Here we report the results of exploratory analyses of the clinical efficacy of HDC/IL-2 in AML with focus on the impact of karyotype aberrations in leukemic cells.
Second, we aimed to define the potential impact of HLA-B -21 variation on the course of AML in a phase 4 trial in which patients received IL-2-based immunotherapy.
In patients with acute myeloid leukemia (AML), treatment with histamine dihydrochloride (HDC) and low-dose IL-2 (HDC/IL-2) in the post-chemotherapy phase has been shown to reduce the incidence of leukemic relapse.
In an international phase IV trial (ClinicalTrials.gov; NCT01347996), 84 patients with AML in first complete remission who had not undergone transplantation received immunotherapy with histamine dihydrochloride (HDC) and low-dose IL-2 with the aim of preventing relapse.
Our results suggest that immunotherapy with HDC/IL-2 in AML entails induction of immunosuppressive T<sub>regs</sub> that may be targeted for improved anti-leukemic efficiency.
For this study, NK cell phenotypes and KIR/HLA genotypes were determined in 81 AML patients who received immunotherapy with histamine dihydrochloride and low-dose IL-2 for relapse prevention (NCT01347996).
NKCA induction by the AML leukemia cells target a subpopulation of peripheral blood NK cells and is interleukin-2 independent but is abrogated by a long-term culture of NK (LTNK) cells at 37°C.
Using this screen, we identified interleukin-2 gamma receptor (IL2Rγ) as a critical growth determinant for a JAK3(A572V) mutation-positive acute myeloid leukemia cell line.
The European Organisation for Research and Treatment of Cancer (EORTC) and Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) Leukemia Groups conducted a randomized trial (AML-12; Combination Chemotherapy, Stem Cell Transplant and Interleukin-2 in Treating Patients With Acute Myeloid Leukemia) in 1,942 newly diagnosed patients with AML, age 15 to 60 years, comparing remission induction treatment containing daunorubicin, etoposide, and either standard-dose (SD) cytarabine (100 mg/m(2) per day by continuous infusion for 10 days) or high-dose (HD) cytarabine (3,000 mg/m(2) every 12 hours by 3-hour infusion on days 1, 3, 5, and 7).
For the first time, we report the use of interleukin-2 to stimulate a graft-versus-leukemia effect and induce complete remission in a patient with BRCA2 Fanconi anemia and refractory acute myelogenous leukemia, suggesting the potential of immunotherapy in this setting.
We determined the prognostic relevance of CD25 (IL-2 receptor-α) expression in 657 patients (≤ 60 years) with de novo acute myeloid leukemia (AML) treated in the Eastern Cooperative Oncology Group trial, E1900.
In contrast, autologous LV-CD80/IL2AML cell cultures provide a weaker stimulation with a lower number of CD8(+) T cells (P = 0.011) and no change in NK cell or Treg numbers.
Treg depletion by a brief course of interleukin-2 diphtheria toxin (IL-2DT) transiently reduced AML disease burden but did not permit long-term survival.
Analysis of in vitro IL-2-expanded NK cells from patients with myelocytic/monocytic acute myeloid leukemia (AML-NK cells) has revealed poor cytolytic functions because of deficient expression of pivotal activation molecules-the natural cytotoxicity receptors (NCRs) NKp30, NKp44, and NKp46.
The purpose of the study is to investigate the tolerability of interleukin 2 (IL-2) after intensive chemotherapy in elderly acute myeloid leukemia (AML) patients in first complete remission (CR).
The authors investigated whether IL-2 may improve the duration of complete remission (CR) and survival in acute myelogenous leukemia (AML) patients in first CR.
From our in vitro data we conclude that B7 molecules play an important role in the alloimmune surveillance of AML as suggested by the high B7 molecule dependency of IL-2 secretion.
In addition, Fas-mediated apoptotic cell death of AML cells is also induced by interleukin-2-activated T cells expressing functional FasL on their surfaces.
Although the high-affinity IL-2R form (ie, the alpha+, beta+, gamma+ IL-2R form) was detectable in a small minority of primary AML samples as well as the KG-1 cell line and IL-2 binding to these cells was sufficient to initiate signal transduction as evidenced by an increase in overall protein tyrosine phosphorylation and more specifically in tyrosine phosphorylation of the Janus kinase (JAK) 3, in none of these cell types did exposure to IL-2 affect cell growth kinetics.
Treatment of patients in remission of acute myelocytic leukemia using immunotherapy with interleukin 2 is a new approach to prolonging remission duration in this disease.
Because of reports showing interleukin 2 receptor expression on AML blasts, it is important to know whether IL-2 may directly influence these leukemic cells.
The eradication of minimal residual blast populations by activation of autologous cytotoxic cells with interleukin 2 (IL-2) is a new promising tool in the treatment of acute myelocytic leukemia (AML).