6.2. Double-/triple-hit lymphoma

5. Primary cutaneous lymphomas, leg type.

6. ALK positive large B cell lymphoma.

52 Hematology - Latest Research and Clinical Advances

8. Primary cutaneous B cell lymphomas.

7. EBV-positive DLBCL NOS.

9. Primary DLBCL of the CNS.

6. Prognosis

1

10. Lymphomatoid granulomatosis.

11. Intravascular large B cell lymphoma.

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,

Original IPI (1 point to each) Age adjusted IPI (1 point to each) NCCN IPI

Elevated serum LDH Elevated serum LDH <sup>1</sup>

Age greater than 60 years Age

Ratio of patient's LDH level to the labs upper limit of normal.

Table 2. Original and modified International Prognostic Index.

Low risk—0–1 Low risk—0 Low risk—0–1

Stage III or IV disease Stage III or IV disease Stage III or IV disease—1 point

More than 1 extranodal site Extranodal sites involving bone marrow,

PS of 2, 3, or 4 PS of 2, 3, or 4 PS of 2 or more—2 points

Low-intermediate risk—2 Low-intermediate risk—1 Low-intermediate risk—2–3 High-intermediate risk—3 High-intermediate risk—2 High-intermediate risk—4–5 High risk—4 or 5 High risk—3 High risk—6 or above

LDH ratio > 1–3—1 point LDH ratio > 3—2 points

CNS, liver/GI tract or lung—1 point

41–60 years—1 point 61–75 years—2 points >75 years—3 points

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 highest acceptable doses.


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