Lineage specific treatment of adult patients with acute lymphoblastic leukemia in first remission with anti-B4-blocked ricin or high-dose cytarabine: Cancer and Leukemia Group B Study 9311.
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.
Szatrowski
Ted P
TP
Weill Medical College of Cornell University, New York, New York, USA.
Dodge
Richard K
RK
Reynolds
Carol
C
Westbrook
Carol A
CA
Frankel
Stanley R
SR
Sklar
Jeffrey
J
Stewart
Carleton C
CC
Hurd
David D
DD
Kolitz
Jonathan E
JE
Velez-Garcia
Enrique
E
Stone
Richard M
RM
Bloomfield
Clara D
CD
Schiffer
Charles A
CA
Larson
Richard A
RA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D016313:Genes, abl; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D012276:Ricin / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D018796:Immunoconjugates; D011948:Receptors, Antigen, T-Cell; C117142:anti-B4 blocked ricin immunoconjugate; D003561:Cytarabine; D012276:Ricin