Peds Heme Flashcards
Lymphoid malignancies
Lymphoma is the most common subtype of the hematologic malignancies and is heralded by LAD
3rd most common malignancy in childhood
Main categories: Non-Hodgkin
Hodgkin lymphoma
Epidemiology and risk factors for lymphoid malignancies
NHL occurs more in men, incidence increases with age
Hodgkin lymphoma has a bimodal age distribution (15-45 yrs and after age 55 yrs)
Mucosa-associated lymphoid tissue (MALT) lymphoma is caused by an underlying infection of H. pylori
Other infections: EBV, HIV, HTLV-1, Hep B, Hep C
Evaluation and dx of lymphoid malignancies- hx
Fever
Night Sweats
Weight loss
B sx
Evaluation and dx of lymphoid malignancies- PE
Number of sites
Size
Consistency
Persistent or enlarging LAD
Evaluation and dx of lymphoid malignancies- labs
CXR CBC with differential ESR CMP Bx -Fine needle aspiration: no LAD architecture -Core bx/excisional bx: LN architecture Biopsy specimen Secondary testing for initial staging Total body PET/CT scan and iliac crest bone marrow bx to complete staging
Biopsy specimen for lymphoid malignancies
Histopathologic- test you must begin with if you suspect lymphoma
Cytogenic
Fluorescence in situ hybridization (FISH)
Immunophenotypic analysis
Gene expression profiling
Classification, staging, and prognosis of malignant lymphoma
NHL has >20 subtypes
-Cell surface antigen expression
-B cell (85%), T cell (13%), or NK (2%) immunophenotype
Standard uptake value
-Indicator of glucose uptake and metabolism
3 prognostic groups
-Indolent, aggressive, and highly agressive
Follicular lymphoma
20% of all NHL cases (70% of indolent) Small cells (CD10, 19, 20, 22) Translocation t(14:18) that causes an overexpression of the BCL2 oncogene
Tx of follicular lymphoma
Local-Rituximab and involved-field radiation therapy
Systemic- riuximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone
Hateopoietic stem cell transplant- younger pts
MALT
Originates in B cells in GI tissue
CD 20 surface antigen
Usually caused by chronic inflammation of an ulcer bed from H. pylori
-Complete remissions achieved in 70% of pts with antimicrobial therapy and concomitant PPI tx
Localized therapy or chemo
Diffuse Large B-Cell Lymphoma (DLBCL)
MC form of lymphoma (30%) Usually presents with advanced dz Most aggressive forms -Burkitt lymphoma -Lymphoblastic lymphoma
Tx for diffuse large b-cell lymphoma (DLBCL)
Standard therapy: R-CHOP
High response rates (80%)
Curative in nearly 50% of pts
What are the types of indolent lymphomas?
Follicular lymphoma
MALT
Types of aggressive lymphomas
Diffuse large b-cell lymphoma (DLBCL)
Mantle cell lymphoma
Cutaneous t-cell NHL
Hodgkin lymphoma
Mantle cell lymphoma
Rare form of NHL
Most present with advanced dz
Cutaneous T-cell NHL
CD4 cells infiltrate skin and cause rash
-Raised plaques, diffuse skin erythema, skin ulcers
Organ infiltration, immunodeficiency, recurrent bacterial infections
Looks like dermatitis if you don’t know better
Tx of cutaneous T-cell NHL
Stage I and II (skin only)- median survival >20 yrs
Topical glucocorticoids
+/- retinoids/PUVA/interferon alfa
What are the four classic histologic subtypes?
Nodular sclerosing
Mixed cellularity
Lymphocyte predominant
Lymphocyte depleted
What is seen under the microscope in Hodgkin lymphoma?
Reed-Sternberg cells that have an owl-eyed appearance
What can cause a mediastinal mass in the anterior mediastinum?
Thymoma
Teratoma
Thyroid cancer
Parathyroid cancer
Presentation of Hodgkin lymphoma
Palpable, firm lymph nodes, +/- B sx
Splenomegaly- 30%
Hepatomegaly- 5%
Tx of Hodgkin lymphoma
Stage I and II dz- radiation +/- chemo (short course)
Stage III and IV dz- full chemo
-Doxyrubicin, bleomycin, vinblastine, decarbazine
-Rituximab is added in CD20-pos dz
Chemo toxicities in Hodgkin lymphoma
Bleomycin-induced pneumonitis
Doxorubicin-induced cardiac dysfunction
Vincristine-induced neuropathy
Prognosis of NHL
Related to stage
3-yr survival rates 70-90%
Prognosis of Hodkin lymphom
90% 5-yr survival rate
Genetic factors of leukemia
+/- chromosomal translocations
Reports of familial leukemia
Predisposing constitutional genotypes to leukemia
Down syndrome
Fanconi anemia
Neurofibromatosis 1
Environmental factors to leukemia
Ionizing radiation
Certain chemo agents
S/sx of leukemia
Bone marrow failure Specific tissue infiltration -LN, liver, spleen, brain, bone, skin, gingiva, testes Fever Pallor Petechiae Ecchymoses Lethargy Malaise Anorexia Bone or joint pain
Chronic myelogenous leukemia
Myeloproliferative disorder
Caused by the Philadelphia chromosome
-Translocation of chromosomes 9 and 22
-Fusion gene called BCR-ABL
S/sx of chronic myelogenous leukemia
Constiutional sx
Splenomegaly
Lab findings of chronic myelogenous leukemia
Granulocytic leukocytosis usually >50K
Peripheral blood
-Reverse transcriptase polymerase chain reaction
-Fluorescence in situ hybridization (FISH)
What chronic myelogenous leukemia looks like under the microscope
Lots of different types- sign of rushed proliferation
Tx of chronic myelogenous leukemia
Tyrosine-kinase inhibitors (TKI) -Imatinib (1st gen) -Improved 8-yr survival from 50% to 87% -QT prolongation Allogenic hematopoietic stem cell transplantation (rare)
Chronic lymphocytic leukemia
B-cell CLL is MC form of adult leukemia Median age of 70 yrs Often asymptomatic at presentation More aggressive in younger pts No definitive causative factors Dx by flow cytometry (CD5 and CD23) Prognosis determined by gene mutation status -Worse if chromosome 17p deletion found
What can be seen under the microscope in CLL?
Some nl mixed with the leukocytes
SMUDGE cells
They are pathognomonic for CLL
Components of concomitant CLL
Autoimmune dz
Recurrent infections
Secondary malignancies
Autoimmune dz in concomitant CLL
ITP
Hemolytic anemia
Recurrent infections in CLL
Sinus
Pulmonary
+/- low serum IgG levels requiring replacement therapy
Tx of CLL
Goal is usually palliation
Combo therapy
-Rituximab and multiagent chemo
–Usually with Fludarabine and cyclosphamide
Allogenic HSCT is reserved for younger pts with aggressive symptomatic dz
Acute Myelogenous Leukemia
An acquired, malignant HSC disorder that may manifest de novo from preceding MDS (myelodysplastic syndromes) or MPN (myeloproliferative neoplasms)
- > 20% myeloblasts in peripheral blood or bone marrow
- RAPID blast division- STAT consult
Findings of acute myelogenous leukemia
Anemia
Neutropenia
Thrombocytopenia
Leukapharesis is a temporizing measure
What is the mean age at presentation of acute myelogenous leukemia?
67, but can occur in kids
What can be seen in microscopy in acute myelogenous leukemia
Auer rod
Lab findings of acute myelogenous leukemia
Pancytopenia or leukocytosis with circulating blasts
Auer rods
DIC if promyelocytic leukemia
Tx of acute myelogenous leukemia
Induction chemo
Acute lymphoblastic leukemia
Seen more commonly in childhood
-75% of all childhood leukemias
-Incidence peaks at 2-5 yrs (boys>girls)
>25% lymphoblasts in blood or bone marrow
Frequently involves the CNS requiring staging by CSF and prophylaxis with intrathecal chemo
Predictors of poor outcome for acute lymphoblastic leukemia
Advanced age B-cell vs T-cell dz More than 30K blasts at dx Poor-risk cytogenetics Philidelphia chromosome also portends poor prognosis but now offers an attractive target to the TKI dasatinib (2nd gen)
Tx of acute lymphoblastic leukemia
Chemo with L-asparaginase
-Induction, Intensification, 2 yrs of maintenance therapy
-Prognosis is better in children than adults
–80% cure rate for childhood ALL
–30-40% of adult ALL cured by chemo
Hematopoietic stem cell transplantation
Primary hemostasis
Injured vessel wall
Von Willebrand factor
Platelets
Hx with bleeding disorders
FHx of bleeding
Meds-NSAIDs
PE of bleeding disorders
Petechiae, ecchymoses, telangiectasias
Splenomegaly
Liver dz- jaundice, spider angioma
Mechanism tested with PT
Extrinsic and common pathway
Nl values of PT
<12 sec beyond neonate
12-18 sec term neonate
Disorder of PT
Defect in vit K-dependent factors Hemorrhagic dz of newborn Malabsorption Liver dz DIC Oral anticoags Ingestion of rat poison
aPTT mechanism tested
Intrinsic and common pathway
aPTT nl values
25-40 sec beyond neonate
70 sec in term neonate
Disorders of aPTT
Hemophilia vWB diz Heparin DEC Deficient factors 12 and 11 Lupus anticoagulant
Thrombin time- mechanism tested
Fibrinogen to fibrin conversion
Nl thrombin time values
10-15 sec beyond neonate
12-17 sec in term neonate
Thrombin time disorders
Fibrin split products DIC Hypofibrinogemia Heparin Uremia
Bleeding time mechanism tested
Hemostasis, capillary and platelet function
Nl values of bleeding time
3-7 min beyond neonate
Disorders of bleeding time
Platelet dysfunction
Thrombocytopenia
vWB dz
Aspirin
Platelet count mechanism tested
Platelet number
Nl platelet values
150K-450K/mL
Platelet disorders
Thombocytopenia differential dx
PFA mechanism tested
Closure time
Blood smear mechanism tested
Platelet number and size
RBC morphology
Blood smear disorders detected
Large platelets suggest peripheral destruction
Fragmented, bizarre RBC morphology suggests microangiopathic process (e.g, hemolytic uremic syndrome, hemangioma, DIC)
X-linked recessive bleeding disorders
Hemophilia A- factor VIII deficiency (1 in 5000)
Hemophilia B- factor IX deficiency (1 in 25K)
Clinical manifestations of X-linked recessive bleeding disorders
Spontaneous bleeding episodes
Hemarthrosis
-Ankle, knee, elbow
Lab findings of hemophilia A and B
Prolongation of aPTT
Nl PT
Tx of hemophilia A and B
Desmopressin (DDAVP)- Hemophilia A (mild)
Factor concentrates- Hemophilia A or B
Von Willebrand dz
The MC inherited bleeding disorder (autosomal dominant) Type I (80%)- quantitative
Clinical manifestations of von Willebrand dz
Mucocutaneous bleeding
Nosebleeds, easy bruising, bleeding gums
Labs for vWB disease
vWF antigen measured functionally in the ristocetin cofactor assay
Tx of vWB dz
Desmopressin
vWF-containing concentrate
Vaccine
DIC
Abnormal coagulation and fibrinolysis
Usually associated with shock/sepsis
Coagulation factors are consumed as are anticoagulant proteins
Lab findings of DIC
Decreased platelets and fibrinogen
Prolonged PT, aPTT
Elevated D-dimer
Tx of DIC
Treat the disorder including DIC first
Support the pt (hypoxia, acidosis, factors, platelets, etc)
