Survival After Second Allogeneic Transplant Is Improved in Recipients by Using the Original Donor

Relapse remains a major problem after allogeneic stem cell transplant (alloHSCT). There are limited data on the outcomes after second alloHSCT. We conducted a single institution retrospective review of 39 subjects who have received two alloHSCTs between 1997-2011. Univariate survival analyses (Kaplan Meier log-rank test) were conducted to investigate factors affecting disease-free survival (DFS) and overall survival (OS). Group differences between cases with/without GVHD were examined by t-tests on engraftment lab variables.

The median age was 44 years (20-70). AML/MDS accounted for 71% of the cases. Indications for second alloHSCT were graft failure (16%) and disease relapse (84%). Myeloablative conditioning was used in 62% of the patients. Median time from first to second transplant was 427 days (49-3835) and median time from relapse to second alloHSCT was 142 days (16-2524). 62% of the second alloHSCTs were from an unrelated donor. 36% of second transplants were from the original donor. OS at 1 and 5 years was 41% and 21% respectively [median 229 days (5 – 5320)]. Factors prolonging OS were: GVHD (P=0.05), chronic GVHD (cGVHD) (P<0.01) and using the same donor for both alloHSCTs (P<0.01). Male recipients, transplant from females to males, and transplants from unrelated donors trended towards better survival rates but were not significant (P=0.069, 0.09, and 0.059 respectively). Survival was not affected by: age, acute GVHD (aGVHD), diagnosis, risk stratification at diagnosis or second alloHSCT, remission status at second alloHSCT, conditioning intensity, HLA compatibility, donor’s sex, or CMV status of the donor/recipient. The median DFS after the second alloHSCT was 112 days (5-4759). Incidence of aGVHD and cGVHD was 41% and 41% respectively. Patients who developed GVHD or cGVHD had better DFS (P<0.01, P=0.03, respectively). Risk of GVHD was higher in patients who received more CD34/kg cells (P=0.02) while CD3/kg dose was not statistically significant. Remission status at the time of the second alloHSCT did not affect OS or DFS. 13% of the patients developed CMV viremia. Median time to neutrophil engraftment was 12 days (4-37), and median platelet engraftment >50,000/mcL was 21 days (9-103). Patients who developed GVHD had earlier platelet engraftment (Means: 16 vs. 30 days, P=0.04).

This single center experience of second alloHSCT suggests this treatment results in long-term survival in select patients. Survival is improved when the original donor is used as the second donor. Future studies will focus on predictive modeling to help choose patients who may benefit most from a second alloHSCT.