SUMMARY

1. MANAGEMENT OF INDOLENT
LYMPHOMA

2. • FOLLICULAR LYMPHOMA GRADE 1-2
• Marginal zone lymphoma (MZL):
Extranodal (MALT lymphoma)
Nodal
Splenic
• Lymphoplasmacytic Lymphoma

3. FOLLICULAR LYMPHOMA GRADE 1-2
• second most common lymphoma
• 30% of all NHLs and up to 70% of low-grade
lymphomas reported
• affects predominantly older adults, with a slight
female predominance
• Most patients have widespread disease at diagnosis,

4. • Despite the advanced stage, the clinical course is
generally indolent; however, the disease is not
usually curable with available treatment
• has a favorable outcome in the intermediate term,
with 5- to 8-year survival rates from 70% to 80%
• relapse rate of 15% to 20% per year
• follicular lymphomas eventually evolve into
aggressive lymphomas
• transformation risk of 28% in 10 years

5. Workup

7. Staging

8. Lymph node regions

9. • stage remains important
• for selection of treatment strategy
• predicting prognosis in each histologic category.

12. Follicular Lymphoma: Stages I/II
• The treatment historically for stage I/II FL has been
RT alone
• 20% of FL patients present with localized (stage I and
stage II) disease and are largely curable with
radiation therapy

13. Clinical evidence of treatment of
limited-stage indolent NHL

15. • The reported series were accumulated over a long
period
• Patients stage differently
• Treated with varying doses and field
• Different lymphoma in older pathologic
classifications.

16. Common results
• Five- and 10-year OS is high 75% to 90%
• Early deaths from lymphoma in this group are quite uncommon.
• The FFS rate is less, 40% to 80%.
• Stage 1 better than 2
• Radiation doses and field varied widely.
• The local control rate was greater than 90%with no dose response
demonstrated above 30 Gy
• No evidence of improved survival with field size

17. • DOSE-
• most current radiotherapy series for stage I and II
indolent lymphomas usually employ 30 to 40 Gy
• in-field recurrences have been uncommon

18. ROLE OF CHEMOTHERAPY
• Randomized studies conducted in the 1970s failed to
demonstrate that non adriamycin-containing
combination chemotherapy regimens plus RT were
superior to RT alone
• British national lymphoma study compared RT vs RT
chlorambucil
• No OS or DFS

19. • A single-arm study of 91 stage I to II patients treated
at the M. D. Anderson Hospital with COP OR CHOP
• In addition RT improved DFS compared to historical
control but no increase in OS

20. OBSERVATION ALONE?
• The Stanford group -43 patients with early stage follicular
lymphoma who were not immediately treated with XRT.
• Reasons for no initial therapy included physician choice,
large abdominal radiation field required, advanced age,
concern for xerostomia, and patient refusal.
• At a median follow-up of 86 months, 27 patients (63%)
had not required any therapy
• OS comparable with immediately treated with RT

21. Rx SUMMARY OF FL GR 1-2 STAGE 1-2
• 1 Most patients have a good prognosis after local-regional RT
alone.
• 2 Selected patients may be initially observed without initial
intervention.
• 3 For patients whose prognosis is less certain, such as those
with stage II disease with multiple sites of involvement or
bulky nodes
• chemotherapy followed by involved-field irradiation may
provide more durable remissions

22. Therapy of Disseminated Follicular
Lymphoma
• Advance stage generally considered incurable
• The optimal treatment strategy for patients with
advanced-stage follicular lymphoma is unclear
• Many years of clinical investigation have failed to
prove that immediate aggressive therapy improves
survival compared with conservative therapy.

23. • The NCI initiated a prospective randomized study
• comparing conservative treatment (no initial therapy) VS
• Aggressive combined modality therapy with ProMACE
(prednisone, methotrexate-leucovorin, doxorubicin,
cyclophosphamide, etoposide)/MOPP
(mechlorethamine, vincristine, procarbazine, prednisone)
chemotherapy
• followed by low-dose (24 Gy) total lymphoid RT

24. • The disease-free survival was significantly higher in
the combined modality therapy group at 4 years
(51% vs. 12%)
• no differences in OS were seen.

25. WHEN TO CONSIDER TREATMENT
• Symptomatic disease
• Threatened end organ function
• Cytopenia secondary to lymphoma
• Bulky disease (single > 7 cm or 3 or more >3 cm)
• Splenomegaly or steady progression over at least 6
months

26. CHEMOTHERAPY REGIMEN
• FL is quite responsive to a variety of systemic agents,
• alkylating agents
• Anthracyclines
• purine analogs
• vinca alkaloids
• Corticosteroids
• monoclonal antibodies

27. • single alkylating agents (cyclophosphamide or
chlorambucil) are directly compared with
• combinations of three drugs (COP), significant
differences in long-term outcome, including survival,
are not observed
• Southwest Oncology Group of 415 patients
• doxorubicin-containing treatment did not prolong
the overall median survival
• compared with results with less aggressive regimen

28. • Why combination therapy?
• speed of response
• possibly prolonged disease-free interval compared
with less intense programs
• Combinations of fludarabine with mitoxantrone have
demonstrated very high response rates

29. Role of rituximab
• Hainsworth et al.used rituximab (375 mg/m2 iv per week for 4
consecutive weeks) as initial therapy
• Patients who did not progress received an additional 4-week
course of rituximab every 6 months for 2 years.
• In 62 chemotherapy-naive patients, most of whom had stage
III or IV disease
• 37% complete remissions and median PFS was 34 months

30. Chemotherapy-Biologic Combinations
• Marcus et al. randomized previously untreated patients with
advanced stage follicular lymphoma
• 8 cycles of CVP plus rituximab (R-CVP) or CVP alone.
• Overall and complete response rates were 81% and 41% in
the R-CVP arm versus 57% and 10% in the CVP arm.
• At a median follow-up of 30 months, patients treated with R-
CVP had a very significantly prolonged time to progression
(median 32 months vs. 15 months for CVP)

31. • a randomized trial comparing mitoxantrone, chlorambucil,
and prednisone (MCP) alone with rituximab plus MCP (R-
MCP).
• Also showed superior result on addition of rituximab
• Bendamustine along with rituximab
• Higher PFS and CR
• Similar ORR

32. • The use of the radiolabeled monoclonal antibody iodine-131
tositumomab in previously untreated patients has also been
reported to produce a high CR rate
• chemoimmunotherapeutic approach
• combining standard induction chemotherapy (CHOP) followed
by consolidation with 131I tositumomab
• CR PFS better than chemo alone

33. CHEMOTHERAPY REGIMENS
• R COP or R CHOP preferred
• BR
• Single agent Rituximab or oral
cyclophosphomide in elderly frail patients

34. Consolidation
• Who had CR or PR
• Remission Maintenance: Role of Rituximab
• Rituximab maintenance after chemotherapy alone
provides significant benefit as far as PFS and
borderline OS benefit
• Maintenance therapy with Rituximab once in 8 week
for 2 years

35. Rx for relapsed or progressive ds
• Histologically document to r/o transformation
• R-FCM regimen
• RIT( RADIO IMMUNOTHERAPY)
• radiolabeled monoclonal antibody iodine-131
tositumomab and yttrium-90 ibritumomab tiuxetan

36. Role of RT

37. Extranodal Marginal Zone B-Cell Lymphoma
• Low-Grade B-Cell Lymphoma of Mucosa-Associated Lymphoid
Tissue
• accounts for the majority of low-grade gastric lymphomas and
almost 50% of all gastric lymphomas
• ocular adnexa, they make up approximately 40% of the cases,
and they account for the majority of low-grade pulmonary
lymphomas
• Patients are usually older adults
• female predominance has been reported .

38. • The majority of patients present with localized stage I
or II extranodal disease
• The stomach is the most frequent site
• salivary glands, skin, orbit, conjunctiva, lung, thyroid,
larynx, breast, kidney, liver, bladder, prostate,
urethra, small intestine, rectum, pancreas, and even
in the intracranial dura
• Twenty-five percent of gastric MALT lymphomas and
46% of nongastric MALT lymphomas had evidence of
disseminated disease

39. • Many patients have a history of autoimmune disease
• Sjogren's syndrome or Hashimoto's thyroiditis
• Helicobacter gastritis in the case of gastric MALT
lymphoma
• Mediterranean abdominal lymphoma, a heavy-chain
and immunoproliferative small intestinal disease- C
Jejni

40. • Gastric MALT lymphoma
• C/F- Dyspepsia ,abdominal pain, reflux, nausea,
weight loss
• Endoscopic biopsy
• Erythema, erosion and ulceration

42. Therapy of Mucosa-Associated Lymphoid
Tissue Lymphomas
• these diseases tend to remain localized for long
periods of time
• local treatment (surgery or radiation therapy [RT]) is
effective at long-term control of disease
• low doses of RT (30 Gy) almost always control sites of
disease

43. • Local control rates ranged from 97% to 100%
• 5-year PFS and OS were approximately 76% and 91%,
respectively
• Gastric MALT lymphoma is frequently associated
with chronic gastritis and H. pylori infection.
• antibiotics against H pylori
• 70% of patients remained in complete remission

44. • If PR further antibiotics should be considered
• RT ?
• NO response with abx
• Negative for H pylori(t 11: 18)
• local control and relief of symptoms in greater than
90% of patients
• Dose 30- 35 Gy 1.8-2 Gy per fraction

46. • Sx good result but increased morbidity
• Role of chemotherapy
• In local disease chemo inferior to RT
• Disseminated ds got similar role as in FL

47. • NON GASTRIC MALT LYMPHOMA
• Stage 1-2 IFRT 24-30 Gy
• Observation if diagnostic biopsy excisional

48. Nodal Marginal Zone B-Cell Lymphoma
• monocytoid B-cell lymphomas
• rare disorder, accounting for 1% of the cases
• presented with isolated or generalized nodal disease
• Peripheral nodes involved in > 95%
• Thoraccic or abdominal in 50%

49. • bone marrow was involved in 30%
• Patients are frequently treated with regimens that
are used for follicular lymphoma

50. Splenic Marginal Zone Lymphoma
• commonly seen in elderly men, the disease can occur in
both genders and in young patients
• Patients typically present with weakness, fatigue, or
symptoms related to splenomegaly
• splenomegaly in almost all patients
• hepatomegaly in up to 40% of patients
• Peripheral lymphadenopathy is rare but splenic hilar
nodes usually involved

51. • Thoracic or abdominal nodes in 30%
• Lymphocytosis is a uniform finding, but extreme
lymphocytosis is unusual.
• Anemia and thrombocytopenia are present in a minority
of patients
• Most have stage IV disease, principally because of bone
marrow involvement(85%)

52. • prognostic factors
• hemoglobin level less than 12 g/dL
• LDH level greater than normal
• albumin level less than 3.5 g/dL
• low-risk group (41%) with no adverse factors(88%)
• intermediate-risk group (34%) with one adverse
factor(73%)
• high-risk group (25%) with 2 or 3 adverse factors(50%).

53. Treatment
• Observation – asymptomatic with out cytopenia and
splenomegaly
• HCV infection in 35% of SMZL
• IF +ve anti HCV Therapy with ribavirine and INF @

54. • HCV –ve
• Splenectomy (80-90% Overall response and MS 93
Months)
• R or R COP

55. Follow up

57. RADIATION THERAPY TECHNIQUE
• Extended radiation treatment fields for NHL

61. Involved-fi eld radiation therapy (IFRT)

64. Lymphoplasmacytic lymphoma
• neoplasm of small B lymphocytes, plasmacytoid
lymphocytes, and plasma cells
• involving bone marrow, lymph nodes, and spleen,
• lacking CD5, usually with a serum monoclonal
protein with hyperviscosity or cryoglobulinemia.
• Cells may contain intranuclear inclusions of periodic
acid Schiff positive IgM (Dutcher bodies).

65. • The cells have surface and cytoplasmic (some cells)
Ig, usually of IgM type; usually lack IgD;
• strongly express B-cell associated antigens (CD19,
CD20, CD22, CD79a).
• The cells are CD5, CD10, CD23; CD25 or CD11c may
be faintly positive in some cases
• the median age was 63 years and 53% were men;
• most (73%) had bone marrow involvement.

66. • Lymph node and splenic involvement is common
• A monoclonal serum paraprotein of IgM type, with
or without hyperviscosity syndrome in most cases
• Most cases of mixed cryoglobulinemia have been
shown to be related to HCV infection

67. Treatment
• Treatment of patients with HCV and
cryoglobulinemia with interferon to reduce viral load
has been associated with regression of the
lymphoma.
• chlorambucil with or without prednisone
• Fludarabine with or with out rituximab
• Thalidomide and bortezomib