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Lineage specific treatment of adult patients with acute lymphoblastic leukemia in first remission with anti‐B4‐blocked ricin or high‐dose cytarabine
Author(s) -
Szatrowski Ted P.,
Dodge Richard K.,
Reynolds Carol,
Westbrook Carol A.,
Frankel Stanley R.,
Sklar Jeffrey,
Stewart Carleton C.,
Hurd David D.,
Kolitz Jonathan E.,
VelezGarcia Enrique,
Stone Richard M.,
Bloomfield Clara D.,
Schiffer Charles A.,
Larson Richard A.
Publication year - 2003
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.11219
Subject(s) - medicine , ricin , cytarabine , minimal residual disease , acute lymphocytic leukemia , immunotoxin , immunology , leukemia , gastroenterology , antibody , monoclonal antibody , biology , lymphoblastic leukemia , toxin , biochemistry
BACKGROUND Anti‐B4‐blocked ricin is an immunotoxin comprised of an anti‐CD19 murine monoclonal antibody (B4) conjugated to blocked ricin , which has cytotoxic activity in patients with lymphoid malignancies. METHODS Adults with untreated acute lymphoblastic leukemia (ALL) were treated with a previously developed and tested chemotherapeutic regimen. Patients with CD19 positive ALL were given anti‐B4‐blocked ricin as 2 7‐day continuous infusions 1 week apart. Patients with CD19 negative ALL received high‐dose cytarabine. Serial polymerase chain reaction (PCR) assays of BCR‐ABL , immunoglobulin heavy chain ( IGH ), and T‐cell receptor ( TCR ) genes were used to measure the impact of lineage specific intensification treatment on minimal residual disease. RESULTS Eighty‐two adults were enrolled, and 78 were eligible. The median age was 34 years (range, 17–81 years). Sixty‐six patients (85%) achieved complete remission. Forty‐six patients received the anti‐B4‐blocked ricin, which generally was well tolerated; 80% were able to receive both courses. The most common toxicity was asymptomatic transient elevation of liver function tests in 72% of patients. Lymphopenia occurred in 46% of patients. Two patients developed antibodies to the anti‐B4‐blocked ricin. Molecular monitoring before and after the experimental course of intensification did not show a consistent change in the number of leukemia cells remaining, and the immediate posttreatment PCR studies did not correlate with remission duration. CONCLUSIONS Intensification therapy with anti‐B4‐blocked ricin is feasible for patients with CD19 positive ALL, although there is little evidence of an additional clinical benefit from the anti‐B4‐blocked ricin. Cancer 2003;97:1471–80. © 2003 American Cancer Society. DOI 10.1002/cncr.11219