PB2350 EFFICACY AND SAFETY OF POST HEMATOPOIETIC STEM CELL TRANSPLANTATION DONOR LYMPHOCYTE INFUSION IN PATIENTS WITH ACUTE LEUKEMIA. RETROSPECTIVE ANALYSIS IN OUR CENTER
Authors: Romero Y. Gonzalez , Mora J. , Cortes M. A. , Luis S. Fernandez , Gomez D. , Cabero A. , Fernandez C. , Garcia S. , Insunza A. , Amunarriz C. , Yañez L. , Romon I. , Duarte M. Lopez , Bermudez A. , Ocio E. , Martin G. 
Published: June 2019

Background:

Relapse of acute leukemia (AL) after allogenic hematopoietic stem cell transplantation (alloHSCT) worsens patients’ prognosis. Donor lymphocyte infusion (DLI) may be an effective therapy in these patients.

Aims:

Our objective was to asses the efficacy and safety of DLI in three different settings after alloHSCT: therapeutic (relapse or progression), pre‐emptive (positive minimal residual disease or mixed chimerism) and prophylactic (patients at high risk of relapse).

Methods:

Retrospective analysis of 30 patients with AL who received DLI after alloHSCT from 2000 to 2018. Patients in 2nd or further complete remission (CR), positive MRD or adverse cytogenetics were considered at high risk for relapse. Median age was 37 years (5‐71). Twenty one patients were males. The baseline characteristics of the patients are shown in table 1.

Twenty two patients had a matched donor (14 related, 8 unrelated), 5 patients received a mismatched graft and 3 patients a haploidentical graft. Fourteen patients received DLI therapeutically, 11 pre‐emptive and 5 as prophylaxis. At DLI, only one patient had mild chronic graft versus host disease. All patients were off immunosuppresive therapy at DLI. Seven patients received reinduction chemotherapy before the DLI.

Fifty eight doses of DLI were administered, with a median of 1 (1‐5) dose per patient. The maximum infused dose varied, depending on the type of donor and degree of HLA disparity: 5,4 (1 ‐15,3), 4,2 (1‐10), 1,9 (0,2‐4,6) and 0,5 (0,2‐1)  × 10^7/kg in matched related donor, matched unrelated donor, missmatch and haploidentical, respectively. The dose was higher in the therapeutic group. Median time until triggering event of DLI (relapse, appearance of MRD or loss of chymerism) was 132 days (21‐547) and median time from alloHSCT until first DLI was 179 days (38‐771)

Leukemia Free Survival (LFS) and overall survival (OS) were calculated using de Kaplan‐Meier (KM) method and compared using the log‐rank test. The median follow‐up was calculated with the inverse of KM. SPSS software was used for the data analysis.

Results:

Nine out of 14 patients in the therapeutic group reached CR and 1 PR. Among 11 patients in pre‐emptive group, 5 reached CR. Four out of 5 patients in the prophylactic group remained in CR. The median follow up after DLI was 65 (IC 95% 16,3 to 113,6) months. Median OS and LFS for the entire cohort were 14 (IC 95%, 3, 9 to 24,1) and 9 (IC 95%, 1,1 to 16,9) months, respectively.

Median OS and LFS in the therapeutic group were 7 (CI 95%, 1, 5‐12,5) and 4 (CI 95%, 0‐12,5) months, respectively. Median OS and LFS in the pre‐emptive group, were 14 (CI 95% 7, 7‐20,3) and 5 (CI 95%, 0‐38) months, respectively. In the prophylactic group, the median OS (p = 0,029) and LFS (p = 0,01) were not reached. The LFS probability at 1, 2 and 3 years was 80% (IC 95%, 77 to 82).

Patients in CR after DLI (n = 14) had a median LFS of 17 months (IC 95% 5,5 to 28)

After DLI, 14 (46,7%) patients developed GvHD: grade III‐IV acute GvHD in 2 (6,7%) and moderate‐severe chronic GvHD in 5 (16,6%). Two patients with chronic GvHD died of related complications. The causes of death were: relapse (n = 13), severe infection (1), demyelinizing neuropathy (1) and 2 unknown.

Summary/Conclusion:

Our data suggest that prophylactic DLI could improve LFS in high risk patients. Therapeutic and pre‐emptive DLI was useful in a subgroup of patients with relapsed leukemia or positive MRD. More than half of relapsed patients reached CR after DLI. DLI was a safe treatment, GVHD being the most frequent complication but with a low incidence of severe forms.

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