waarom niet meteen het abstract (het gaat over 13 patiënten die gemiddeld al vijf behandelingen achter de rug hadden)?
OS6-8 - PHASE I STUDY OF ADOPTIVE TRANSFER OF HAPLOIDENTICAL EXPANDED NK CELLS
Lucia Silla1, Vanessa Valim2, Cristiane Weber2, Alini Vargas2, Dayane Catelli2, Bruna Correa1, Maria da Silva3, Bruna Amorin2, Bruna Zambonato2, Juliana Nobrega4, Fernanda Scherer5, Claudia Astigarraga6, Lisandra Rigoni2, Liane Daudt1, Rosane Bittencourt2, Mariana Michalowski1, Fernando Duarte7, Nelson Hamerschlak8, Vicente Odone9, Mariana Jobim2, Joice Merzoni2, Samantha Nichele10, Laura Fogliatto2, Juliano Perez2, Raul Rodrigues1, Nicole Kilian11, Jeniffer dos Anjos1, Leo Sekine2, Alessandra Paz12, Dean A Lee13
1 Federal University of Rio Grande do Sul, Porto Alegre, Brazil,
2 Hospital de Clinicas de Porto Alegre - HCPA, Porto Alegre, Brazil,
3 Hosptal de Clinicas - HCPA, Porto Alegre, Brazil,
4 Privety Sector, Recife, Brazil,
5 Hospital de Clinicas de Porto Alegre - HCPA, Porto Algre, Brazil,
6 Hospital Moinhos de Vento, Porto Alegre, Brazil,
7 Federal University of Ceara, Fortaleza, Brazil,
8 Hospita Albert lEinstein, Sao Paulo, Brazil,
9 Hospital Albert Einstein, Sao Paulo, Brazil,
10 Federal University of Parana - Bone Marrow Transplant, Curitiba, Brazil,
11 Uniritter, Porto Alegre, Brazil,
12 Federal Unviersity of Rio Grande do Sul, Porto Alegre, Brazil,
13 Nationwide Childrens Hospital, Collumbus, OH, United States
Background:
Patients with relapsed, refractory, or CNS-positive AML respond poorly to chemotherapy.
NK cells have anti-leukemic activity but are deficient in number and function in AML patients and are ablated by high-dose chemotherapy.
Therefore, we initiated a Phase I study of adoptive transfer of haploidentical expanded NK cells to restore NK cell number and anti-leukemia function in patients with relapsed/refractory AML
Methods:
Haploidentical donors were selected after HLA and KIR typing.
NK cells were expanded on feeder cells and cryopreserved for infusion at the assigned dose level, then thawed and infused thrice weekly for six doses after fludarabine, cytarabine, and G-CSF (FLAG).
Patients were treated in 3 dose cohorts of 106, 5x106, and 107 NK cells/kg/infusion.
Response was assessed at day 30.
Results:
NK cell production was feasible for all subjects.
13 patients were treated (one treated twice), age 1-61y (median 22y), with primary refractory (n= 5) or relapsed (n=8) AML.
Patients had a median of five prior therapies, including nine with prior stem cell transplantation.
Two patients had CNS, one bone and nerve root disease and one CNS probable mycetoma.
Therapy was tolerated with manageable toxicity in such an ill population of patients.
Median neutrophil and platelet recovery were at day 33 and 44, respectively.
Complete response and overall response rate were 50% and 78.5%, respectively, including unexpected CNS responses that were associated with localized inflammation.
Median OS and DFS after treatment were 271 and 90 days, respectively.
Conclusions:
Repeated infusions of high doses of cryopreserved expanded NK cells are feasible and well-tolerated after high-dose chemotherapy and demonstrate encouraging systemic and CNS responses in high-risk AML.
Clinical Trial Registry: IRB/HCPA 00000921; CAI: 44444214.7.0000.5327 CinicalTrials.gov, NCT02809092
Disclosure:
DECIT/MS/SUS; FINEP/CNPq/MCTC and CAPES/ME - Brazilian Government