Cellular immunosuppression in children with acute lymphoblastic leukemia: Effect of consolidation chemotherapy

Komada, Yoshihiro; Zhang, Shaoli; Zhou, Yi; Hanada, Motoi; Shibata, Takeo; Azuma, Eiichi; Sakurai, Minoru

doi:10.1007/bf01789334

Cited by 46 publications

(32 citation statements)

References 17 publications

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“…A recent abstract showed that NK cell numbers are preserved during induction for pediatric ALL, whereas nonmalignant B cells, and to a lesser degree T cells, are significantly decreased. 31 Furthermore, in pediatric patients with ALL in remission, Komada et al 32 found that overall lymphocyte counts were depressed and that percentages of CD81 T cells were increased. Finally, NK cell numbers in autologous grafts have been shown to correlate with ALC posttransplant, whereas CD191 and CD31 cells do not.…”

Section: Immune Status In Acute Leukemiamentioning

confidence: 99%

Absolute lymphocyte count is a novel prognostic indicator in ALL and AML

Angulo¹,

Yuen²,

Palla³

et al. 2007

Cancer

112

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BACKGROUND.Leukemia is the leading cause of disease‐related death in children, despite significant improvement in survival and modern risk stratification. The prognostic significance of absolute lymphocyte counts (ALC) was evaluated in young patients with acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL).METHODS.In all, 171 consecutive de novo cases of AML and ALL, age ≤21 years, were analyzed. Age, initial white blood cell count, cytogenetics, and bone marrow response were compared with lymphocyte, neutrophil, and platelet counts at weekly intervals during induction chemotherapy.RESULTS.ALC is a significant independent predictor of relapse and survival. For example, in patients with AML an ALC on Day 28 of induction (ALC‐28) <350 cells/μL predicts very poor survival, with a 5‐year relapse‐free survival (RFS) of only 10% (hazard ratio [HR] 3.7, P = .003). In contrast, an ALC‐15 >350 cells/μL carries an excellent prognosis, with a 5‐year overall survival (OS) of 85% (HR 0.2, P = .012). Similarly in ALL, an ALC‐15 <350 cells/μL predicts poor survival, with a 6‐year RFS of 43% (HR 4.5, P = .002), whereas an ALC‐15 >350 cells/μL predicts excellent outcome, with a 6‐year OS of 87% (HR 0.2, P = .018). Importantly, ALC remains a strong predictor in multivariate analysis with known prognostic factors.CONCLUSIONS.ALC is a simple, statistically powerful measurement for patients with de novo AML and ALL. The results, when combined with previous studies, demonstrate that ALC is a powerful new prognostic factor for a range of malignancies. These findings suggest a need for further exploration of postchemotherapy immune status and immune‐modulating cancer therapies. Cancer 2008. © 2007 American Cancer Society.

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Section: Immune Status In Acute Leukemiamentioning

confidence: 99%

Absolute lymphocyte count is a novel prognostic indicator in ALL and AML

Angulo¹,

Yuen²,

Palla³

et al. 2007

Cancer

112

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“…The chemotherapeutic regimens for malignancies restrict the effectivity of the immune system and significantly decrease the level of NK cells (23). The activity of NK cells is also affected by some cytostatic drugs (24).…”

Section: Introductionmentioning

confidence: 99%

Effect of frequently used chemotherapeutic drugs on the cytotoxic activity of human natural killer cells

Márkász

Stuber

Vanherberghen

et al. 2007

Molecular Cancer Therapeutics

101

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Tumors are considered to be possible targets of immunotherapy using stimulated and expanded autologous or allogeneic natural killer (NK) cells mismatched for MHC class I molecules and inhibitory NK receptors. NK cellbased immunoadjuvant therapies are carried out in combination with standard chemotherapeutic protocols. In the presented study, we characterized the effect of 28 frequently used chemotherapeutic agents on the capacity of NK cells to kill target cells. We found that treatment of NK cells with the drugs vinblastine, paclitaxel, docetaxel, cladribine, chlorambucil, bortezomib, and MG-132 effectively inhibited NK cell -mediated killing without affecting the viability of NK cells. On the other hand, the following drugs permitted efficient NK cell -mediated killing even at concentrations comparable with or higher than the maximally achieved therapeutic concentration in vivo in humans: asparaginase, bevacizumab, bleomycin, doxorubicin, epirubicin, etoposide, 5-fluorouracil, hydroxyurea, streptozocin, and 6-mercaptopurine. [Mol Cancer Ther 2007;6(2):644 -54]

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“…Effect of chemotherapeutic agents on immune cell function is considered to be involved in the immunosuppression associated with myelosuppression or drug cytotoxicity 31. However, the immune cell function, particularly regarding liver immunity at the local anatomical site with distant CRC metastasis, during chemotherapy, remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Effect of bevacizumab plus XELOX (CapeOX) chemotherapy on liver natural killer cell activity in colorectal cancer with resectable liver metastasis

Hirata

Ishiyama

Tanaka

et al. 2018

Annals of Gastroent Surgery

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AimWe investigated the chemotherapy effect of resectable colorectal cancer with liver metastasis (CRLM) on the function of intrahepatic immune cells.MethodsWe classified patients into adjuvant chemotherapy (bevacizumab+CapeOX) after hepatectomy group (group A) and neoadjuvant chemotherapy followed by hepatectomy group (group B), and collected peripheral blood mononuclear cells (PBMC) and liver mononuclear cells (LMNC) to ascertain phenotypic and functional differences.ResultsThere were no significant differences in lymphocyte fractions of either PBMC or LMNC between groups, except for the significantly lower percentage of natural killer (NK) cells in LMNC in group B than in group A. Significantly higher percentage of natural‐killer group 2, member D (NKG2D)‐ positive NK cells in PBMC and percentage of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐, NKp30‐, and signal regulatory protein β (SIRPβ)‐positive NK cells in LMNC were found in group B. Furthermore, significantly higher expressions of NKG2D and SIRPβ in peripheral blood NK cells and of NKp46 and CD122 in liver NK cells were found in group B. When LMNC were incubated with interleukin (IL)‐2 in vitro, no difference was observed in the expression of these molecules in NK cells between groups. Consistently, there was no difference in the cytotoxic activity of those LMNC against a colon adenocarcinoma cell line between groups.ConclusionColorectal cancer with liver metastasis patients treated with neoadjuvant chemotherapy showed enhanced expression of activation markers on peripheral blood and liver NK cells in comparison with patients who did not receive therapy; however, the difference in those function remains unclear. These results suggest that neoadjuvant chemotherapy does not have a negative impact on intrahepatic immune cells in resectable CRLM patients.

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Cellular immunosuppression in children with acute lymphoblastic leukemia: Effect of consolidation chemotherapy

Cited by 46 publications

References 17 publications

Absolute lymphocyte count is a novel prognostic indicator in ALL and AML

Absolute lymphocyte count is a novel prognostic indicator in ALL and AML

Effect of frequently used chemotherapeutic drugs on the cytotoxic activity of human natural killer cells

Effect of bevacizumab plus XELOX (CapeOX) chemotherapy on liver natural killer cell activity in colorectal cancer with resectable liver metastasis

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