NHL B-Cell Low-grade




  • Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
  • CD5/CD23(+)


  • 83% have stage IV disease at presentation
  • 4% of patients present with local only disease


  • Local RT for local only disease after pathologic review to rule-out MALT
  • Fludarabine is the most active single agent.


  • Includes cleaved follicular and large non-cleaved follicular center cells.
  • 2nd most common type of NHL (30%)
  • 70% of low-grade NHL.
  • Grade of follicular lymphoma depends upon # centroblasts (large cells) per high-power field.

MALT (mucosa associated lymphoid tissue)/ marginal zone

  1. low-grade B cell tumors associated with trisomy 3, t(11:18)
  2. Helicobacter pylori.
  3. typically malignant appearing cells in the stomach, thyroid, salivary glands, breast, lung, orbit, skin, and bladder.
  4. can transform to intermediate grade.
  5. **Monocytoid B cell **lymphoma
  6. occurs in older patients involving nodes and is similar to MALT lymphomas.

Mantle cell

  1. Generalized disease to spleen, BM and GI tract.
  2. Cells appear similar to those in the mantle region surrounding the germinal centers of nodes.
  3. > 90% have t(11;14) tranlocation.
  4. Nuclear cyclin D1 protein is present in all cases and is the gold standard of diagnosis.


  • IFRT (20-25 Gy)  CHOP
  • Very responsive to radiation and provides durable palliation
  • Most if not all have disseminated disease (OS-3 \~ 80%), but survival continues to decline with years

Indolent (Low-grade) B-cell Lymphoma Antigen & Genetic Profile

== Antigen & Genetic Profile ==


  • Rituxamab works on CD20+ cancer

Low grade stage I and II (Small Lymphocytic and Follicular G1/G2)

Treatment Suggestions

  1. Standard treatment is RT alone to 30-35 Gy
  2. Observation is NOT recommended for all patients because a plateau in DFS (only 4/47 patients who survived 10 years subsequently relapsed) for RT treated patients beyond 10 years, suggestive of cure.[2],[1]
  3. Local relapse rates of 50% at 10 and 15 years
  4. typically relapses at contigious nodal sites if TLI is not done.
  5. Local control rates in excess of 95%.
  6. No trials to determine appropriate dose.
  7. No advantage of extended fields over involved fields.
  8. For more bulky or advanced stage II and stage III Chemotherapy (cyclophosphamide or chlorambucil) followed by IFRT may provide more durable remissions.


  1. The 10-year FFF from 41% to 49%.
  2. The 10-year OS from 43% to 79%
  3. median survival of 11.9 to 15.3 years.
  4. Nine large series (defined as 50 or more patients per study) reporting results of treatment for follicular grade I to II. All but one study contains stage I and stage II patients (in approximately equal frequencies).
  5. In Foundation Bergonie study the majority of patients received some form of systemic treatment. The freedom from treatment failure and OS in this combined RT and chemotherapy study was no better than in the radiation-alone studies.

Low grade stage III and IV:

  • Long survival (median of 7 to 8 years) despite frequent relapse.
  • Overall Survival at 10 years ~45% with DFS of ~30%.
  • If asymtomatic then observation and then median time to symtoms is 3 years.
  • If patient becomes symptomatic then use single agent chlorambucil or combined therapy CVP with 70% response (cyclophosphamide, vincristine, and prednisone).
  • ALso, TBI can be done with doses of 15 cgy twice a week to a total of 150 cgy.
  • These are not cures but places patient in remissions.
  • There have been alternative attempts: IL2, purine analogues, monoclonal antibodies, BM transplant with longer remission length.
  • GELA (French) showed that delayed treatment in asymtomatic patients did not influence overall outcome.
  • There is another study that showed aggressive use of ProMACE-MOPP with TNI has resulted in improved DFS but not OS.
  • The probability of transformation to a higher grade is 22% at 5 years and 31% at 10 years with association of poorer survival.
  • Palliation
  • * 2 Gy x 2 have been studied by Johannsson IJROBP 2002 fo rCLL and INHL with 87% response rate.


  • When single alkalating agents (cyclophosphamide or chlorambucil) are directely compared to cominbations of three drugs (COP), no difference in long-term survival are observed.
  • Combination therapy however dose have more rapid and more complete response and prolonged disease-free interval compared to less intense programs.
1. P. M. Petersen, M. Gospodarowicz, R. Tsang, M. Pintilie, W. Wells, D. Hodgson, A. Sun, M. Crump, B. Patterson, D. Bailey, Long-term outcome in stage I and II follicular lymphoma following treatment with involved field radiation therapy alone. ASCO Meeting Abstracts Jul 15 2004: 6521.
2. MP Mac Manus, RT Hoppe. Is radiotherapy curative for stage I and II low-grade follicular lymphoma? Results of a long-term follow-up study of patients treated at Stanford University. JCO Apr 1 1996: 1282-1290.
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