ABSTRACT
Fludarabine in combination with cyclophosphamide is an effective treatment for newly diagnosed as well as relapsed follicular lymphoma. The anti-CD20 antibody rituximab has been employed successfully for the same indications. No such data were available on a combined use of these agents. Therefore, we conducted a phase II study to evaluate the safety and efficacy of a combination of rituximab (375 mg/m2), fludarabine (4 x 25 mg/m2) and cyclophosphamide (1 x 750 mg/m2), for the treatment of relapsed follicular lymphoma. An unexpected, severe hematologic toxicity with significant, prolonged thrombocytopenias WHO grade III/IV in 6 (35%) of 17 patients treated in total occurred, leading to early termination of the trial. Cytologic and serologic analyses point toward a direct toxic effect. Older patients (mean age 64.7 vs. 56.5 yr) were significantly (P = 0.02) more likely to suffer from this toxicity, whereas no other clinical or hematologic parameter differed statistically between the patients suffering from thrombocytopenia and those who did not. The addition of rituximab to fludarabine/cyclophosphamide employed at doses given above in relapsed follicular lymphoma may have led to this increase in thrombocytopenias. Therefore, caution should be exercised when combining these drugs for the treatment of patients with relapsed follicular lymphoma, especially when treating older patients.
Subject(s)
Antibodies, Monoclonal/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cyclophosphamide/administration & dosage , Lymphoma, Follicular/drug therapy , Vidarabine/analogs & derivatives , Adult , Aged , Antibodies, Monoclonal, Murine-Derived , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Female , Humans , Male , Middle Aged , Recurrence , Rituximab , Vidarabine/administration & dosageABSTRACT
Only two patients with adequately documented oxaliplatin-induced autoimmune haemolytic anaemia have previously been reported. We report here a third patient with an immune-haematological finding favouring a bispecific mechanism (immune-complex and penicillin type) of oxaliplatin-induced haemolysis.
Subject(s)
Anemia, Hemolytic/chemically induced , Antineoplastic Agents/adverse effects , Organoplatinum Compounds/adverse effects , Anemia, Hemolytic/diagnosis , Anemia, Hemolytic/immunology , Autoimmune Diseases/chemically induced , Autoimmune Diseases/diagnosis , Autoimmune Diseases/immunology , Female , Humans , Middle Aged , OxaliplatinABSTRACT
Alloimmunization to the neutrophil antigen NB1 (HNA-2a, CD177) can result in immune neutropenia and transfusion-related acute lung injury. Recently, we were able to elucidate the primary structure of NB1. To shed light also on the molecular basis of the NB1-negative phenotype, we studied the neutrophils of 2 women with NB1-specific alloantibodies for intracellular and extracellular NB1 expression, NB1-specific mRNA production, and the presence of the NB1 gene. No antibody binding to neutrophils was observed by immunofluorescence and immunoblot using a variety of human and monoclonal NB1-specific antibodies. By reverse transcription-polymerase chain reaction with NB1-specific primers we could not detect NB1 cDNAs without accessory sequences, which were found to be introns. The NB1 gene was present in the genome of both patients. Our data indicate that the NB1-negative phenotype is the result of different off-frame insertions on RNA level, resulting in NB1 deficiency on neutrophils.
