Outcomes after Donor Lymphocyte Infusion for Insufficient Donor Chimerism Following Hematopoietic Cell Transplantation for Non-Malignant Disorders

Background:

Little is reported of the utility of donor lymphocyte infusion (DLI) following HCT for non-malignant disorders (NMD). We describe outcomes after DLI for insufficient donor chimerism after HCT in a large NMD cohort.

Patients/Methods:

We queried the Institutional BMT Database for patients with NMD receiving DLI for insufficient post-HCT donor chimerism. HLA typing, graft selection and conditioning were per institutional guidelines. The use, timing and dosing of DLI was at the discretion of the treating physician. Donor chimerism values on the myeloid fraction of peripheral blood at pre-DLI and most-recent time-points were reviewed. Patients were considered best DLI responders if donor chimerism improved (pre-DLI to most-recent) and most recent chimerism was ³ 80%.

Results:

Twenty-three patients (43% female) were identified. Table 1 shows patient, disease, transplant and DLI characteristics. The median zenith chimerism post-HCT (but pre-DLI) was 84% (IQR, 39 - 99%), observed at a median 28 days post-HCT. The median chimerism just prior to first DLI was 40%. The median time to first DLI was 90 days. Patients underwent a median 2 cycles (IQR, 2 - 3; maximum, 5) of DLI; the median cumulative per-patient CD3+ dose was 11.5 x 10⁶/kg. Post DLI, two patients developed aGvHD and 2 patients developed cGvHD.

Five patients (22%) were best DLI responders. At a mean 3.6 years post-HCT, they retained mean chimerism of 94% (mean increase from pre-DLI of 37%). Of the 18 non-best responders (78%), median chimerism at last follow-up was 10% (IQR, 2 - 25%). Seven patients underwent repeat HCT. Best response to DLI did not depend on HCT total nucleated cell dose, donor relatedness, serotherapy agent of HCT regimen, chimerism prior to DLI, or total DLI CD3+ dose. Best responders tended to have undergone myeloablative conditioning, be HLA-matched to the donor and receive first DLI later post-HCT (median 102 days, versus 83 days).

Conclusions:

In a large NMD cohort undergoing DLI after HCT, sustained high donor chimerism response was observed in 22%. Ongoing analyses aim to assess those with intermediate response (many of whom also enjoy improved or stable NMD), as well as the impact of peri-DLI immune suppression on outcomes.