Treatment

• Treatment and prognosis determined by histopathologic classification rather than stage

• Indolent: goal is symptom management (bulky disease. cytopenias."B" sx)

Options include radiation for localized disease, single-agent chemotherapy (chlorambucil, cyclophosphamide, fludarabine), combination chemotherapy, and rituximab. Newer rituximab radioimmunotherapy (RIT) conjugates include I131 tositumomab and Y90 ibritumomab tiuxetan.

• Aggressive (DLBCL): goal is cure (jco 2005:236387)

CHOP-R (cyclophosphamide, doxorubicin bydroxydaunorubicm. vincristine Qncovorin. prednisone, ptuximab) (nejm 2002:346:235); CHOP alone if CD20 negative 5-y progression-free survival 54%; overall survival 58% (jco 2005:23 4117) + Radiation for localized or bulky disease

CNS prophylaxis w intrathecal or systemic high-dose methotrexate if paranasal sinus, testicular, breast, periorbital, paravertebral, or bone marrow involved; ¿2 extranodal site f t LDH may also warrant Relapse: salvage chemo; high-dose chemo • auto-HSCT (nejm 1995:333:1540); allo-HSCT if beyond 2nd relapse

• Highly Aggressive

Burkitts: treat with short bursts of intensive chemotherapy (Blood 2004.104 3009) Low risk defined as nl LDH & single focus of disease 10 cm; all others high risk Low risk Rx CODOX-M (cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate - rituximab) (Leu* lymph 2004:45:761) High risk Rx CODOX-M IVAC (above w ifosfamide. etoposide. high-dose cytarabine) All Pts receive CNS prophylaxis and tumor lysis syndrome prophylaxis Lymphoblastic lymphoma (B- or T-cell): treated like ALL (see "Acute Leukemia")

Prognosis

• Indolent: i response to chemotherapy, but long median survival

Follicular Lymphoma International Prognostic Inde* (FLIPI)

Factors: age

60. stage III/ IV. Hb < 12 g dl. >4 nodal areas. LDH >nl

# Factors

5-y Overall Survival

10-y Overall Survival

0-1

90%

71%

2

78%

51%

i3

52%

35%

(Mood 2004:104:1258)

* Aggressive: Î chance of cure, but overall worse prognosis

(Mood 2004:104:1258)

* Aggressive: Î chance of cure, but overall worse prognosis

International Prognostic Index (IPI) for Aggressive NHL

Factors: age

-60. stage III IV. -2 extranodal sites, performance status -2. LDH n]

# Factors

Complete Response

5-y Overall Survival

0-1

87%

73%

2

67%

51%

3

55%

43%

4-5

44%

26%

Revised IPI Prognosis in Patients Rx'd with CHOP-R

# Factors

% at dx

4-y Overall Survival

0

10%

94%

1-2

45%

79%

3-5

45%

55%

(NEJM 1993:329.987; Blood 2007:109 1857)

(NEJM 1993:329.987; Blood 2007:109 1857)

HIV-associated NHL (Blood 2006.107:13)

• HIV 0 imparts 60-100 - relative risk

• NHL is an AIDS-defining malignancy along with Kaposi's, cervical CA. anal CA

• Concurrent HAART & chemotherapy likely provides survival benefit

• DLBCL & immunoblastic lymphoma (67%). CD4 • 100. EBV associated

Treat as non-HIV (CHOP-R). but avoid rituximab if CD4 100

• Burkitts and Burkitt's-like (20%): can occur with CD4 200

Treat as non-HIV disease, though prognosis is significantly worse

• Primary CNS lymphoma (16%): CD4 <50. EBV associated

Treat with high-dose methotrexate • steroids • RT

Treat with standard CHOP, but poor prognosis

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