Leukemia Flashcards

Question

T-cell Acute Lymphoblastic Leukemia (T-ALL) Translocations

Answer 1

Juxtaposition of a proto-oncogene to TCR ⇒ _over-expression of a normally silent gene_ **t(1;14)** → BCL9-IGH

Answer 2

* **Morphologically and immunophenotypically indistinguishable from ALL** * _Distinction is based on:_ * **Site of disease** * **Amount of bone marrow involvement** * 20% lymphoblasts in the bone marrow ⇒ ALL * \< 20% lymphoblasts in the bone marrow w/ extramedullary manifestations ⇒ LBL * Management is similar for both

Answer 3

* Fever, pallor, fatigue * Organomegaly (30-50 % w/ HSM) * Adenopathy * Bone pain, limp, arthritis (40 %) * Headache, cranial nerve palsy * Prolonged “viral illness” * Bruising, petechiae, bleeding

Answer 4

* _Physical exam:_ * **Head to toe, w/ emphasis on testes, CNS, lymphadenopathy, organomegaly** * Testicles and CNS are termed sanctuary sites * Difficult for chemotherapy to reach * _Labs:_ * CBC w/ diff; peripheral smear; coags; type and cross; * Uric acid, Ca, PO4, Cr, K * _Flow cytometry_ (peripheral blood vs bone marrow) * _Bone marrow biopsy_

Answer 5

* _Morphology_ * _Cytochemical staining_ * **⊕ PAS** * **⊖ MPO, SBB, Nonspecific esterase** * _Immunophenotype_ * _Flow cytometry_: **B-cell or T-cell antigens** * _Cytogenetics_ * Ig and TCR gene rearrangement studies

Answer 6

* Immature blasts are lymphocyte-like * Minimal cytoplasm * Nucleoli present * Larger than RBCs

Answer 7

**Marrow almost completely replaced by abnormal cells**

Answer 8

* **CNS disease (20%)** * Higher risk of relpase * **Early response to therapy** * **Morphologic:** Rapid early responders do better * Obtaining remission by day 14, with **⊖** MRD by day 28 * **Measurable residual disease (MDR)** * Measurement of very low levels (1 in 1000) of leukemic cells by PCR * High MRD at the end of induction ⇒ higher risk of relapse

Answer 9

**Children ⇒ \> 95% achieve remission and 80% are cured** **Adults ⇒ 65-85 %achieve remission w/ cure rates of 35-40%** * _What made the difference?_ * Development of complex chemotherapeutic regimens * Improvements in supportive care * Recognition of CNS as sanctuary site * Risk adaptive therapy * Bone Marrow Transplant for highest risk pts

Answer 10

* **Induction (3 or 4 drug):** 95% will achieve remission * **Consolidation** * **Interim maintenance** * **Delayed intensification** * **Maintenance** (to complete 2 years of therapy for girls, 3 years of therapy for boys) * _High-risk_ ⇒ **allogeneic transplant** * Refractory disease * MRD positive * Poor-risk

Answer 11

* **Induction** (Hyper CVAD, pediatric regimen, etc) * Vincristine, Steroids, Cytoxan and Anthracycline * **Consolidation** * High dose Cytarabine, Cytoxan, Methotrexate, Asparaginase * SCT may be used * **Maintenance (2-3 years)** * 6-MP, Methotrexate, monthly steroids, and Vincristine * **CNS Prophylaxis** * _High-risk_ ⇒ **allogeneic transplant**

Answer 12

* Group of (mostly) clonal hematologic disorders * **Characterized by accumulation of mature cells** * Accumulation can involve one or more cell lines * No age, sex or race predilection * Rare disorders w/ collective annual incidence of 5/100,000

Answer 13

* **Most common in middle-aged adults** * _Clinical signs and symptoms include:_ * **Leukocytosis w/ left-shift** (often in asymptomatic individuals) * **Basophilia** * **Elevated LDH and uric acid** * **Splenomegaly**

Answer 14

**Dx can be confirmed by demonstration of the t(9;22) by:** * Karyotyping * Fluorescent In-Situ Hybridization (FISH) * BCR-ABL mRNA by PCR Although dx of CML requires demonstration of t(9;22), not all diseases w/ t(9;22) are CML.

Answer 15

**t(9;22) is both sufficient and required to develop CM** _Disease goes through three phases_: * _Chronic phase_ ⇒ **↑ WBC w/ left shift** * Typically remains stable for 3-4 years (up to 10 years) * Pts generally have no or minimal sx * W/o treatment median survival is 5-7 years * Disease inevitably will progress to accelerated phase and blast crisis * _Accelerated phase_ ⇒ **Additional cytogenetic abnormalities, uncontrollable WBC, ↑ basophilia** * Median survival w/o treatment is 12-18 months * _Blast phase_ (acute leukemia)

Answer 16

Numerous different types of granulocytes at different stages of maturation

Answer 17

**Allogeneic stem cell transplantation** * **Only tx modality w/ curative potential** * Cure rates vary * 80%+ for young (\<40 years) pts w/ an HLA-identical sibling donor * 40% for elderly pts undergoing a matched-unrelated donor transplant * Cure rates are much worse for pts transplanted in accelerated phase (40%) or blast crisis (20%) * Somewhat worse for pts transplanted \> 1 year after diagnosis

Answer 18

* Novel therapeutic options for CML (“targeted therapy”) * **Tyrosine kinase inhibitor** * Occupies ATP binding site in BCR-ABL oncoprotein ⇒ ⊗ of BCR-ABL tyrosine kinase activity * Side effects are minimal * **Treatment-of-choice for most pts w/ CML in chronic phase** * 65% of pts in chronic phase will achieve a sustained (\> 7 years) complete cytogenetic response w/ imatinib * No Ph chromosome on cytogenetic exam * 30-40% of pts will not have e/o BCR-ABL transcript by PCR * BCR-ABL fusion gene presence can still be demonstrated in isolated ‘stem’ cells

Answer 19

* **Lymphoma / leukemia composed of small clonal B-cells** * **M \> F, Age \> 50 yrs** * **Considered low grade, but incurable** * **SLL and CLL are morphologically, phenotypically, and genotypically indistinguishable** * Differ only in degree of peripheral blood lymphocytosis * 5K WBCs regardless of lymphadenopathy ⇒ CLL * \< 5K WBCs ⇒ SLL * SLL is 7% of NHL * **CLL is the most common leukemia in western world**

Answer 20

* **Mostly asymptomatic** * Often identified on routine blood work w/ isolated lymphocytic leukocytosis * **± Recurrent respiratory infections** due to hypogammaglobulinemia * **± Immunologic issues such as hemolytic anemia or immune thrombocytopenic purpura**

Answer 21

* _Peripheral blood flow cytometry_ * **⊕ for CD19, CD20, CD23** * **⊖ CD10** * **CD5 usually ⊕** * Bone marrow biopsy is not required

Answer 22

_Prognostic studies include:_ * _FISH_ * **del(13q)** = good * **del(17p)** = bad * **IGHV mutation** (immunoglobulin heavy chain variable region) * Presence is favorable * Absence is unfavorable * _Next-generation sequencing (NGS)_ * **TP53 mutation is unfavorable**

Answer 23

* Unless presence of sx from _compressive LNs or splenomegaly_ or _severe cytopenias_ then **observation is preferred** * _Treatment, if required, is dependent on risk-stratification and age:_ * Chemoimmunotherapy * Fludarabine, cyclophosphamide, rituximab (FCR) * Bendamustine, rituximab (BR) * BTK Inhibitors * Ibrutinib * Acalabrutinib

Answer 24

**Numerous mature lymphocytes** **About the size of RBCs**

Answer 25

* Considered a **chronic B-cell lymphoproliferative disorder** * Initially described as leukemic reticuloendotheliosis * **Bone marrow infiltration by** **atypical lymphocyte w/ “hairy” projections** * Characterized by **splenomegaly, pancytopenia** * **4:1 male to female ratio** * **Usu. 40-60 y/o**

Answer 26

Typical presenting symptoms: * **Pancytopenia** w/ infection, bleeding, etc * Can see a monocytopenia * **Splenomegaly**, usually massive

Answer 27

* _Bone marrow biopsy_ * Bone marrow infiltration by **atypical lymphocyte w/ “hairy” projections and indistinct cytoplasmic border** * Stains w/ **TRAP = tartrate resistant acid phosphatase ⊕** * _Immunophenotype:_ * **⊕ for CD103, CD11c, CD25, CD22** * **⊖ for CD5, CD10, CD23** * _Molecular_ * **BRAF mutation**

Answer 28

* **Goal is long-term remission** * **Generally not considered curable w/ standard therapies** * Therapy consists of **chemotherapy ± immunotherapy** * Nucleoside analogs – cladribine, pentostatin * Anti CD20 MoAb – Rituximab * Salvage targets * Vemurafenib (BRAF inhibitor)

Leukemia Flashcards

(54 cards)