Addition of granulocyte macrophage colony stimulating factor does not improve response to early treatment of high-risk chronic lymphocytic leukemia with alemtuzumab and rituximab

Clive S. Zent, Wenting Wu, Deborah A. Bowen, Curtis A. Hanson, Adam M. Pettinger, Tait D. Shanafelt, Neil Elliot Kay, Jose F. Leis, Timothy G. Call

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Thirty-three previously untreated patients with high-risk chronic lymphocytic leukemia (CLL) were treated before meeting standard criteria with alemtuzumab and rituximab. Granulocyte macrophage colony stimulating factor (GM-CSF) was added to the regimen to determine whether it would improve treatment efficacy without increasing toxicity. High risk was defined as at least one of the following: 17p13-; 11q22.3-; unmutated IGHV (or use of VH3-21) together with elevated expression of ZAP-70 and/or CD38. Treatment was subcutaneous GM-CSF 250 μg Monday-Wednesday-Friday for 6 weeks from day 1, subcutaneous alemtuzumab 3 mg-10 mg-30 mg from day 3 and then 30 mg Monday-Wednesday-Friday for 4 weeks, and intravenous rituximab (375 mg/m 2/week) for 4 weeks from day 8. Patients received standard supportive care and were monitored weekly for cytomegalovirus (CMV) reactivation. Using standard criteria, 31 (94%) patients responded to treatment, with nine (27%) complete responses (one with persistent cytopenia) and nine (27%) nodular partial responses. Median progression-free survival was 13.0 months and time to next treatment was 33.5 months. No patient died during treatment, seven (21%) had grade 3-4 toxicities attributable to treatment, and 10 (30%) had CMV viremia. Addition of GM-CSF to therapy with alemtuzumab and rituximab decreased treatment efficacy and increased the rate of CMV reactivation compared to a historical control.

Original languageEnglish (US)
Pages (from-to)476-482
Number of pages7
JournalLeukemia and Lymphoma
Volume54
Issue number3
DOIs
StatePublished - Mar 2013

Fingerprint

B-Cell Chronic Lymphocytic Leukemia
Granulocyte-Macrophage Colony-Stimulating Factor
Cytomegalovirus
Therapeutics
Viremia
Disease-Free Survival
Rituximab
alemtuzumab

Keywords

  • Alemtuzumab
  • Chronic lymphocytic leukemia
  • Early treatment
  • GM-CSF
  • High risk
  • Rituximab

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Addition of granulocyte macrophage colony stimulating factor does not improve response to early treatment of high-risk chronic lymphocytic leukemia with alemtuzumab and rituximab. / Zent, Clive S.; Wu, Wenting; Bowen, Deborah A.; Hanson, Curtis A.; Pettinger, Adam M.; Shanafelt, Tait D.; Kay, Neil Elliot; Leis, Jose F.; Call, Timothy G.

In: Leukemia and Lymphoma, Vol. 54, No. 3, 03.2013, p. 476-482.

Research output: Contribution to journalArticle

Zent, Clive S. ; Wu, Wenting ; Bowen, Deborah A. ; Hanson, Curtis A. ; Pettinger, Adam M. ; Shanafelt, Tait D. ; Kay, Neil Elliot ; Leis, Jose F. ; Call, Timothy G. / Addition of granulocyte macrophage colony stimulating factor does not improve response to early treatment of high-risk chronic lymphocytic leukemia with alemtuzumab and rituximab. In: Leukemia and Lymphoma. 2013 ; Vol. 54, No. 3. pp. 476-482.
@article{deddc3149d2d4ba0a214a1cba3ae21be,
title = "Addition of granulocyte macrophage colony stimulating factor does not improve response to early treatment of high-risk chronic lymphocytic leukemia with alemtuzumab and rituximab",
abstract = "Thirty-three previously untreated patients with high-risk chronic lymphocytic leukemia (CLL) were treated before meeting standard criteria with alemtuzumab and rituximab. Granulocyte macrophage colony stimulating factor (GM-CSF) was added to the regimen to determine whether it would improve treatment efficacy without increasing toxicity. High risk was defined as at least one of the following: 17p13-; 11q22.3-; unmutated IGHV (or use of VH3-21) together with elevated expression of ZAP-70 and/or CD38. Treatment was subcutaneous GM-CSF 250 μg Monday-Wednesday-Friday for 6 weeks from day 1, subcutaneous alemtuzumab 3 mg-10 mg-30 mg from day 3 and then 30 mg Monday-Wednesday-Friday for 4 weeks, and intravenous rituximab (375 mg/m 2/week) for 4 weeks from day 8. Patients received standard supportive care and were monitored weekly for cytomegalovirus (CMV) reactivation. Using standard criteria, 31 (94{\%}) patients responded to treatment, with nine (27{\%}) complete responses (one with persistent cytopenia) and nine (27{\%}) nodular partial responses. Median progression-free survival was 13.0 months and time to next treatment was 33.5 months. No patient died during treatment, seven (21{\%}) had grade 3-4 toxicities attributable to treatment, and 10 (30{\%}) had CMV viremia. Addition of GM-CSF to therapy with alemtuzumab and rituximab decreased treatment efficacy and increased the rate of CMV reactivation compared to a historical control.",
keywords = "Alemtuzumab, Chronic lymphocytic leukemia, Early treatment, GM-CSF, High risk, Rituximab",
author = "Zent, {Clive S.} and Wenting Wu and Bowen, {Deborah A.} and Hanson, {Curtis A.} and Pettinger, {Adam M.} and Shanafelt, {Tait D.} and Kay, {Neil Elliot} and Leis, {Jose F.} and Call, {Timothy G.}",
year = "2013",
month = "3",
doi = "10.3109/10428194.2012.717276",
language = "English (US)",
volume = "54",
pages = "476--482",
journal = "Leukemia and Lymphoma",
issn = "1042-8194",
publisher = "Informa Healthcare",
number = "3",

}

TY - JOUR

T1 - Addition of granulocyte macrophage colony stimulating factor does not improve response to early treatment of high-risk chronic lymphocytic leukemia with alemtuzumab and rituximab

AU - Zent, Clive S.

AU - Wu, Wenting

AU - Bowen, Deborah A.

AU - Hanson, Curtis A.

AU - Pettinger, Adam M.

AU - Shanafelt, Tait D.

AU - Kay, Neil Elliot

AU - Leis, Jose F.

AU - Call, Timothy G.

PY - 2013/3

Y1 - 2013/3

N2 - Thirty-three previously untreated patients with high-risk chronic lymphocytic leukemia (CLL) were treated before meeting standard criteria with alemtuzumab and rituximab. Granulocyte macrophage colony stimulating factor (GM-CSF) was added to the regimen to determine whether it would improve treatment efficacy without increasing toxicity. High risk was defined as at least one of the following: 17p13-; 11q22.3-; unmutated IGHV (or use of VH3-21) together with elevated expression of ZAP-70 and/or CD38. Treatment was subcutaneous GM-CSF 250 μg Monday-Wednesday-Friday for 6 weeks from day 1, subcutaneous alemtuzumab 3 mg-10 mg-30 mg from day 3 and then 30 mg Monday-Wednesday-Friday for 4 weeks, and intravenous rituximab (375 mg/m 2/week) for 4 weeks from day 8. Patients received standard supportive care and were monitored weekly for cytomegalovirus (CMV) reactivation. Using standard criteria, 31 (94%) patients responded to treatment, with nine (27%) complete responses (one with persistent cytopenia) and nine (27%) nodular partial responses. Median progression-free survival was 13.0 months and time to next treatment was 33.5 months. No patient died during treatment, seven (21%) had grade 3-4 toxicities attributable to treatment, and 10 (30%) had CMV viremia. Addition of GM-CSF to therapy with alemtuzumab and rituximab decreased treatment efficacy and increased the rate of CMV reactivation compared to a historical control.

AB - Thirty-three previously untreated patients with high-risk chronic lymphocytic leukemia (CLL) were treated before meeting standard criteria with alemtuzumab and rituximab. Granulocyte macrophage colony stimulating factor (GM-CSF) was added to the regimen to determine whether it would improve treatment efficacy without increasing toxicity. High risk was defined as at least one of the following: 17p13-; 11q22.3-; unmutated IGHV (or use of VH3-21) together with elevated expression of ZAP-70 and/or CD38. Treatment was subcutaneous GM-CSF 250 μg Monday-Wednesday-Friday for 6 weeks from day 1, subcutaneous alemtuzumab 3 mg-10 mg-30 mg from day 3 and then 30 mg Monday-Wednesday-Friday for 4 weeks, and intravenous rituximab (375 mg/m 2/week) for 4 weeks from day 8. Patients received standard supportive care and were monitored weekly for cytomegalovirus (CMV) reactivation. Using standard criteria, 31 (94%) patients responded to treatment, with nine (27%) complete responses (one with persistent cytopenia) and nine (27%) nodular partial responses. Median progression-free survival was 13.0 months and time to next treatment was 33.5 months. No patient died during treatment, seven (21%) had grade 3-4 toxicities attributable to treatment, and 10 (30%) had CMV viremia. Addition of GM-CSF to therapy with alemtuzumab and rituximab decreased treatment efficacy and increased the rate of CMV reactivation compared to a historical control.

KW - Alemtuzumab

KW - Chronic lymphocytic leukemia

KW - Early treatment

KW - GM-CSF

KW - High risk

KW - Rituximab

UR - http://www.scopus.com/inward/record.url?scp=84873374136&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873374136&partnerID=8YFLogxK

U2 - 10.3109/10428194.2012.717276

DO - 10.3109/10428194.2012.717276

M3 - Article

VL - 54

SP - 476

EP - 482

JO - Leukemia and Lymphoma

JF - Leukemia and Lymphoma

SN - 1042-8194

IS - 3

ER -