Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma: a rare clinicopathologic entity with poor prognosis

J Clin Oncol. 2009 Sep 1;27(25):4211-6. doi: 10.1200/JCO.2008.21.5020. Epub 2009 Jul 27.

Abstract

Purpose: 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.

Patients and 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.

Conclusion: 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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anaplastic Lymphoma Kinase
  • Antigens, CD20 / analysis
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Ki-1 Antigen / analysis
  • 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
  • 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
  • Vincristine / administration & dosage
  • Young Adult

Substances

  • Antigens, CD20
  • Biomarkers, Tumor
  • Ki-1 Antigen
  • Oncogene Proteins, Fusion
  • oncoprotein CLTCL-ALK
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Protein-Tyrosine Kinases
  • Receptor Protein-Tyrosine Kinases
  • Prednisone

Supplementary concepts

  • CHOP protocol