Subject(s)
Antibodies, Monoclonal/therapeutic use , Lymphoma, Follicular/therapy , Rituximab/therapeutic use , Adult , Aged , Antibodies, Monoclonal/adverse effects , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Combined Modality Therapy , Female , Fever/etiology , Headache/etiology , Humans , Iodine Radioisotopes/adverse effects , Iodine Radioisotopes/therapeutic use , Kaplan-Meier Estimate , Lymphoma, Follicular/pathology , Male , Middle Aged , Nausea/etiology , Neoplasm Recurrence, Local , Radioimmunotherapy/methods , Rituximab/adverse effects , Thrombocytopenia/etiology , Treatment OutcomeABSTRACT
BACKGROUND: Neutrophilic-chronic myeloid leukemia (CML-N) has been described as a CML variant associated both with a distinctive molecular defect of the Philadelphia chromosome and with a more benign clinical course than classic CML. The translocation (9;22) in CML-N results in the transcription of an e19/a2 type BCR/ABL mRNA that codes for a 230-kD BCR/ABL protein (p230). The indolence of the clinical course of patients with CML-N has been disputed. METHODS: The objectives of this study were to quantify and correlate with clinical outcome the p230 mRNA and protein in patients with CML-N, to describe six new patients and the follow-up (with molecular analysis) of five previously reported patients with CML-N, and to review characteristics of all patients with CML-N and p230 BCR/ABL reported to date in the literature. RESULTS: Quantitative polymerase chain reaction assays on specimens from the great majority of patients with CML-N revealed minimal numbers of molecules of p230 BCR/ABL transcripts per total RNA. This also was associated with a lack of detectable p230 BCR/ABL protein in patient specimens, even in one patient who was followed for 16 years after diagnosis. This may explain the milder leukemic phenotype in most patients with CML-N. A review of all 23 patients who had an e19/a2 type BCR/ABL translocation suggested that the low level of p230 BCR/ABL mRNA and the lack of detectable p230 BCR/ABL protein in patients with no additional cytogenetic abnormalities may predict their indolent clinical course. CONCLUSIONS: Patients with p230 positive CML-N have indolent course, probably as a result of low p230 mRNA and protein levels. This supports the need to conduct additional molecular studies, even if cytogenetic studies have revealed t(9;22), because of the prognostic importance of the molecular findings.