levoleucovorin and Anemia--Hemolytic

We report a case of a 59-year-old woman with metastatic carcinoma of the ileocecal region who received FOLFOX(oxaliplatin/leucovorin/5-fluorouracil) and bevacizumab therapy and exhibited a partial remission with minimal side effects. She developed a mild self-limited episode of immune-mediated hemolytic anemia during her 16th cycle of chemotherapy, which precluded her from receiving further oxaliplatin. We review the literature on oxaliplatin-induced immune-mediated hemolysis, including its mechanism, presenting symptoms, laboratory features, management, and implications for future therapy.

Topics: Anemia, Hemolytic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Cecal Neoplasms; Drug Hypersensitivity; Female; Fluorouracil; Humans; Hypersensitivity, Delayed; Ileal Neoplasms; Intestinal Neoplasms; Leucovorin; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Treatment Outcome

Confusion still exists in the diagnosis of drug-induced immune haemolysis (DIH). The aim of this study was to demonstrate antibodies specific to 5-fluorouracil (5-FU) in a patient with fatal immune haemolysis (IH). The case of a patient who died due to protracted IH is described. A 57-year-old female underwent treatment with oxaliplatin, 5-FU and folinic acid due to cholangiocarcinoma. Following drug administration, she was transfused because of a mild non-haemolytic anaemia and died following haemolysis. Serological testing including antibody screening, direct antiglobulin test and detection of drug-dependent antibodies was performed using standard techniques. The patient's serum was observed to be red in colour due to the presence of free haemoglobin prior to and following blood transfusion, and contained antibodies reactive with RBCs only in the presence of urine from several patients treated with 5-FU (ex vivo antigens). Drug-induced immune haemolysis (DIH) and metabolite-dependent antibodies should always be taken into consideration when a patient being administered any type of drug develops haemolysis.

Topics: Anemia; Anemia, Hemolytic; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Blood Transfusion; Cholangiocarcinoma; Coombs Test; Cryoglobulins; Dialysis; Drug Hypersensitivity; Fatal Outcome; Female; Fluorouracil; Humans; Leucovorin; Low Back Pain; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Specimen Handling; Temperature

We describe an unusual case of hepatosplenic T-cell lymphoma in a 61-year-old man who presented with fever, hepatosplenomegaly, anemia, and thrombocytopenia. A spleen biopsy was consistent with T-cell lymphoma. Cytogenetic studies did not reveal chromosome abnormalities. Using the polymerase chain reaction approach, clonality of the T-cell receptor gamma-chain gene rearrangement could be demonstrated, while Southern blot analysis disclosed only a germline configuration of the T-cell receptor beta chain genes. Of interest, an immune-mediated mechanism was demonstrated and was most likely responsible for erythrocyte and platelet destruction; this is, therefore, the first report of gamma T-cell lymphoma in association with Evans' syndrome. Initial steroid treatment was efficacious in limiting autoimmunity but constitutional symptoms did not subside. Chemotherapy (MACOP-B) was successful in obtaining complete clinical remission. Finally, thrombocytopenia in gammadelta T-cell lymphoma patients should be routinely evaluated for platelet autoantibodies.

Topics: Anemia, Hemolytic; Antineoplastic Combined Chemotherapy Protocols; Autoantibodies; Autoimmune Diseases; Biopsy; Bleomycin; Blood Platelets; Bone Marrow; Cyclophosphamide; Doxorubicin; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; Hepatomegaly; Humans; Hydrocortisone; Leucovorin; Liver Neoplasms; Lymphoma, T-Cell; Male; Methotrexate; Middle Aged; Prednisone; Receptors, Antigen, T-Cell, gamma-delta; Remission Induction; Splenic Neoplasms; Splenomegaly; Syndrome; Thrombocytopenia; Vincristine

Microangiopathic hemolytic anemia (MAHA) and disseminated intravasal coagulation (DIC) as initial paraneoplastic symptoms of a solid tumor present a rare clinical situation.. In 1998 a female patient was admitted due to multiple thrombosis, thrombocytopenia and fever. The initial diagnostic procedures revealed peri-aortic lymphomas and a tumor bulk (7 x 8 cm) in the upper abdomen. Gastroscopy revealed a 2 cm ulcer at the back side of the gastric corpus. Histologically, a signet-ring cell carcinoma was diagnosed. Final diagnosis stated a multilocular metastasising gastric cancer with infiltration of bone, peritoneum and dura and signet-cell infiltration of the bone marrow. Hematologic investigation in view of multiple paraneoplastic thrombosis revealed a microangiopathic hemolytic anemia associated with disseminated intravasal coagulation. Parallel to initial symptomatic therapy of coagulopathy, systemic cytostatic therapy with CDDP and VP-16 was initiated. In addition, radiotherapy of the brain was performed. After histologic confirmation of the diagnosis, weekly therapy with 5-FU (2600 mg/m2) and folinic acid (500 mg/m2) according to the Ardalan protocol was performed. After first signs of moderate response, oxaliplatin (60 mg/m2, day 1) was added. Although the chemotherapy dose had to be reduced due to prolonged neutropenia, the disturbances of hemostasis resolved completely resulting in reduced substitution rates with fresh frozen plasma (FFP) and platelets. Unfortunately, the patient died at home due to pulmonary embolism.. Tumor-associated hemostaseologic alteration requires immediate substitution of FFP and platelets. However, it should be followed by specific therapy of malignancy, since tumor-induced metabolites (e.g. mucin) maintain the alteration of hemostasis. Chemotherapy may therefore be the best strategy to prevent complications such as MAHA and DIC.

Topics: Algorithms; Anemia, Hemolytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Neoplasms; Carcinoma, Signet Ring Cell; Cisplatin; Diagnosis, Differential; Disseminated Intravascular Coagulation; Etoposide; Female; Fluorouracil; Hemorrhagic Disorders; Humans; Leucovorin; Middle Aged; Neoplasm Metastasis; Precancerous Conditions; Stomach; Stomach Neoplasms; Thrombocytopenia

Topics: Adult; Anemia, Hemolytic; DNA; Fanconi Syndrome; Female; FIGLU Test; Folic Acid Antagonists; Folic Acid Deficiency; Glutathione Reductase; Hemoglobinuria, Paroxysmal; Histidine; Humans; Leucovorin; Male; Thalassemia; Vitamin B 12 Deficiency; Waldenstrom Macroglobulinemia

Topics: Anemia; Anemia, Hemolytic; Anemia, Megaloblastic; Folic Acid; Humans; Leucovorin