Abstract
Anti-CD20 monoclonal antibodies (mAbs), unlabeled rituximab (Rituxan®, Biogen Idec Inc., Cambridge, MA; and Genentech Inc., South San Francisco, CA) or radiolabeled 90Y-ibritumomab (Zevalin®, Biogen Idec Inc., Cambridge, MA) and 131I-tositumomab (Bexxar®; Glaxo Smith Kline, Research Triangle Park, NC), have proven to be effective therapy for non-Hodgkin's lymphoma (NHL), but also induce immediate and persistent decreases in normal peripheral blood lymphocytes (PBLs). Lym-1, a mAb that selectively targets malignant lymphocytes, also has induced therapeutic responses and prolonged survival in patients with NHL when labeled with iodine-131 ( 131I). We have retrospectively examined its effect on PBLs in 41 NHL patients that had received 131I-Lym-1 therapy. Absolute lymphocyte counts (ALCs) were evaluated before and after the first and last 131I-Lym-1 infusion. Modest decreases in PBLs were observed in most of the patients. Using strict criteria to define recovery, time to recovery was determined for 19 patients, with the remainder censored because of insufficient follow-up (median follow up for censored patients: 22 days). Using Kaplan-Meier estimates, it would be predicted that 31% of patients would recover by 28 days and that median time to recovery would be 44 days after the last 131I-Lym-1 infusion. No predictors were found for time to recovery, considering such factors as the administered Lym-1 or 1311 dose, spleen volume, or radiation doses to the body, marrow, or spleen. The data suggest that the effect of 131I-Lym-1 on ALC is the result of a nonspecific radiation effect, rather than a specific Lym-1 mAb effect. The shorter time required for ALC recovery after 131I-Lym-1 when compared to that reported for anti-CD20 mAbs, whether radiolabeled or otherwise, is probably related to differing mechanisms for lymphocytotoxicity and lesser Lym-1 antigenic density on normal B-lymphocytes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 521-530 |
| Number of pages | 10 |
| Journal | Cancer Biotherapy and Radiopharmaceuticals |
| Volume | 22 |
| Issue number | 4 |
| DOIs | |
| State | Published - Aug 2007 |
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Keywords
- Antibody
- Lymphocyte
- Lymphoma
- Radioimmunotherapy
ASJC Scopus subject areas
- Cancer Research
- Pharmacology
- Oncology
Cite this
Effect of antilymphoma antibody, 131I-Lym-1, on peripheral blood lymphocytes in patients with non-Hodgkin's lymphoma. / Schillaci, Orazio; Denardo, Gerald L; DeNardo, Sally J.; Goldstein, Desiree S.; Kroger, Linda A.; O'Donnell, Robert T; Lamborn, Kathleen R.
In: Cancer Biotherapy and Radiopharmaceuticals, Vol. 22, No. 4, 08.2007, p. 521-530.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effect of antilymphoma antibody, 131I-Lym-1, on peripheral blood lymphocytes in patients with non-Hodgkin's lymphoma
AU - Schillaci, Orazio
AU - Denardo, Gerald L
AU - DeNardo, Sally J.
AU - Goldstein, Desiree S.
AU - Kroger, Linda A.
AU - O'Donnell, Robert T
AU - Lamborn, Kathleen R.
PY - 2007/8
Y1 - 2007/8
N2 - Anti-CD20 monoclonal antibodies (mAbs), unlabeled rituximab (Rituxan®, Biogen Idec Inc., Cambridge, MA; and Genentech Inc., South San Francisco, CA) or radiolabeled 90Y-ibritumomab (Zevalin®, Biogen Idec Inc., Cambridge, MA) and 131I-tositumomab (Bexxar®; Glaxo Smith Kline, Research Triangle Park, NC), have proven to be effective therapy for non-Hodgkin's lymphoma (NHL), but also induce immediate and persistent decreases in normal peripheral blood lymphocytes (PBLs). Lym-1, a mAb that selectively targets malignant lymphocytes, also has induced therapeutic responses and prolonged survival in patients with NHL when labeled with iodine-131 ( 131I). We have retrospectively examined its effect on PBLs in 41 NHL patients that had received 131I-Lym-1 therapy. Absolute lymphocyte counts (ALCs) were evaluated before and after the first and last 131I-Lym-1 infusion. Modest decreases in PBLs were observed in most of the patients. Using strict criteria to define recovery, time to recovery was determined for 19 patients, with the remainder censored because of insufficient follow-up (median follow up for censored patients: 22 days). Using Kaplan-Meier estimates, it would be predicted that 31% of patients would recover by 28 days and that median time to recovery would be 44 days after the last 131I-Lym-1 infusion. No predictors were found for time to recovery, considering such factors as the administered Lym-1 or 1311 dose, spleen volume, or radiation doses to the body, marrow, or spleen. The data suggest that the effect of 131I-Lym-1 on ALC is the result of a nonspecific radiation effect, rather than a specific Lym-1 mAb effect. The shorter time required for ALC recovery after 131I-Lym-1 when compared to that reported for anti-CD20 mAbs, whether radiolabeled or otherwise, is probably related to differing mechanisms for lymphocytotoxicity and lesser Lym-1 antigenic density on normal B-lymphocytes.
AB - Anti-CD20 monoclonal antibodies (mAbs), unlabeled rituximab (Rituxan®, Biogen Idec Inc., Cambridge, MA; and Genentech Inc., South San Francisco, CA) or radiolabeled 90Y-ibritumomab (Zevalin®, Biogen Idec Inc., Cambridge, MA) and 131I-tositumomab (Bexxar®; Glaxo Smith Kline, Research Triangle Park, NC), have proven to be effective therapy for non-Hodgkin's lymphoma (NHL), but also induce immediate and persistent decreases in normal peripheral blood lymphocytes (PBLs). Lym-1, a mAb that selectively targets malignant lymphocytes, also has induced therapeutic responses and prolonged survival in patients with NHL when labeled with iodine-131 ( 131I). We have retrospectively examined its effect on PBLs in 41 NHL patients that had received 131I-Lym-1 therapy. Absolute lymphocyte counts (ALCs) were evaluated before and after the first and last 131I-Lym-1 infusion. Modest decreases in PBLs were observed in most of the patients. Using strict criteria to define recovery, time to recovery was determined for 19 patients, with the remainder censored because of insufficient follow-up (median follow up for censored patients: 22 days). Using Kaplan-Meier estimates, it would be predicted that 31% of patients would recover by 28 days and that median time to recovery would be 44 days after the last 131I-Lym-1 infusion. No predictors were found for time to recovery, considering such factors as the administered Lym-1 or 1311 dose, spleen volume, or radiation doses to the body, marrow, or spleen. The data suggest that the effect of 131I-Lym-1 on ALC is the result of a nonspecific radiation effect, rather than a specific Lym-1 mAb effect. The shorter time required for ALC recovery after 131I-Lym-1 when compared to that reported for anti-CD20 mAbs, whether radiolabeled or otherwise, is probably related to differing mechanisms for lymphocytotoxicity and lesser Lym-1 antigenic density on normal B-lymphocytes.
KW - Antibody
KW - Lymphocyte
KW - Lymphoma
KW - Radioimmunotherapy
UR - http://www.scopus.com/inward/record.url?scp=34548621763&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548621763&partnerID=8YFLogxK
U2 - 10.1089/cbr.2007.374
DO - 10.1089/cbr.2007.374
M3 - Article
C2 - 17803447
AN - SCOPUS:34548621763
VL - 22
SP - 521
EP - 530
JO - Cancer Biotherapy and Radiopharmaceuticals
JF - Cancer Biotherapy and Radiopharmaceuticals
SN - 1084-9785
IS - 4
ER -