A Recycling Defect as a Characteristic of Natural Killer Cells in Childhood Acute Lymphoblastic Leukemia

Yabuhara, Akihiko; Kawai, Hiroshi

doi:10.1203/00006450-199012000-00004

Cited by 7 publications

(8 citation statements)

References 13 publications

(25 reference statements)

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“…The recovery of the immune system after chemotherapy takes at least 1 year, according to the data in the medical literature [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Most of the immune functions normalize 12 months after the completion of the therapy; however, some parameters can remain pathologic in some cases [16,20,21,24,26,28].…”

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confidence: 98%

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Late Immune Recovery in Children Treated for Malignant Diseases

Kovàcs

Barany

Schlick

et al. 2008

Pathol. Oncol. Res.

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In this study we analyzed the recovery of the immune system in children after completion of the therapy. We analysed 88 children (51 boys, 37 girls, mean age at diagnosis: 7.8 years) receiving chemotherapy for malignant diseases (43 acute lymphoblastic leukemia, 15 lymphoma, 20 bone tumor, ten other solid tumors). Serum immunoglobulin levels (Ig), natural killer activity (NK), antibody-dependent cellular cytotoxicity (ADCC) and T and B cell proliferation were determined 1 year after cessation of therapy. The mean levels of Ig were in the normal range at a mean of 13 months after chemotherapy (IgG: 11.2 +/- 3.3, IgA: 1.6 +/- 0.9, IgM: 1.0 +/- 0.5 g/l), however in the leukemic patients serum IgG was below the lower limit of the normal range in 3/43 (7.0%) cases, serum IgA was low in 5/43 (11.6%) and serum IgM was decreased in 4/43 (9.3%) cases. In the solid tumor patients IgG values were within the normal range and only 2-2/45 children had lower values for IgA and IgM (4.4%). NK activity decreased in 7/43 (16.3%) leukemic patients, and in 3/45 (6.7%) solid tumor patients, ADCC decreased in 8/43 (18.6%) and 3/45 (6.7%), respectively (p < 0.001). B-cell blastic transformation was decreased in 3/43 (7%) leukemic patients and in 4/45 (8.9%) solid tumor patients. At the same time T-cell blastic transformation was altered in 5/43 (11.6%) and in 4/45 (8.9%) cases, respectively. Leukemic patients had significantly more infections during the first year after chemotherapy than solid tumor patients (1.60 +/- 1.18 vs 0.96 +/- 1.14; p = 0.011). No significant correlations could be found between the investigated immune parameters and the number and severity of infections. It is concluded, that cytotoxic therapy can lead to long-term depression of the immune system, first of all in leukemic patients.

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confidence: 98%

“…Most of the immune functions normalize 12 months after the completion of the therapy; however, some parameters can remain pathologic in some cases [16,20,21,24,26,28]. After bone marrow transplantation the regeneration of the immune system can last for 2-4 years [29][30][31][32][33][34].…”

mentioning

confidence: 99%

Late Immune Recovery in Children Treated for Malignant Diseases

Kovàcs

Barany

Schlick

et al. 2008

Pathol. Oncol. Res.

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“…In-vitro-induced LAK activity of pretreated CMLphtients was low in comparison with healthy controls (not statistically significant) but a significant increase above normal levels was observed after concomitant CMI in the CML group and in CML plus HD patients (P <0.05) as well as during and after sequential CMI in patients with lymphoma and leukemia (P <0.05). Low NK and LAK activities were previously reported in CML [13] as well as in other hematological malignancies [8,29] but this functional depression occurred only in a fraction (40%-50%) of the patients [8,39] and sometimes was related to the stage of the disease [1,29,53]. Pretreatment spontaneous killing activity, observed in our untreated patients, was comparable with that in healthy donors, but should be cautiously evaluated, since we have only evaluated a relatively small group of patients.…”

Section: Discussionmentioning

confidence: 91%

“…The low killing activity observed in cancer patients could be restored by cytokine activation in vitro [1,9,27,28,37,53] or after in vivo administration of rIFNa or rIL-2 in a variety of hematological malignancies [12,34,36,38,44,46,50,51]. Augmentation of the nonspecific cell-mediated cytotoxicity could also be achieved in PBMC derived from healthy donors [6] and patients with CML [9] as well as from patients with cancer of the cervix [37] after a combined in vitro exposure to rIL-2 and rIFNa.…”

Section: Discussionmentioning

confidence: 99%

“…Since natural killer cells derived from fresh or interleukin-2(rIL-2)-activated peripheral blood mononuclear cells (PBMC) efficiently lyse tumor cells in vitro [16,21,33,52], while defects in their functions are often associated with a higher incidence of malignancies [8,13,29], it has been postulated that these non-MHC-restricted cytotoxic cells are potentially important in tumor cell immunosurveillance [ 18,41]. Indirect supportive data for the possible role of cytokines in tumor growth control arose when their ability to improve the impaired tumor-directed killing activity of cancer patients through cytokine activation in vitro [1,9,27,28,37,53] or by in vivo administration of interferon-(z (rIFNa) [34] and rIL-2 [12,36,51] was demonstrated.…”

Section: Introductionmentioning

confidence: 98%

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Immunological evaluation of patients with hematological malignancies receiving ambulatory cytokine-mediated immunotherapy with recombinant human interferon-α2a and interleukin-2

Morecki

Revel‐Vilk

Nabet

et al. 1992

Cancer Immunol Immunother

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Immunological parameters were evaluated in patients treated with cytokine-mediated immunotherapy (CMI) consisting of low doses of recombinant human interferon alpha 2a (rIFN alpha) and recombinant human interleukin-2 (rIL-2) administered either concomitantly or sequentially by subcutaneous self-injections in an outpatient setting. Twenty-six patients with hematological malignancies and 2 metastatic melanoma patients in a progressive stage were enrolled in this clinical trial. Of the 26 patients, 24 were at a stage of minimal residual disease, including 14 patients who had received autologous bone marrow transplantation (ABMT) 2-5 months previously, 7 chronic myelogenous leukemia (CML) and 3 acute myeloid leukemia (AML) patients. Two patients (1 CML and 1 mult. myeloma) were treated at a stage of progressive disease. Non-MHC-restricted cytotoxicity directed against natural-killer(NK)-resistant (Daudi) and NK-sensitive (K562) target cells was assessed before, during and after CMI, either in fresh peripheral blood samples (spontaneous activity) or after in vitro rIL-2 activation (induced activity). Spontaneous killing activity was low prior to treatment, but increased upon termination of treatment in 10/15 evaluated cycels. rIL-2-activated cytotoxicity in vitro was markedly elevated in 8/12 and 6/8 patients after one and two cycles, respectively, of sequential treatment, as well as in 3/8 CML and 5/6 patients after one and two cycles, respectively, of concomitant treatment. Activation of the T cell mitogenic response was demonstrated in 6/9 patients after concomitant CMI, while no such effect was observed throughout a sequential treatment in lymphoma and leukemia patients after ABMT. Although a direct correlation between immune stimulation and the in vivo antitumor response cannot yet be determined, our clinical observations support a beneficial therapeutic effect in a substantial number of patients. These results indicated that the ambulatory CMI protocol of rIL-2 and rIFN alpha could stimulate the host defense immune system and may be helpful in mediating the in vivo antitumor response in patients with minimal residual disease.

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Lack of association between childhood common acute lymphoblastic leukaemia and an HLA‐C locus dimorphism influencing the specificity of natural killer cells

et al. 1998

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Previous serological studies documenting an association between acute lymphoblastic leukaemia (ALL) and HLA‐Cw antigens suggested that the HLA‐C locus might influence susceptibility to ALL. However, associations with more than one Cw antigen suggest that polymorphic variants shared by more than Cw allele could be involved. Recent studies have shown that the HLA‐C locus encodes two ligands (NK1 and NK2) recognized by receptors on natural killer (NK) cells. HLA‐Cw alleles encoding these ligands are dimorphic, dependent on whether they encode one or other NK ligand. To determine whether susceptibility to the common (CD10+) form of childhood ALL (c‐ALL) is associated with NK1 or NK2, we carried out a molecular analysis of 94 childhood c‐ALL patients and 136 infant controls. We found no difference in the frequency of NK1 and NK2 alleles, phenotypes or genotypes between the patients and controls, suggesting that this does not explain the role of the HLA‐C locus in susceptibility to childhood c‐ALL.

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A Recycling Defect as a Characteristic of Natural Killer Cells in Childhood Acute Lymphoblastic Leukemia

Cited by 7 publications

References 13 publications

Late Immune Recovery in Children Treated for Malignant Diseases

Late Immune Recovery in Children Treated for Malignant Diseases

Immunological evaluation of patients with hematological malignancies receiving ambulatory cytokine-mediated immunotherapy with recombinant human interferon-α2a and interleukin-2

Lack of association between childhood common acute lymphoblastic leukaemia and an HLA‐C locus dimorphism influencing the specificity of natural killer cells

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