ALL

Question 1

The ETV6/RUNX-1 t(12;21) is found in what patient population more so and what kind of prognosis do we see with this?

Answer 1

It is more so found in pediatric patients and it is associated with a favorable prognosis. Only 2% of adult patients have this.

Question 2

In general how do we treat Ph like B-ALL with ABL translocations?

Answer 2

You treat them with a BCR ABL TKI plus chemo just like you would for typical Ph+ B-ALL. And Allo SCT in CR1.

Question 3

What regimens are approved for upfront tx for Ph+ ALL in patients younger than 65 years or age? What about for patients 65 years or older? High yield!

Answer 3

Younger than 65: Blinatumomab + TKI or hyperCVAD w/TKI
TKI options: Ponatinib, Nilotinib, Imatinib, Dasatinib, Bosutinib
(Ponatinib preferred due to T315I mutation)
65 and older: TKI in combination with Blinatumomab, steroid, or Vincristine+Dexamethasone. Can also use mini-hyperCVAD+TKI
Clinical trial preferred for all ages per NCCN
New standard: Blinatumomab+Ponatinib

Question 4

What is the mechanism of action of Blinatumomab? Inotuzumab?

Answer 4

It is a bi-specific antibody that binds to CD19 receptors and CD3 receptors on T cells leading to T-cell activation and lysis of B-cells
Iontuzumab-binds to CD 22

Question 5

For ph+ ALL what are the options for consolidation following induction therapy in those with MRD negative disease? High yield!

Answer 5

Allo SCT, TKI alone, TKI+Blinatumomab, TKI+hyperCVAD (multiagent chemo). In NCCN it doesn’t say Allo SCT is preferred.

Question 6

When looking at transcripts 210 and 190 which belongs to what disease. If a patient presents with B-ALL with a p210 what does this classify them as?

Answer 6

p210-CML
p190-B-ALL
If they have a p210 they could have de-novo CML blast phase or it can just be B-ALL either w/o CML or they may have underlying CML right after treatment of B-ALL or several months after tx

Question 7

What is the mechanism of action of Inotuzumab?

Answer 7

It is a antibody drug conjugate. It binds to CD22 and releases calicheamicin which induces DNA breaks.

Question 8

What are the side effects you can see with Asparginase toxicity?

Answer 8

Allergic rxn (anaphylaxis), pancreatitis, thrombosis, intracranial hemorrhage, hyperglycemia, hypertriglycerdemia, hepatotoxicity.

Question 9

What are the second line options for relapsed Ph+ B-ALL? For those with Ph- disease? High Yield. Remember the treatment strategy is you give second line therapy followed by allo SCT (even if they got a prior SCT).

Answer 9

TKI alone, Blinatumomab +/- TKI, TKI+ chemo (you use regimens that are used in front line setting), Inotuzumab +/- TKI, CAR-T: Brexi-cel (following therapy that includes a TKI), Tisa cel (less than age 26 and failure with one TKI or failure after 2 TKIs), Obeca-cel (following failure with one TKI) all followed by HCT (besides CAR-T?). Ph neg-the options above, but without TKIs (refer to other flashcard regarding when to use CAR-T).

Question 9

What is the immunophenotype for T-ALL? Low Yield but can be aware.

Answer 9

Usually positive for CD7, CD3 (surface or cytoplasmic), CD4/8, CD1a, CD2, CD5, CD38

CD1a, sCD3-, My+, due to the poor prognosis these patients require allo SCT.

Question 10

What is the treatment of T-ALL? Low yield but can be aware.

Answer 10

Tx includes CTX, HD ara-C, asparaginase (now nelarabine included). Maintenance POMP x2-3 years. Mediastinal XRT for Bulky Dx. Should get Allo-SCT.

Question 11

Which patients absolutely require Allo SCT in B-ALL? Low Yield

Answer 11

Any patient w/MRD after induction therapy, Those with poor risk cytogenetics, ALL-MLL t(11q23), Precursor T-ALL, Complex cytogenetics with 5 or more abnormalities, low hypoploidy (less than 40 chromosomes), TP-53 mutation, Ph like with CRLF2 w/JAK 2 mutation.

Question 12

What maintenance therapy can you use in B-ALL Ph+ disease? You can be aware of this but I think it’s low yield

Answer 12

Monthly vincristine/prednisone +TKI (for 2-3 years). TKI alone (after SCT or if they received Blinatumomab+TKI). POMP- methotrexate+daily 6 mercaptopurine.

Question 13

What is the maintenance options in B-ALL Ph- disease? Low Yield

Answer 13

Weekly methotrexate plus daily 6-MP plus monthly vincristine/prednisone pulses

Question 14

What translocations identify a Burkitt type B-ALL?

Answer 14

t(8;14), t(8;2), t(8;22)
New one: c-MYC w/BCL2 or BCL6

Question 15

When looking at B-ALL vs T-ALL what are the phenotypic markers?

Answer 15

B lineage cells: CD19, CD10, TdT, PAX5, CD79a, CD20, or CD22 (can also express CD38)
T lineage cells: cCD3, CD5, CD2, CD7, TdT, CD20, HLA-DR, CD38

Question 16

What is the treatment for Burkitt Leukemia ALL?

Answer 16

Remember that the regimen must include Rituximab. You can use R-Hyper-CVAD or you can use DA-R-EPOCH. They will also need IT therapy for CNS prophylaxis.

Question 17

What cytogenetic marker in B-ALL portends a poor prognosis where patients directly proceed to transplant s/p first remission? HighYield

Answer 17

t(4;11)(q21;q23)-KMT2A-AF4

Question 18

What genetic abnormalities define Ph like ALL and how do you treat these patients? Low yield I think, but still know.

Answer 18

They have a non CRLF2 mutation meaning they have a ABL translocation partner with another gene other than BCR gene or they may have CRLF2 mutations (about 20% of cases, CRLF2 +/-JAK mutations). E.g of non CRLF2 mutation-NUP214/ABL-1. He also mentions the translocation EBF1/PDGFRB. You treat non-CRLF2 with BCR/ABL TKI plus chemo just like you would for Ph+ dx. (e.g. Hyper-CVAD). For CRLF2-chemo+CD 19 (Blinatumomab), CD 20, or CD 22 (Ionotuzumab) mAB. All patients get allo SCT in CR1. Refer to page 9 of NCCN for full mutations

Question 19

Lets say a patient receives induction therapy but they have MRD+ disease what would be the best next step? What are the post re-induction options? High yield!

Answer 19

ABL kinase mutation testing. The options are Blinatumomab+ TKI (appropriate TKI based on mutation present), hyperCVAD+TKI, or TKI alone
Post SCT: Allo SCT followed by TKI maintenance or TKI maintenance alone

Question 20

Remember that at any point if they have MRD+ disease or marrow disease following induction or consolidation therapy the best next step is to get BCR mutation testing.

Question 21

Remember that with post-remission therapy it is important to give CNS prophylaxis using intrathecal chemo: high dose MTX and Cytarabine

Question 22

Which ALL patient has the highest risk of CNS disease?

Answer 22

Those with a high tumor burden as evidenced by a high WBC and LDH

Question 23

What is a important side effect of Ionotuzumab? Blinatumomab?

Answer 23

Ionotuzumab-Hepatic Sinusoidal syndrome and myelosuppression
Blinatumomab-Cytokine release syndrome, neurotoxicity

Question 24

Historically Ph like ALL used to have a poor prognosis but with BCR/ABL TKIs this has gotten better, but in general Ph+ ALL still has a better prognosis that Ph like ALL.

Question 25

With the new standard for B-ALL Ph+ being Ponatinib (or Dasatinib-less preferred now) plus Blinatumomab know that a lot of these patients can avoid allo-SCT due to having MRD neg dx. The boards may still list Dasatinib+hyperCVAD followed by allo SCT as the correct answer though.

Question 26

Remember that all ALL patients will need CNS prophylaxis, what are the options?

Answer 26

Systemic-MTX, Cytarabine and/or IT: MTX, Cytarabine Triple IT tx: MTX, Cytarabine, steroids

Question 27

In general for patients up to age 40 it is preferred to treat them with a pediatric regimen as the OS is far superior than historical regimens.

Question 28

Which risk factors are assoc with CNS relapse?

Answer 28

High LDH and high WBC