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Back to Basics 2015: Pediatric Hematology/Oncology April 1, 2015 Lesleigh Abbott MD FRCPC Children’s Hospital of Eastern Ontario [email protected] • No conflicts of interest to declare Outline • Pediatric Hematology • Pediatric Oncology Hematology • CBC: WBC, Hemoglobin, Platelets – Number and morphology (and function) • MCV: mean corpuscular volume • MCHC: mean corpuscular hemoglobin concentration • RDW: red cell distribution width • Reticulocytes: immature RBCs • Bleeding/Thrombosis – PTT • intrinsic: I, II, V, VII, IX, X, XI, XII • Mixing study – PT/INR • extrinsic: I, II, V, VII, X Blood smear Normal Blood Smear MCQ The following are causes of microcytic anemia in a child A) Folate deficiency B) B12 deficiency C) Hypothyroidism D) Thalassemia E) Recent blood loss Low Retics (Inadequate Response) Anemia Microcytosis Normocytic Macrocytosis High Retics (Adequate Response) Hemolytic disorders Thalassemia Recent blood loss B12 Deficiency Hemoglobinopathy Sickle Cell Disease Chronic Disease Malignancy/marrow infiltration Folate deficiency Enzymopathy G6PD, PK Iron Deficiency Chronic Renal Failure Drugs Membranopathy spherocytosis, elliptocytosis Lead intoxication Transient Erythroblastopenia of Childhood (TEC) Hypothyroidism Extrinsic factors DIC, HUS, TTP, Burns Sideroblastic Anemia Marrow aplasia Chronic Liver disease Immune autoimmune, isoimmune,drug HIV Alcohol Chronic Inflammatory disease Reticulocytosis Myelodysplasia Bone marrow failure syndromes MCQ You are seeing 2 year old girl in clinic, well nourished, but very pale, low energy and picky eater. Her blood smear shows the following: Your diagnosis is: A) Iron deficiency anemia B) Thalassemia C) Sickle Cell Disease D) Spherocytosis E) G6PD deficiency MCQ Which of the following is not the cause of unconjugated jaundice in a newborn infant A) Rh incompatibility B) G6PD deficiency C) Spherocytosis D) Biliary atresia E) ABO incompatibility Hemolytic Disease of the Newborn • Alloimmune condition • IgG of mom pass through the placenta to baby and attacks the RBCs of baby causing hemolysis – Anemia and Increased reticulocytes – Unconjugated hyperbilirubinemia • Incompatibility of red blood cells – Rh : Anti-D to Rh Negative Mothers – ABO: Mom usually type O blood • Treatment – For jaundice: phototherapy, exchange transfusion MCQ Other than a CBC and smear, which of the following WOULD NOT be a part of a hemolysis work-up? A) AST and ALT B) Reticuolcytes C) DAT D) LDH E) Bilirubin Direct Antibody Test or Coombs test Looking for antibodies attached to red cell surface Indirect Antibody Testing Recipient’s antibodies from serum and donor’s blood sample: cross match and antibody screen Hemoglobinopathies: Sickle Cell Disease • Sickle Cell Disease – Genetic defect in β-globin genes – Autosomal recessive – Red cell sickle under stress (low pO2, dehydration, fever, acidosis) • Results in infarction of tissue: spleen, lungs, bone, brain, digits – Functional asplenia • Greatest cause of mortality is infection/sepsis – Acute Chest syndrome – Vaso-occlusive crisis – Aplastic crisis vs. Acute splenic sequestration – Stroke – Priapism MCQ You are on-call and get a phone call from a patient with Sickle Cell Disease with a fever in the middle of the night. What do you do? A) Advise to take Tylenol B) If they fell unwell, see their doctor in the morning C) Go to the closest ER for broad spectrum antibiotics and possible admission D) Go to the closest ER for assessment of possible antibiotics E) Ask the patient why they woke you up and go back to sleep Sickle Cell Treatment • Lifelong condition • Chronic • Education • Counseling for reproduction • Acute crisis – Fluids, Pain control – Antibiotics – Straight transfusions vs. Exchange transfusion – Oxygen – – – – Penicillin prophylaxis Vaccinations Hydroxyurea Chronic transfusion program – Transcranial doppler ultrasounds – Multidisciplinary clinic Hemoglobinopathies • Hereditary Spherocytosis – Autosomal Dominant – Abnormality in RBC membrane proteins (spectrin) – Most common hereditary hemolytic anemia – High osmotic fragility • More prone to physical degradation – Functional asplenia – Treatment: • Supportive care • Immunization against encapsulated organisms – Pneumococcus, meningococcus, HiB G6PD: Glucose-6-Phosphate Dehydrogenase Deficiency • Sensitivity of RBC to oxidative stress • X-linked • Hemolysis mediated by oxidative stress, drugs, infection, foods (fava beans) • Neonatal jaundice • G6PD assay • Heinz bodies and bite cells • Avoid triggers • Transfuse as necessary Non-Immune Destruction • DIC, TTP/HUS, ECMO/Bypass, Sepsis, Preeclampsia/HELLP syndrome, drug induced MCQ • What is the predominant cell type in the last smear? A) Shistocyte B) Spherocyte C) Pappenheimer bodies D) Ringed Sideroblasts E) Microcytes Non-Immune Thrombocytopenia HUS: Hemolytic Uremic Syndrome • Infants and young children • Preceding colitis with bloody diarrhea • E.coli verotoxin (O157:H7) • Presentation • Thrombocytopenia • Microangiopathic Hemolytic Anemia • Renal failure • Management: – Dialysis – Supportive care TTP: Thrombotic Thrombocytopenic Purpura • Classic diagnostic pentad – Microangiopathic hemolytic anemia – Thrombocytopenia – Renal manifestations – Fever – Neurological findings • Management: Plasmapheresis • Steroids, Rituximab • Decreased ADAMTS13 – With or without associated antibody – Breaks down vWF large multimers MCQ The following are lab findings for TTP except: A) Schistocytes and helmet cells on smear B) Elevated LDH C) Reticulocytosis D) DAT Positive E) Normal coagulation studies ITP: Immune Thrombocytopenia Purpura • Most common cause of thrombocytopenia in childhood • Peak age: 2-6 years • Caused by antibodies that bind to platelet membranes – Leads to splenic uptake and destruction MCQ Presentation of ITP includes: A) Neutropenia B) Small Platelets on blood smear C) Anemia D) Lymphadenopathy E) Epistaxis MCQ All are treatments for ITP, except: A) Observation B) Corticosteroids C) IVIG D) Dapsone E) Anti-D MCQ The inheritance pattern of hemophilia A and B is: A) X-linked B) Autosomal Recessive C) Autosomal Dominant D) Autosomal Dominant with incomplete penetrance Bleeding Disorders: Hemophilia • • • • • Most common inherited bleeding disorder X-linked Hemophilia A (F VIII deficiency) Hemophilia B (F IX deficiency) Presentation – Bleeding: joints, muscles, GU tract, excessive post trauma • Labs: Prolonged PTT – No change with mixing study – Low factor levels • Treatment – DDAVP – Recombinant factor concentrate • Inhibitor development – Supportive MCQ The features of von Willebrand factor includes all of the following except: A) platelet adhesion B) carrier of F VIII C) exists as circulating multimers D) vitamin K dependent factor E) acute phase reactant Von Willebrand’s Disease • Most common bleeding disorder • Symptoms: mostly mucocutaneous bleeding • Treatment: – Increase vWF: DDAVP, Antifibrinolytics, vWF concentrates • Type 1: mild quantitative defect – Decreased amount of vWF • Type 2: qualitative defect – Dysfunctional vWF • Type 3: severe total quantitative defect – No vWF produced Lymphadenopathy • Constitutional symptoms – Fevers, night sweats, weight loss • Infectious exposures – Travel, animals, camping/ticks • On exam: – Location, size, consistency, fixation, tenderness – Liver, spleen, • Investigations: – CBC, CXR, PPD,Inflammatory viral testing, otherNeoplastic imaging, biopsy Infectious Bacterial (TB) Autoimmune (RA, SLE) Lymphoma Viral (EBV, CMV, HIV) Drug hypersensitivity Leukemia Parasitic (toxoplasmosis) Fungal (histoplasmosis) Metastatic cancer Childhood Cancers • ~850 new diagnoses per year in Canada – ~85% of children will achieve long term survival • Incidence relatively stable since 1985 • Causes: no absolute known cause, risk factors – – – – Chromosomal syndromes: T21 Prior malignancy Neurocutaneous syndromes: NF1, Tuberous sclerosis Immunodeficiency syndromes – Association with lymphoma – Family history – Li-Fraumeni Syndrome – Exposure to radiation, chemical, biologic agents Important Labs in Oncology • CBC with differential and smear… • K, Ca, PO4, Creatinine – WHY? • • • • LDH Tumour markers: Beta-HCG, AFP Ferritin, ESR Looking for chemo side effects Treatment: Chemotherapy, Radiation, Surgery • Cytotoxic, targeted, combination…. • Special considerations in children: – Long term toxicity • Growth • Development/Neurocognitive • Puberty/Fertility • Bone health • Physical and mental health • End organ disease –Cardiac, Lung, Renal, Liver… MCQ What is the most common type of childhood cancer? A) Lymphoma B) Leukemia C) Brain Tumours D) Wilms’ Tumour E) Sarcomas Most common types of childhood cancer 1) Leukemia 2) Brain tumours 3) Lymphomas 4) Neuroblastoma 5) Wilms’ tumour 6) Sarcoma Leukemia • Acute Lymphoblastic Leukemia (ALL) • Most common type of leukemia <18 yrs old • Presentation: • Bone Marrow, CSF, testicular • Hepatosplenomegaly, lymphandenopathy • Fever, fatigue. Weight loss • Mediastinal mass • Risk group: Age and WBC • Cytogenetics, ploidy, response (MRD) • Treatment • Multiagent chemotherapy • Intrathecal chemotherapy • Craniospinal radiation • Excellent overall survival…because of clinical trials • BCR-Abl: Philadelphia chromosomal translocation Brain Tumours • Red flags: morning headache, vomiting, papilledema, gait/balance changes, focal deficits • Associations with neurocutaneous diseases – Neurofibromatosis, Tuberous Sclerosis • Classified by location and histology • Investigations: Head/Spine MRI • Treatment depends on location and pathology – Don’t always need biopsy if characteristic image findings MCQ You are seeing a 11 year old boy with lymphadenopathy and fever. B symptoms refer to all of the following except: A) Drenching night sweats B) Unexplained fevers C) Poor sleep E) Weight loss Lymphoma Hodgkin • Ages 15-34yrs and 50+ • Persistent, painless, rubbery lymphadenopathy • B symptoms • Reed-Sternberg cell • Treatment: chemotherapy and radiation based on response and risk group Non-Hodgkin • Incidence peak 7-11 yrs • Rapidly growing with distant mets • Types – Lymphoblastic lymphoma – Burkitt’s • Endemic (EBV) vs. sporadic – Diffuse large B cell – Anaplastic large T cell • Primary treatment with chemotherapy MCQ This patient is in your office and you feel an abdominal mass. Next step: A) Observation B) Ultrasound of abdomen C) Surgical consultation D) MRI abdomen Abdominal Mass Wilms’ Tumour • Most common primary renal neoplasm of childhood • 2-5 years of age • Asymptomatic, unilateral abdominal mass • Renal symptoms: HTN, hematuria, abdo pain, vomiting • Treatment: – Surgical with nephrectomy – Chemotherapy +/- radiation – 90% long term survival Neuroblastoma • Neural crest cells arising from sympathetic tissues • Originate from any site in sympathetic nervous system • Presentation based on location of mass • Common to have mets • Treatment can vary • Observation to…. • Chemo/Rads/Surgery/ Bone marrow transplant/ Targeted therapy Sarcomas • Bone: mostly teens – Osteosarcoma – Ewing Sarcoma • Soft Tissue: younger – Rhabdomyosarcoma • Presentation – Mass – +/-Pain – X-ray of primary site • Treatment – Local control: radiation and/or surgery – Systemic control: chemotherapy Osteosarcoma: Survival What changed at point d? Treatment: Surgery/Local Control Rotationplasty MCQ You are seeing a child with lymphadenopathy and fever. What is your most important first test after your physical exam? A) Chest X-ray B) ALT and AST C) Creatinine and BUN D) CBC with differential E) Bilirubin and albumin MCQ It’s July 1st…you are seeing a teenager in the ER with Hemophilia A and a swollen knee. What will you give for treatment? A) Recombinant factor VIII concentrate B) Cryoprecipitate C) ASA D) Platelet transfusion E) FFP Thank-you! Good luck everyone Lesleigh Abbott [email protected]