Treatment of primary mediastinal large B cell lymphoma with an alternating chemotherapy regimen based on high-dose methotrexate.
Primary mediastinal large B cell lymphomas (MLCL) differ from other diffuse large cell lymphomas, leading to a description as a separate entity in the current World Health Organization classification. Dose intensification improves long-term results, but no standard therapy has been established so far. We investigated the use of a high-dose methotrexate-based alternating chemotherapy regimen (B-ALL protocol of the German ALL study group) followed by consolidative mediastinal radiotherapy first as a single-center trial, then later as a prospective multicenter trial in 44 patients with a median age of 33 years. Response rates exceeded 90% with an overall survival rate of 80% in the single-center group (8.6 years median follow-up) and 82% in the multicenter group (2.5 years follow-up).Short-term toxicity was manageable, but required hospitalization: the rates of grade 3 or 4 toxicity were 20% (for mucositis), 42% (for neutropenia), 29% (for thrombocytopenia), and 9% (for neutropenic fever). No relapse occurred more than 2 years after diagnosis and initiation of treatment, but unfortunately, no patient with overt progression or relapse within these 2 years could be salvaged. Future directions in the treatment of MLCL will not focus on further dose intensification, but rather on the incorporation of (radio)immunotherapy as a therapeutic tool and gene expression profiling as well as positron emission tomography-computed tomography as stratifying tools.
Department of Medicine III, Charité-Campus Benjamin Franklin, Berlin, Germany. thomas.fietz@charite.de
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Fietz
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Knauf
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Hänel
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Franke
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Freund
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Thiel
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D003937:Diagnosis, Differential; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000145:classification / Q000175:diagnosis / Q000188:drug therapy*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis; D008297:Male; D008479:Mediastinal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D008727:Methotrexate / Q000008:administration & dosage* / Q000633:toxicity; D008875:Middle Aged; D012008:Recurrence; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
D008727:Methotrexate