Cytogenetics
Define hypodiploid
Less than 44 chromosomes.
This is a poor risk cytogenetic result.
Which is the most common BCR-ABL transcript in Ph+ ALL?
p190
p210 is more common in CML
Minimal residual disease is defined as 1 blast per how many cells?
10 ^ -4 or 1 in 10,000
By NGS even deeper levels of disease can be detected (10 ^ -5 or -6)
Blinatumomab has a black box warning for:
A) Thrombocytopenia
B) Pancreatitis
C) Liver toxicity
D) Cytokine release syndrome
E) Hypersensitivity reaction
D) Cytokine release syndrome
Blinatumomab is a bi specific T-cell engager, as such it can cause cytokine release syndrome and ICANs similar to CAR-T (black box warning for both)
Ponatinib overcomes which mutation leading to resistance to other TKIs?
T3151
3/4 of patients will relapse with this clone.
Which cytogenetic abnormality should be referred to genetic counseling and why?
A) t(9;22)
B) tp53
C) IKZF1
D) Hyperdiploid
B) tp53
Should be referred to genetics to rule out germline tp53 mutation which could suggest Li Fraumeni, which is important to know before considering donors for allogeneic transplant.
IHC for T-cell ALL
cyCD3, CD5, CD7, TdT, CD34
33F with history of B-cell ALL received peg-asparaginase based induction therapy. Following induction she is found to have minimal residual disease on bone marrow biopsy. What treatment do you offer?
A) Allo transplant
B) Blinatumomab
C) Inotuzumab
D) CAR-T
E) Auto sct
B) Blinatumomab
Approved for MRD+ disease following induction therapy. In studies 78% of patients who received this therapy converted to MRD negative.
Name 2 Side effects of dasatinib?
QTc prolongation, fluid accumulation, GI disturbance, cytopenias
What is the target for CAR-T for R/R B-ALL?
CD19
Currently two products approved for R/R ALL (tisagenleucel, brextacabtagene)
45M with recently diagnosed Ph- B-cell ALL. Which of the following is a poor risk cytogenetic group?
A) Hyperdiploid
B) Hypodiploid
C) t(12;21)
D) Trisomy 10
E) Trisomy 17
B) Hypodiploid
Patients with poor risk cytogenetics who are MRD negative following induction therapy should be considered for allo SCT.
37M with history of HIV presents to the ED with fatigue, bone pain, bruising. Labs show pancytopenia . He undergoes bone marrow biopsy. IHC is pending but the pathologist describes sheets of atypical lymphoid cells with basophilic cytoplasm and prominent vacuoles with large areas of necrosis/hemorrhage. This morphology suggests what diagnosis?
L3 morphology suggests Burkitt lymphoma.
A classic "starry-sky" pattern is usually present with numerous benign macrophages (histiocytes) that have ingested apoptotic tumor cells.
Name 2 indications for allo transplant in ALL
Ph+
MLL
Hypodiploid
Early T-cell precursor
Name 2 side effects of peg-asparaginase
Pancreatitis, hypersensitivity, DIC, abnormal LFTs
Inotuzumab is a monoclonal antibody against?
CD22
Gene expression associated with Ph-like ALL
A) NOTCH
B) CRFL2
C) RUNX1
D) p53
B) CRFL2
Ph-like ALL is a provision WHO classification that has a similar gene expression to Ph+ without BCR-ABL fusion. Associated with poor prognosis.
42M presents to his PCP with fatigue, pallor. CBC shows wbc 9k (30% blasts), Hb 9.2, plt 65k. Bone marrow biopsy performed shows the following IHC:
CD3- CD5- CD7- CD13- CD33- MPO-
TdT+, CD45+ CD19+ CD20+, CD22+
What is the diagnosis?
A) T-cell ALL
B) B-cell ALL
C) Mixed phenotype acute leukemia
D) AML
E) APL
B) B-cell ALL
B-cell markers will be positive in b-cell ALL (as listed). Myeloid antigens may be expressed (CD13, CD33) but MPO should always be negative.
19F with recently diagnosed Ph+ ALL. She has a brother who is an HLA match. Which of the following is not necessarily a standard therapeutic option for this patient?
A) Induction therapy + TKI
B) Allo transplant as consolidation
C) Intrathecal MTX
D) Maintenance therapy with TKI
B) Allo transplant as consolidation
There is data that for patients < 21 years of age, if MRD negativity is achieved allo transplant may not confer advantage over chemo + TKI.
Ponatinib has a black box warning for:
A) diffuse alveolar hemorrhage
B) myocardial infarction
C) PML
D) Kidney injury
E) Neutropenia
B) myocardial infarction
Ponatinib has BBW for arterial occlusive events, heart failure, hepatotoxicity, VTE
Mechanism of blinatumomab
Bi-specific T-cell engager that links T-cells with CD19 on B-cells
Translocation associated with multilineage leukemia
A) t(9;22)
B) t(8;14)
C) t(4;11)
D) t(11;14)
C) t(4;11)
This is a poor risk prognostic group. Generally would proceed to transplant after consolidation.
17M with recently diagnosed Ph- B-cell ALL after he presented with pancytopenia. Bone marrow flow cytometry shows a population of blasts that are positive for CD34, TdT, HLA-DR, CD10, CD22. Cytogenetics reveals 35XY karyotype. What is the most likely molecular alteration that he has?
A) STK11
B) tp53
C) RUNX1
D) CEBPA
E) CRFL2
B) tp53
Low hypodiploid is associated with high frequency of tp53 mutations.
52F presents to the ED with fatigue, bone pain and epistaxis. Labs show anemia, neutropenia, thrombocytopenia. Bone marrow biopsy is performed and shows small lymphoblasts that are positive for CD19, CD20, Cd34, negative for MPO. Cytogenetic reveal t(9;22) in all metaphases. What induction therapy do you offer?
A) Cyclophosphamide, daunorubicin, vincristine, prednisone, peg-asparaginase + dasatinib
B) HyperCVAD + imatinib
C) R-HyperCVAD + dasatinib
D) Anthracycline + cytarabine
E) R-CHOP
C) R-HyperCVAD + dasatinib
This patient has Ph+ B-cell ALL. Given his age (> 40) would likely not offer pediatric regimen. HyperCVAD is appropriate, with addition of rituximab given CD20+ and dasatinib as TKI of choice.
42F with history of good risk ALL undergoes induction chemotherapy and achieves MRD. She decides to forego transplant and is started on POMP maintenance. 10 months after she starts maintenance she is noted to have rising wbc with 5% blasts in the periphery. She received inotuzumab for relapsed disease, achieves MRD negativity and proceeds with allo transplant. On day +7 after transplant she reports abdominal distension, RUQ pain and yellowing of her eyes. What is the likely etiology?
A) Portal vein thrombosis
B) CMV reactivation
C) ABO mismatch
D) Hepatic leukemic infiltrates
A) Portal vein thrombosis
Inotuzumab is a risk factor for development of veno-occlusive disease, especially after transplant. Prophylax with ursodiol. Treatment is with defibrotide.
Inotuzumab carries the chemotoxin:
A) Monomethyl Auristatin E
B) Calicheamicin
C) Amatoxin
D) Duocarmycin
B) Calicheamicin
Inotuzumab is an anti-CD22 ADC that carries calicheamicin. Upon internalization the latter binds DNA inducing dsDNA breaks leading to apoptosis.