Immunological Characterization and Antibacterial Function of Persisting Granulocytes in Leukemic Patients Receiving Pulse Cytosine Arabinoside-Consolidation Chemotherapy on Days 1, 3, and 5

Abstract

High-dose cytosine arabinoside (HiDAC) and intermediate-dose cytosine arabinoside (IDAC) have been introduced as effective and safe consolidation chemotherapy in acute myeloid leukemia, with relatively low rates of life-threatening infections despite the high total dose of the cytostatic drug. To explore the biological background of low toxicity, we examined the numbers, immunophenotype, and functional properties of granulocytes in patients with acute myeloid leukemia receiving HiDAC or IDAC. Interestingly, the absolute numbers of neutrophils remained >500/μl until day 10 in 92 of 125 (74%) HiDAC cycles and in 106 of 113 (94%) IDAC cycles. As assessed by electron microscopy, these day-10 granulocytes surviving chemotherapy were found to be mature cells containing secondary granules and phagolysosomes. They also expressed opsonization- and phagocytosis-linked surface Ags (C3biR, CR1, C1qR, C5aR, FcγRI, FcγRII, FcγRIII, and G-CSF and GM-CSF receptors) like neutrophils in healthy controls. Moreover, these day-10 neutrophils exhibited oxidative burst activity and took up and digested bacteria in the same way as neutrophils in healthy controls. There was a negative correlation between absolute neutrophil counts and severe infections in HiDAC- and IDAC-treated patients with a later onset of infections in IDAC patients (median: IDAC, day 18; HiDAC, day 16). Together, functionally mature neutrophils are detectable at least until day 10 in patients treated with HiDAC or IDAC, and may explain the relatively low hematologic toxicity of these consolidation protocols. IDAC is a superior protocol in this regard and may therefore be most suitable for elderly patients and those at high risk for severe infections.

Comparative Analysis of Metabolic Compositions and Trace Elements of Inonotus hispidus Mushroom Grown on Five Different Tree Species

“…Analysis of the Characteristics of Sugars and Glycosides in I. hispidus Grown on Five Different Trees Species. Recent investigations have revealed that sugars and glycosides are important bioactive components in mushrooms, such as G. lucidum polysaccharides having antibacterial, 17 antitumor, 18 immunomodulatory, 19 and inflammation effects. 20 In this study, 19 sugars and 42 glycoside metabolites were identified in I. hispidus grown on five different tree species (Table 2).…”

Maintenance therapy with histamine plus IL-2 induces a striking expansion of two CD56bright NK cell subpopulations in patients with acute myeloid leukemia and supports their activation

“…days 1-7) and etoposide (100 mg/m 2 i.v., days 1-5) and 3 or 4 cycles of consolidation chemotherapy with high or intermediate dose ARA-C (i.e. 2x 3g/m 2 , days 1,3,5 or 2x 1g/m 2 , days 1,3,5, respectively) [48–50]. After achieving hematologic remission, patients were treated with HDC (0.5 mg) plus recombinant IL-2 (16400 IU/Kg) twice-daily s.c. for 21 days per cycle, according to an established protocol [18].…”

Ludwig Boltzmann Cluster Oncology (LBC ONC): first 10 years and future perspectives

“…Therefore, members of the LBC ONC and the Medical University of Vienna conducted a clinical trial exploring the clinical tolerability and efficacy of a special form of intensified consolidation after remission induction in older patients with AML [ 92 ]. The consolidation regimen was developed on the basis of a previous study showing that intermediate ARA‑C (cytosine arabinoside) is not only a highly effective but also a less toxic and extremely well-tolerated type of consolidation chemotherapy [ 93 , 94 ]. In the trial conducted recently, AML patients ≥ 60 years in complete remission after induction therapy received fludarabine and ARA-C in consolidation cycle 1 and intermediate-dose ARA-C (IDAC) in cycles 2 through 4.…”