Which requires a longer maintenance tx, AML or ALL?
ALL- often get HyperCVAD alternating with HD MTX + Ara-C w/ intrathecal tx then followed by POMP maintenance Tx for 2-3 YEARS
What kind of consolidation should be done in AML t(6;9)?
Allo-HSCT in first remission due to poor risk cytogenetic; if no donor can do HiDAC but really try for alloHSCT asap
What CD markers are associated with AML M7?
CD 41 + CD61, note these are also associated with GpIIb/IIIa which is the target of plavix; makes sense as M7 is megakaryoblastic AML
What percent of quantitative BCR-ABL transcript predicts for relapse in in Ph + ALL?
>0.1 %; if this is the case then the patient should undergo an allo-HSCT
This class of drug is notorious for causing mutations in the MLL (Mixed Lineage Leukemia) gene at the 11q23 locus leading ot MDS 1-3 years later
Topoisomerase II inhibitor (Etoposide)
Deletions of chromosome 5 and 7 are often seen in AML with what previous treatement?
What is HyperCVAD?
Hyperfractionated Cyclophosphamide, Vincristine, Adriamycin, and dexamethasone alternating with HD MTX and cytarabine
ALL with EPOR or JAK2 rearrangements is a type of Philadelphia-positive-like ALL sensitive to _______
Why is Blinatumumab only used in B cell ALL
It is a BiTE (Bispecific T cell engager) it directs CD8 T cells to destory the B cell. Wouldn't work if the T cells were the problem
What are the two well known extramedullary presentations of AML?
Leukemia cutis and Myeloid Sarcoma (Chloroma)
ALL with ABL1, ABL2, CSF1R, PDGFRB fusions is a type of philadelphia-positive-like ALL sensitive to ______
What is the dosing of HiDAC?
3g/m2 q12h as a bolus rather than infusional (i.e. infusional intermediate dose Ara-C is in 7+3)
What are some molecular mutations that guide therapy in AML with normal cytogenetics (5)?
NPM1, CEBPA, KIT, FLT3-ITD, FLT3-TKD
How should you manage a CR in Ph- ALL who achieve CR and have no MRD?
Can continue maintenance chemo; if MRD present or bad risk cytogenetics go with alloHSCT
How should all patients with FLT3-ITD be consolidated?
Consolidate with allo-HSCT; obviously if no donor can do HiDAC
What type of AML is associated with CD235a?
Who is Blinatumumab used in?
Blinatumumab is used in Philadelphia negative precursor B cell ALL who have refractory or relapsed disease
What type of ALL does NOT require maintenance?
Burkitt lymphoma does not require long maintenance period. But all other types require 2-3 year maintenance period.
Why would chronic GVHD lead to increased risk of infection with encapsulated organisms?
Can lead to hyposplenia and compromised splenic macrophage function; also often causes hypogammaglobulinemia
ALL with ETV6-NTRK3 is a type of Philadelphia-positive-like ALL that is senstive to ______
Crizotinib (also used in ALK lung adeno)
What is AML-M3v?
Hypogranular variant of APML (20% of APML)
What do you do if you have a patient on Ara-C and they develop cerebellar toxicity which resolves?
Do NOT give another trial of cytarabine; consider another consolidative tx such as autoHSCT if good cytogenetics; allo if bad
Which types of AML should have an LP performed during remission due to increased risk of CNS disease?
M4 (myelomonocytic) and M5 (monocytic) as well as Biphenotypic (myeloid + lymphoid features)
What WBC count confers a higher risk of differentation syndrome in APML?
What type of AML causes gingival hyperplasia?
What are 3 favorable karyotypes in which HiDAC consolidation is preferred over allo-HSCT in AML?
t(8;21), inv(16) t(16;16)
What are the two variants of APML?
M3 and M3v; Hypergranular and Hypgranular
What CD marker is monocytic leukemia (M5) associated with?
CD11c, CD14 (Macrophage), and CD64; note that CD11c is also fairly specific for Hairy Cell Leukemia
Why does the M5 subtype of AML often cause diffuse alveolar hemorrhage during induction phase of treatment?
M5 = acute monocytic leukemia so they have monocytic differentiation, they want to go to tissues to become MO so often cause gum and lung infiltration; when chemo started causes DAH
Which purine analog showed a potential benefit in AML in one study?
Cladribine; fludarabine did not show benefit
CD11c, CD14, and CD64 are associated with what type of AML? What other leukemia is assoc with CD11c?
M5 (Monocytic); Hairy cell leukemia
How long is the maintenance tx of APML?
1-2 years often with ATRA, 6-MP, and MTX
Which type of AML requires a long maintenance phase?
APML, there is induction, consolidation, and then a 1-2 year maintenance phase
What is the general schematic for consolidation regimens of APML?
>2 cycles of anthracycline based therapy + 1-2 weeks ATRA +/- cytarabine
Which type of AML is most likely to cause diffuse alveolar hemorrhage during induction chemo?
AML M5 because it is acute monocytic leukemia and goes to the lungs
What is the general schematic for induction regimens in APML?
ATRA + Anthracycline +/- cytarabine
What is AML M4?
What type of leukemia is associated with CD41 + CD61?
M7- Megakaryoblastic leukemia
What CD marker is associated with erythroleukemia (M6)?
This is the definition of complex cytogenetics in AML
More than 3 abnormalities
The RATIFY study evaluated what drug in treatment of pts with newly diagnosed AML with FLT3 positivity?
What are the side effects of arsenic trioxide?
Can cause QTc prolongation due to blockage of potassium channels
What is the general schematic for maintenance chemo in APML?
ATRA + 6-MP + MTX for 1-2 YEARS
How does Blinatumumab work?
BiTE (Bispecific T cell engager) which directs CD8 T cells to destroy B cells. Does so by acting as a connector between CD3 on T cells and CD19 on B lymphoblasts; only used in philadelphia negative
What is the major treatment difference between B cell and T cell ALL?
In T cell ALL, mediastinal irradiation may be beneficial but otherwise the Tx is the same, both require intrathecal ppx
What is a long term side effect of topoisomerase II inhibitors?
Bone marrow damage leading to MDS 1-3 years after exposure because of rearrangements of the MLL gene (mixed lineage leukemia) @ 11q23 locus
Intermediate risk cytogenetics for AML are what?
Normal cytogenetics, i.e. normal male or female karyotype