Non-hodgkin and hodgkin lymphoma - DSA

Question 1

Essentials of diagnosis of NHL

Answer 1

o Painless lymphadenopathy

o Pathologic dx of lymphoma made by pathologic examination of tissue

Question 2

NHL considerations

Answer 2

o Present as enlarging LNs
o Burkitt Lymphoma – t(8q;14q) → overexpression of c-myc
• Malignant transformation of B-cell proliferation
o Follicular lymphoma – t(14;18) → overexpressed BCL2
• Protect against apoptosis in B cells
o 85% B-cell, 15% T or NK cell origin

Question 3

S/S of NHL

Answer 3

• Lymphadenopathy – isolated or widespread
• LNs periperhally or centrally (retroperitoneum, mesentery, pelvis)
• Indolent lymphomas disseminated at time of dx
• Bone marrow frequently involved
• Constitutional sx: fever, drenching night sweats, wt loss > 10% prior body weight
• “B” symptoms
• Exam: extranodal sites – skin, GI tract, liver, bone marrow may be found
• Burkitt lymphoma – abdominal pain or fullness – predilection of dz for abdomen
• Stage with whole body PET/CT scan, bone marrow bx
• LP for high grade lymphoma or intermediate-grade lymphoma with high risk features

Question 4

Lab findings for NHL

Answer 4

• Peripheral blood normal even with extensive marrow involvement
• Circulating lymphoma cell not commonly seen
• Marrow: paratrabecular monoclonal lymphoid aggregates
• High grade lymphomas – meninges involved, malignant cells in CSF
• Serum LD – prognostic marker
• Dx by tissue bx
• Needle aspiration may yield evidence for NHL
• LN bx or bx of involved extranodal tissue required for accurate dx and classification

Question 5

Most common indolent NHL

Answer 5

• Follicular lymphoma
• Marginal zone lymphoma
• Small lymphocytic lymphoma (CLL)

Question 6

Treatment of indolent NHL

Answer 6

• Tx depends on stage of dz and clinical status of pt
• Limited dz with 1 or 2 contiguous abnl LN tx with localized irradiation with curative intent

• 85% - disseminated dz at dx, not curable
o tx only when sx develop or for high tumor bulk
o following each tx experience relapse at shorter intervals

• 8% spontaneous temporary remission

• Ritiximab 375 mg/m2 IV weekly x4weeks
o Screen for HBV – rare fatal fulminant hepatitis described with anti-CD20 use
o Added to chemo regimes including bendamustine, cyclophosphamide, vincristine, prednisone (R-CVP) and cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)
o Radioimmunoconjugates that fuse to anti-B cell monoclonal Abs → high response rates
• Yttrium-90, ibritumomab tiuxetan and iodine-131 tositumomab

• Clinically aggressive, low-grade lymphomas – candidates for allogenic stem cell transplant with curative intent

• MALTomas of stomach – tx H.pylori w/ abx and acid blockade
o Frequent endoscopic monitoring
o Confined to stomach cured w/ whole-stomach radiotherapy

Question 7

Types of Aggressive NHL

Answer 7

Diffuse large B cell lymphoma
Mantle cell lymphoma
Primary CNS lymphoma
High-grade lymphomas - Burkitt or Lymphoblastic
Peripheral T cell lymphomas

Question 8

Diffuse Large B cell lymphoma

Answer 8

treat with curative intent
• Localized dz – 3 courses of R-CHOP plus localized involved-field radiation or 6 cycles of R-CHOP without radiation
• Advanced dz – 6 cycles of R-CHOP
• Relapse after initial tx – cured by autologous hematopoietic stem cell transplantation if dz remains responsive to chemo
• “Double hit lymphoma” : t(8;14) – MYC and t(14;18) BCL2 = very aggressive course; 25%
o dose adjusted R-EPOCH therapy

Question 9

Mantle Cell Lymphoma

Answer 9

• Intensive initial immunochemo including autologous hematopoietic stem cell transplantation improves outcomes
• Reduced intensity allogenic stem cell transplant curative potential for select patients
• Ibrutinib – in relapsed or refractory

Question 10

Primary CNS lymphoma

Answer 10

• Repetitive cycles of high dose IV methotrexate with rituximab early in tx – better results than whole-brain radiotherapy with less cognitive impairment

Question 11

High grade lymphomas - Burkitt or Lymphoblastic

Answer 11

• Urgent, intense, cyclic chemo in hospital (like ALL)

* Interthecal chemo as CNS prophylaxis

Question 12

Peripheral T cell lymphomas

Answer 12

• Advanced stage nodal and extranodal dz
• Inferior response rates to therapy compared to aggressive B cell dz
• Autologous stem cell transplant incorporated in first line tx
• Brentuximab vedotin – significant activity in relapsed CD30+ peripheral T cell lymphomas like anaplastic large cell lymphoma

Question 13

Prognosis of indolent NHL

Answer 13

median survival 10-15 yrs

• Become refractory to chemo as progresses to more aggressive form

Question 14

Prognosis of aggressive NHL

Answer 14

• Adverse prognosis category: >60 yo, elevated serum LD, stage III or IV, more than 1 extranodal site, poor performance status
• Cure rate: 80% for low risk (0 risk factors); less than 50% for high risk (4+ risk factors)

Question 15

Prognosis of relapsed pt after initial chemo tx for NHL

Answer 15

depends on responsiveness to chemo

• Responsive – autologous hematopoietic stem cell transplant offers 50% chance of long term survival

Question 16

Prognosis of older patients with NHL

Answer 16

poorer tolerance of aggressive chemo

• Use myeloid growth factors and prophylactic abx to reduce neutropenic complications may improve outcomes

Question 17

Hodgkin lymphoma essentials of dx

Answer 17

o Painless lymphadenopathy
o Constitutional sx may or may not be present
o Pathologic dx by LN bx

Question 18

Hodgkin lymphoma considerations

Answer 18

o Reed-Sternberg cells in reactive cellular background

o B-lymphocyte of germinal center origin

Question 19

Clinical findings of hodgkin lymphoma

Answer 19

o Bimodal age distribution – 20s and over 50 yo
o Painless mass commonly in neck
o Others constitutional sx – fever, wt loss or drenching night sweats or generalized pruritus
o Unusual sx – pain in involved LN following alcohol ingestion
o Arise within single LN areas, spread in orderly fashion to contiguous areas of LN; late course vascular invasion → widespread hematogenous dissemination
o Subtypes:
• Classic – nodular sclerosis, mixed cellularity, lymphocyte rich, lymphocyte depleted
• Non-classic – nodular lymphocyte predominant
o Occasionally confused with reactive LN in infectious mononucleosis, cat-scratch dz or drug reactions – phenytoin

Question 20

Staging of hodgkin lymphoma

Answer 20

o Staging: serum chemistries, whole-body PET/CT scan, marrow bx
• Stage I – 1 LN region involved
• Stage II: two or more LN regions on one side of diaphragm
• Stage III: LN regions on both sides of diaphragm involved
• Stage IV: disseminated dz with extranodal involvement
• A if no constitutional symptoms; B if 10% wt loss over 6 mo, fever, or drenching night sweats

Question 21

Treatment options for hodgkin lymphomas

Answer 21

o Chemo regimens:
• ABVD: doxorubicin, bleomycin, vinblastine, dacarbazine – first line
• BEACOPP: bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone

o Low risk – stage I or II without bulky lymphadenopathy or systemic inflammation
• Short course chemo with involved-field radiotherapy or full course of chemo alone

o High risk – Stage III or IV or with Stage II dz and a large mediastinal or other bulky mass
• Full course of ABVD for 6 cycles
• End of tx PET/CT scan with stage II bulky dz who can avoid traditional involved field radiotherapy

o Pulmonary toxicity with bleomycin or radiation – treat aggressively in these pts as can lead to permanent fibrosis and death

o Classic – relapse: may be treatable with high dose chemo and autologous hematopoietic stem cell transplant
• 35-50% chance of cure when chemo-responsive
• brentuximab vedotin – activity for relapsing after transplant

Question 22

Prognosis of hodgkin lymphoma

Answer 22

o Treat with curative intent
o Cure rate 75% if 0-2 risk features, 55% if 3+ risk features
o Excellent: IA or IIA – 90% 10 yr survival
o Stage III or IV – 50-60% 10 yr survival
o Poorer results in older pts, bulky dz, lymphocyte depletion or mixed cellularlity
o Non-classic: highly curable with radiotherapy alone for early dz – high stage dz – long survival with repetitive relapses after chemo