levoleucovorin and Hemolysis

Hemolytic anemia has been noted during treatment with a variety of chemotherapeutic agents. We observed mild compensated hemolytic anemia in a patient receiving capecitabine during a randomized, controlled trial of adjuvant therapy. In order to investigate the hypothesis that hemolysis is the underlying cause of the hyperbilirubinemia sometimes observed during capecitabine treatment, we evaluated factors associated with hemolysis in ten patients. Factors were also analyzed in ten patients receiving 5-fluorourocil/leucovorin (5-FU/LV).. Twenty chemotherapy-naïve patients undergoing surgery for Dukes' C colon cancer were included in the phase III, 'X-ACT' trial, and randomized to receive 24-week adjuvant treatment with either oral capecitabine (eight cycles of 1,250 mg/m2 twice daily for 14 days, followed by a 7-day rest period) (n=10) or 5-FU/LV administered according to the Mayo Clinic regimen (six cycles of LV 20 mg/m2 followed by 5-FU 425 mg/m2, administered as an i.v. bolus on days 1-5 every 28 days) (n=10). Ten patients randomized in each treatment arm were evaluated. Hemolytic parameters evaluated included bilirubin, lactate dehydrogenase, haptoglobin, and reticulocytes.. Seven patients receiving capecitabine and three patients receiving 5-FU/LV experienced grade 1/2 elevations of bilirubin during the 24-week treatment period. In most cases, hyperbilirubinemia was associated with concomitant alterations in other hemolytic parameters. Five episodes of grade 1 compensated hemolytic anemia were reported in four capecitabine-treated patients, all of which were associated with hyperbilirubinemia.. Adjuvant treatment with capecitabine or 5-FU/LV in a small sample of patients with Dukes' C colon cancer was associated with alterations in hemolytic parameters. These alterations, in particular hyperbilirubinemia, were associated in some patients with low-grade compensated hemolytic anemia. All changes were clinically insignificant, fully reversible, and may represent a fluoropyrimidine class effect. Further studies are indicated to evaluate the incidence and implications of this effect.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colonic Neoplasms; Deoxycytidine; Fluorouracil; Hemolysis; Humans; Hyperbilirubinemia; Injections, Intravenous; Leucovorin; Middle Aged

Oxaliplatin is an effective chemotherapeutic agent frequently used in the treatment of colorectal carcinoma. Rare cases of renal failure and hemolytic reactions have been reported as separate side effects of oxaliplatin. Here we present a clinical picture of immune-related intravascular hemolysis and acute tubular necrosis in a patient receiving this drug. This case suggests a mechanistic explanation of renal failure in patients treated with oxaliplatin.

Topics: Acute Kidney Injury; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Colonic Neoplasms; Fluorouracil; Hemolysis; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Prognosis

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Colonic Neoplasms; Fluorouracil; Hemolysis; Humans; Immunoglobulin G; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Thrombocytopenia

IgG anti-cell antibodies are inefficient in inducing cell lysis by complement. C mediated lysis by anti-cell IgG can be augmented by the use of C fixing anti-antibody. We have studied augmentation of rabbit anti-Forssman IgG, rabbit anti-methotrexate IgG and rabbit anti-folinic acid IgG antibodies by rabbit anti-allotype IgG antibodies. Large variability (from a low of 2 to a high of over 100) was found in augmentation efficiency even with the same anti-allotype antibody; the variability was primarily the function of the anti-hapten antibody. It was concluded that quantitative studies on anti-hapten IgG production relying on augmented hemolysis may lead to misleading conclusions.

Topics: Animals; Antibodies, Anti-Idiotypic; Complement System Proteins; Forssman Antigen; Haptens; Hemolysis; Immunoglobulin G; Leucovorin; Methotrexate; Rabbits

Topics: Complement Activation; Complement C1; Complement Fixation Tests; Dose-Response Relationship, Immunologic; Haptens; Hemolysis; Humans; Immunoglobulin M; Leucovorin; Methotrexate

Improved methods are presented for the detection of antigens and haptens by the use of the passive hemolysis inhibition test. The test is capable of detecting nanogram quantities of proteins (e.g., ferritin, IgE) and haptens (e.g., folinic acid, methotrexate). The method is also useful for studying quantitative and qualitative aspects of antibody-antigen interaction.

Topics: Animals; Antibody Specificity; Antigen-Antibody Complex; Antigens; Complement Fixation Tests; Cross Reactions; Dose-Response Relationship, Immunologic; Erythrocytes; Haptens; Hemolysis; Immunization; Kinetics; Leucovorin; Methotrexate; Rabbits

Short-term IgM memory is established within 1 day after primary injection. This 1 day priming is independent of cell division as it can take place in the pressence of methotrexate or hydroxyurea. The primary response involves a similar 1 day nonproliferative phase. On the contrary, cells responding to a second injection of antigen after short priming intervals begin to proliferate within hours. This implies a qualitative difference between the antigen-sensitive cells in primed and normal animals. After 1 day, further proliferative expansion of memory can occur, which is probably antigen dependent. The response to several dose regimens indicates that repeated antigenic contact is needed to maintain the IgM response.

Topics: Animals; Antigen-Antibody Reactions; Antigens; Cell Division; Erythrocytes; Female; Hemolysis; Hydroxyurea; Immune Tolerance; Immunoglobulin M; Injections, Intraperitoneal; Leucovorin; Male; Methods; Methotrexate; Mice; Spleen; Time Factors