Second Allogeneic Hematopoietic Cell Transplantation Versus Donor Cellular Infusion for Relapse after Transplant

Disease relapse is still a major cause of treatment failure after allogeneic hematopoietic cell transplant (HCT). Although outcomes are still poor, donor cellular infusions (DCI) and second HCT are still the more commonly used treatment strategies to treat relapse after transplant. Little is known, however, regarding the comparable efficacy of either strategy. We thus undertook this retrospective review of patients relapsing after allogeneic HCT. We identified 73 patients who had relapsed after their first allogeneic transplant and received either a DCI (n=38) or second HCT (n=35), as defined by CIBMTR criteria. Patients in the two groups were matched according to basic demographic information including gender, race, performance status, comorbidity index, transplant type, donor source, and diagnosis, which included both myeloid and lymphoid hematologic malignancies. Patients who underwent a DCI were slightly older, median 51 years (18-67) compared to those who received 2^nd transplant, median 46 years (range 16-66), p=0.06; and had a worst grade of GVHD after their first transplant, ≥grade 2, n=14, 37% for DCI, and n=5, 14% for 2^nd transplant, p=0.028. Most patients who underwent DCI received cytoreductive chemotherapy prior to infusion, n=24/36 (67%); likewise patients who underwent 2^nd HCT also received some form of therapy prior to their second procedure, n=17/34, (50%).

Patients who underwent 2^nd transplant had a higher incidence of acute grade 2-4 GVHD, 43% compared to 13% for DCI at 6 months, p=0.032, with no significant differences in severe grade 3-4 GVHD, p=0.15. There were also no significant differences in chronic GVHD, 35% for 2^nd HCT compared to 26% for DCI at 3 years, p=0.58. Relapse mortality was significantly higher in recipients of DCI compared to 2^nd transplant, 56% compared to 33%, p=0.011, respectively; whereas non-relapse mortality was significantly higher in 2^nd HCT, 56% compared to 32% in DCI recipients, p=0.024. Overall survival at 5 years was similar in both groups, 10% in 2^nd HCT recipients versus 12% in DCI recipients, p=0.44. In multivariable analysis, months from 1^st HCT HR 0.76 per 6 month increase (95% CI 0.62-0.93, p=0.007) and DCI (HR 2.06, 95% CI 1.02-4.15, p=0.043) were risk factors for relapse mortality. Conversely, 2^nd HCT was associated with higher non-relapse mortality compared to DCI (HR 2.38, 95% CI 1.15-5, p=0.019). Months from initial transplant (HR 0.92, 95% CI 0.85-0.99, p=0.028), and blast count prior to second procedure (HR 1.12 per 10% increase, 95% CI 1.02-1.23, p=0.017) were the only risk factors for all-cause mortality.  

In summary, we found no differences in overall survival between DCI and 2^nd HCT.  DCI was associated with higher relapse mortality, whereas 2^nd HCT was associated with higher non-relapse mortality. Both modalities have poor survival rates and improved therapeutic options are needed for relapse after HCT.