Direct and complement dependent cytotoxicity in CLL cells from patients with high-risk early-intermediate stage chronic lymphocytic leukemia (CLL) treated with alemtuzumab and rituximab

Clive S. Zent; Charla R. Secreto; Betsy R. LaPlant; Nancy D. Bone; Timothy G. Call; Tait D. Shanafelt; Diane F. Jelinek; Renee C. Tschumper; Neil E. Kay

doi:10.1016/j.leukres.2008.05.014

Direct and complement dependent cytotoxicity in CLL cells from patients with high-risk early-intermediate stage chronic lymphocytic leukemia (CLL) treated with alemtuzumab and rituximab

Clive S. Zent, Charla R. Secreto, Betsy R. LaPlant, Nancy D. Bone, Timothy G. Call, Tait D. Shanafelt, Diane F. Jelinek, Renee C. Tschumper, Neil E. Kay

Research output: Contribution to journal › Article › peer-review

66 Scopus citations

Abstract

The mechanism of cytotoxicity of alemtuzumab and rituximab in chronic lymphocytic leukemia (CLL) is not well understood. We obtained fresh CLL cells from early-intermediate stage high-risk patients just prior to treatment with alemtuzumab and rituximab to study mechanisms of action and resistance. Alemtuzumab had minimal direct cytotoxicity but caused significant complement dependent cytotoxicity (CDC) although a subpopulation of CLL cells had intrinsic resistance. Rituximab had no direct cytotoxicity and caused minimal CDC in cells from most patients. These data suggest that CDC has a therapeutic role in patients treated with alemtuzumab and that measures to decrease resistance to CDC could increase efficacy.

Original language	English (US)
Pages (from-to)	1849-1856
Number of pages	8
Journal	Leukemia Research
Volume	32
Issue number	12
DOIs	https://doi.org/10.1016/j.leukres.2008.05.014
State	Published - Dec 2008

Keywords

Alemtuzumab
Chronic lymphocytic leukemia (CLL)
Complement
Cytotoxicity
Rituximab

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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10.1016/j.leukres.2008.05.014

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Zent, C. S., Secreto, C. R., LaPlant, B. R., Bone, N. D., Call, T. G., Shanafelt, T. D., Jelinek, D. F., Tschumper, R. C., & Kay, N. E. (2008). Direct and complement dependent cytotoxicity in CLL cells from patients with high-risk early-intermediate stage chronic lymphocytic leukemia (CLL) treated with alemtuzumab and rituximab. Leukemia Research, 32(12), 1849-1856. https://doi.org/10.1016/j.leukres.2008.05.014

Direct and complement dependent cytotoxicity in CLL cells from patients with high-risk early-intermediate stage chronic lymphocytic leukemia (CLL) treated with alemtuzumab and rituximab. / Zent, Clive S.; Secreto, Charla R.; LaPlant, Betsy R. et al.
In: Leukemia Research, Vol. 32, No. 12, 12.2008, p. 1849-1856.

Research output: Contribution to journal › Article › peer-review

Zent, CS, Secreto, CR, LaPlant, BR, Bone, ND, Call, TG, Shanafelt, TD, Jelinek, DF, Tschumper, RC & Kay, NE 2008, 'Direct and complement dependent cytotoxicity in CLL cells from patients with high-risk early-intermediate stage chronic lymphocytic leukemia (CLL) treated with alemtuzumab and rituximab', Leukemia Research, vol. 32, no. 12, pp. 1849-1856. https://doi.org/10.1016/j.leukres.2008.05.014

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title = "Direct and complement dependent cytotoxicity in CLL cells from patients with high-risk early-intermediate stage chronic lymphocytic leukemia (CLL) treated with alemtuzumab and rituximab",

abstract = "The mechanism of cytotoxicity of alemtuzumab and rituximab in chronic lymphocytic leukemia (CLL) is not well understood. We obtained fresh CLL cells from early-intermediate stage high-risk patients just prior to treatment with alemtuzumab and rituximab to study mechanisms of action and resistance. Alemtuzumab had minimal direct cytotoxicity but caused significant complement dependent cytotoxicity (CDC) although a subpopulation of CLL cells had intrinsic resistance. Rituximab had no direct cytotoxicity and caused minimal CDC in cells from most patients. These data suggest that CDC has a therapeutic role in patients treated with alemtuzumab and that measures to decrease resistance to CDC could increase efficacy.",

keywords = "Alemtuzumab, Chronic lymphocytic leukemia (CLL), Complement, Cytotoxicity, Rituximab",

author = "Zent, {Clive S.} and Secreto, {Charla R.} and LaPlant, {Betsy R.} and Bone, {Nancy D.} and Call, {Timothy G.} and Shanafelt, {Tait D.} and Jelinek, {Diane F.} and Tschumper, {Renee C.} and Kay, {Neil E.}",

note = "Funding Information: This work was supported by the National Institutes of Health—National Cancer Institute University of Iowa/Mayo Clinic SPORE Grant CA97274 and R01 Grant CA95241, Bayer Health Care Pharmaceuticals, and Genentech.",

year = "2008",

month = dec,

doi = "10.1016/j.leukres.2008.05.014",

language = "English (US)",

volume = "32",

pages = "1849--1856",

journal = "Leukemia Research",

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T1 - Direct and complement dependent cytotoxicity in CLL cells from patients with high-risk early-intermediate stage chronic lymphocytic leukemia (CLL) treated with alemtuzumab and rituximab

AU - Zent, Clive S.

AU - Secreto, Charla R.

AU - LaPlant, Betsy R.

AU - Bone, Nancy D.

AU - Call, Timothy G.

AU - Shanafelt, Tait D.

AU - Jelinek, Diane F.

AU - Tschumper, Renee C.

AU - Kay, Neil E.

N1 - Funding Information: This work was supported by the National Institutes of Health—National Cancer Institute University of Iowa/Mayo Clinic SPORE Grant CA97274 and R01 Grant CA95241, Bayer Health Care Pharmaceuticals, and Genentech.

PY - 2008/12

Y1 - 2008/12

N2 - The mechanism of cytotoxicity of alemtuzumab and rituximab in chronic lymphocytic leukemia (CLL) is not well understood. We obtained fresh CLL cells from early-intermediate stage high-risk patients just prior to treatment with alemtuzumab and rituximab to study mechanisms of action and resistance. Alemtuzumab had minimal direct cytotoxicity but caused significant complement dependent cytotoxicity (CDC) although a subpopulation of CLL cells had intrinsic resistance. Rituximab had no direct cytotoxicity and caused minimal CDC in cells from most patients. These data suggest that CDC has a therapeutic role in patients treated with alemtuzumab and that measures to decrease resistance to CDC could increase efficacy.

AB - The mechanism of cytotoxicity of alemtuzumab and rituximab in chronic lymphocytic leukemia (CLL) is not well understood. We obtained fresh CLL cells from early-intermediate stage high-risk patients just prior to treatment with alemtuzumab and rituximab to study mechanisms of action and resistance. Alemtuzumab had minimal direct cytotoxicity but caused significant complement dependent cytotoxicity (CDC) although a subpopulation of CLL cells had intrinsic resistance. Rituximab had no direct cytotoxicity and caused minimal CDC in cells from most patients. These data suggest that CDC has a therapeutic role in patients treated with alemtuzumab and that measures to decrease resistance to CDC could increase efficacy.

KW - Alemtuzumab

KW - Chronic lymphocytic leukemia (CLL)

KW - Complement

KW - Cytotoxicity

KW - Rituximab

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AN - SCOPUS:51649110602

SN - 0145-2126

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JO - Leukemia Research

JF - Leukemia Research

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ER -

Direct and complement dependent cytotoxicity in CLL cells from patients with high-risk early-intermediate stage chronic lymphocytic leukemia (CLL) treated with alemtuzumab and rituximab

Abstract

Keywords

ASJC Scopus subject areas

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