Heme Malignancies: Leukemias and Lymphomas

____________ clonal myeloproliferative neoplasm defined by the uncontrolled proliferation and survival of mature granulocytes, predominantly neutrophils, driven by an oncogenic driver.

Chronic Myelogenous Leukemia (CML)

Which specific chromosomal translocation defines the pathophysiology of Chronic Myelogenous Leukemia (CML)?

t(9;22)(q34;q11) reciprocal translocation; BCR-ABL gene

The _____________ is created by reciprocal translocation between long arms of chromosomes 9 and 22 (BCR-ABL fusion gene).

Philadelphia Chromosome

What is the primary biochemical activity of the novel hybrid protein produced by the BCR-ABL fusion gene, which drives uncontrolled myelopoiesis in CML?

Deregulated tyrosine kinase activity

A 55-year-old male is incidentally found to have a white blood cell (WBC) count of 110,000/mcL on routine screening. He is completely asymptomatic. A peripheral smear shows a full spectrum of mature and maturing granulocytes with a low percentage of blasts (<5%). What phase of CML is this patient currently in?

Chronic phase

__________ (85-90% patients) present with <2-10% blasts and are typically asymptomatic with elevated WBC/neutrophils on routine labs.

Chronic phase CML

__________ present with >10% blasts and have symptoms secondary to anemia; thrombocytopenia, splenomegaly, priapism, sternal bone pain. (20% skip this phase)

Accelerated phase CML

__________ presents with >20%blasts and will have worsening constitutional symptoms; bleeding, fever, infections, symptoms secondary to extramedullary hematopoiesis. (patients appear ill)

Blast phase CML

___________  of the peripheral blood or bone marrow is the diagnostic hallmark used to detect and quantify BCR-ABL fusion transcript levels, which is also critical for monitoring treatment response.

Polymerase Chain Reaction (PCR) assay

What is the preferred first-line therapeutic class of medications used to manage chronic phase CML?

Tyrosine Kinase Inhibitors (TKIs)

_____________ was the first-generation prototype that selectively binds the ATP-binding pocket of BCR-ABL, blocking its kinase activity and dramatically improving survival.

Imatinib (Gleevec)

A CML patient taking first-generation Imatinib is found to have a suboptimal molecular response. What second-generation tyrosine kinase inhibitors (TKIs) are approved as preferred alternatives that offer more potent target inhibition?

Dasatinib (Sprycel) or Nilotinib (Tasigna)

What is the World Health Organization (WHO) define the threshold in the bone marrow or peripheral blood required to establish a diagnosis of Acute Myelogenous Leukemia (AML)?

≥ 20% myeloblasts

What are the classic needle-like, crystalline cytoplasmic inclusions observed in myeloblasts on a peripheral blood smear in AML?

Auer rods

What enzyme do Auer rods contain?

Myeloperoxidase

A 64-year-old male presents with sudden-onset fatigue, bruising, and recurrent mucosal bleeding over the past 2 weeks. On physical exam, he is noted to have swollen, boggy, and bleeding gums. This classic clinical sign of gingival hyperplasia is most commonly associated with which leukemia?

Acute Myelogenous Leukemia (AML)

What rare but clinically significant skin manifestation occurs when malignant leukemic cells directly infiltrate cutaneous tissue, producing raised, purple-gray lesions that signal advanced disease?

Leukemia cutis

What is the definitive diagnostic procedure required to confirm a suspected diagnosis of Acute Myelogenous Leukemia (AML), evaluate cell morphology, and perform cytogenetic profiling?

Bone marrow aspiration and core biopsy

What classic chemotherapy regimen, combining an antimetabolite and an anthracycline, forms the backbone of induction therapy for patients with newly diagnosed AML?

"7+3" regimen (Cytarabine and an anthracycline like Doxorubicin or Daunorubicin)

What highly curable subtype of AML (comprising 5-15% of cases) is characterized by a reciprocal t(15;17) chromosomal translocation and a massive clinical risk of intravascular coagulation?

Acute Promyelocytic Leukemia (APL)

Which dual targeted, non-chemotherapeutic drug regimen is utilized as the preferred treatment for patients diagnosed with Acute Promyelocytic Leukemia (APL), achieving cure rates exceeding 90%?

All-Trans-Retinoic Acid (ATRA) and Arsenic Trioxide (ATO)

What is the most common adult leukemia in Western countries, characterized by the slow, indolent accumulation of long-lived, immunologically dysfunctional B lymphocytes?

Chronic Lymphocytic Leukemia (CLL)

In ________, the malignant clones are primarily found circulating in the peripheral blood and bone marrow.

CLL

In _________ , the disease is clinically restricted to the lymphatic tissues and lymph nodes.

Small Lymphocytic Lymphoma (SLL)

What is the minimum absolute clonal lymphocyte count required in the peripheral blood to establish a formal diagnosis of CLL?

≥ 5,000 cells/microL (for at least 3 months)

______ are the classic morphological hallmark of CLL, neoplastic B lymphocytes that lack cytoplasmic membrane integrity and easily rupture when making a blood smear.

Smudge cells (or Basket cells)

Which diagnostic test is the gold standard tool used to evaluate the cell-surface protein markers of circulating lymphocytes in a CLL patient?

Peripheral blood flow cytometry

Which three classic markers co-express on malignant B-cells in CLL?

• CD5

• CD19

• CD23

________________  is the strongest genetic predictor of adverse outcomes in CLL, conferring resistance to chemoimmunotherapy and demanding targeted novel agents.

Deletion of chromosome 17p [del(17p) / TP53 mutation]

True or False: A bone marrow aspiration and biopsy are mandatory, first-line diagnostic requirements to confirm a suspected clinical diagnosis of CLL.

False

_____________ is characterized by the transformation of CLL into a high-grade diffuse large B-cell lymphoma (DLBCL), carrying an extremely poor median survival of about 1 year.

Richter's Transformation (or Richter's Syndrome)

What rapid, fast-growing hematologic malignancy represents the most common childhood cancer, peaking in children younger than five years of age?

Acute Lymphoblastic Leukemia (ALL)

A 6-year-old child presents with a limp, progressive bone pain, and a refusal to walk. A CBC reveals pancytopenia with circulating immature lymphoid cells. Bone tenderness in ALL is clinically caused by what mechanism?

Leukemic infiltration of the bone marrow stretching the periosteum

A 16-year-old male with T-cell predominant ALL presents with acute dyspnea, facial swelling, and engorged, dilated veins across his chest wall. What oncologic complication is this patient demonstrating?

Superior Vena Cava (SVC) Syndrome

A positive _________ occurs when bilateral arm elevation leads to transient facial plethora, cyanosis, and respiratory distress.

Pemberton maneuver

____________ is a DNA polymerase expressed exclusively in immature pre-B and pre-T lymphoblasts

Terminal deoxynucleotidyl transferase (TDT)

Staining _______ for TDT and ________ for myeloperoxidase (MPO) definitively confirms a lymphoid lineage, confirming ALL.

positive; negative

A peripheral blood smear in a patient with a white blood cell count of 80,000/mcL reveals hundreds of immature mononuclear cells.

True or False: The presence of Auer rods on this smear would confirm a diagnosis of ALL.

False

Because a high percentage of patients with ALL will develop meningeal leukemia, what mandatory diagnostic and therapeutic intervention must be performed during the induction phase of treatment?

Lumbar puncture with intrathecal chemotherapy (CNS prophylaxis)

What is the three-phase chemotherapeutic structure utilized to treat patients with ALL, aiming to first achieve remission and then prevent disease relapse?

1. Remission Induction

2. Consolidation (Intensification)

3. Maintenance Therapy

What life-threatening metabolic oncologic emergency is characterized by the massive, rapid release of intracellular electrolytes and nucleic acids into the bloodstream following the initiation of chemotherapy?

Tumor Lysis Syndrome (TLS)

What are the four cardinal laboratory electrolyte and chemical abnormalities that define the Cairo-Bishop diagnostic criteria for Tumor Lysis Syndrome?

• Hyperkalemia

• Hyperphosphatemia

• Hyperuricemia

• Hypocalcemia

A patient undergoing chemotherapy for lymphoma develops muscle cramps, severe tetany, and hyperreflexia. Tapping on his facial nerve eliciting ipsilateral twitching of the lip and nose is known as what physical sign?

Chvostek's sign

What is the primary pathophysiological mechanism by which acute kidney injury (AKI) develops in patients with untreated or severe Tumor Lysis Syndrome?

Precipitation of uric acid and calcium phosphate crystals within the renal tubules

What medication is administered beforehand to block the formation of new uric acid, even though it cannot degrade pre-existing uric acid in TLS?

Allopurinol

What drug is indicated for the prevention and treatment of TLS in high-risk patients because it directly catalyzes the breakdown of active uric acid into highly soluble allantoin?

Rasburicase (Recombinant Urate Oxidase)

Rasburicase is contraindicated in patients with _______.

G6PD deficiency

______________ is defined by a small number of Reed-Sternberg cells (neoplastic B-cells), surrounded by an abundant inflammatory background of non-malignant reactive immune cells.

Hodgkin Lymphoma (HL)

___________ are large, atypical, multinucleated or bilobed cells that have an "Owl Eyes" appearance and is highly diagnostic for classic Hodgkin Lymphoma.

Reed-Sternberg cells

A 24-year-old female presents with painless, firm, 'rubbery' lymphadenopathy in her left neck. She notes a unique, highly specific symptom: she experiences severe, aching pain in these lymph nodes immediately after drinking a glass of wine. What is the most likely diagnosis?

HL

__________ is characterized by collagen bands that divide the lymph node into nodules, and it carries an excellent prognosis with high cure rates. (70% of HL in young adults)

Nodular Sclerosis

What is the gold standard diagnostic procedure required to confirm a suspected diagnosis of Hodgkin Lymphoma?

Excisional lymph node biopsy

What is the gold standard chemotherapy regimen used to treat patients with Stage I and II classic Hodgkin Lymphoma?

ABVD regimen

What drugs make up the ABVD regimen?

• Adriamycin (Doxorubicin)

• Bleomycin

• Vincristine (Oncovin)

• Dacarbazine

_______________  highly sensitive for staging Hodgkin Lymphoma because Reed-Sternberg and reactive immune cells have high metabolic activity, picking up the radiotracer.

Integrated FDG PET-CT scan (skull base to mid-thigh)

____________ consists of over 30 different subtypes of B-cell, T-cell, or NK-cell cancers and is by its lack of RS cells; it’s characteristically unpredictable, non-contiguous lymphatic spread.

Non-Hodgkin Lymphoma (NHL)

What are the two most common histological types of Non-Hodgkin Lymphoma, classified by their clinical aggressiveness and cell growth rate?

• Diffuse Large B-Cell Lymphoma (DLBCL - aggressive)

• Follicular Lymphoma (indolent)

A 52-year-old male with a history of chronic Helicobacter pylori gastritis is diagnosed with a gastric Mucosa-Associated Lymphoid Tissue (MALT) lymphoma. What is the first-line treatment strategy to achieve remission in this lymphoma?

H. pylori eradication therapy (antibiotics and proton pump inhibitors)

Which oncogenic virus is strongly associated with the development of primary Central Nervous System (CNS) lymphoma in immunocompromised patients, particularly those with advanced HIV/AIDS?

Epstein-Barr Virus (EBV)

What is the absolute gold standard diagnostic procedure required to confirm a diagnosis of Non-Hodgkin Lymphoma,

Excisional lymph node biopsy

What is the gold standard multi-agent chemotherapy regimen used to treat patients with aggressive Diffuse Large B-Cell Lymphoma (DLBCL)?

R-CHOP regimen

What drugs make up the R-CHOP regimen?

• Rituximab (monoclonal anti-CD20 antibody)

• Cyclophosphamide

• Doxorubicin (hydroxydaunorubicin)

• Vincristine (Oncovin)

• Prednisone

What are the five clinical risk factors used in the International Prognostic Index (IPI) to risk-stratify patients with aggressive Non-Hodgkin Lymphoma?

• Age >60

• Elevated serum LDH

• Stage III or IV

• >1 Extranodal site

• Poor Performance Status

__________ is a malignant hematologic neoplasm arising from terminal B-cell differentiation, resulting in the excess production of non-functional monoclonal heavy and/or light chain proteins.

Multiple Myeloma (MM)

The __________ represents the clonal product of neoplastic plasma cells; most frequently of the IgG or IgA class and appears as a narrow, sharp peak on a Serum Protein Electrophoresis (SPEP)

M-protein (M-spike)

What classic clinical acronym represents the four hallmark diagnostic features of end-organ damage caused by Multiple Myeloma?

CRAB

• Hypercalcemia

• Renal insufficiency

• Anemia

• Bone lesions

What is the specific medical term for the free monoclonal immunoglobulin light chains (kappa or lambda) that are filtered by the glomerulus and excreted in the urine of Multiple Myeloma patients?

Bence-Jones proteins

______________ is when cells are stacked like a 'pile of coins', due to high serum protein, on a peripheral smear.

Rouleaux formation

Why is a standard Nuclear Medicine bone scan (Tc-99m) highly insensitive and inappropriate for evaluating bone involvement in patients with Multiple Myeloma?

Bone scans only detect osteoblastic (bone-building) activity, while Multiple Myeloma lesions are purely osteolytic (bone-destructive)

What is the definitive diagnostic threshold of clonal bone marrow plasma cells required to diagnose Multiple Myeloma?

≥ 10% clonal plasma cells on bone marrow biopsy

What premalignant plasma cell disorder is characterized by a serum M-spike <3 g/dL, <10% clonal bone marrow plasma cells, and the complete absence of CRAB end-organ damage?

Monoclonal Gammopathy of Undetermined Significance (MGUS)

_________ is a CD38-targeting monoclonal antibody that is highly effective but binds CD38 on RBCs, interfering with blood bank antibody screening.

Daratumumab

What critical step must be performed when prescribing Daratumumab?

A baseline type and screen

What is the preferred consolidation strategy for newly diagnosed Multiple Myeloma patients who are fit and have completed induction therapy to achieve deep, durable remissions?

Autologous Stem Cell Transplantation (ASCT)

What acquired clonal neoplasm of the hematopoietic myeloid stem cells is characterized by prominent cytopenias, dysplastic cell morphology, and highly ineffective hematopoiesis?

Myelodysplastic Syndrome (MDS)

________ is the clinical hallmark and most frequent presenting sign of MDS.

Macrocytic anemia

The __________ is a primary morphologic marker of dysplasia in the granulocytic line, neutrophils with dumbbell-shaped, bilobed nuclei which distinguish MDS from nutritional anemias.

Pseudo-Pelger-Huet anomaly

What definitive bone marrow biopsy finding, highlighted by a Prussian blue stain, is commonly observed in the erythroid line of MDS patients?

Ringed sideroblasts

What is the absolute maximum percentage of myeloblasts for an MDS patient before the disease is reclassified as Acute Myelogenous Leukemia (AML)?

< 20% myeloblasts

What specific chromosomal deletion, identified on cytogenetic analysis of patients with lower-risk MDS, is associated with a highly favorable prognosis and a remarkable therapeutic response to Lenalidomide?

Deletion of the long arm of chromosome 5 [del(5q)]

A 75-year-old female presents with persistent, asymptomatic macrocytic anemia and mild thrombocytopenia. Her bone marrow biopsy shows multi-lineage dysplasia with 3% blasts. What is the standard management strategy for this asymptomatic, lower-risk patient?

Observation (Watch and Wait) with periodic clinical monitoring