Hematology Flashcards

Question

What are the two variants of osteosarcoma?

Answer 1

- two variants of osteosarcoma: parosteal and periosteal osteosarcoma; have characteristic clinical features o parosteal is a low-grade and well-differentiated, does not invade medullary cavity, commonly in posterior aspect of distal femur; surgical resection alone often curative as low propensity for metastatic spread o periosteal osteosarcoma is rare, arises on surface of bone, ↑rate of metastases, intermediate prognosis

Answer 2

Diagnosis - suspect if deep bone pain, nighttime awakening, palpable mass, and radiographic lesion - classic radiographic appearance: sunburst pattern - need MRI of primary lesion and entire bone for evaluating proximity to nerves and blood vessels, soft tissue and joint extension, and skip lesions o - need a tissue bx to determine the dx - metastatic work-up done pre-bx: chest CT and radionuclide bone scan (for mets) o go to lungs first !! - ddx of lytic bone lesion: histiocytosis, Ewing sarcoma, lymphoma, bone cyst

Answer 3

Treatment - need chemo and surgery, 5-yr dz-free survival with nonmetastatic extremity osteosarcoma is 65–75% - need complete surgical resection for cure - prognostic factors: histologic response to chemotherapy (very impt) - pre-surgery, if tumors on weight-bearing bones, should use crutches to avoid pathologic fractures

Answer 4

- Extremely rare among African-American children - Is an undifferentiated sarcoma of bone, also may arise from soft tissue - anatomic sites of bone bone tumors: distributed evenly b/w extremities and central axis (pelvis, spine, chest wall) - usually in the diaphysis of bones and flat bones

Answer 5

- classic radiography: onion-skinning ; see large associated soft tissue mass on MRI or CT - metastatic evaluation: chest CT, radionuclide bone scan, and BM aspirate and bx - MRI of tumor and entire length of involved bone to determine extension of soft tissue and bony mass, proximity to neurovascular structures - Impt to obtain adequate tissue

Answer 6

- best prognosis if small, nonmetastatic, distally located extremity tumors (cure rate up to 75%) - type of chromosomal translocation may be related to prognosis - with metastatic dz at dx (esp bone or BM mets) have a poor prognosis (<30%) - need long-term f/u for late effects of tx (anthracycline cardiotoxicity); 2nd malignancies (esp in radiation field); and late relapsess

Answer 7

``` Medulloblastoma/primitive neuroectodermal tumor Juvenile pilocytic astrocytoma Low-grade astrocytoma High-grade astrocytoma Ependymoma Craniopharyngioma ```

Answer 8

Late effects from radiotherapy: - hypopituitarism - second malignant neoplasm - somnolence syndrome (not a late effect) – can sleep for 22 hrs / day - memory problems

Answer 9

- During fetal life and early childhood, the rates of synthesis of γ and β chains and the amounts of Hb A and Hb F are inversely related. - The average life span for a neonatal RBC is 60–90 days, approximately ½ to⅔ that of an adult RBC. - With increasing degrees of prematurity, remarkably shorter red cell life spans (35–50 days) are found

Answer 10

CNS tumours

Answer 11

DDAVP: releases subendothelial stores of VIII, V and platelet aggregation (can’t give > 2 doses in 24 hr period?

Answer 12

Intrinsic pathway: Factors 12, 11, 9 (kind of 8)

Answer 13

Extrinsic pathway: Factors 7, 5, 10 PT = INR. Not prolonged with deficiencies in VIII, IX, XI or XII

Answer 14

. XIII: umbilical stump bleeding (can make clot, but can’t stabilize it)

Answer 15

Actively bleeding pt, looking for etiology: - CBC (for plt), PT, PTT - VIII (only one not produced in liver), IX (hemophilia), VII (extrinsic pathway), V (sensitive in early DIC)

Answer 16

- FFP: gives all factors – give to someone who is vit K deficient until factors kick in - Cryo: (plasma that’s been spun): fibrinogen and VIII (and VWF and XIII) – for DIC

Answer 17

Protein C/S, Antithrombin III and tissue factor pathway inhibitor (TFPI)

Answer 18

Factor V Leiden : Common mutation in factor V that is associated with significant risk of thrombosis. The mutation in factor V prevents inactivation of factor Va by activated protein C, hence, persistence of factor Va. Dx is established by DNA testing

Answer 19

high homocysteine (secondary genetic mutations) causes homocystinuria – pred. to art and venous clots and arteriosclerosis

Answer 20

Manifestations: - Severity of coagulation abnormalities correlates with extent of hepatocellular damage - Typically have normal levels of VIII in plasma - Reduction in Vit K dependant coagulation factors is common. Inability to correct coagulopathy with Vit K indicates that the coagulopathy may be caused by reduced levels of clotting factors that are not vitamin K dependant and/or by inadequate production of precursor vitamin K proteins

Answer 21

Definition: - a systemic thrombohemorrhagic d/o seen in association with well-defined clinical situations AND - Laboratory evidence of: o Procoagulant activation o Fibrinolytic activation o Inhibitor consumption o Biochemical evidence of end-organ damage/failure Thrombotic microangiopathy that results in consumption of clotting factors, platelets, and anticoagulant proteins.  Consequences: o widespread intravascular deposition of fibrin, leading to tissue ischemia and necrosis, o a generalized hemorrhagic state o hemolytic anemia

Answer 22

``` The mnemonic device CHINA Connective tissue diseases Helminthic infections Idiopathic HES Neoplasia Allergies ```

Answer 23

- Two major features contribute to the pathogenesis of sequelae of β-thalassemia: o inadequate β-globin gene production, leading to decreased levels of Hb o imbalance in α- and β-globin chain production - In BM, leads to ineffective erythropoiesis (hyperactive marrow with few retics and severe anemia) - there is an excess of α-globin chains relative to β- and γ-globin chains; α-globin tetramers (α4) are formed. These inclusions interact with the red cell membrane and shorten red cell survival, leading to anemia and increased erythroid production

Answer 24

- If un tx, usually become symptomatic as a result of progressive hemolytic anemia, with profound weakness and cardiac decompensation (around Hgb 40) during the 2nd 6 mo of life. - Pallor, hemosiderosis, and jaundice may combine to produce a greenish brown complexion. - The classic findings in children with severe thalassemia : typical facies, pathologic bone fractures, marked hepatosplenomegaly, and cachexia, are primarily seen in developing countries - Features of ineffective erythropoiesis include expanded medullary spaces (where massive expansion of the marrow of the face and skull lead to maxillary hyperplasia, flat nasal bridge and frontal bossing), extramedullary hematopoiesis, and a huge caloric need

Answer 25

Iron toxicity: o Anemia leads to an increase in iron absorption from the GI tract: o Endocrine dysfunction may include hypothyroidism, gonadal failure, hypoparathyroidism, and diabetes mellitus. Congestive heart failure and cardiac arrhythmias are potentially lethal complications Complications - Mainly result from transfusional hemosiderosis - Serum ferritin helps to assess iron trends, but doesn’t accurately predict stores. Liver biopsy is gold standard, but may not accurately predict changes in cardiac iron. Ferritometer and specialized MRI are alternatives. o Prevention occurs by giving deferoxamine (iron chelator). o Side effects: ototoxicity (high frequency hearing loss), retinal changes, bone dysplasia with truncal shortening

Answer 26

Investigations - Infant is born with only Hb F. Eventually, develop severe anemia (Hgb 50 if untx), few reticulocytes, microcytosis - Unconjugated bili increased - Iron accumulation leads to increased ferritin and saturation of transferring - Bone marrow hyperplasia on radiographs - Dx confirmed by electrophoresis always abnormal

Answer 27

- Obtain a red cell phenotype before initiating transfusions - Blood products need to be leukoreduced and phenotypically matched for Rh and Kell antigens. If considering BMT, give CMV – and irradiated blood. - Transfusions usually occur monthly – aim for Hgb 95-105

Answer 28

- Frequently misdiagnosed as iron deficiency in children because the two are similar hematologically and iron deficiency is much more prevalent. A short course of iron and re-evaluation is all that is required to identify children who will need further evaluation. - Children who have β-thalassemia trait have a persistent RDW, and on hemoglobin analysis, they have  Hb F and diagnostically increased Hb A2. , profound microcytosis , high RBC - There are “silent” forms of thalassemia trait, and if the family history is suggestive, further studies may be indicated.

Answer 29

- Prenatally, may become sx because Hb F requires sufficient α-globin gene production, whereas postnatally, infants with β-thalassemia become symptomatic because Hb A requires adequate production of β-globin genes

Answer 30

``` α silent trait 1 α globin gene affected Normal MCV, Hgb Barts H < 3% Common in African Americans No treatment required ```

Answer 31

2 α globin genes Microcytic anemia, Hgb analysis n, except in NN period, Bart H < 8% but > 3%, high RBC Looks like iron deficiency anemia Treatment: iron trial. If no improvement, conduct α-globin gene deletion analysis (if known alpha trait, no iron)

Answer 32

Hb H dz 3 α globin genes Barts H > 25% (with 1 parent with trait). Later on, excess β = Hb H. MCV 51-73, Hgb 70-110 Marked microcytosis, anemia, splenomegaly, occ, sceral icterus or cholelithiasis May need transfusion

Answer 33

4 α globin genes No normal Hgb at birth (all Barts, with Gower 1,2 and Portland) Hydrops fetalis (ζ-globin gene essential for fetal survival) If fetus survives, imm exchange transfusion Transfusion dependant. BMT only cure

Answer 34

Overall, consists of folate supplementation, possible splenectomy, intermittent transfusion during severe anemia. Should not be exposed to oxidant medications

Answer 35

Differentiating α thal minor from iron deficiency - Both have hypochromia and microcytosis. But microcytosis is much more profound, and the anemia much milder, than that seen in iron deficiency anemia. - Patients with beta thalassemia minor/trait also tend to have total red blood cell counts higher than normal, often into the "polycythemic" range. Patients with beta thalassemia trait almost always have a hematocrit >30 percent, and a mean corpuscular volume of the red cells (MCV) <75 fL. In contrast, patients with iron deficiency rarely become microcytic (MCV <80 fL) until the hematocrit has dropped below 30. Another potentially useful indicator is the red cell distribution width (RDW). The RDW in patients with thalassemia trait tends to be normal, since virtually all cells are hypochromic and microcytic. In contrast, there is considerable heterogeneity in cell size in the early and intermediate stages of iron deficiency, producing an increased RDW.

Answer 36

Etiology - 1/5,000 in people of Northern European descent. AD, but also sometimes AR. ~ 25% individuals have no FHx - It is the most common inherited abnormality of the red blood cell (RBC) membrane.

Answer 37

- Affected individuals may be asymptomatic, without anemia and with minimal hemolysis, or may have severe hemolytic anemia - The decreased deformability of the spherocytic RBCs impairs cell passage from the splenic cords to the splenic sinuses, and the spherocytic RBCs are destroyed prematurely in the spleen. Splenectomy markedly improves RBC life span and cures the anemia

Answer 38

Clinically - hemolytic disease in the newborn and may present as anemia and hyperbilirubinemia sufficiently severe to require phototherapy or exchange transfusions - Severity of sx’s is variable – some are asymptomatic and others may have severe anemia, with pallor, jaundice, fatigue, and exercise intolerance - Severe cases may be marked by expansion of the diploë of the skull and the medullary region of other bones, but to a lesser extent than in thalassemia major. - After infancy, the spleen is usually enlarged, and pigmentary (bilirubin) gallstones may form as early as age 4–5 yr. At least 50% of unsplenectomized patients ultimately form gallstones, although they may be asymptomatic. - Aplastic crisis: o Because of the increased RBC turnover and heightened erythroid marrow activity, kids are susceptible to aplastic crisis, (Parvo B19 infection) and to hypoplastic crises associated with various other infections. o The erythroid marrow failure may result rapidly in profound anemia (hematocrit <10%), high-output heart failure, hypoxia, cardiovascular collapse, and death. White blood cell and platelet counts may also fall.

Answer 39

- hemolysis (hgb 60-100, but can be normal, can show increased haptoglobin and gallstones on u/s) and indirect hyperbilirubinemia. Retics increased 6-20% (mean 10%). MCV n - spherocytes are smaller and hyperchromic - Erythroid hyperplasia is evident on BM - Dx is made on blood film, FHx and on seeing splenomegaly - Presence of spherocytes can be confirmed with an osmotic fragility test

Answer 40

Treatment - Splenectomy (esp if hgb > 100 and retic < 10%) - Folic acid 1mg daily (to prevent deficiency and resultant decreased in erythorpoiesis) - For patients with more severe anemia and reticulocytosis or those with hypoplastic or aplastic crises, poor growth, or cardiomegaly, splenectomy is recommended after age 5–6 yr to avoid the heightened risk of postsplenectomy sepsis in younger children

Answer 41

Epi/etiology - induced by infections, certain drugs or, rarely, fava beens - X-linked - 13% of male African-Americans have a mutant enzyme (G6PDA-) with an RBC G6PD activity ≤5–15%. - 5-40% of Italians, Greeks, and other Mediterranean, Middle Eastern, African, and Asian ethnic have G6PDB- (G6PD Mediterranean) with RBC G6PD activity <5% of normal.

Answer 42

Clinically - sxs develop 24-48 hrs after a pt has ingested a substance that has oxidant properties - The degree of hemolysis varies with the inciting agent, the amount ingested, and the severity of the enzyme deficiency. In severe cases, hemoglobinuria and jaundice result, and hgb may drop - can be life-threatening. - Associated reticulocytosis may produce a compensated hemolytic process. - In A-G6PD deficiency, spontaneous hemolysis may occur in premature infants, but not in term infants. - When a pregnant woman ingests oxidant drugs, they may be transmitted to her G6PD-deficient fetus, and hemolytic anemia and jaundice may be apparent at birth.

Answer 43

aspirin in high doses, sulfonamides, chloramphenicol, nitrofurontoin, antimalarials, phenacetin, vit K analogs, methylene blue, probenacid, acetylsalicylic acid, phenazopyridine, benze, naphthalene, DKA, hepatitis, sepsis

Answer 44

o Heinz bodies being seen on the smear in the first 3-4 days of illness - Dx depnds on direct (<10%) or indirect demonstration of decreased G6PD activity in RBCs - Also diagnosed if G6PD activity is within low-normal range in the presence of a high retic count - Screening tests are based on decoloration of methylene blue, reduction of methemoglobin, or fluorescence of NADPH

Answer 45

- 1:5000 males. 85% VIII, 10-15% IX. Hemostatic level FVIII: > 30-40%, FIX: > 25-30% - Most common severe inherited bleeding disorders. High rate of spontaneous mutation. - Genese are carried on the long arm of X chromosome. Can be detected in amniotic fluid - Affects all racial groups

Answer 46

- PTT usually 2-3x normal. Platelets, BT, INR, TT are normal. - In newborns, they may have an abnormally high factor VIII level (acute phase response to birth process). On the other hand, factor IX levels are naturally low in the newborn period. - Because factor VIII is carried in plasma by von Willebrand factor, the ratio of factor VIII to von Willebrand factor is sometimes used to diagnose carriers of hemophilia. - When possible, specific genetic mutations should be identified in the propositus and used to test other family members who are at risk for either having hemophilia or being carriers - Unless inhibitors have developed, mixing of normal plasma with pt plasma corrects the PTT o Inhibitors (antibodies) develop in 25-35% of pts – Bethesda assays are used to measure titers. - Perform Factor VIII or IX assay to make dx of hemophilia

Answer 47

Clinical manifestations - VIII and IX don’t cross the placenta – bleeding may occur from birth or in the fetus o 2% of neonates get ICH, 30% males bleed with circumcision - Clinical severity proportional to # of factor ( < 1: severe, 1-5: mod, mild 5-40%) - Easy bruising, intramuscular hematomas, and hemarthroses. Bleeding from minor traumatic lacerations of the mouth (a torn frenulum) may persist for hr or days and may cause the parents to seek medical evaluation. - Hallmark of hemophilia is hemarthrosis induced by minor trauma; many hemarthroses are spontaneous. o The earliest joint hemorrhages appear most commonly in the ankle. o In the older child and adolescent, hemarthroses of the knees and elbows are common. o After repeated bleeding episodes into the same jt, they may develop a “target” joint. Recurrent bleeding may then become spontaneous because of the underlying pathologic changes in the joint - Iliopsoas bleeds: pts may loose large amounts of blood, present in shock and hold their hip in flexed, internally rotated position due to irritation of iliopsoas. Dx is made clinically (unable to extend hip) – confirm with CT.

Answer 48

Treatment - Mild to moderate bleeding: levels of factor VIII or factor IX must be raised to hemostatic levels : 35–50% - Life-threatening or major hemorrhages: dose should aim to achieve levels of 100% activity - Do a DDAVP challenge (von willebrand’s carries factor VIII: if he reacts well, this could replace VIII for minor bleeding episodes)

Answer 49

Desmopressin (DDAVP®) is used to help stop bleeding in patients with von Willebrand's disease or mild hemophilia A. DDAVP causes the release of von Willebrand's antigen from the platelets and the cells that line the blood vessels where it is stored. Von Willebrand's antigen is the protein that carries factor VIII.

Answer 50

- Lifelong prophylaxis is given at onset of first joint hemorrhage (in severe pts, usually not in mild-mod) to prevent spontaneous joint bleeding. - Treatment is usually provided every 2–3 days to maintain a measurable plasma level of clotting factor (1–2%) when assayed just before the next infusion (trough level) - If moderate arthropathy develops, prevention of future bleeding will require higher plasma levels of clotting factors. - In the older child who is not given primary prophylaxis, secondary prophylaxis is frequently initiated if a target joint develops

Answer 51

Severe hemophilia: <1 percent factor activity Moderate hemophilia: factor activity level ≥1 percent of normal and ≤5 percent of normal Mild hemophilia: factor activity level >5 percent of normal and <40 percent of normal

Answer 52

- Chronic hemophilic arthropathy with risk of developing articular fusion. - the development of an inhibitor to either factor VIII or factor IX - risk of transfusion-transmitted infectious diseases.

Answer 53

Factor XI Deficiency (Hemophilia C) Epi and Dx - autosomal deficiency - mild to moderate bleeding symptoms. - It is frequently encountered in Ashkenazi Jews - The deficiency of factor XI can be confirmed by specific factor XI assays. - The bleeding tendency is not as severe as in factor VIII or factor IX deficiency - Chronic joint bleeding is rarely a problem, and for most patients, factor XI deficiency is a concern only at the time of major surgery unless there is a second underlying hemostatic defect (e.g., von Willebrand disease).

Answer 54

Treatment: - Unless the patient previously had surgery without bleeding, replacement therapy should be considered and given preoperatively. - There is no approved concentrate of factor XI available in the United States; therefore, use FFP - Bleeding during minor surgery can be controlled with local pressure; patients undergoing dental extractions can be monitored closely and treated only if hemorrhage occurs.

Answer 55

Von Willebrand Dz

Answer 56

Epi: Most common hereditary bleeding d/o. Present in up to 1-2% of the population. F>M. Chromosome 12 contains gene for WVF.

Answer 57

Classification: Type 1: (85%) protein is quantitatively reduced, but not absent Type 2: qualitatively abnormal Type 3: (1/250 000) absent (with normal levels VIII) – intracranial bleed, major epistaxis and menorrhagia Mutations in different loci that code for different functional domains of the VWF protein cause the variants of VWD

Answer 58

- mucocutaneous hemorrhage (including excessive bruising, epistaxis, menorrhagia, post op bleeding (esp after mucosal surgery – tonsillectomy or wisdom tooth extraction). Bleeding is much more profound in type 3 or homozygous VWD. - VWF is an acute-phase protein – stress increases its level. Pts may not bleed with procedures that incur major stress (appendectomy and child birth). Levels increase 2-3x in pregnancy - Can have GI telangiectaisa - Pts with severe type 3 can have joint hemorrhages and spontaneous CNS bleeding.

Answer 59

- Because there is no single assay that has demonstrated the ability to rule out VWD, if the history is suggestive of a mucocutaneous bleeding disorder, VWD testing should be undertaken, including: o quantitative assay for VWF antigen and testing for: o VWF activity (ristocetin cofactor activity) o plasma factor VIII activity o determination of VWF structure (VWF multimers) o platelet count (may be normal except in type 2B) - Levels may vary with blood type ( O < A < B < AB) - ** Consider it in adolescent females that present with menorrhagia and anemia

Answer 60

Type 1 VWD. - Bleeding symptoms include epistaxis, bruising, and menorrhagia. If bleeding is excessive: o desmopressin (DDAVP). Intranasal DDAVP (Stimate) is particularly helpful for the outpatient treatment of bleeding episodes. Type 2 VWD - Intermittent response to DDAVP - Some pts will require infusion of VWF Type 3 VWD - is the homozygous or compound heterozygous inheritance of VWF deficiency. These patients will have major hemorrhage, but only rarely have joint hemorrhages. Bleeding episodes require treatment with: o VWF-containing concentrates. VWF is both a plasma and a platelet protein. DDAVP is not effective in type 3 VWD - Overall : Aimed at increasing the plasma level of VWF and factor VIII. Dental extractions and sometimes nosebleeds can be managed with both DDAVP and an antifibrinolytic agent, such as ε-aminocaproic acid (Amicar)

Answer 61

2–7 days of age ``` Sites fo Hemorrhage: Gastrointestinal Ear-nose-throat–mucosal Intracranial Circumcision Cutaneous Injection sites ``` Etiology: Vitamin K deficiency Breast-feeding Prevented by parenteral vitamin K at birth. Oral vitamin K regimens require repeated dosing over time Incidence ≈2% if not given vitamin K

Answer 62

EARLY ONSET 0–24 hr ``` Sites of Hemorrhage: Cephalohematoma Subgaleal Intracranial Gastrointestinal Umbilicus Intra-abdominal ``` Etiology: Maternal drugs (phenobarbital, phenytoin, warfarin, rifampin, isoniazid) that interfere with vitamin K Inherited coagulopathy Prevention: Possible vitamin K at birth or to mother (20 mg) before birth Avoid high-risk medications Very rare

Answer 63

1–6 mo ``` Sites of Hemorrhage Intracranial Gastrointestinal Cutaneous Ear-nose-throat–mucosal Injection sites Thoracic ``` ``` Etiology: Cholestasis—malabsorption of vitamin K (biliary atresia, cystic fibrosis, hepatitis) Abetalipoprotein deficiency Idiopathic in Asian BF infants Warfarin ingestion ``` Prevented by parenteral and high-dose oral vitamin K during periods of malabsorption or cholestasis

Answer 64

Although “late” hemorrhagic disease - reported in BF infants, but vitamin K deficiency occurring after the neonatal period is usually secondary to lack of oral intake of vitamin K - alterations in the gut flora due to the long-term use of broad-spectrum antibiotics - malabsorption of vitamin K - Intestinal malabsorption of fats may accompany cystic fibrosis or biliary atresia and result in a deficiency of fat-soluble dietary vitamin, with reduced synthesis of vitamin K–dependent clotting factors (factors II, VII, IX, and X, and protein C and protein S).

Answer 65

Increased AFP

Answer 66

- peak incidence between 2–6 yrs, boys > girls

Answer 67

``` Down syndrome Fanconi syndrome Bloom syndrome Diamond-Blackfan anemia Schwachman syndrome Klinefelter syndrome Turner syndrome Neurofibromatosis type 1 Ataxia-telangiectasia Severe combined immune deficiency Paroxysmal nocturnal hemoglobinuria Li-Fraumeni syndrome ```

Answer 68

- Usually non-specific and relatively brief history - Anorexia, fatigue, irritability, low grade intermittent fever - Bone or jt pain exp in lower extremities, may be severe and wake pt at night - With disease progression, show S&S of BM failure including pallor, fatigue, bruising, epistaxis, fever - PE findings: pallor, listlessness, purpuric and petechial skin lesions, MM hemorrhage, lyphadenopathy, splenomegaly, hepatomegaly, bony tenderness o May have signs of ↑ ICP if leukemic involvement of CNS (papilledema, retinal hemorrhages, CN palsies) [CNS involvement in 5%] o Resp distress secondary to anemia or airway obstruction d/t large anterior medistinal mass (usually with T cell ALL) - Early pre–B-cell ALL is the most common, onset b/w 1–10 yrs, high leuks (median 33), HSM in 30-40% - Testicular (20%) and ovarian (30%) involvement also occurs

Answer 69

Risk factors - CNS, testicular + - Age < 1, > 10 - WBC > 50 - Also based on minimum residual disease and response to induction

Answer 70

Diagnosis - anemia and thrombocytopenia see in most pts - leukemic cells in peripheral blood - can present with leuks < 10, so a high leuk count is not necessary for dx - if smear suggests possibility of leukemia, then need bone marrow (aspiration usually sufficient, bx may be needed to exclude other causes of BM failure) - ALL dx’d if BM shows >25% homogeneous population of lymphoblasts - Need a CSF examination at dx (if lymphoblasts found and ↑ leks, then have CNS/meningeal leukemia – worse stage, need additional CNS and systemic tx)

Answer 71

- Remission induction – 4 wks of tx: vincristine, steroids, L-asperaginase; intrathecal cytarabine or MTX - Intensification/Consolidation - Delayed Intensification, Interim Maintenance

Answer 72

Vincristine

Answer 73

Prognosis - most children can expect long-term survival, with survival rate >80% at 5 yr - poorer outcome with hypodiploidy, Philadelphia chromosome, and MLL gene rearrangements and translocations [t(1:19) or t(4;11)] - favorable characteristics: rapid response to tx, hyperdiploidy, trisomies of specific chromosomes, and rearrangements of the TEL/AML1 genes

Answer 74

- Features that can present with and are different from ALL include subcutaneous nodules or “blueberry muffin” lesions, infiltration of gingiva, S&S of DIC (M3, acute promyelocytic leukemia), and discrete masses known as chloromas or granulocytic sarcomas [more likely to have coagulation problems than ALL] o Masses may occur in absence of apparent BM involvement, assoc with M2 and t(8;21) translocation - CNS symptoms more common in AML than ALL

Answer 75

- 14x risk, ratio of ALL to AML in pts with T21 is same as in general population - If develop ALL, expected outcome of tx is same as for non-T21 kids, have ↑ sensitivity to MTX and substantial toxicity if standard doses given - In AML, T21 pts have much better outcomes (>80% long-term survival), need less intensive therapy

Answer 76

- 10% of neonates with DS get transient leukemia or myeloproliferative syndrome o characterized by high leukocyte counts, blast cells in peripheral blood, and associated anemia, thrombocytopenia, and hepatosplenomegaly o usually resolve in days to weeks, may need temporary transfusion support but NOT chemo o need close F/U as 20–30% will develop leukemia (often M7 - acute megakaryocytic leukemia) by 3 yrs - note: transient myeloproliferative dz may occur in pts w/o phenotypic features of T21, blasts may be T21 suggesting mosaic state

Answer 77

- CML 2–3% of all cases of childhood leukemia | - 99% characterized by a specific translocation, t(9;22)(q34;q11), known as the Philadelphia chromosome

Answer 78

- assoc with exposure to ionizing radiation, but very few children with CML have such a hx - clinically, have an initial chronic phase - spleen often greatly enlarged (can give LUQ pain), can also have mild anemia and thrombocytosis - chronic phase terminates 3–4 yr after onset, then CML moves into accelerated or “blast crisis” phase o blood counts rise dramatically, cannot control with drugs such as hydroxyurea o can also have hyperuricemia and neuro symptoms, related to ↑blood viscosity with ↓CNS perfusion - nonspecific presenting symptoms; include fever, fatigue, wt loss, and anorexia; splenomegaly also present

Answer 79

Infant Leukemia - 2% of cases of leukemia occur <1 yr, ratio of ALL to AML is 2 : 1 - unique biologic features (rearrangement MLL gene), particularly poor prognosis, very high relapse rate - present with hyperleukocytosis and tissue infiltration giving organomegaly and CNS disease - subcut, known as leukemia cutis, and tachypnea d/t diffuse pulmonary infiltration by leukemic cells observed - very intensive chemo including SCT stem cell transplantation

Answer 80

- 60% of all lymphomas in children/ado. Represents 8–10% of all malignancies in children between 5–19 yr of age. - Although >70% of patients present with advanced dz at dx, the px has improved dramatically, with survival rates of 90–95% for localized disease and 60–90% with advanced dz

Answer 81

o BL : with abd (sporadic type) or head & neck (endemic type) dz with involvement of bone marrow or CNS.

Answer 82

o LL : with an intrathoracic or mediastinal supradiaphragmatic mass, and also has a predilection for spreading to the bone marrow and CNS.

Answer 83

DLBCL : with either an abdominal or mediastinal primary and, rarely, dissemination to bone marrow/CNS.

Answer 84

o ALCL : either with a primary cutaneous manifestation (10%) or with systemic disease (fever, weight loss) with dissemination to liver, spleen, lung, mediastinum, or skin; spread to the bone marrow or CNS is rare

Answer 85

Investigations - CBC, lytes, UA, Ca, Phos, BUN, creat, ALT, AST, bone marrow aspiration & Bx, LP with CSF cytology, cell count and protein; - CXR, neck, chest, abdominal, and pelvic CT scans, - PET scan and bone scan (optional), and head CT scan (optional) - The tumor tissue (i.e., biopsy, bone marrow, CSF, or pleural/paracentesis fluid) should be tested by flow cytometry for immunophenotypic origin (T, B, or null) and cytogenetics (karyotype). - Additional tests might include fluorescent in situ hybridization (FISH) or quantitative RT-PCR for specific genetic translocations, T and B cell gene rearrangement studies, and molecular profiling by oligonucleotide microarray