PB2374 OUTCOMES OF PATIENTS WHO RECEIVED DONOR LYMPHOCYTE INFUSION FROM HAPLOIDENTICAL DONOR; SINGLE INSTITUTE EXPERIENCE
Authors: Yagasaki H. , Nakahara E. , Ito M. , Morioka I. 
Published: June 2019

Background:

Donor lymphocyte infusions from HLA‐matched donor have been performed in patients with posttransplant relapse of chronic myeloid leukemia. In contrast, acute leukemia is refractory to such a conventional DLI. Haploidentical donor stem cell transplantation (H‐SCT) has been employed for refractory acute leukemia because H‐SCT has a potent graft‐versus‐leukemia (GVL) effect. Therefore, acute leukemia is a main target of DLI from haploidentical donor (H‐DLI).

Aims:

We aimed to clarify the role of H‐DLI.

Methods:

A total of 11 children received H‐SCT for refractory leukemia or lymphoma in our institute. After this study was approved by the institutional review board, we analyzed these patients’ outcomes retrospectively.

Results:

Median age of patients is 9 years old (range, 1‐17). Underlying diseases were acute lymphocytic leukemia (ALL) (n = 6), acute myelocytic leukemia (n = 4) and lymphoma (n = 1). H‐SCT was the 1st SCT (n = 5) and 2nd SCT (n = 6). All patients received H‐SCT at non‐remission status after myeloablative conditioning. Six patients received multiple DLIs (DLI group) and 5 did not (non DLI group). Median starting time of DLI was day 72 (range, 43‐270). Median of DLI times, cell dose of CD3+/DLI and duration were 16 (range, 4‐69), 1 × 107(range, 1 × 106‐1 × 107) and 11 months (range, 1‐26). Median fractions of infused cells were followings (range);CD3, 67(56‐74)%, CD4, 40(32‐42)%, CD8, 28(14‐38)%, CD19, 21(18‐25)% and CD56, 14(9‐19)%.

All 5 patients died in non‐DLI group, in contrast, 2 of 6 patients in DLI group have survived without disease for more than 4 years after H‐SCT. Survival duration after H‐SCT was significantly longer in DLI group (median 21 months, range 7‐71) than in non‐DLI group (median 2 months, range 0.5‐30) (log‐rank test, p = 0.012). DLI‐associated acute GVHD (Grade II‐IV) were observed in all 6 patients, therefore, we stopped DLI completely in 3 patients. Other 3 patients continued DLIs under immunosuppressive drugs with prednisolone and tacrolimus. Chronic GVHD is observed in these 3 patients; skin sclerosis in 2 patients and bronchiolitis obliterance in 1 patient. This latter patient relapsed and died at 3 years after H‐SCT.

Summary/Conclusion:

Our DLI strategy was exceptional in terms of its frequency and duration, however, these may be the most important advantage of H‐DLI. As a result, 2 have survived for more than 4 years after H‐SCT. Surprisingly, one of them had poorly prognostic ALL with t(17;19). H‐SCT often fails due to HLA loss on the leukemic cells and T‐cell senescence even if H‐SCT possesses a potent GVL effect. Long‐term DLI therapy can provide fresh, non‐exhausted T and NK cells, and successfully enabled to overcome the immune escape mechanism. Of course, careful observation for organ damage particularly lungs is required. Yet, scarce data regarding the efficacy and safety of H‐DLI are available. Since the use of post‐transplant cyclophosphamide has successfully removed the barrier for H‐SCT, the indications for and limitations of H‐DLI must be clearly defined. There are some limitations in this study; this is a retrospective analysis and small number of patients are included. In the future, a prospective study including infused cell dose, frequency and timing (therapeutic, preemptive or prophylactic) should be planned. In summary, the current case series indicated the possibility to sustain long‐term remission in patients with refractory leukemia using intensive H‐DLI under minimal immunosuppression.