B-ALL and Myelofibrosis Quiz

Inherited Platelet Function Defects (Primary)

• Impaired platelet adhesion due to endothelium failure to produce normal amounts of vWf (von Willebrand factor), Reduced factor VIII (vWf is carrier for VIII)
• Mucosal bleeding (nosebleeds, dental work, heavy menses), ecchymoses, purpura, petechiae
• Bernard-Soulier Syndrome: Impaired platelet adhesion, enlarged platelets, lack of platelet GPIb
• Glanzmann Thrombasthenia: Impaired platelet aggregation, lack of platelet GPIIb/IIIa
• Von Willebrand's Disease: Low vWF, low vWF activity, low factor VIII. Type 1 & 3 – deficient vWF; Type 2 – defective vWF. Autosomal dominant, chromosome 12
• Treatment: Desmopressin (increases vWf release), recombinant vWF, cryoprecipitate

Clotting Factor Deficiencies (Secondary Hemostasis)

• Hemophilia A: Deficiency of factor VIII. X-linked recessive
• Factor VII Deficiency, Factor X Deficiency, Factor V Deficiency, Factor II (prothrombin) Deficiency, Factor I (fibrinogen) Deficiency: Uncommon, mucosal or deep bleeds. Autosomal recessive inheritance pattern
• Treatment: Factor VIII concentrates (plasma-derived or recombinant), cryoprecipitate

Vitamin K Deficiency

• Impaired platelet coagulation, prolonged PT (Prothrombin time) or PPT (partial thromboplastin time)
• Can be caused by warfarin usage
• Treatment: Hold warfarin and wait if stable, give vit K. If bleeding, administer factor concentrates, prothrombin complex concentrate, and plasma

Disseminated Intravascular Coagulation

• Platelet coagulation is impaired
• Prolonged PT and PTT, decreased platelet count, decreased fibrinogen, increased D-dimers, increased fibrin split products
• Underlying disorders can cause this
• Treatment: Treat the underlying condition, supportive care

Inherited Thrombophilia

• Factor V Leiden: Most common thrombophilia, Factor V resistant to breakdown by activated protein C

Thrombocytopenia Purpura

• Life-threatening formation of blood clots in small vessels, microangiopathic hemolytic anemia
• Symptoms: Fever, hemolytic anemia, renal dysfunction, thrombocytopenia, neuro dysfunction
• Causes: ADAMTS13 absence/decrease (congenital or acquired), autoantibodies against phospholipid-binding proteins

Acute Myeloid Leukemias (AML)

• Most common adult leukemia, average age of diagnosis ~67
• Symptoms: Fatigue, weakness, shortness of breath, fever/infections, bleeding/bruising, aches/pains, weight loss, night sweats
• Diagnostic markers: Presence of myeloid lineage cells (CD33, CD13, MPO), at least 20% blasts/promyelocytes/promonocytes in bone marrow/blood
• Treatment: 7+3 induction chemotherapy +/- stem cell transplant (high cure rates), hypomethylating agents for older patients

Myelodysplastic Syndrome (MDS)

• Clonal populations with defective maturation (cytopenias)
• Often develops from cancer, radiation, exposure to benzene
• High risk of progression to Acute Myeloid Leukemia (AML)
• Treatment: Varies based on risk assessment; hypomethylating agents used in high risk, prevention of disease progression

Chronic Myeloid Leukemia (CML)

• Average age of diagnosis is ~60
• Often asymptomatic, found through routine labs
• Some symptoms: fatigue, malaise, splenomegaly (extramedullary hematopoiesis –abdominal pain, early satiety, weight loss)
• Diagnostic marker: markedly increased WBC count, increased myeloid cells (especially neutrophils), basophilia, usually < 10% blasts
• Treatment: Imatinib (TK inhibitor, tyrosine kinase inhibitor)

Polycythemia Vera (PV)

• Symptoms: Pruritus (itchiness), splenomegaly, hepatomegaly, erythromelalgia, arterial or venous thrombosis (common cause of death due to acute coronary syndrome)
• Diagnostic marker: Elevated hemoglobin/hematocrit, decreased EPO
• Treatment: Aspirin, phlebotomy, and hydroxyurea

Essential Thrombocythemia (ET)

• Symptoms: Elevated platelets, may progress to a spent phase (marrow fibrosis, splenomegaly) or AML.
• Diagnostic marker: Elevated platelets, normo/mildly hypercellular marrow, lack of true fibrosis.
• Treatment: Aspirin and observation (low risk); aspirin and hydroxyurea (high risk).

Myelofibrosis

• Replacement of marrow space by fibrosis without preceding myeloproliferative neoplasm (MPD)
• Characterized by immature forms of cells produced into blood and worsening of anemia/thrombocytopenia.

B-cell Acute Lymphoblastic Leukemia (ALL)

• Usually leukemic, lymphoblasts fill the marrow
• Symptoms: fever, bone pain, weakness, fatigue
• Diagnosis: TdT and CD34 lymphoid markers. B-ALL diagnosed with CD10 and CD19

T-cell Acute Lymphoblastic Leukemia (T-ALL)

• Usually lymphomatous, mediastinal mass
• Symptoms: fever, bone pain, weakness, fatigue
• Diagnosis: TdT and CD34 Lymphoid markers, CD5, CD7, and CD3

Mature Cell Lymphomas

• Originates from germinal center and marginal zone B cells, bimodal age distribution (15–35 and >55), slightly more males

Hodgkin Lymphoma

• Continuous, orderly spread of disease (lymph node to spleen to liver to bone marrow)
• Diagnosis: Reed-Sternberg cells (large, prominent nuclei and nucleolus, lots of cytoplasm) and reactive infiltrate
• Subtypes: Nodular sclerosis (most common, low EBV association), Mixed cellularity (abundance cell mix, moderate EBV association), Lymphocyte rich (best prognosis, low EBV association), Lymphocyte depleted (worst prognosis, high EBV association)

B-cell Lymphomas (High Grade/Aggressive)

• Diffuse Large B-cell Lymphoma (DLBCL): Rapidly growing, doubling time under 24hrs, high incidence of tumor lysis syndrome
• Burkitt Lymphoma: Rapidly fatal, increased incidence in immunocompromised individuals
• Treatment: Varies greatly

B-cell Lymphomas (Low Grade/Indolent)

• Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia (CLL/SLL)
• Mantle Cell Lymphoma (MCL): Aggressive disease presents in older adults (63 YO)
• Follicular Lymphoma: Presents in older adults, involves lymph nodes, spleen, liver, bone marrow
• Marginal Zone Lymphoma (MZL)

Hairy Cell Leukemia

• Originates in memory B cells
• Common in elderly males
• Often involves spleen, marrow, and blood
• Diagnosis: TRAP stain, Hairy looking cells
• Treatment: Cladribine (adenosine analog)

Plasma Cell Neoplasms

• Plasmacytoma: Bony lesions, can be found anywhere in the body
• Multiple Myeloma: Infiltration of plasma cells into bone or other organs, anemia, bone pain, acute renal dysfunction, fatigue, hypercalcemia
• Treatment: Radiation of localized tumor, chemo, stem cell transplant

Immunoglobulin Abnormalities

• Monoclonal Gammopathy of Uncertain Significance (MGUS): Asymptomatic, preneoplastic condition
• Smoldering Myeloma: Asymptomatic, preneoplastic condition; elevated monoclonal protein

Viral Associations

• Adult T-cell Leukemia/Lymphoma (ATLL): HTLV-1 associated (endemic)
• Extranodal NK/T-cell lymphoma

Primary Amyloidosis

• Impairment of kidney function, various hematological, neurological, and musculoskeletal issues
• Diagnosis: Congo red stain

Other

• Langerhans Cell Histiocytosis (LCH)
• Mycosis Fungoides/Sézary Syndrome(MF/SS)
• Peripheral T-cell lymphoma (PTCL)