Human leukocyte antigen (HLA) class-I mismatches that trigger donor-versus-recipient natural killer (NK)-cell alloreactivity reduce the incidence of leukemia relapse and improve survival of acute myeloid leukemia patients after T-cell-depleted HLA-haplotype mismatched ("haploidentical") hematopoietic transplantation. In murine graft-versus-host disease (GvHD) models, alloreactive NK-cells also prevent GvHD. Here we report the results of a non-interventional, prospective study performed on behalf of the Cellular Therapy and Immunobiology Working Party of the European Society for Blood and Marrow Transplantation. The study was aimed at re-assessing the role of NK-cell alloreactivity in a cohort of haploidentical transplants performed in Europe between 2012 and 2015 and composed of unmanipulated, as well as T-cell-depleted transplants. One hundred thirty-eight patients with acute myeloid or lymphoid leukemias were analyzed. Eighty-six patients received ex-vivo T-cell-depleted transplants, 52 patients received unmanipulated transplants. Fifty patients were transplanted from NK alloreactive donors, 88 from non-NK alloreactive donors. NK cell alloreactivity did not impact on GvHD/relapse-free survival (GRFS) in unmanipulated transplants (HR: 1.66 (0.9-3.1), p = 0.1). In contrast, it did impact beneficially on GRFS in T-cell-depleted transplants (HR: 0.6, (0.3-1.2), p = 0.14, interaction p < 0.001). This effect was the consequence of reduced incidences of acute and chronic GvHD and non-relapse mortality.
- MeSH
- akutní myeloidní leukemie * terapie MeSH
- buňky NK MeSH
- haploidentická transplantace MeSH
- lidé MeSH
- myši MeSH
- nemoc štěpu proti hostiteli * prevence a kontrola MeSH
- prospektivní studie MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- ruxolitinib,
- MeSH
- dítě MeSH
- infekce epidemiologie klasifikace MeSH
- inhibitory Janus kinas aplikace a dávkování farmakologie MeSH
- léková rezistence MeSH
- lidé MeSH
- lymfocyty MeSH
- reakce štěpu proti hostiteli * imunologie účinky léků MeSH
- recidiva MeSH
- riziko MeSH
- statistika jako téma MeSH
- steroidy MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- klinická studie MeSH
Outcome data were collected from the European Society for Blood and Marrow Transplantation registry on 373 children from 120 centers with relapsed leukemia (214 with acute lymphoblastic leukemia [ALL] and 159 with acute myelogenous leukemia [AML]) who underwent second allogeneic hematopoietic stem cell transplantation (HSCT) between 2004 and 2013. Overall survival (OS) was 38% at 2 years and 29% at 5 years, and leukemia-free survival (LFS) was 30% at 2 years and 25% at 5 years. Median follow-up after second HSCT was 36.4 months in the ALL group and 50.2 months in the AML group. In the ALL group, OS was 43% at 2 years and 33% at 5 years, and LFS was 34% at 2 years and 31% at 5 years. In the AML group, OS was 32% at 2 years and 24% at 5 years, and LFS was 24% at 2 years and 17% at 5 years. The 2-year nonrelapse mortality (NRM) rate was 22% in the ALL group and 18% in the AML group. Favorable prognostic factors (P < .05) for OS and LFS included >12 months between transplantations and chronic graft-versus-host disease after the first HSCT (in both groups), complete response before the second HSCT (ALL group only), and age >12 years (AML group only). Findings were more consistent over time in the ALL group, with no significant differences between 2-year and 5-year rates of relapse, NRM, and LFS. Children with relapsed acute leukemias have a substantial likelihood of long-term survival following second HSCT. Given the many novel targeted and immunomodulation therapies currently under development, it is important to identify specific patient subpopulations that may benefit from a second HSCT compared with those better suited to new approaches.
- MeSH
- akutní lymfatická leukemie mortalita terapie MeSH
- akutní myeloidní leukemie mortalita terapie MeSH
- analýza přežití MeSH
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- nemoc štěpu proti hostiteli mortalita MeSH
- předškolní dítě MeSH
- prognóza MeSH
- recidiva MeSH
- reoperace MeSH
- retrospektivní studie MeSH
- transplantace hematopoetických kmenových buněk metody mortalita MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
