Prognostic Indicators

Prognosis in patients with DLBCL

  • Despite advancements in the treatment of DLBCL, approximately 40% of patients relapse after treatment or are refractory to treatment9
  • A greater understanding of the biology of DLBCL and an assessment of favorable or poor prognosis may facilitate better treatment decisions in the future, ultimately resulting in improved patient outcomes9
  • Investigative efforts to define patient subsets associated with favorable or unfavorable prognoses focus on clinical factors recognized in the International Prognostic Index (IPI), gene expression profiles such as germinal center B-cell (GCB) or activated B-cell (ABC) gene expression, and molecular factors as characterized by immunohistochemistry6-9

Clinical prognostic models

  • Prognostic models have been developed to help in predicting outcomes on the basis of patients' clinical characteristics before treatment8

The International Prognostic Index (IPI)

  • The IPI is a clinical tool developed by oncologists to aid in predicting the prognosis of patients with aggressive NHL8,16

Table 5. IPI risk factors16

IPI risk factors

(1) Age >60 years
(2) Ann Arbor stage III/IV
(3) More than 1 extranodal site
(4) Serum lactate dehydrogenase (LDH) level above normal
(5) ECOG performance status ≥2
  • These risk factors help identify low-risk (0-1 factors), low/intermediate-risk (2 factors), intermediate/high-risk (3 factors), and high-risk (4-5 factors) patients (Table 4)16

Table 6. The International Prognostic Index (1993)16

Risk group

IPI score

Percentage of patients

5-year OS

Complete response rate

Low 0-1 35% 73% 87%
Low-intermediate 2 27% 51% 67%
High-intermediate 3 22% 43% 55%
High 4-5 16% 26% 44%
  • The IPI predicts risk of disease recurrence and overall treatment outcome through 5 adverse prognostic risk factors: disease stage, age, performance status, serum LDH levels, and the presence or absence of multiple extranodal sites of lymphoma (Table 5)16

Molecular prognostic models

Gene expression profiling

  • Understanding the biological heterogeneity of DLBCL could lead to a more patient-specific and genetically based approach toward treatment of this disease9
  • DLBCL patients can be divided into clinical risk groups based on results from gene expression profiling17
    • Germinal center B-cell (GCB) DLBCL has a gene expression profile that is characteristic of B cells of the germinal center of the lymph node. Patients with GCB-derived disease have been shown to have better survival outcomes compared with patients with non–GCB-derived disease17
    • Activated B-cell (ABC) DLBCL is derived from B cells that are in the process of differentiating from germinal center B cells to plasma cells. ABC patients have been found to have poorer outcomes than GCB patients17
    • Primary mediastinal large B-cell lymphomas (PMBL) express a gene signature similar to the malignant cells of Hodgkin's lymphoma. PMBL characteristically arises in the mediastinum and a thymic remnant is often found associated with tumor mass. This is a clinically favorable subgroup of DLBCL18
    • Double-hit lymphomas (DHLs), characterized by chromosomal rearrangements of both MYC and BCL2, occur in approximately 5% of DLBCL patients; the prognosis for these patients is very poor19
      • Immunohistochemical analysis has shown that MYC and BCL2 protein overexpression has significant prognostic value. Overexpression of these proteins can occur in the absence of chromosomal rearrangements20