Prognostic factors for diffuse large B-cell lymphoma in the R(X)CHOP era

Ann Oncol. 2014 Nov;25(11):2124-2133. doi: 10.1093/annonc/mdu109. Epub 2014 Mar 13.


Background: The introduction of rituximab (R) to conventional CHOP chemotherapy for newly diagnosed diffuse large B-cell lymphoma (DLBCL) led to an unequivocal improvement in survival, establishing RCHOP as the standard of care. Still, nearly 40% of DLBCL patients will eventually die of relapsed disease. Efforts to improve outcomes by addition of new biologic agents (X) to the RCHOP backbone are underway. In this era of R(X)CHOP, it is imperative to develop prognostic and predictive markers, not only to identify patients who will suffer a particularly aggressive course, but also to accurately select patients for clinical trials from which they will most benefit.

Design: The following review was undertaken to describe prognostic factors in DLBCL, with emphasis on markers that are accurate, relatively available, and clinically applicable in 2014.

Results: The International Prognostic Index retains its validity in the era of RCHOP, although with limited ability to predict those with <50% chance of long-term survival. Gene expression profiling has provided novel insights into the biology of DLBCL and led to the development of immunohistochemistry (IHC) algorithms that are in routine practice. Identification of a 'double-hit' (DH) lymphoma by fluorescent in situ hybridization with aberrations involving MYC and/or BCL2 and BCL6 genes has important implications due to its extremely dismal prognosis with RCHOP. Other markers such as the absolute lymphocyte count (ALC), serum immunoglobulin free light chains, vitamin D levels, serum cytokines/chemokines, and imaging with positron emission tomography (PET) have all shown promise as future predictive/prognostic tests.

Conclusions: The future for new treatment options in DLBCL is promising with current clinical trials testing novel targeted agents such as bortezomib, lenalidomide, and ibrutinib as the 'X' in R(X)CHOP. Predictive factors are required to select and randomize patients appropriately for these trials. We envision the day when 'X' will be chosen based on the biological characteristics of the tumor.

Keywords: double hit; large cell; lymphoma; non-Hodgkin; prognosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Murine-Derived / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Clinical Trials as Topic
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives*
  • Humans
  • Immunoglobulin Light Chains / blood
  • In Situ Hybridization, Fluorescence
  • Lymphocyte Count
  • Lymphoma, Large B-Cell, Diffuse / blood
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Monocytes / pathology
  • Prednisone / administration & dosage
  • Prognosis*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • Rituximab
  • Treatment Outcome
  • Vincristine / administration & dosage
  • Vitamin D / blood


  • Antibodies, Monoclonal, Murine-Derived
  • Immunoglobulin Light Chains
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc
  • Vitamin D
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • CHOP protocol, modified