title: 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.
abstract: 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.
authors.affiliation: Weill Medical College of Cornell University, New York, New York, USA.
authors.forename: Ted P
authors.initials: TP
authors.lastname: Szatrowski
authors.forename: Richard K
authors.initials: RK
authors.lastname: Dodge
authors.forename: Carol
authors.initials: C
authors.lastname: Reynolds
authors.forename: Carol A
authors.initials: CA
authors.lastname: Westbrook
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Frankel
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Sklar
authors.forename: Carleton C
authors.initials: CC
authors.lastname: Stewart
authors.forename: David D
authors.initials: DD
authors.lastname: Hurd
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kolitz
authors.forename: Enrique
authors.initials: E
authors.lastname: Velez-Garcia
authors.forename: Richard M
authors.initials: RM
authors.lastname: Stone
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
authors.forename: Charles A
authors.initials: CA
authors.lastname: Schiffer
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
mesh_terms: 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
chemical_list: D000964:Antimetabolites, Antineoplastic; D018796:Immunoconjugates; D011948:Receptors, Antigen, T-Cell; C117142:anti-B4 blocked ricin immunoconjugate; D003561:Cytarabine; D012276:Ricin