesized that relapse-directed interventions would be more effective for patients with high-risk malignancy after HCT with nonmyeloablative conditioning compared to myeloablative conditioning. We retrospectively analyzed outcomes among 195 patients treated for acute leukemia (AML, n=123; ALL, n=28), chronic myeloid leukemia beyond accelerated phase (n=21), or high-risk myelodysplastic syndromes (n=23) that recurred after HCT with myeloablative or nonmyeloablative conditioning between 1995 and 2004. Relapse-directed interventions included withdrawal of immunosuppression (WIS), chemotherapy, and donor lymphocyte infusion (DLI) used singly or in combination as allowed by clinical circumstances. Interventions were used for 68% and 87% of patients who had recurrence < 100 days after HCT with myeloablative or nonmyeloablative conditioning, respectively, and for 83% and 95% of those who had recurrence ≥ 100 days after HCT.

The incidence rates of life-threatening GVHD and remission were 6% and 25% among patients with myeloablative conditioning, compared to 19% and 26% among those with nonmyeloablative conditioning (Table 1). The incidence of remission was higher among patients who had recurrence ≥ 100 days after HCT as compared to < 100 days after HCT (p = 0.04). Contrary to our hypothesis, interventions were not more effective among patients with nonmyeloablative conditioning compared to myeloablative conditioning, as measured by remission rates (Table 1) or survival. The 2-year survival rates among patients with recurrence < 100 days after HCT were 4% and 0% among patients who had myeloablative and nonmyeloablative conditioning regimens, respectively. The corresponding 2-year survival rates among patients with recurrence ≥ 100 days after HCT were 12% and 5%. In summary, with either myeloablative or nonmyeloablative conditioning regimens, limited clinical benefit is gained from the interventions typically used for management of early recurrent high-risk hematologic malignancy after HCT. Thus, innovative and more effective strategies are needed for treatment of recurrent high-risk malignancy after allogeneic HCT.

Interventions and outcomes among patients treated for recurrent high-risk hematologic malignancy after allogeneic HCT Total WIS Chemo DLI GVHD* CR *GVHD, life-threatening graft-versus-host disease; CR, complete remission. **Recurrence was detected at 100–200 days from HCT in 9 cases and >200 days in 11 cases. Myeloablative conditioning Recurrence < Day 100, n (%) 87 78 51 11 6 16 (90) (59) (13) (7) (18) Recurrence ≥ Day 100–200, n (%) 65 50 55 13 3 21 (77) (85) (20) (5) (32) Non-myeloablative conditioning Recurrence < Day 100, n (%) 23 18 13 5 5 5 (78) (57) (22) (22) (22) Recurrence ≥ Day 100, n (%)** 20 13 15 2 3 6 (65) (75) (10) (15) (30)