Proof of principle that lymphocytosis is quiescent cells
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Persistent lymphocytosis with ibrutinib does not indicate early relapse

Persistent lymphocytosis lasting more than 12 months in patients with chronic lymphocytic leukemia undergoing treatment with ibrutinib is not associated with a greater likelihood of early relapse.

A prospective observational study in 85 relapsed or refractory patients with chronic lymphocytic leukemia treated with ibrutinib showed lymphocytosis occurred in 77% in patients, persisting at 12 months in 20% of patients.

Dr. Jennifer A. Woyach of Ohio State University, Columbus, and her colleagues found no significant differences in progression-free survival between patients who responded to treatment but showed persistent lymphocytosis, and those with a partial or complete response to treatment without lymphocytosis.

They also found no significant differences in gene expression profiles in persistent lymphocytosis, suggesting that the lymphocytosis most likely represented the movement of quiescent cells (Blood 2014;123:1810-17).

Two authors were unpaid consultants for, three were paid consultants for, and two were employees of Pharmacyclics. One author received research funding from Janssen. The study was funded by the Four Winds Foundation, the Leukemia and Lymphoma Society, and several other organizations. Ibrutinib was provided by Pharmacyclics for in vitro experiments.

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As more treatments targeting B-cell receptors became available, it was important for physicians to understand that lymphocytosis associated with this treatment was not indicative of treatment resistance or disease aggressiveness. The study by Woyach et al. provides the proof of principle that prolonged lymphocytosis produced by ibrutinib is composed of quiescent leukemic cells and provides a biological rationale in support of the current revisions of CLL [chronic lymphocytic leukemia] response criteria.

Dr. Davide Rossi and Dr. Gianluca Gaidano of the Amedeo Avogadro University of Eastern Piedmont, Alessandria, Italy, provided these comments in an editorial accompanying Dr. Woyach’s study (Blood 2014;123:1772-4). They declared that had no conflicts of interest.

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As more treatments targeting B-cell receptors became available, it was important for physicians to understand that lymphocytosis associated with this treatment was not indicative of treatment resistance or disease aggressiveness. The study by Woyach et al. provides the proof of principle that prolonged lymphocytosis produced by ibrutinib is composed of quiescent leukemic cells and provides a biological rationale in support of the current revisions of CLL [chronic lymphocytic leukemia] response criteria.

Dr. Davide Rossi and Dr. Gianluca Gaidano of the Amedeo Avogadro University of Eastern Piedmont, Alessandria, Italy, provided these comments in an editorial accompanying Dr. Woyach’s study (Blood 2014;123:1772-4). They declared that had no conflicts of interest.

Body

As more treatments targeting B-cell receptors became available, it was important for physicians to understand that lymphocytosis associated with this treatment was not indicative of treatment resistance or disease aggressiveness. The study by Woyach et al. provides the proof of principle that prolonged lymphocytosis produced by ibrutinib is composed of quiescent leukemic cells and provides a biological rationale in support of the current revisions of CLL [chronic lymphocytic leukemia] response criteria.

Dr. Davide Rossi and Dr. Gianluca Gaidano of the Amedeo Avogadro University of Eastern Piedmont, Alessandria, Italy, provided these comments in an editorial accompanying Dr. Woyach’s study (Blood 2014;123:1772-4). They declared that had no conflicts of interest.

Title
Proof of principle that lymphocytosis is quiescent cells
Proof of principle that lymphocytosis is quiescent cells

Persistent lymphocytosis lasting more than 12 months in patients with chronic lymphocytic leukemia undergoing treatment with ibrutinib is not associated with a greater likelihood of early relapse.

A prospective observational study in 85 relapsed or refractory patients with chronic lymphocytic leukemia treated with ibrutinib showed lymphocytosis occurred in 77% in patients, persisting at 12 months in 20% of patients.

Dr. Jennifer A. Woyach of Ohio State University, Columbus, and her colleagues found no significant differences in progression-free survival between patients who responded to treatment but showed persistent lymphocytosis, and those with a partial or complete response to treatment without lymphocytosis.

They also found no significant differences in gene expression profiles in persistent lymphocytosis, suggesting that the lymphocytosis most likely represented the movement of quiescent cells (Blood 2014;123:1810-17).

Two authors were unpaid consultants for, three were paid consultants for, and two were employees of Pharmacyclics. One author received research funding from Janssen. The study was funded by the Four Winds Foundation, the Leukemia and Lymphoma Society, and several other organizations. Ibrutinib was provided by Pharmacyclics for in vitro experiments.

Persistent lymphocytosis lasting more than 12 months in patients with chronic lymphocytic leukemia undergoing treatment with ibrutinib is not associated with a greater likelihood of early relapse.

A prospective observational study in 85 relapsed or refractory patients with chronic lymphocytic leukemia treated with ibrutinib showed lymphocytosis occurred in 77% in patients, persisting at 12 months in 20% of patients.

Dr. Jennifer A. Woyach of Ohio State University, Columbus, and her colleagues found no significant differences in progression-free survival between patients who responded to treatment but showed persistent lymphocytosis, and those with a partial or complete response to treatment without lymphocytosis.

They also found no significant differences in gene expression profiles in persistent lymphocytosis, suggesting that the lymphocytosis most likely represented the movement of quiescent cells (Blood 2014;123:1810-17).

Two authors were unpaid consultants for, three were paid consultants for, and two were employees of Pharmacyclics. One author received research funding from Janssen. The study was funded by the Four Winds Foundation, the Leukemia and Lymphoma Society, and several other organizations. Ibrutinib was provided by Pharmacyclics for in vitro experiments.

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Persistent lymphocytosis with ibrutinib does not indicate early relapse
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Persistent lymphocytosis with ibrutinib does not indicate early relapse
Legacy Keywords
lymphocytosis, lymphocytic leukemia, ibrutinib, leukemia patient,
Dr. Jennifer A. Woyach,
Legacy Keywords
lymphocytosis, lymphocytic leukemia, ibrutinib, leukemia patient,
Dr. Jennifer A. Woyach,
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Major finding: Patients with chronic lymphocytic leukemia who experienced persistent lymphocytosis associated with ibrutinib treatment did not have a greater likelihood of early relapse.

Data source: Prospective observational cohort study in 85 patients with relapsed or refractory chronic lymphocytic leukemia undergoing treatment with ibrutinib.

Disclosures: Two authors were unpaid consultants and three were paid consultants for Pharmacyclics, and two authors were employees of the company. One author received research funding from Janssen. The study was funded by the Four Winds Foundation, the Leukemia and Lymphoma Society, and several other organizations. Ibrutinib was provided by Pharmacyclics for in vitro experiments.