Cancer Education Day Pediatric Hematology May 13, 2016 Dr. Mohammad Jarrar

Case 1 18 month old boy of middle eastern origin presents to your office for a routine check up. You noticed that the child is pale. Physical exam did not reveal any lymphadenopathy, hepatomegaly, splenomegaly or bruising. You requested a CBC and reticulocyte count.

Case 1-cont. CBC shows: WBC= 7.8 RBC= 3.4 Hb= 90 Plt= 525 MCV=68 MCH=19 RDW= 20 Retic= 1.3 % (Absolute 40) ANC= 2.7 (Rest of WBC differential is normal)

Case 1-cont. Question What is the most likely diagnosis: 1.Alpha thalassemia trait 2.B-Thalassemia trait 3.Iron deficiency anemia 4.Vitamin B 12 deficiency 5.Lead poisoning

Hypochromic Microcytic Anemia Iron deficiency anemia is the most common cause in pediatrics. Other causes include B-thalassemia trait, Alpha- thalassemia trait and lead poisoning. In toddler and young children, iron deficiency is usually due to nutritional causes. No need to look for an underlying cause unless there are clues in the history or it is resistant to oral iron therapy. In adolescents investigating the cause is warranted. Treatment of iron def anemia: 4-6 mg/kg/day of elemental iron X 3 months

Lab Findings DiagnosisB-thalassemia traitA-thalassemia traitIron deficiency HbSlightly low Low (variable) MCVLow MCHLow RDWNormal Increased RBCSlightly high Low Retic countNormal Low FerritinNormal Low Hb electrophoresisIncreased Hb A2NormalDecreased Hb A2

Uncommon Causes Of Anemia With Low Retic Count If isolated (i.e. normal WBC and platelets): Pure red cell aplasia (Diamnod-Blackfan Anemia) in early infancy and TEC (transient erythrocytopenia of childhood) in toddlers and pre-school children If associated with neutropenia and or thromboyctopenia: bone marrow failure syndromes (e.g. Fanconi Anemia) Hint: MCV is usually high in bone marrow failure syndromes; if B12 and folate deficiency are ruled out, think of BMF syndromes.

Case 2 3-year old presents with pallor, jaundice and dark urine. CBC shows: – WBC 5.6, Hb 65, Plt 256. – MCV 85, MCH 25. – WBC diff normal. – Retic count = 15%

Question Differential diagnosis includes all of the following except: – B-Thalassemia Intermedia – Hereditary Spherocytosis – Autoimmune hemolytic anemia – Iron deficiency anemia – Pyruvate Kinase deficiency

Hemolytic anemia Low Hb & increased retic count, increased bilirubin and increased LDH. If intravascular hemolysis also decreased haptoglobin. Either autoimmune (AIHA) or due to an inherited RBC disorder: – RBC membrane disorder; e.g. Hereditary Spherocytosis – RBC enzyme disorder; e.g. G6PD def & Pyruvate kinase def. – Hemoglobinopathy; e.g. Thalassemia & Sickle cell disease Treatment involves PRBC transfusion & folic acid supplementation in inherited disorders while steroids are indicated for AIHA.

Sickle Cell Disease Can be due to Hb SS or Hb SC or Hb S/B- thalassemia. Most common complications include veno- oclussive disease (pain crisis) and infections. Treatment of VOD involves hydration and analgesics including morphine. Fever in these patient require blood culture and IV antibiotic (e.g. ceftriaxone) for at least 48 hrs till culture results are back.

Case 3 18-month old boy presents with temp of 40 C. He has no respiratory or GI symptoms. UA & C/S are negative. CBC and Blood culture obtained. He has no history of recurrent or serious infections. His growth is normal. No organomegaly or lymphadenopathy on exam. CBC showed: – WBC 4.5, Hb 120, Plt 321. – ANC (absolute neutrophil count) = 0.1 – Rest of WBC differential is normal. He was admitted and started on IV ceftriaxone pending culture results. CBC was repeated twice a week for 3 weeks. ANC remained at 0.1

Question The most likely etiology of neutropenia in this case: – Severe congenital neutropenia (SCN-Kostmann’s syndrome) – Acute lymphoblastic leukemia (ALL) – Benign childhood neutropenia – Aplastic anemia – Cyclic neutropenia

Benign Childhood Neutropenia A condition that occurs between age of 6 months and 5 years. Etiology is autoimmune (anti neutrophil antibodies) Bone marrow is able to produce neutrophils normally and therefore ability to fight infections is not impaired. Cultures and IV antibiotics are indicated for the first few febrile episodes till diagnosis is ascertained.

Cyclic Neutropenia These patients have a dip in the neutrophil count in a cyclic pattern (typically every 3 weeks). They usually have fever, malaise, gingivitis and mouth ulcers during the ANC nadir (3-6 days). Depending on the severity of the symptoms, treatment with G-CSF (Neupogen) may be indicated. It is usually caused by mutation in ELANE gene.

Severe Congenital Neutropenia (SCN) These patient present in early infancy with recurrent severe bacterial infections. There is no cyclic pattern. BM shows decreased myeloid precursors and or early maturation arrest. It is caused by ELANE or some times HOX2 gene mutations and can predispose to AML. Unless treated with G-CSF or bone marrow transplant, it is usually fatal by age of 2 years.

Case 4 5-year old girl presents with 2-3 days history of increasing bruising on various parts of the body. She also had epistaxis couple of times. No recent fevers. No organomegaly or lymphadenopathy on exam. No joint swelling. CBC shows: – WBC 7.8, Hb 115, Plt 5. – ANC 3.5. Rest of WBC differential is normal. – PTT 32. INR 1.

Question Which of the following is not usually indicated: – Platelet transfusion – IVIG (intravenous immunoglobulins) – Oral prednisone – Anti D antibodies (WinRo) – Hospital admission for observation

Immune Thrombocytopenic Purpura (ITP) Caused by the production of auto antibodies against platelet antigen. Because antibodies are directed against common platelet antigen, transfused platelets will be destroyed as well. Bone marrow biopsy is not usually needed if Hb, WBC, ANC are normal and exam does not show enlarged liver or spleen or lymphadenopathy.

ITP-cont % of cases of ITP in children resolve by 6 months from diagnosis (Acute ITP). Few more resolve between 1-12 months from diagnosis (Acute persistent ITP) % become chronic. Treatment options for symptomatic acute ITP in children include IVIG, WinRo and short course of steroids (either 4 mg/kg/day X 4 days or 2 mg/kg/day X 1 week then taper of 2 more weeks). Treatment options for chronic ITP: Rituximab, Splenectomy, Immunosuppressive drugs and thrombopoietin agonists (e.g. Romiplostim).

Neonatal Thrombocytopenia Can be secondary to transient bone marrow suppression due to perinatal asphyxia, placental insufficiency or infections. Treatment if needed: Platelet transfusion. Can be secondary to maternal auto antibodies; typically resolves in 1-4 weeks (clue mother has low platelets due to ITP). Treatment: IVIG. Can be due to alloimmune thrombocytopenia (severe, in first 72 hrs., well-appearing baby). Caused by the rare situation when mom is PA1 negative and baby is PA1 positive. Treatment with PA1 negative irradiated platelets and if not available platelet transfusion+IVIG.

Acute Lymphoblastic Leukemia (ALL) ALL is the most common cancer in children (25-28% of all cancer cases). Peak age of diagnosis is 2-3 yrs. Commonly of B-cell origin. Common presenting features include: prolonged fever without focus, pallor, ecchymosis, hepato- splenomegaly, lymphadenopathy, bone and joint pain. Bi or pancytopenia. WBC may be low or high. Treatment is with chemotherapy for 2-3 years. Cure rates in children are in the range of 80-95%.