title: Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma: a rare clinicopathologic entity with poor prognosis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: L'Institut National de la Santé et de la Recherche Médicale, U.563, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Laurent
authors.forename: Catherine
authors.initials: C
authors.lastname: Do
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Laurence
authors.initials: L
authors.lastname: Lamant
authors.forename: Loïc
authors.initials: L
authors.lastname: Ysebaert
authors.forename: Guy
authors.initials: G
authors.lastname: Laurent
authors.forename: Georges
authors.initials: G
authors.lastname: Delsol
authors.forename: Pierre
authors.initials: P
authors.lastname: Brousset
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D018951:Antigens, CD20 / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D017730:Ki-1 Antigen / Q000032:analysis; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000032:analysis; D011241:Prednisone / Q000008:administration & dosage; D011505:Protein-Tyrosine Kinases / Q000032:analysis* / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases; D012189:Retrospective Studies; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D018951:Antigens, CD20; D014408:Biomarkers, Tumor; D017730:Ki-1 Antigen; D015514:Oncogene Proteins, Fusion; C408996:oncoprotein CLTCL-ALK; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D011241:Prednisone