Pediatric Hematology/Oncology: Blood, Body, and Beyond. Geoffrey S. Kannan, PhD, MD Pediatric Neuro-oncology Pediatric Hematology/Oncology
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1 Pediatric Hematology/Oncology: Blood, Body, and Beyond Geoffrey S. Kannan, PhD, MD Pediatric Neuro-oncology Pediatric Hematology/Oncology
2 Disclosures Nothing to disclose Discuss standard of care for common hematologic disorders
3 Objectives The role of the pediatric hematologist/oncologist Discuss common reasons for referral to heme/onc Disorders of red cells Disorders of white cells Disorders of platelets Brain tumors
4 The hematologist s family tree
5 Disorders of Red cells Red cell production problems Red cell destruction problems
6 Evaluation of anemia Anemia Reticulocyte count inappropriately low Reticulocyte count appropriately elevated HYPOCHROMIC/MICROCYTIC - Iron deficiency - Thalassemia - Anemia of chronic disease - Lead poisoning NORMOCHROMIC/NORMOCYTIC - Aplastic anemia - Drugs - Tumor infiltration - Hematologic malignancy - Renal failure - Myelofibrosis - Toxin exposure - Anemia of chronic disease - Infection (TB, HIV, etc.) - Radiation exposure MACROCYTIC - B12 deficiency - Folate deficiency - Drugs - Myelodysplasia BLEEDING HEMOLYSIS IMMUNE - Autoimmine - Drug-induced - Fetal rh incompat. - Alloimmune (transfusion) NON-IMMUNE - Membrane defecit - Enzyme defect - Fragmentation - Hemoglobinopathy - Infection - Hypotonicity
7 Hemoglobin the heart of the erythrocyte
8 Hemoglobin variants Embryo: Gower 1 z2e2 Gower 2 a2e2 Hb Portland I: z2g2 Hb Portland II: z2b2 Fetus: Hb F: a2g2 Adult: Hb A: a2b2 Hb A2: a2d2 Hb F: a2g2 Variants: Hb H: b4 Hb Barts: g4 Hb S: a2b s 2 Hb C: a2b c 2 Hb E: a2b e 2 Hb Fairfax Wood W. G., (1976). Br. Med. Bull. 32, 282
9 The normal H/H
10 Iron deficiency anemia Microcytic, hypochromic, hypoproductive Often detected in asymptomatic patients May have pallor, less energy, pica Presents at any age Iron deficiency due to dietary causes Early introduction of cow s milk in infants Excessive (>24 oz) cow s milk in toddlers
11 Iron Deficiency Anemia Labs: Complete blood count Hemoglobin Hematocrit MCV RDW Red cell count Reticulocyte count Ferritin TIBC Serum Iron
12 Iron deficiency anemia Treatment is with 3-6 mg/kg/day of elemental iron Fer-in-sol Vitron-C Eliminate milk intake (and bottle use, if applicable) Increase iron- and vitamin C-rich foods 3 months of treatment Anemia corrects before iron stores are repleted Limited role for IV iron GI absorption deficiences Correct iron deficiency before investigation for thalassemia
13 The hematologist s family tree
14 Disorders of white cells Neutropenia Lymphadenopathy
15 Neutropenia Age WBC (cells/ul) ANC (cells/ul) Fetus > 30 weeks 7710 ( ,700) Birth 18,100 ( ,000) 11,000 ( ,000) 24 hours 18,900 ( ,000) 11,500 ( ,000) 1 week 12,200 ( ,000) 5500 ( ,000) 1 month 10,800 ( ,500) 3800 ( ) 1 year 11,400 ( ,500) 3500 ( ) 10 years 8100 ( ,500) 4400 ( ) Mild: cells/ul Moderate: cells/ul Severe: < 500 cells/ul
16 Evaluation of neutropenia Functional consequence of neutropenia susceptibility to infection CBC samples a very small percentage of the body s neutrophils Key question how many neutrophils can get to site of infection Bone marrow reserve determines ability to respond to infection Propensity to infection is related to degree and cause of neutropenia Most patients will have adequate bone marrow reserve Also consider the APC (neutrophils + monocytes)
17 Etiologies of neutropenia Low to no risk Chronic benign Ethnic Post-infectious Hypersplenism Moderate risk Transient neonatal neutropenia Post-infectious (decreased marrow reserve) Drug-induced Cyclic Nutritional Immune (antibodymediated) Immune (SLE, CVID) High risk Shwachman-Diamond Kostmann Drug-induced (absent marrow reserve) Chemotherapy Aplastic anemia Marrow infiltration/mds/leuk emia
18 How can we help with neutropenia? Anemia/thrombocytopenia with neutropenia call heme Repeat CBC with differential; ESR/CRP Drugs, temporary bone marrow suppression Medical history bacterial infections (Cyclical? Unusual?) Periodontal disease mouth sores, etc. Family history Bone marrow biopsy/aspirate NK/T cell/immunoglobulin subsets Genetic testing
19 How can you help with neutropenia? We ll manage together Does the child mount a neutrophil response to being sick? Chronic benign neutropenia patients can be treated as other children Management is related to severity and cause of the (bone marrow) problem Most children can be safely vaccinated Limited role for growth factors
20 Lymphadenopathy Most often benign as a result of an inflammatory/reactive process Cause of great concern for families, especially with family history of hematologic malignancy Physical exam to describe extent/character of LN (including testicular exam)
21 Lymphadenopathy signs for concern Systemic symptoms: fever, night sweats, weight loss Supraclavicular lymphadenopathy Persistent generalized lymphadenopathy Fixed non-tender nodes; matted nodes > 1 cm with onset in neonatal period >/= 2 cm that increase in size or do not respond to two weeks of abx Abnormal CXR Abnormal CBC Persistently elevated or rising CRP/ESR
22 Stepwise approach to diagnosis Avoid glucocorticoids Rule out common causes (Strep, cat-scratch, EBV, CMV, TB (if history suggests)) Consider 2 week trial of abx Consider observation if otherwise well No correct time to wait for referral in the absence of other symptoms Consider chest X-ray, ultrasound of nodes Excisional biopsy
23 The hematologist s family tree
24 Immune Thrombocytopenic Purpura (Idiopathic) Thrombocytopenic Purpura Immune ThrombocytoPenia Isolated thrombocytopenia (<100,000) with rest of BM function normal Cause unknown (viral infection, immunologic trigger, environmental)
25 ITP Presentation Petechiae/bruising/bleeding May be wet purpura Child usually appears well lack of systemic symptoms Preceding illness or vaccination (MMR) Very rarely intracranial hemorrhage CBC usually only shows thrombocytopenia Abnormalities in other cell lines should prompt further investigation
26
27 ITP management Bone marrow examination is not required at diagnosis (may be required for treatment failure) No platelet transfusion unless there is life-threatening bleeding Activity restriction Avoid aspirin/ibuprofen Observation
28 ITP management Intravenous immunoglobulin (IVIG) 1 g/kg Anti-D immune globulin (in Rh+, DAT neg patients) Glucocorticoids Second line Rituximab, thrombopoeitin receptor agonists (eltrombopag, romiplostim) Less used therapies Recombinant factor VIIa Vincristine Aminocaproic acid Splenectomy
29 ITP management Treatments are not curative Spontaneous recovery in 3-6 months w/w/o treatment Weekly monitoring of platelet count Recommendations stratified to age/activity level/patient goals First-line therapies usually effective in ~70-80% of patients Response may not be sustained, relapses treated same as initial presentation
30 Chronic ITP Thrombocytopenia persisting beyond 12 months after presentation 10-20% of cases Risk factors Older age Less severe thrombocytopenia at presentation Insidious onset of symptoms Lack of preceding infection or vaccination Evaluate for other causes of thrombocytopenia Infection Bone marrow biopsy Treatment is similar to acute ITP Still expect spontaneous remission (2 years in 30% of children, 5 years in 50%) Consider Rituximab, TPO receptor agonists, immune modulating agents (azathioprine, 6MP, danazol, interferon, cyclosporine, dapsone, MMF, rapamycin, cyclophosphamide)
31 Follow up questions 1. A four-year-old male presents with a 6 week history of persistent anterior cervical lymphadenopathy (3 cm) which has not improved with multiple courses of antibiotics. The infectious disease, ENT, and hematology/oncology teams all agree that a tissue sample is required. Which is the preferred diagnostic procedure for persistent lymphadenopathy? A. Fine needle aspiration B. Excisional biopsy C. Core needle biopsy
32 Follow up questions 2. You have just diagnosed a 15 month (12 kg) female with iron deficiency anemia. Which dose of ferrous sulfate are you going to start? A. 12 mg elemental iron per day B. 24 mg elemental iron per day C. 60 mg elemental iron per day D. 90 mg elemental iron per day
33 Follow up questions 2. Which of the following laboratory values is indicative of iron deficiency anemia? Hemoglobin MCV Ferritin TIBC A Low Low High Low B Low Low Low High C Low High High Low D Low High Low High
34 Follow up questions 4. A 12 month male was incidentally noted to have neutropenia (ANC 400) on a CBC ordered for hemoglobin screening at 9 months. A repeat CBC 2 weeks later was similar he had a normal platelet count, total WBC count, and hemoglobin/hematocrit but a persistently low ANC. He has been thriving and has not had an unusual number of infections. His test for anti-neutrophil antibodies was positive, and he was diagnosed with autoimmune neutropenia of infancy. Which of the following is true? A. At his 12 month visit, he should not receive any vaccines B. At his 12 month visit, he can receive all vaccines except MMR and varicella C. At his 12 month visit, he can receive all routine vaccines
35 Follow up questions 5. Which of the following treatment approaches can be used in children with acute ITP? A. IVIG B. Systemic steroids C. Anti-D immunoglobulin D. Observation E. All of the above
36
37 Brain tumors Two major concerns for pediatricians Increasing head size Persistent headache/vomiting Benign vs metastatic when it comes to pediatric brain tumors Low grade vs high grade CNS is composed of specific cell types Tumors arise from these cells Metastases to the brain are rare in pediatrics
38 1. Glial cells A. Astrocytes B. Oligodendrocytes C. Ependyocytes 2. Neurons A. Medulloblastoma B. Pineoblastoma C. PNET* 3. Choroid Plexus A. Choroid Plexus Papilloma B. Choroid Plexus Carcinoma C. Atypical Choroid Plexus 4. Germ Cells A. Germinoma B. Non-germinomatous 5. Craniopharyngioma
39 Thank you for your attention Geoffrey S. Kannan, PhD, MD Center for Cancer and Blood Disorders 6565 Arlington Blvd, Suite 200 Falls Church, VA Ph: Fax:
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