IC-01. The role of NK-cells associated factors in outcomes of haploidentical hemopoietic stem cells transplantation performed after selective depletions
Svetlana Yu. Glushkova, Viktoria A. Vedmedskaya, Dmitriy E. Pershin, Yakov O. Muzalevskii, Alexei S. Kazachenok, Elena E. Kurnikova, Svetlana A. Radygina, Maria A. Ilushina, Rimma D. Khismatullina, Larisa N. Shelikhova, Dmitriy E. Balashov, Alexei A. Maschan, Michael A. Maschan
Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
Contact: Dr. Svetlana Yu. Glushkova, phone: +7 (963) 672-72-19, e-mail: Rizoiu.svetlana@gmail.com
Summary
TCRαβ+/CD19+ cells depletion allows reducing the risks of severe complications after haplo-HSCT and also retains NK-cells in the graft. In this retrospective analysis we attempt to focus on the relationship between simple NK-related factors, namely KIR mismatch, NK graft content, peripheral blood NK cells counts on day +30 after HSCT and transplant outcomes, such as relapse or transplant-related mortality (TRM) incidence, in a cohort of children with acute leukemia transplanted in complete remission.
Materials and methods
The study cohort includes 296 patients diagnosed with ALL (acute lymphoblastic leukemia) in 190, AML (acute myeloblastic leukemia) in 94, and ABL (acute biphenotypic leukemia) in 12 cases, accordingly. All patients received their first haplo-HSCT with αβ T cell depletion from January 2012 to April 2021. KIR match or mismatch was predicted based on ligand-ligand model for all patients. Patients cohorts were divided by median absolute count of graft NK cells subpopulation and peripheral blood NK cells count on day +30 after the HSCT. The relapse and TRM risks were calculated for each group by cumulative risk method, groups were compared by Gray test.
Results
The cumulative relapse incidence was 28.6% (23.5%-34.9%) in the whole cohort, 28.6% (22.6%-36.3%) among patients with ALL, 26.8% (18.3%-39.4%) among patients with AML, and 42.7% (19.6%-93.2%) in the small ABL cohort. There were 16 non-relapse mortality cases in the whole cohort. The cumulative TRM incidence was 5.9% (3.7%-9.6%) in the whole cohort, 8.1% (4.9%-13.5%) for ALL, and 2.1% (0.5%-8.4%) for AML patients. KIR mismatch was predicted for 32.7% donor-recipient pairs. We failed to detect a correlation of KIR mismatch and relapse or TRM incidence either in whole cohort or in smaller ALL and AML cohorts. There were only 2 TRM cases in the AML group, both of them inside KIR-mismatched cohort. No correlation was detected between NK cells dose in the graft and leukemia relapse incidence in the whole cohort, while there was a trend for lower relapse rate in ALL patients receiving higher NK-cells dose (p=0.140). There was also a trend to higher TRM in patients with receiving higher than median NK-cells dose (p=0.135 for total cohort, p=0.087 for ALL cohort). The higher dose of NK cells has a trend to correlate with lower leukemia relapse risk in the group with donor-recipient KIR mismatch (p=0.06) and there was no correlation in the KIR-matched patients’ cohort. Among patients with AML without KIR mismatch, surprisingly, higher relapse incidence was seen among patients with higher dose of NK cells in the graft (p=0.002). In the whole AML patients’ cohort higher peripheral blood NK cells counts on day +30 also correlated with higher relapse risk (p=0.025).
Conclusions
A higher dose of NK cells in the graft was associated with a lower relapse risk for KIR mismatch patients with acute leukemia, both ALL and AML. Paradoxically, higher dose of graft NK cells was associated with higher relapse risks in patients with AML receiving KIR-matched HaploHSCT.
Keywords
Hematopoietic stem cell transplantation, TCRαβ+/CD19+ depletion, acute leukemia, immune reconstitution, HSCT complications.
