Comprehensive Leukemia & Myeloproliferative Disorders Review

Comprehensive practice flashcards reviewing the classification, epidemiology, pathophysiology, clinical presentation, diagnosis, cytogenetics, and treatment regimens for acute leukemias (ALL, AML, APL), chronic leukemias (CML, CLL, HCL), and myeloproliferative disorders (PV, ET, MF).

How is leukemia defined based on its cellular origin and behavior?

A neoplastic proliferation of abnormal white blood cells originating in the bone marrow and circulating in the blood.

How has global leukemia incidence changed from 1990 to recent decades, and what factors drive this increase?

Global cases increased from approximately $79{,}400$ in 1990 to over $144{,}000$ per year recently, driven by aging populations and improved diagnostics worldwide.

What is the annual incidence of Acute Myeloid Leukemia (AML) and its typical demographic distribution?

The incidence is $3\text{--}4.4\text{ per }100{,}000$ individuals per year, occurring more commonly in men and older adults ($50\text{--}60\text{ years}$).

What is the annual pediatric incidence of Acute Lymphoblastic Leukemia (ALL), and what percentage of pediatric leukemia cases does it represent?

ALL occurs at a rate of $46\text{ per million}$ children per year and accounts for $76\%$ of all pediatric leukemia cases.

What bone marrow blast threshold defines acute leukemia?

A bone marrow blast count of $>20\%$.

What key morphological features characterize leukemic blasts on a peripheral smear and bone marrow biopsy?

They are large, immature cells with prominent "punched-out" nucleoli, scant cytoplasm, and a high nuclear-to-cytoplasmic ratio.

What cellular consequences result from leukemic blasts crowding out normal hematopoiesis in the bone marrow?

Anemia (reduced RBC production), thrombocytopenia (platelet deficiency leading to bleeding risk), and neutropenia (impaired immune defense leading to infections).

What diagnostic nuclear marker is positive in lymphoblasts and functions as a DNA polymerase marking immature lymphoid cells?

Terminal deoxynucleotidyl transferase ($\text{TdT}$).

Which congenital chromosomal condition is associated with Acute Lymphoblastic Leukemia (ALL), particularly in children older than 5 years?

Down syndrome (trisomy $21$).

Which flow cytometry surface markers distinguish B-ALL from T-ALL?

B-ALL ($80\text{--}85\%$ of cases) expresses $\text{CD10}$, $\text{CD19}$, and $\text{CD20}$, whereas T-ALL ($15\text{--}20\%$ of cases) expresses $\text{CD3}$ and $\text{CD7}$.

What anatomical presentation in T-ALL can cause airway obstruction?

A mediastinal mass.

What are the durations and specific objectives of the induction, consolidation, and maintenance phases of ALL treatment?

Induction ($4\text{--}8\text{ weeks}$) eliminates leukemic blasts to achieve complete remission; Consolidation ($4\text{--}8\text{ months}$) eradicates residual disease to prevent relapse; Maintenance ($2\text{--}3\text{ years}$) sustains remission.

Why is CNS prophylaxis required in ALL treatment, and what agent is typically administered?

The central nervous system is a common sanctuary site for ALL; prophylaxis is administered via intrathecal methotrexate.

What is the clinical role of Rasburicase during the initiation of acute leukemia therapy?

It reduces uric acid levels to prevent tumor lysis syndrome ($\text{TLS}$) and protect renal function.

What key cytochemical enzyme marker is positive in myeloblasts and confirms a diagnosis of AML?

Myeloperoxidase ($\text{MPO}$).

What pathognomonic crystalline cytoplasmic inclusions are characteristic of myeloblasts in AML?

Auer rods.

What oral clinical finding associated with Acute Myeloid Leukemia (FAB subtypes M4 and M5) is shown in the image?

Gingival hyperplasia.

What chromosomal translocation and fusion protein define Acute Promyelocytic Leukemia (APL, M3)?

The $t(15;17)$ translocation, which produces the $\text{PML-RAR}\alpha$ fusion protein that blocks promyelocyte differentiation.

What life-threatening hematologic coagulopathy is a major risk in Acute Promyelocytic Leukemia (APL)?

Disseminated intravascular coagulation ($\text{DIC}$).

What pharmacologic combination is urgently administered for APL, and what is the mechanism of the primary agent?

All-trans retinoic acid ($\text{ATRA}$) plus arsenic trioxide; $\text{ATRA}$ induces terminal differentiation of leukemic promyelocytes.

What is the standard induction chemotherapy regimen for Acute Myeloid Leukemia (AML)?

The "$7+3$" regimen, consisting of cytarabine plus an anthracycline.

What are the clinical manifestations and emergency management of leukostasis syndrome in acute leukemia?

It causes dyspnea, blurred vision, thrombosis, and stroke due to vascular obstruction from hyperleukocytosis; emergency management involves rapid leukocyte reduction via leukapheresis and Rasburicase.

Which cytogenetic abnormality in ALL is considered a favorable prognostic indicator?

The $t(12;21)$ translocation ($\text{ETV6-RUNX1}$) or hyperdiploidy ($>50$ chromosomes).

Which chromosomal translocation in ALL carries an unfavorable prognosis?

The Philadelphia chromosome translocation $t(9;22)$.

Which cytogenetic and molecular findings are associated with a favorable prognosis in AML?

Translocation $t(8;21)$ ($\text{RUNX1-RUNX1T1}$), $t(15;17)$ ($\text{PML-RAR}\alpha$), $\text{inv}(16)$, and normal karyotype with $\text{NPM1}$ mutation without $\text{FLT3-ITD}$.

What genetic translocation and resulting constitutively active kinase define Chronic Myeloid Leukemia (CML)?

The Philadelphia chromosome translocation $t(9;22)$, forming the $\text{BCR-ABL}$ fusion gene which produces a constitutively active tyrosine kinase.

What percentage of blasts is found in the chronic phase of Chronic Myeloid Leukemia (CML)?

Blasts remain $<5\%$ in the chronic phase.

What is the gold standard diagnostic method for confirming Chronic Myeloid Leukemia (CML)?

$\text{BCR-ABL}$ detection by $\text{PCR}$ or $\text{FISH}$.

What is the standard first-line tyrosine kinase inhibitor (TKI) used in CML, and what second-generation TKIs are available for resistance or intolerance?

Imatinib (Gleevec) is standard first-line; Dasatinib and Nilotinib are second-generation alternatives.

What classic cellular artifact is visible on a peripheral smear in Chronic Lymphocytic Leukemia (CLL)?

Smudge cells (fragile lymphocytes disrupted during smear preparation).

Which immunophenotypic cluster of differentiation markers defines clonal B cells in CLL?

$\text{CD5}^+$, $\text{CD19}^+$, and $\text{CD23}^+$.

What is Richter transformation in Chronic Lymphocytic Leukemia (CLL)?

The conversion of indolent CLL into an aggressive diffuse large B-cell lymphoma, occurring in approximately $5\text{--}10\%$ of patients.

What point mutation is present in nearly all cases of Hairy Cell Leukemia (HCL)?

The $\text{BRAF V600E}$ mutation.

What are the first-line purine analogue treatments for Hairy Cell Leukemia?

Cladribine ($2\text{-CdA}$) or Pentostatin.

Which mutation is found in approximately 95% of Polycythemia Vera (PV) cases, and what is its first-line treatment?

The $\text{JAK2 V617F}$ mutation; first-line treatment is therapeutic phlebotomy to reduce hematocrit.

What platelet count threshold is used in the diagnosis of Essential Thrombocythemia (ET)?

A platelet count of $>450{,}000/\mu\text{L}$.

What are the classic peripheral smear and bone marrow biopsy findings in primary Myelofibrosis?

Teardrop-shaped red blood cells (dacrocytes) on peripheral smear, and a "dry tap" (inability to aspirate marrow due to fibrosis) on biopsy.