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1
Q

Significance of HL

A
  • 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
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2
Q

Hodgkin Lymphoma

A
  • 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

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3
Q

epidemiology

A

-much less frequent than NHL
-overall M>F, (but F>M in NS subtype)
-peak incidence in 3rd decade
7800 cases dx annually (2007)

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4
Q

Associated etiological factors

A
  • EBV infection
  • smaller family size
  • higher SE status (SES)
  • white>non-white
  • possible genetic predisposition
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5
Q

Epidemiology of HL

A
  • bimodal age distribution
  • male>female
  • white>non-white
  • 2.5 risk in family members
  • peak incidence in January and December
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6
Q

What causes HL?

A
  • mutation
  • virus - EBV
  • immune dysfunction
  • We do not know for the majority
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7
Q

HL Pathology

A
  • 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
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8
Q

WHO Classification

A
  • 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%
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9
Q

HL Pathology

A
  • Classical HL
  • -CD30+
  • -CD15+
  • -CD20-
  • NLPHL
  • -CD30-
  • -CD15-
  • -CD20+
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10
Q

Presentation

A

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

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11
Q

Dx and work-up

A

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

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12
Q

HL Tx

A

Tx is driven by stage
Goal of tx is cure with minimal long term SE
minimize risk of leukemia or other SE

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13
Q

What factors determine appropriate therapy

A

bulk
prognostic factors
duration of therapy
possible SE

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14
Q

complications of HL Tx

A
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%
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15
Q

Frontline Regimens: ABVD

A

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
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16
Q

Frontline Regimen: BEACOPP

A

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
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17
Q

Frontline Regimen: Escalated BEACOPP

A

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
18
Q

Frontline Regimen: BEACOPP 14

A

same doses given on sane day as baseline during a 14d cycle

GCSF SQ d9-13

19
Q

Frontline Regimen: Stanford V

A
  • 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
20
Q

International Prognostic Score (IPS)

A
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
21
Q

Frontline Tx and Px Summary

A

ABVD remains the preferred tx regimen

5-year OS >90% in early stage HL; ~80% in advanced disease

22
Q

Tx of refractory or relapsed HL

A

Disease requiring secondary tx
Refractory: progression during or within <3 months of primary tx
Relapsed: progression >3 months after primary tx

23
Q

Current HL TX: First Line

A

Multi-agent chemo +/- RT
ABVD
Stanford V
BEACOPP

24
Q

Current HL TX: Second Line

A

multi-agent chemo
ICE, C-MOPP, ChIVPP, DHAP, ESHAP, GVD, IGEV, Mini-BEAM, MINE, VIM-D

HDCT/ASCT

25
Q

Current HL TX: Third-Line

A

Chemo/RT New Agents
Allograft
Palliation

26
Q

Tx of R/R HL Goals of TX

A

treated so they are candidates for transplant
pts need cytoreduction prior to chemo
what is appropriate choice for cytoreduction?
what is appropriate txp? auto vs allo

27
Q

Second-Line TX

ICE

A

ifosfamide
carboplatin
etoposide

28
Q

Second Line TX

C-MOPP

A

cyclophosphamide
vincristine
procarbazine
prednisone

29
Q

second line tx

ChlVPP

A

chlorambucil
vinblastine
procarbazine
prednisone

30
Q

second line tx

DHAP

A

dexamethasone
cisplatin
high dose cytarabine

31
Q

second line tx

ESHAP

A

etoposide
methylprednisolone
high dose cytarabine
cisplatin

32
Q

second line tx

GVD

A

gemcitabine
vinorelbine
pegylated liposomal doxorubicin

33
Q

second line tx

IGEV

A

ifosfamide
gemcitabine
vinorelbine

34
Q

second line tx

Mini BEAM

A

carmustine
cytarabine
etoposide
melphalan

35
Q

second line tx

MINE

A

etoposide
ifosfamide
mesna
mitoxantrone

36
Q

second line tx

VIM-D

A

etoposide
ifosfamide
mitoxantrone
dexamethasone

37
Q

second line tx

GCD

A

gemcitabine
carboplatin
dexamethasone

38
Q

R/R disease presents a challenge

A

up to 30% of pts with HL will eventually relapse
only 1 in 4 pts achieves a CR with salvage chemo
Auto HSCT is effective in only 50% of pts w/ R/R HL
-pts who are PET negative have best px
-risk factors reduce survival (extranodal sites, CR <1 year, primary refractory disease, B symptoms, detectable disease at txp, bulky disease at dx)

39
Q

Unmet medical need in R/R post ASCT

A

Chemo options post ASCT

  • largely palliative
  • induce substantial morbidity
  • no approved tx
  • NCCN guidelines list no standard tx for R/R HL
  • pronounced unmet need
40
Q

Other tx options in RR HL

A

Everolimus (mTORi)
Lenalidomide
Bendamustine