Leukemia Flashcards
Incidence of acute megakaryocytic leukemia In Down syndrome
Children with Down syndrome have a 10- to 100-fold elevated incidence of acute leukemia. The
incidence 80% ALL
20%, AML
. Megakaryocytic leukemia is the most common type of myeloid leukemia in
patients with Down syndrome, with 500-fold excess risk.
key markers used to indicate lineage in the WHO system
Myeloid: myeloperoxidase positivity
T-lineage: cytoplasmic CD3 or surface CD3
B-lineage: CD19, CD79a
Define mixed-phenotype acute leukemia?
(WHO) acute leukemia containing 2 distinct populations of blasts fulfilling diagnostic criteria for 2 different lineages (bilineal leukemia) or a single blast population expressing mixed markers (biphenotypic leukemia).
**flow cytometry on at least 20% of blasts for surface markers and 10% for cytoplasmic markers (european )
MPAL frequency ( Bilineal)
B-lymphoid/myeloid, 60%
T-lymphoid/myeloid, 33%
T-/B-lymphoid, 4%
Trilineage, 3%
Acute undifferentiated leukemia (AUL) markers
These usually express CD34, HLA-DR, CD38, and sometimes TdT but no specific myeloid/lymphoid markers.
Two common genetic mutation in MPAL
BCR-ABL1 fusion and KMT2A rearrangement
**2 genetic subclassifications of MPAL are included in the WHO system:
Comparing the toxicity profiles of younger patients with acute lymphoblastic leukemia (1-15 years) to adolescents and young adults (1-30 years), which toxicity is more common in younger patients compared to older patients?
Adolescents and young adults with ALL treated with pediatric-based regimens have higher rates of toxicities, particularly hepatic and often associated with asparaginase. They also have higher rates of regimen-related mortality and require dedicated supportive measures.
Younger patients, however, have higher rates of febrile neutropenia.
Name two translocation that occurs in utero
ETV6::RUNX1 and KMT2A translocations
CD10+/CD19+/dimCD45/CD22+/weak CD13/33+
which leukemia ?
classic pre-B ALL immunophenotype
CD3+/CD4+/TdT+/CD1a+/CD34+
which leukemia?
classic T-ALL phenotype
CD33+/CD34+/weak CD38+/variable HLA-DR/weak MPO+
which leukemia ?
AML
CD10+/CD20+/bright CD45+/TdT-/kappa-restricted
which leukemia ?
mature B-cell phenotype, given the TdT negativity and the kappa restriction
CD3+, CD7+, TdT+, CD1a-, CD117+
which leukemia?
ETP ALL
lymphoblasts are immunophenotypically defined by absent CD8 and CD1a expression, weak CD5 expression, and robust expression of 1 or more myeloid and/or stem cell markers.
infants <90 days of age with ALL KMT2A rearrangements are designated high risk and they have historically had poor outcomes. which drug showed improve DFS and OS compared to traditional chemo?
Of note, CD22 negativity is observed more commonly in KMT2A-rearranged ALL.
Blinatumomab added to Interfant-06 chemotherapy was recently shown to improve 2-year DFS and OS compared to traditional chemotherapy and this treatment strategy for infant ALL is now being pursued by treatment consortia internationally.
Gemtuzumab
CD33 antibody-drug conjugate used in treatment of AML.
Patients with Down syndrome ALL and CRLF2 have lesser frequency of….
Less frequency of BCR::ABL1-like phenotype in children with DS-ALL with CRLF2 overexpression, JAK inhibitor therapy is not indicated.
Burkitt leukemia
Think of it in a patient with mediastinal mass,
deeply basophilic cytoplasm and cytoplasmic vacuoles, surface kappa light chains, and a t(2; 8)(p12;q24)
c-Myc locus at 8q24 to an immunoglobulin heavy or light chain gene. The immunoglobulin kappa gene is located at 2p12.
typically are treated in the same way as patients with advanced stage Burkitt lymphoma
t AML causes
1-Alkylating agents (eg, cyclophosphamide, ifosfamide): long latency (3 to 5 years) with a long preleukemic MDS phase. monosomy 7 or 5q-,
2- topoisomerase inhibitors (eg, etoposide, doxorubicin) short latency (6 to 18 months) with a more explosive presentation. MLL rearrangment t(9;11).
Markers of AMKL
CD41, CD42 and CD61
treatment of CML - chronic phase
CML chronic phase:
- high WBC ( crazy number 700k) with a “normal” maturation of the myeloid lineage in the peripheral blood (including only a small percentage of myeloblasts) along with minimal symptoms like splenomegaly, The normal platelet count and hemoglobin are also consistent with this. Tx: Imatinib ( or second generation kinase inhibitor, such as dasatinib or nilotinib)
CML - phases
- Chronic Phase (CP): <10% blasts in marrow and blood
- +/- Accelerated Phase (AP): 10% to 19% blasts in marrow or blood, or 20% basophils in peripheral blood
Blast Crisis (BC): (2/3 AML, 1/3 B-ALL)
1) 20% blasts in marrow or blood;
2) presence of an extramedullary proliferation of blasts; or
3) presence of increased lymphoblasts in the peripheral blood or bone marrow
AMKL treatment in DS
Induction chemotherapy with anthracyclines and cytarabine, at least one course of intensive cytarabine, and intermittent dosing of intrathecal cytarabine over the course of treatment
TKI resistance
patient who achieved cytogentic and major molecular response remission suddenly has elevated BCR-ABL in CML.
Need to do ABL sequencing to detect resistance mutations can help guide alternative TKI choice.
patients with T315I mutations should receive ponatinib.
AML prognosis tests
initial risk stratification is based include favorable cytogenetics and molecular markers (inv(16), t(8;21), NPM1, CEBPA), unfavorable cytogenetics and molecular markers (monosomy 7, monosomy 5 or deletion 5q, FLT3-ITD high allelic ratio), and induction response.
