HIV-associated malignancies Flashcards
HIV is associated with what THREE AIDS-defining cancers?
KAPOSI sarcoma
high grade B cell non-Hodgkin LYMPHOMA
invasive CERVICAL cancer
What virus causes Kaposi sarcoma?
Kaposi sarcoma herpesvirus or human herpesvirus 8 (HHV8)
Where in the body does KS typically present?
cutaneous or mucosal lesions
What proportion of people with KS have visceral disease?
14%
What THREE factors are included in the KS clinical staging system?
1) TUMOUR related criteria
2) host IMMUNOLOGICAL status
3) presence of SYSTEMIC illness
What TWO factors confer an improved prognosis in KS?
1) FIRST AIDS illness
2) increasing CD4, improvement with every 100cells
What TWO factors confer a poorer prognosis in KS?
1) age >50 yrs
2) SYSTEMIC disease
What blood test gives idea of KS tumour burden and acts as a prognostic indicator?
HHV8 DNA level
What are the FIVE stages of response criteria for KS?
1) Complete response
2) Clinical complete response
3) Partial response
4) Stable disease
5) Progressive disease
What is the difference between complete response and clinical complete response in KS criteria?
complete - clinical and histological
clinical - no KS lesions, no histological confirmation
What is the reduction in KS since HAART introduction?
14% (1980s) to 2% (2000s)
Which antivirals have been shown to reduce the risk of KS?
GANCICLOVIR
FOSCARNET
Which common antiviral has NOT been shown to reduce the risk of KS?
ACICLOVIR
What has been most effective against HHV8 replication - ART or antivirals such as ganciclovir?
ART
LOCAL therapies for cutaneous KS are now uncommon due to ART - list FIVE?
RADIOTHERAPY RETINOIDS VINBLASTINE CRYOTHERAPY EXCISION
What proportion of patients with KS starting ART experience IRIS?
up to 29%
How is IRIS KS managed?
systemic CHEMOTHERAPY
When is systemic cytotoxic chemotherapy recommended for KS?
ADVANCED
SYMPTOMATIC
rapidly PROGRESSIVE
Poor prognostic risk index
Which TWO chemotherapy classes are typically used against KS?
LIPOSOMAL ANTRACYCLINES (doxorubicin)
&
TAXANES (Paclitaxel)
Which chemotherapy is GOLD STANDARD against KS?
LIPOSOMAL ANTRACYCLINES (doxorubicin)
What side effects are associated with LIPOSOMAL ANTHRACYCLINE ie doxorubicin?
ALOPECIA
EMESIS
MYELOSUPPRESSION
When might interferon-A be used for KS?
RARELY
residual KS
reconstituted immune system
What other targeted therapies may be useful in treatment of KS?
anti-VEGF-A monoclonal antibody (BEVACUZIMAB)
c-kit (IMATINIB)
inhibition of Ras/Raf/MEK/ERK (SELUMETINIB - MEK inhibitor)
What is RECOMMENDED local therapy for KS?
RADIOTHERAPY
or
INTRALESIONAL VINBLASTINE
What is SECOND line chemotherapy for KS?
TAXANES (ie paclitaxel)
What are the TWO most common subtypes of Non-Hodgkin lymphoma for PLW HIV?
Diffuse large B cell
&
Burkitt’s lymphoma/leukaemia
At what stage do PLW HIV present with Non-Hodgkin lymphoma?
ADVANCED clinical stage
B symptoms
EXTRANODAL involvement inc bone marrow
What is the survival for PLW HIV and non-HOdgkin lymphoma?
On ART:
near HIV negative population
dependent on HISTOLOGICAL type
What BASELINE investigations are required for work up of AIDS-related lymphoma?
BLOOD tests
CT
BONE MARROW aspirate and trephine
Why is PET scan recommended in AIDS-related lymphoma work up?
Improves STAGING accuracy
When should CSF sampling be done in work up for AIDS-related lymphoma?
CNS symptoms or involvement of: PARANASAL sinus BREAST EPIDURAL TESTICULAR
Which Non-Hodkin lymphoma subtype has a high risk of CNS involvement?
BURKITTS
What staging classification should be used for AIDS-related lymphoma?
Ann Arbor
Which PLW HIV are more at risk of infection-related mortality during treatment for AIDS-related lymphoma?
CD4 cell count <50
Which parts of the body should be CT scanned for work up for AIDS-related lymphoma?
Neck, chest, abdomen, pelvis
What infections should be screened for in the work up for AIDS-related lymphoma?
Hepatitis B (HBsAg, sAB, cAb)
Hepatitis C (HCV Ab)
Varicella (VZV IgG)
CMV IgG
In addition to renal, liver and bone profile what other biochemistry is required for work up for AIDS-related lymphoma?
LDH URATE IMMUNOGLOBULINS PROTEIN ELECTROPHORESIS B2 MICROGLUBULIN CRP
Which blood test result is used in prognostic scoring for non-Hodgkin lymphoma?
LDH
Pre-HAART what limited clinical outcomes with chemotherapy for AIDS-related lymphoma?
Risk of opportunistic INFECTION
and
DEATH
(despite lymphoma response)
What TWO factors has led to conventional chemotherapy and doses to be able to be used for PLW HIV with AIDS-related lymphoma?
1) HAART
2) haematopoietic growth factors (G-CSF)
FIRST LINE treatment for diffuse large B cell lymphoma?
CHOP cyclophosphamide doxorubicin vincristine prednisolone
What is the potential advantage of EPOCH vs CHOP chemotherapy for diffuse large B cell lymphoma?
Potentially as effective with less toxicity
Multi-agent
LOW dose
PROLONGED exposure
When is radiotherapy indicated for diffuse B cell lymphoma?
stage I or II disease
in combination with chemo
Not common
What are the BENEFITS of addition of RITUXIMAB to chemotherapy for diffuse B cell lymphoma in PLW HIV?
Improved RESPONSE rate
reduced PROGRESSION of lymphoma on treatment
reduced DEATH due to lymphoma
What is the RISK of addition of RITUXIMAB to chemotherapy for diffuse B cell lymphoma in PLW HIV?
increase DEATH due to INFECTION
CD4 cell count <50
Is RITUXIMAB recommended for PLW HIV and diffuse B cell lymphoma?
YES
What additional prophylactic measures should be taken if a PLW HIV has CD4 cell count <50 and is being treated with RITUXIMAB as part of diffuse B cell lymphoma chemotherapy?
antimicrobial PROPHYLAXIS - cotrimoxazole - fluconazole - aciclovir - azithromycin preemptive G-CSF prompt treatment of opportunistic infection
What is the BENEFIT of HAART in treatment of AIDS-related lymphoma?
reduce OPPORTUNISTIC infection
superior RESPONSE rate
&
SURVIVAL
What is the difference in treatment strategy for HIV Burkitts lymphomas vs HIV diffuse B cell lymphoma?
more INTENSIVE
CNS penetration
FIRST LINE treatment for Burkitts lymphoma in PLW HIV?
CODox-M/IVAC cyclophosphamide vincristine doxorubicin methotraxate ifosamide etoposide cytarabine
What is an ALTERNATIVE treatment for Burkitt’s lymphoma in PLW HIV to CODox-M/IVAC?
DA-EPOCH dose adjusted etoposide prednisone vincristine cyclophosphamide hydroxydaunorubicin
What chemotherapy related toxicity is universal in treatment for Burkitts lymphoma?
NEUTROPENIC fever
MUCOSITIS
due to intensive regimen
Is RITUXIMAB recommended for PLW HIV and Burkitt’s lymphoma?
YES
What is the impact of HIV on risk of CNS involvement with lymphoma?
HIGHER incidence
What is the prognostic implication of SECONDARY CNS lymphoma (ie in context of other systemic lymphoma type)?
VERY POOR prognosis
How can the risk of secondary CNS lymphoma be reduced?
PREVENTIVE treatment as part of FIRST LINE chemotherapy
Which anatomical sites affected by lymphoma increase the risk of CNS relapse?
TESTES PARANASAL PARASPINAL EPIDURAL BREAST RENAL TESTICULAR
Which lymphoma subtype should include INTRATHECAL CNS chemotherapy in PLW HIV?
BURKITT’S
What adverse event is common when giving chemotherapy for a cancer with high tumour burden, especially so for lymphoma?
TUMOUR LYSIS SYNDROME
Within what time frame does tumour lysis syndrome most commonly occur after chemotherapy for lymphoma?
12-72 hours
What preventative therapy can be used to reduce the effect of tumour lysis syndrome?
HYDRATION
anti-URATE (rasburicase or allopurinol)
measurement and correction of electrolyte disturbance
For RELAPSED or REFRACTORY AIDS-related lymphoma, what is the treatment?
INTENSIFIED chemotherapy inc PLATINUM
&
AUTOLOGOUS STEM CELL TRANSPLANT (ASCT)
What might be a typical INTENSIFIED second line treatment of RELAPSED AIDS-related lymphoma?
DHAP
dexamethasone
high-dose cytarabine
cisplatin
When is response to first line treatment usually first assessed for AIDs-related lymphoma?
HALF WAY through treatment
What imaging modality is SUPERIOR when assessing for treatment response at the end of treatment for AIDS-related lymphoma?
PET scan
Which chemotherapy is associated with cardiomyopathy and heart failure and might need follow up in people treated for AIDs-related lymphoma?
ANTHRACYCLINES (doxorubicin)
Which haematological malignancies are associated with chemotherapy for lymphoma?
MYELODYSPLASIA
ACUTE MYELOID LEUKAEMIA
What is the definition of primary CNS lymphoma?
non-hodgkin lymphoma
confined to cranio-spinal axis
no systemic involvement
What virus is found in CNS cells in HIV-associated primary CNS lymphoma?
EBV
How does primary CNS lymphoma most commonly present on CT scan?
DIFFUSE and MULTIFOCAL supratentorial brain masses
Which parts of the eye can be involved in primary CNS lymphoma?
VITREOUS
RETINA
OPTIC nerve
What additional work up is recommended for primary CNS lymphoma?
CT
Bone marrow biopsy
Testicular ultrasound
On identifying brain lesions, in addition to work up for primary CNS lymphoma what initial treatment should be given?
anti-TOXOPLASMOSIS treatment
TWO weeks
sulfadiazine 1g 4xdaily
pyrimethamine 75mg daily
What impact has HAART had on the incidence of primary CNS lymphoma?
REDUCED dramatically
What is the preferred treatment of primary CNS lymphoma for PLW HIV on HAART?
TWO chemotherapy agents
METHOTREXATE
+
cytarabine
When is radiotherapy indicated for primary CNS lymphoma?
if TOXICITY with chemotherapy too high
or
PALLIATIVE for symptom control
What is primary EFFUSION lymphoma?
HIV-associated non-HOdgkin lymphoma SEROUS body cavities - pleural - peritoneum - pericardial NO tumour mass or lymphadenopathy
Which virus is primary effusion lymphoma associated with?
HHV8
What is proportion of HIV-related non-Hodgkins lymphoma does primary effusion lymphoma account for?
4%
What is proportion of NON-HIV-related non-Hodgkins lymphoma does primary effusion lymphoma account for?
<1%
Does primary effusion lymphoma affect MEN or WOMEN?
MEN
In addition to HHV8, which other virus MAY play a role in primary EFFUSION lymphoma?
EBV