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Back to Basics: Pediatric Hematology/Oncology Review Lesleigh Abbott MD FRCPC Children’s Hospital of Eastern Ontario March 22, 2017 • No conflicts of interest to declare Question • You are called to the ER to see a 2yr old girl with a large abdominal mass palpable on exam. She is previously well. • She has some respiratory distress. Her uric acid is 150. • She has not been feeding well and is irritable. Objectives • Key messages of pediatric hematology/oncology for your exam Childhood Cancers • Risk factors – Chromosomal syndromes – T21 • ~850 new diagnoses per year – Prior malignancy in Canada – Mostly treatment related – ~85% of children will achieve long term survival – Neurocutaneous syndromes • Incidence relatively stable – NF1, Tuberous sclerosis since 1985 – Immunodeficiency syndromes: • Causes: no absolute known Association with lymphoma cause, some known risk – Ataxia-telangiectasia factors – Hereditary cancer syndromes – Li-Fraumeni Syndrome – Exposure to radiation, chemical, biologic agents 35% Relative incidence rates of childhood cancers 30% 1. Leukemia 25% 2. Brain tumors 20% 3. Lymphoma 15% 4. NBL is the most common extracranial solid tumor of childhood 10% 5% 0% Leuk Lymph Brain/S Soft tis Wilms Neurob Bone Retino Germ C Epith Other Principles of Oncology • Clinical findings…to…diagnosis – Imaging – Biopsy – Pathology • Staging work up: where is the cancer – Where does that type of cancer like to go? • Define stage/Risk group • Baseline organ function • Decide on treatment protocol – Local/systemic control Important Labs in Oncology • • • • CBC with differential and smear LDH Tumor markers: Beta-HCG, AFP K, Ca, PO4, Creatinine, Uric acid – WHY? Tumor Lysis Syndrome Hyperhydration Hyperphosphatemia http://www.learnpicu.com/_/rsrc/1467886157441/oncology/tumor-lysis-syndrome/TLS2.png What do you see? Lymphadenopathy • Constitutional symptoms – Fevers, night sweats, weight loss • Infectious exposures – Travel, animals, camping/ticks • On exam – Location, size, consistency, fixation, tenderness – Supraclavicular**always abnormal – Liver, spleen Lymphadenopathy Inflammatory Neoplastic • Constitutional symptoms – Fevers, night sweats, weight loss Bacterial (TB) Autoimmune (RA, SLE) Lymphoma • Infectious exposures Viral (EBV, CMV, HIV)animals, Drugcamping/ticks hypersensitivity Leukemia – Travel, • On exam: Parasitic (toxoplasmosis) Metastatic cancer – Location, size, consistency, fixation, tenderness Infectious – Supraclavicular**always abnormal Fungal (histoplasmosis) – Liver, spleen, • Investigations: – CBC, CXR, PPD, viral testing – Other imaging – Biopsy Indications for LN Biopsy • • • • • Hard, firm, rubbery, non-tender Progressive growth over short period Failure of antibiotic treatment Odd locations – supraclavicular >2cm Leukemias Bone marrow testing Leukemia Bone Marrow Biopsy Normal bone marrow Bone marrow replaced by leukemia Childhood Leukemias Aldrich et al. 2006 Acute Lymphoblastic Leukemia (ALL) • Most common type of leukemia <18 yrs • Presentation – Fever, fatigue, weight loss – HSM, lymphadenopathy – Bone Marrow – CSF, testes, mediastinal mass • Symptoms due to – Infiltration of bone marrow – Decreased production of normal marrow elements ALL • Pathology: B vs. T cell, cytogenetic markers • Treatment • Multi-agent chemotherapy with maintenance phase – Up to 3.5 years of treatment • Intrathecal chemotherapy • Excellent overall survival…because of large scale international clinical trials Query patient with new leukemia • 10 year old with low energy, petechiae, bony pain, fevers • Work-up: – CBC with differential and smear • See blasts • Not normal to see blasts in peripheral smear!! – Leukemia – GCSF – Extreme sepsis – TLS – Chest x-ray… Patient with suspected leukemia Patient with suspected leukemia Anterior Mediastinum • T-cell – Lymphoma – Leukemia • Thymus • Teratoma • Thyroid Lymphoma Lymphoma Non-Hodgkin’s Hodgkin’s 60% 40% Any age Adolescents Rare < 2 yrs Rare < 5 yrs of age Lymphoma Hodgkin Non-Hodgkin • AYAs and 50+ • Persistent, painless, rubbery lymphadenopathy • B symptoms • Reed-Sternberg cell • Treatment: chemo +/radiation • Incidence peak 7-11 yrs • Rapidly growing +/- distant mets • Types – Lymphoblastic lymphoma – Burkitt’s • Endemic (EBV) vs. sporadic – Diffuse Large B Cell – Anaplastic Large T Cell • Chemotherapy Presentation of Hodgkin Lymphoma • Plethora, engorgement of face, upper limbs, dilation of veins Superior Vena Cava Mediastinal Syndrome • SVC – thin-walled, low intra-luminal pressure • Surrounded by lymph nodes, thymus • Tumor can compress SVC: venous stasis • Compression, clotting, edema: – Minimize tracheal airflow – Reduce venous return from the head, neck, upper thorax Symptoms and Physical Findings in Patients with mediastinal mass • • • • • • • • Finding Cough/dyspnea Wheezing Pleural Effusion Pericardial Effusion Hoarseness Facial Edema Chest Pain % 68 63 50 19 19 12 6 Mediastinal Mass Management • Emergency! • Do not lay flat! • Oxygen, IV access x2 (lower limbs) • If intubation is required – Ensure max support, most skilled intubator – Consider awake intubation (no neuromusc blockade) in ICU with ECMO available • Call PICU and Anesthesia (early!) • Call Oncology – Steroids? – Diagnostic work-up • Echo – Rule out effusion/tamponade • Careful imaging and biopsy Question • 4 year old girl presents with acute onset of loss of walking • She’s been incontinent in the last 24 hours • Next steps: Oncologic Emergency: Spinal Cord Compression May be initial presentation or presentation of relapsed/refractory disease (NB, EWS) Acute weakness/paralysis/sensory findings Management Emergent imaging Steroids Emergent Neurosurgical evaluation Laminectomy vs. Radiation vs. Chemo Abdominal Masses Wilms Tumor Most common primary renal neoplasm of childhood • 2-5 years of age • Asymptomatic, unilateral abdominal mass • Renal symptoms: HTN, hematuria, abdo pain, vomiting Mass • Treatment: – Surgical with nephrectomy – Chemotherapy – +/- radiation – 90% long term survival Kidney Neuroblastoma • Neural crest cells arising from sympathetic tissues • Originate from any site in sympathetic nervous system – Adrenal gland most commonly – Presentation based on location of mass – Common to have mets at diagnosis • Treatment can vary – Observation to…. – Chemo/Rads/Surgery/ Bone marrow transplant/ Targeted therapy NBL Clinical Presentation • Asymptomatic mass • neck • thorax • abdomen • Pelvis • Spinal Cord Compression • “Raccoon eyes” • Hepatomegaly • Opsoclonus/myoclonus Systemic symptoms Weight loss Irritability Fever Hypertension Intractable diarrhea (VIP) Bone pain Limp Refusal to walk Pallor Skin lesions Sarcomas Sarcomas • Bone: mostly teens – Osteosarcoma – Ewing Sarcoma • Soft Tissue: younger – Rhabdomyosarcoma – Non-Rhabdo Soft tissue sarcoma –Alveolar Soft Part Sarcoma –Sinovial Sarcoma –Desmoid Tumor • Presentation – Mass +/-Pain – X-ray of primary site – MRI primary site including lymph node imaging – Imaging of possible sites of metastatic disease – Bone marrows – PET scan and/or Bone scan • Treatment – Local control: radiation and/or surgery – Systemic control: chemotherapy OS vs. EWS Radiology Osteosarcoma • Bone destruction, moth eaten appearance • Periosteal reaction: sunburst, Codman triangle Ewing Sarcoma • Onion skinning: splitting or thickening of cortex by tumor cells Codman Triangle Sunburst Onion Skinning Osteosarcoma: Survival What changed at point d? Treatment: Surgery/Local Control Rotationplasty Brain tumors Neurooncology • Red flags: signs of increased ICP: morning headache, vomiting, papilledema – gait/balance changes, focal deficits – Seizures – Endocrine abnormalities • Associations with neurocutaneous diseases – Neurofibromatosis, Tuberous Sclerosis • Classified by location and histology – Astrocytoma, Medulloblastoma, Ependymoma • Treatment: depends on location and pathology – Multimodality: surgery, radiation, chemo • Late effects: neurocognitive, secondary cancers, endocrinopathies Bone Marrow Transplant Autologous Allogenic • Donor • • • • Collection of own cells High dose chemotherapy Can do 1-4 in a row Indications: – – – – Neuroblastoma Medulloblastoma Relapsed solid tumors Relapsed Hodgkin Lymphoma – Related, unrelated • GVHD • Immune suppression • Indications: – – – – – Relapsed leukemias Severe Idiopathic Aplastic Anemia Sickle Cell Disease, Thalassemia Congenital immune deficiencies Metabolics: Hurler’s syndrome Bone marrow transplant http://media-2.web.britannica.com/eb-media/16/67716-004-C53DF929.jpg What else? • Late effects: – Surgery: limb, bone, organ removal – Organ effects: kidney, liver, cardiac – Growth – Secondary malignancies • Targeted therapies – Limit toxicities – Sequencing • PROFYLE study Hematology A few reminders in brief… 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 Blood smear 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 Sickle Cell Disease • Autosomal recessive – Beta-globin gene mutation • Causes polymerization of hemoglobin leading to effects of decreasing blood flow, tissue hypoxia, leading to acute and chronic damage https://www.thelondonphysician.com/wp-content/uploads/Risk-Factors-for-Sickle-Cell-Anemia_12.jpg Sickle Cell Complications • Acute – – – – – Stroke Chest crisis Vaso occlusive crisis Aplastic crisis Priapism • Chronic – School performance – Vasculopathy – Infections Sickle Cell Treatment • Lifelong condition • Chronic • Education • Counseling for reproduction • Acute crisis – Fluids, Pain control – Broad Spectrum Antibiotics – Straight transfusions vs. Exchange transfusion – Oxygen – – – – Penicillin prophylaxis Vaccinations Hydroxyurea Chronic transfusion program – Transcranial doppler ultrasounds – Multidisciplinary clinic Questions 1) What type of cell is this? MCQ 1) What is the predominant cell type? A) Shistocyte B) Spherocyte C) Pappenheimer bodies D) Ringed Sideroblasts E) Microcytes 2) What is your diagnosis for this type of anemia? MCQ 2) What is your diagnosis for this type of anemia: A) G6PD deficiency B) Thalassemia C) Sickle Cell Disease D) Spherocytosis E) Iron deficiency anemia MCQ 3) Which is most likely to cause hemolytic disease of the newborn: A) Biliary atresia B) G6PD deficiency C) Spherocytosis D) Rh incompatibility E) ABO incompatibility MCQ 4) Presentation of ITP often includes: A) Neutropenia B) Small Platelets on blood smear C) Large platelets on blood smear D) Purpura E) Lymphadenopathy MCQ 5) What is the most commonly used treatment for pediatric ITP? A) Observation B) Corticosteroids C) IVIG D) Splenectomy E) Anti-D MCQ 6) You are seeing a 3 day old baby boy who is bleeding excessively post circumcision. What condition are you most concerned to rule out? A) von Willebrand’s disease B) Platelet function disorder C) Factor VIII Deficiency D) Factor XI Deficiency E) Factor XIII Deficiency MCQ 7) Other than a CBC and smear, which of the following is a work-up for hemolysis? A) B) C) D) Smear, Retics, DAT, LDH, Bilirubin, Haptoglobin Differential, Retics, IAT, LDH, Bilirubin Smear, Retics, IAT, LDH, Bilirubin, Haptoglobin Differential, Retics, DAT, LDH, Bilirubin, Haptoglobin MCQ 8) 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 acetaminophen 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 Question 9) 15 year old male in respiratory distress with first episode of wheeze in ER. Resolved with ventolin and IV methylpred. One week later, radiologist sees mediastinal mass on CXR. Name three differential diagnoses. MCQ 10) The following are causes of microcytic anemia in a child A) Folate deficiency B) B12 deficiency C) Hypothyroidism D) Thalassemia E) Recent blood loss MCQ 11) You are seeing a 11 year old boy with lymphadenopathy and a mediastinal mass. B symptoms refers to: A) Drenching night sweats, poor sleep, weight loss B) Drenching night sweats, unexplained fevers, weight loss C) Poor sleep, unexplained fevers, weight loss D) Unexplained fever, weight loss, bulk disease E) Drenching night sweats, unexplained fevers, bulk disease 12) Is this a leukemia blast or a normal lymphocyte? 13) What is the most common types of childhood cancer: put in order of most common to least common Brain tumours Lymphomas Leukemia Neuroblastoma Sarcoma 14) Question • You are called to the ER to see a 2yr old girl with a large abdominal mass palpable on exam. She is previously well. • She has some respiratory distress. Her uric acid is 150. • She has not been feeding well and is irritable. • DDx: name 3? Thank-you! Good luck everyone