Anaplastic Lymphoma Kinase–Positive Diffuse Large B-Cell Lymphoma: A Rare Clinicopathologic Entity With Poor Prognosis

• Published in: Journal of clinical oncology Vol. 27; no. 25; pp. 4211 - 4216
• Main Authors: Laurent, Camille, Do, Catherine, Gascoyne, Randy D., Lamant, Laurence, Ysebaert, Loïc, Laurent, Guy, Delsol, Georges, Brousset, Pierre
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 01.09.2009
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, CD20 - analysis; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Biological and medical sciences; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Cyclophosphamide - administration & dosage; Doxorubicin - administration & dosage; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Hematologic and hematopoietic diseases; Humans; Kaplan-Meier Estimate; Ki-1 Antigen - analysis; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - enzymology; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - mortality; Lymphoma, Large B-Cell, Diffuse - pathology; Male; Medical sciences; Middle Aged; Neoplasm Staging; Oncogene Proteins, Fusion - analysis; Prednisone - administration & dosage; Protein-Tyrosine Kinases - analysis; Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases; Retrospective Studies; Risk Assessment; Time Factors; Treatment Outcome; Tumors; Vincristine - administration & dosage; Young Adult; Cancerology; Histopathology; Prognosis; Lymphoproliferative syndrome; Diffuse large B cell lymphoma; B cell neoplasm; Malignant hemopathy; Anaplastic lymphoma kinase; Cancer
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.2008.21.5020

Anaplastic lymphoma kinase (ALK) -positive diffuse large B-cell lymphoma (DLBCL) is a rare variant of DLBCL that has been described only in small case reports. To shed more light on the clinical and pathologic features and outcome of these tumors, we reviewed data from 38 patients. We retrospectively analyzed 38 patients with ALK-positive DLBCL treated with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or CHOP-like regimens from different institutions to better define the presenting features, clinical course, and response to treatment. The histologic findings in all patients were similar. All patients expressed ALK fusion proteins, but virtually all were CD30 and CD20 negative. The median age was 43 years with a 5:1 ratio of males to females. Most patients (60%) followed an aggressive clinical course with advanced stage at diagnosis, frequent marrow infiltration, and poor outcome. Overall survival was 20.3 months (95% CI, 12.2 to 42.6 months). Of note, the median survival was only 12.2 months (95% CI, 9.1 to 32.5 months) in patients with advanced-stage disease. ALK-positive DLBCLs display clinicopathologic features that distinguish them from common DLBCL. Conventional therapy, as used for typical DLBCL, is of limited efficacy. Recognition of this new entity and the characteristic lack of CD20 expression are paramount. Novel front-line intensive chemotherapy regimens should be evaluated in this group of patients.