The incidence of HIV associated Castleman’s disease

Professor Mark Bower

Chelsea & Westminster Hospital

London, UK

Castleman’s disease

Synonyms

Multicentric Angiofollicular Hyperplasia

Angiofollicular Lymph Node Hyperplasia

Angiomatous Lymphoid Hyperplasia

Castleman Tumor

Giant Benign Lymphoma

Hamartoma of the Lymphatics

Giant Lymph Node Hyperplasia

Castleman’s disease

Hyaline vascular Plasmablastic

Localised

Multi-centric HIV-MCD

IgM light chain restricted (monotypic polyclonal)

HHV8 in plasmablasts in MCD

MCD incidence in CWH cohort

1983-2007

10,997 patients

56,202 patient years follow-up

Overall incidence KS & MCD

MCD KS

Cases 24 1180

Incidence per 10,000 PY (95%CI)

4.3

(2.7-6.4)

210

(198-222)

MCD incidence multivariate analysis

Unlike KS, incidence not related to:

Gender

Prior AIDS diagnosis

MCD incidence multivariate analysis

MCD risk associated with:

Increasing age

Non-Caucasian ethnicity

Shorter duration HIV positive

Higher CD4 nadir count

Not on HAART

Risk by nadir CD4 count

0.1

1

10

100

1000

>200/mm3 50-200/mm3 <50/mm3

MCD

KS

MCD rising incidenceIncidence

/104 patient years of follow up

Pre HAART (83-96)

0.58

(95 % CI: 0.02-4.2)

P <0.05Early HAART (97-01)

2.8

(95% CI: 0.9-6.5)

Post HAART (02-07)

8.3

(95% CI: 4.6-12.6)

Changing incidence over time

0.01

0.1

1

10

100

1000

Pre HAART(1983-1996)

Early HAART(1997-2001)

Post HAART(2001-2007)

MCD

KS

Plasma HHV8 viraemia

HHV8 detectable

HIV+ MCD 25/30 (83%)

2 p <0.0001HIV+ KS 26/73 (35%)

HIV+ Lymphoma 2/74 (3%)

HIV+ controls 0/53 (0%)

Lightcycler quantitative PCR for orf-72

240 HIV+ individuals

Median HHV8 VL

Median in detected

MCD 26,000 41,000

KS 0 3,900

1

10

100

1000

10000

100000

1000000

1E7

HH

V8

VL

MCD KS Other cancer HIV

Higher viral load HHV8 in MCD

Management of MCD

Rituximab

Splenectomy if splenomegally

Etoposide if severe symptoms

Overall survival

0

.2

.4

.6

.8

1C

um. S

urvi

val

0 1 2 3 4 5 6 7Years

N=42

5 year overall survival = 67%

Conclusions

• The incidence of MCD is rising

• MCD is not associated with degree of immunosuppression

• Plasma HHV8 is a diagnostic marker of MCD

• Long term remissions and 5 year survival of 67% can be achieved