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Significance of HL
- first demonstration of the effectiveness of combination chemotherapy
- CURABLE using different modalities depending on the extent of disease
- distinguishing HL from NHL is useful because px and tx are different
Hodgkin Lymphoma
- a lymphoid neoplastic disorder of B cell origin
- characterized by the presence of Reed-Sternberg cells (or variants of RS cells) in the affected tissues
epidemiology
-much less frequent than NHL
-overall M>F, (but F>M in NS subtype)
-peak incidence in 3rd decade
7800 cases dx annually (2007)
Associated etiological factors
- EBV infection
- smaller family size
- higher SE status (SES)
- white>non-white
- possible genetic predisposition
Epidemiology of HL
- bimodal age distribution
- male>female
- white>non-white
- 2.5 risk in family members
- peak incidence in January and December
What causes HL?
- mutation
- virus - EBV
- immune dysfunction
- We do not know for the majority
HL Pathology
- lymphoid neoplasm defined by the presence of Reed-Sternberg (RS) cells
- RS cells express CD30
- The classical RS cell is binucleate, with an “owl eye” appearance
- nodular lymphocyte predominant HL has distinctive surface markers and morphologic features such as numberous tightly packed nodules
WHO Classification
- Classical HL 95%
- -nodular sclerosing HL 55%
- -mixed cellularity HL 25%
- -Lymphocyte rich classical HL 5%
- -Lymphocyte depletion HL 1-2%
- -not classifiable 5%
- Lymphocyte predominant, nodular HL 5%
HL Pathology
- Classical HL
- -CD30+
- -CD15+
- -CD20-
- NLPHL
- -CD30-
- -CD15-
- -CD20+
Presentation
General
- lymphadenopathy: supradiaphramatic, commonly lower nece, small % subdiaphramatic
- rubbery, painless nodes
- cough, dyspnea, chest pressure (mediastinal mass >/ 10cm)
- unexplained pruritus, young patients
B symptoms: unexplained fever, night sweats, unexplained weight loss
Dx and work-up
History
physical exam: lymphadenopathy, organomegaly
Labs - CBC, chem panel, liver/kidney function, ESR, HIV
Imaging - CT, FDG-PET, CXR
Biopsy - preferably excitional for lymph nodes, BM
bone scan if bone pain present and PET n/a
HL Tx
Tx is driven by stage
Goal of tx is cure with minimal long term SE
minimize risk of leukemia or other SE
What factors determine appropriate therapy
bulk
prognostic factors
duration of therapy
possible SE
complications of HL Tx
Second malignancy (chemo, XRT, splenect): 18% Sepsis (chemo, XRT, splenect) 1-2% Pericarditis (XRT, Adriamycin) 15% Pneumonitis (XRT, Bleomycin) 5-10% Sterility (MOPP, TNI) >80% Growth retardation (XRT) kids Hypothyroidism (XRT) >50%
Frontline Regimens: ABVD
28d cycle
- doxorubicin 25mg/m2 IV d 1, 15
- bleomycin 10mg/m2 IV d 1, 15
- Vinblastine 6mg/m2 IV d 1, 15
- Dacarbazine 375mg/m2 IV d 1, 15
Frontline Regimen: BEACOPP
21d cycle
- Bleomycin 10mg/m2 IV d8
- Etoposide 100mg/m2 IV d 1-3
- Doxorubicin 25mg/m2 IV d 1
- cyclophosphamide 650 mg/m2 IV d 1
- vincristine 1.4 mg/m2 IV d 8
- procarbazine 100mg/m2 PO d 1-7
- Prednisone 40mg/m2 PO d 1-7
Frontline Regimen: Escalated BEACOPP
21d cycle
- Bleomycin 10mg/m2 IV d8
- Etoposide 200mg/m2 IV d 1-3
- Doxorubicin 35mg/m2 IV d 1
- cyclophosphamide 1250 mg/m2 IV d 1
- vincristine 1.4 mg/m2 IV d 8
- procarbazine 100mg/m2 PO d 1-7
- Prednisone 40mg/m2 PO d 1-7
Frontline Regimen: BEACOPP 14
same doses given on sane day as baseline during a 14d cycle
GCSF SQ d9-13
Frontline Regimen: Stanford V
- mustard 6mg/m2 IV weeks 1-5-9
- bleomycin 5mg/m2 IV weeks 2-4-6-8-10
- doxorubicin 25mg/m2 IV weeks 1-3-5-7-9-11
- etoposide 60mg/m2 IV weeks 3-7-11
- vinblastine 6mg/m2 IV weeks 1-3-5-7-9-11
- vincristine 1.4mg/m2 IV weeks 2-4-6-8-10
- prednisone 40mg/m2 PO q other day, taper weeks 10-12
International Prognostic Score (IPS)
IPS for stage advanced III/IV HL 1-point per factor Serum albumin <4 g/dl Hgb <10.5 g/dl Male gender Ann Arbor Stage IV disease Age >/ 45 WBC>/ 15000/mm3 lymphocyte count <600/mm3 or <8% of WBC
Frontline Tx and Px Summary
ABVD remains the preferred tx regimen
5-year OS >90% in early stage HL; ~80% in advanced disease
Tx of refractory or relapsed HL
Disease requiring secondary tx
Refractory: progression during or within <3 months of primary tx
Relapsed: progression >3 months after primary tx
Current HL TX: First Line
Multi-agent chemo +/- RT
ABVD
Stanford V
BEACOPP
Current HL TX: Second Line
multi-agent chemo
ICE, C-MOPP, ChIVPP, DHAP, ESHAP, GVD, IGEV, Mini-BEAM, MINE, VIM-D
HDCT/ASCT
