Relapse or progression after hematopoietic cell transplantation using nonmyeloablative conditioning: effect of interventions on outcome

Objective This study analyzes the effect of interventions aimed at reinducing remissions in patients with relapse or progression of malignant disease following allogeneic hematopoietic cell transplantation (HCT) using nonmyeloablative conditioning. Methods We performed a retrospective analysis of 81 instances of relapse or progression occurring among 224 patients given HCT as treatment of their hematologic malignancies. All patients received conditioning with 2 Gy total-body irradiation with or without fludarabine and with postgrafting immunosuppression with mycophenolate mofetil and cyclosporine. Results Overall survival of patients after relapse or progression was 36%. Fifteen of the 81 patients were given no interventions. Three of these 15 (20%) patients are alive with disease while 12 died with disease progression. Sixty-six patients (81%) received interventions, including withdrawal of immunosuppression (n = 32), donor lymphocyte infusions (n = 13), or chemotherapy (n = 21). Twenty of the 66 (30%) are alive, 5 in complete remission, 4 in partial remission, 1 with stable and 10 with progressive disease. The overall response rate to intervention was 27%. Forty-six (70%) of the patients given interventions died, mainly due to relapse/progression. Patients not receiving interventions had a 1-year survival estimate of 15% compared to 41% in patients given interventions. Factors associated with survival in patients given intervention were disease response (p = 0.002), disease category (p = 0.001), and time to relapse from transplantation (p = 0.0005). Conclusion While the overall prognosis of patients relapsing or progressing after nonmyeloablative HCT is poor, interventions such as the combined use of immunotherapy and chemotherapy can improve patient survival.