6. Prognosis

#### 6.1. International Prognostic Index (IPI)

Staging in DLBCL has a limited value. The original IPI was developed to identify variables that could predict OS and PFS (Table 2). The factors included were age >60 years, elevated serum lactate dehydrogenase (LDH), Eastern Cooperative group (ECOG) performance status ≥2, clinical stage III or IV, more than 1 involved extranodal disease sites. One point was given for each of the characteristics ranging from zero to five. Five-year survival rates worsened as the scores increased. Five-year overall survival rates for patients with scores of zero to one, two, three, four to five were 73, 51, 43, 26%, respectively [58] (project TIN-HsLPF). This was before the rituximab era. The utility of IPI was reassessed in a retrospective analysis of patients with DLBCL treated with R-CHOP in the province of British Columbia to assess the value of IPI [5]. They redistributed the IPI into revised IPI which identified 3 distinct prognostic groups of very good (score-0), good (scores 1, 2) and poor (scores 3, 4, 5) with a 4 year OS of 94, 79 and 55%, respectively. The NCCN incorporated detailed information about the variables in the original IPI and the location of extranodal disease is used rather than the number of extranodal disease as the lymphomatous involvement in major organs (bone marrow, CNS, liver/GI tract or lung) appeared to be a stronger predictor for a worse prognosis. It stratifies patients into four risk groups low—0–1 points, low-intermediate risk—2–3 points, high-intermediate risk—4–5 points and high risk—≥6 points with OS of 94, 72, 54, 35%, respectively. Both the R-IPI and the NCCN-IPI predict clinical outcome with accuracy and the use of R-IPI or the NCCN-IPI

Recent Advances in Diffuse Large B Cell Lymphoma http://dx.doi.org/10.5772/intechopen.74263 53

routinely to better understand the prognosis of these patients is recommended [59].

Several strategies with intense regimens have been tried to mitigate this risk. Table 3 illustrates the studies of these regimens. Additional randomized control trials are needed to evaluate the efficacy of intense regimens. Based on these small data sets, R-CHOP is associated with inferior outcome. Current literature indicates better outcomes when treated with DA-EPOCH-R in this group of patients [60]. The regimen is a dose adjusted regimen combining etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin in an infusional manner targeting prolonged drug exposure to reduce resistance and dynamic dose adjustments allowing for

Treatment PFS OS

10.9 months

p = 0.001)

12.1 months 22.2 months\* 18.9 months 18.9 month

25% 32% 67%

PFS (R-CHOP): 7.8 months vs. 26.6 months (intensive regimen 21.9 months (p = 0.14)


OS with R-EPOCH vs. R-CHOP (p = 0.057)

6.2. Double-/triple-hit lymphoma

highest acceptable doses.

Study Number of

Petrich et al. [44] Induction therapy with HDSCT

patients

Oki et al. [43] 129 R-CHOP

Howlett et al. [46] 394 R-CHOP

\*p = 0.032 (significant at p <0.05).

311 R-CHOP (32%)

Hyper CVAD/MA (2%) R-EPOCH (21%) R-CODOX-M/IVAC (14%)

R-Hyper CVAD/MA R-EPOCH

Table 3. Intense regimen studies for MYC rearranged with/without BCL2 rearrangement.

R-EPOCH R-Hyper-CVAD/MC R-CODOX-M/R-IVAC

Dunleavy et al. [45] 52 DA-REPOCH 79% (14 months follow up) 77%


Table 2. Original and modified International Prognostic Index.

three, four to five were 73, 51, 43, 26%, respectively [58] (project TIN-HsLPF). This was before the rituximab era. The utility of IPI was reassessed in a retrospective analysis of patients with DLBCL treated with R-CHOP in the province of British Columbia to assess the value of IPI [5]. They redistributed the IPI into revised IPI which identified 3 distinct prognostic groups of very good (score-0), good (scores 1, 2) and poor (scores 3, 4, 5) with a 4 year OS of 94, 79 and 55%, respectively. The NCCN incorporated detailed information about the variables in the original IPI and the location of extranodal disease is used rather than the number of extranodal disease as the lymphomatous involvement in major organs (bone marrow, CNS, liver/GI tract or lung) appeared to be a stronger predictor for a worse prognosis. It stratifies patients into four risk groups low—0–1 points, low-intermediate risk—2–3 points, high-intermediate risk—4–5 points and high risk—≥6 points with OS of 94, 72, 54, 35%, respectively. Both the R-IPI and the NCCN-IPI predict clinical outcome with accuracy and the use of R-IPI or the NCCN-IPI routinely to better understand the prognosis of these patients is recommended [59].
