SET4 Flashcards
These tend to be CD13+, CD33+, MPO+, and CD116+
Myeloid Cells
Name 3 drugs or situations that increase a patients risk of HBV reactivation
Anti-CD20 drugs (Rituximab, Obinutuzumab), Alemtuzumab (Anti-CD52), and Allo-HSCT; should be on HBV ppx at least 6 months after last cycle
This drug is an anti-CD22 immunoconjugate carrying calicheamicin used in relapsed or refractory B ALL?
Inotuzumab ozogamicin
This is when a person develops fever during neutrophil recovery after allo-HSCT
Engraftment Syndrome; fever, skin rash, and pulmonary capillary leak can occur
What drug has been shown to cause atypical fractures of the diaphyseal femoral shaft? MOA?
Denosumab, RANKL inhibitor
True or false: CNS ppx is not needed for T-ALL presenting with mediastinal Dz
False, CNS ppx is needed for all pts with any ALL
What is the best drug for HBV reactivation ppx in pts on Rituximab or Obinutuzumab, or Alemtuzumab?
Entacavir is best (others are Tenofovir, Lamivudine, Adofovir, and Telbivudine)
This drug showed a statistically significant improvement in the treatment of chemotherapy-induced peripheral neuropathy
Duloxetine
The molecular weight of BCR-ABL depends on where the chromosome breakpoint occurs: What is the MC transcript in ALL and what is the MC transcript in CML?
ALL most commonly has p190 and CML most often has p210
What can you say about the endometrial cancers that occur due to tamoxifen use?
They occur often after 5 years of use and are usually well-differentiated and early stage
If ALL has CD20+ what effect does this have on prognosis? What do you do about it in Tx?
Worse prognostic indicatior; add rituximab i.e. R-HyperCVAD
The greatest cumulative risk of endometrial CA occurs after how long of exposure to tamoxifen?
5- years, the cancers are usually well-differentiated and occur at early stage
Explain the two signalling events required for T Cell Activation
1) TCR binds to antigent on APC via MHC 1 and MHC 2; CD28 on T cell (Co-stimulatory receptor) binds to B7 ligand on B cell (B7-1 = CD80, B7-2 = CD86); these events lead to T cell proliferation and cytokine release; this process is checked by CTLA upregulation on T cells which tries to downregulate CD28
Although 5-FU overdose can occur for a number of reasons due to human error, deficiency of what enzyme can lead to 5-FU overdose? What drug can tx?
Dihydropyridine Dehydrogenase; Uridine Triacetate
What ALL medications allergic reaction can be Tx with Erwinia chrysanthem?
Allergies to Pegasparaginase
How frequently does Philadelphia positivity occur in ALL pts? General mgmt?
20-30% they should get a TKI in addition to multiagent chemo and since it confers poor prognosis would do allo HSCT in first remission
What are two cytogenetic abnormalities associated with favorable prognosis in ALL?
Hyperdiploidy and TEL-AML1 gene mutation t(12;21)(p13;q22)
These tend to be CD2+, CD3+, CD5+, CD7+, and CD30+
T cells
A patient with MM on denosumab complains of hip pain, what should you do and why?
Image hip as the denosumab causes atypical femoral neck fx so the pain may be due to denosumab and not dz progression
Explain why Ph + ALL has aggressive biology (of note it is usually L2 morphology and CD10+ and CD20+)
Often has many epigenetic changes downstream of BCR-ABL that contribute to its aggressive biology
How does T cell ALL often present?
Can present with marked leukocytosis, mediastinal dz given that T cells mature in thymus and CNS dz
Which drug is a BiTE?
Blinatumumab (Blincyto) BiTE = Bispecific T cell Engager; it works by directing CD8+ T cells to CD19 expressing B cells and so is used in refractory or relapsed ALL
What is the mechanism of action of Inotuzumab ozogamicin and what is its clinical use?
Anti-CD22 immunoconjugate carrying calicheamicin (ozogamicin) and is internalized by B-Cell ALL cells and causes double stranded DNA breaks and apoptosis
What is the most common AE of Cladribine when used to Tx Hairy Cell Leukemia?
Fever, thought to be due to release of cytokines from the apoptotic hairy cells; NSAIDs good for these fevers
What drug is a peptide thrombopoetin mimetic? Non-peptide thrombopoeitin mimetic?
Romiplostin consists of IgG Fc fragment with thrombopoeitin (TPO) peptides attached; Eltrombopag is non-peptide thrombopoeitin mimetic
What drug is approved for 5-FU and capecitabine overdoses?
Uridine Triacetate
What is the mechanism of action of Blinatumumab? Clinical use?
It is a Bispecific T-cell Engager that directs CD8+ T cells to CD19 which is expressed on B cells; used in relapsed or refractory B-cell ALL
When anticoagulation needed in setting of DVT in cancer most clinical practice guidelines say to continue AC for how long?
As long as the cancer is active; LMWH (lovenox) preferred
Cancer cells that overexpress folate carrier type 1 susceptible to this
Praletrexate, enters via folate carrier type 1
All pts with ALL need ppx for what sanctuary site?
CNS (intrathecal MTX or Ara-C OR HD MTX given systemically)
How do you treat engraftment syndrome?
Steroids
Name two agents that have shown shown single agent activity in relapsed or refractory B-cell ALL
Inotuzumab ozogamicin and Blinatumumab
These tend to be CD34+, CD117+, CD123+, and HLA-DR +
Blasts
This tends to be CD11c + and CD103+
Hairy Cell Leukemia
When doing allo-HSCT, is it better to have a CMV + donor or CMV -
CMV + because the donor will be able to mount a more robust immune response should a CMV reactivation occur
How is Hypodiploidy defined in ALL? Effect on prognosis?
Less than 44 chromosomes; poor prognosis
What are the most common toxicities of asparaginase?
Hepatic and Pancreatic (pancreatitis very common, monitor); I saw a pt die of hepatic failure
Why do patients with Hairy Cell Leukemia on Cladribine get febrile?
Cladribine leads to apoptosis of the Hairy Cells and this can cause fevers; should still work up for infectious cause
What is Romiplostin?
A peptide based Thrombopoetin analog consisting of IgG Fc fragment with 4-14 amino acid TPO peptides attached; in contrast to Eltrombopag which is non-peptide TPO analog
B7 ligand is present on APCs and interacts with CD28 (costimulatory signal on T cell) what are the two subtypes of B7 ligand
B7-1 is CD80, B7-2 is CD86
When does VZV most commonly occur following a allo-HSCT?
It is a common late phase infection i.e. after 100 days
What is the drug Uridine Triacetate approved for?
5-FU and Capecitabine overdose
What setting is Nelaribine used in ALL?
Sometimes used in relapsed T-cell ALL
Routine prophylaxis of ambulatory cancer is not generally recommended except in what situation?
When thalidomide or lenalidomide are being used, very high DVT risk; LMWH (lovenox) preffered
Explain how CTLA-4 inhibitors “unleash” the immune system
Basically when a T cell binds an antigen the CD28 receptor on T cell and B7 on the APC (2 subtypes) interact and lead to T cell proliferation; in response to this CTLA is upregulated on the T cell and competes for CD28 to prevent overactivation of the immune system but ipilimumab blocks CTLA-4 allowing the immune system to go nuts
What are the 6 poor risk groups in ALL?
Hypodiploidy, t(v;11q23) MLL rearranged; t(11:14), t(4;11), t(9;22), complex karyotype (more than 5 chromosomal abnormalities)
What are the treatment options for PD-1 and Ipilimumab related GI toxicity?
GI toxicity is autoimmune mediated so it is autoimmune colitis; tx is with steroids and in refractory cases infliximab
The studies showing that Ph + ALL need allo-HSCT in first remission were done before what “era”?
The imatinib era, they probably still need allo HSCT but just keep in mind they were not on TKIs in these studies
True or False: TEL-AML1 gene rearrangements t(12;21)(p13;q22) is a good cytogenetic risk in ALL
True, as is hyperdiploidy i.e. 51-65 chromosomes
These tend to be CD19+, CD20+, CD22+, CD79+, and PAX5+
B-Cells
BCR-ABL p190 most commonly occurs in this setting ____ whereas p210 is most common here ______
p190 more common in ALL though p210 possible; p210 more common in CML though p190 still possible
What two drugs have been implicated in Transplant Associated Thrombotic Microangiopathy
Cyclosporine and Tacrolimus
What is Eltrombopag?
A non-peptide thrombopoeitin analog; in contrast to Romiplostin which is a peptide based thrombopoetin mimetic
What is CD45
The Leukocyte common antigen
What is Engraftment Syndrome?
A condition in which a person develops a febrile syndrome during neutrophil recovery following a transplant; fever and skin rash in addition to pulmonary leak are common
How is complex karyotype defined in ALL
More than 5 cytogenetic abnormalities
Thymic T-ALL confers a better prognosis and often expresses this _____
CD1a
What are some ways that CMV reactivation can present in the transplant setting?
Hepatitis, Pneumonitis, Retinitis, and Encephalitis
What is true of TEL-AML1 gene rearrangements in childhood ALL and adult ALL?
Both associated with favorable prognosis, occurs in 20% of childhood ALL but only 2% of adult ALL
How does praletrexate (anti-folate drug) enter the cancer cell
Via folate carrier type 1
Maintenance therapy with this regiment is common in ALL
POMP
