Predictive Factors for Adverse Outcomes after Use of Donor Cell Infusion (DCI) in Patients with Relapsed Hematological Malignancies Treated with Allogeneic Hematopoietic Cell Transplantation (Allohct)

DCI is administered after AlloHCT to enhance the graft-versus leukemia effect and thereby induce remission in patients (pts) with relapsed hematological malignancies. The purpose of this retrospective study was to identify risk factors for post-DCI progression and mortality. We identified 47 pts with hematological malignancies who received DCI from 02/1996 to 07/2011 for disease relapse. We analyzed variables such as pts baseline demographics, malignancy type, donor relationship, type of AlloHCT, presence of GVHD, duration of post-transplant remission, use of remission induction chemotherapy prior to DCI and DCI cell dose. Among pts treated with DCI, 36 (77%) had myeloid malignancies. Myeloablative regimen was used in 36 pts (77%) and 35 pts (74%) had HLA-identical sibling donor transplant. 45 pts (96%) had grade <2 aGVHD and 40 pts (85%) had limited or no cGVHD. Median time of post-transplant relapse was 6.0 months (range, 0.9-84.6) and the median time from transplant to DCI therapy was 7.8 months (range, 2.3- 114). DCI was used once in 89% of pts and it was preceded with chemotherapy in 35 of 45 pts (78%). Median CD34 and TNC doses for the first DCI were 2.0x106 and 3.9x108 respectively. The rate of post-DCI grade 3-4 aGVHD was 2% vs. 17% for extensive cGVHD. With a median follow-up of 40.8 months (range, 2.3-174.1), 38 pts (77%) had died and 29 (62%) relapsed. Relapse was the most common cause of death (n = 25, 69%) after DCI. Although pts who received unrelated DCI tended to have less post-DCI relapses (42% vs. 69%), deaths (50% vs. 86%) or fatal events due to relapse (50% vs. 73%), the numbers were too small to detect statistically significant differences between groups. Recursive partitioning analysis indicated that pts who had disease relapse within 20 months after transplant (n = 39) were at higher risk of post-DCI relapse, worse OS and RFS. Multivariable analysis demonstrated that a bone marrow cell source was associated with poor OS (HR = 2.6; 95% CI 1.3-5.6, p = 0.01) compared to peripheral blood, and that post-transplant disease relapse within 20 months was an adverse predictor for post-DCI relapse (HR = 5.2; 95% CI 1.2-22.3, p = 0.025), OS (HR = 5.5; 95% CI 1.6-18.5, p = 0.006) and RFS (HR = 3.5; 95% CI 1.2-9.9, p = 0.02). With long follow-up we demonstrated that disease relapse within 20 months of AlloHCT portends poor clinical outcome despite DCI, but for patients with longer remission duration, DCI can result in long-term progression free survival.