Leukocytosis and Leukemias in pediatric pt (Brandau) Flashcards
There is prominent periorbital
Swelling and a vesiculopustular
rash on the face and trunk
PE unremarkable
no LAD
splenic tip palpable
liver edge descended 5 cm below costal margin
WBC–> 73,200 (very high)
52% blasts
atypical lymphocytes
platelets 973,000 high!
lactate dehydrogenase high (lots of cell turnover)
CSF - blasts
Transient myeloproliferative disorder with trisomy 21 mosaicism
some cells have trisomy 21
tzanck test?
herpes infection
in herpetic infections what is going on with the WBC count and predominantly what cell type?
WBC count tends to be marginally elevated and predominated by lymphocytes later in the course of the illness
what is leukemoid reaction
defined as the elevation of normal leukocytes to counts greater than 50,000 cells/μL
must be distinguished from CML
decreased margination of leukoctyes
Exercise
Catecholamines
neutrophilic leukoctyosis
Acute bacterial infections, especially those caused by pyogenic organism; sterile inflammation caused by, for example, tissue necrosis (myocardial infarction, burns)
eosinophilic leukocytosis
Allergic disorders such as asthma, hay fever;
certain skin diseases (e.g., pemphigus, dermatitis herpetiformis);
parasitic infestations; drug reactions; certain malignancies (e.g., Hodgkin and some non- Hodgkin lymphomas); collagen vascular disorders and some vasculitides; atheroembolic disease (transient)
basophilic leukocytosis
rare
Myleoproliferative disorder
monocytosis
Chronic infections (e.g., tuberculosis), bacterial endocarditis, rickettsiosis, and malaria; collagen vascular diseases (e.g., systemic lupus erythematosus); inflammatory bowel diseases (e.g., ulcerative colitis)
lymphocytosis
Accompanies monocytosis in many disorders associated with chronic immunological stimulation (e.g., tuberculosis, brucellosis); viral infections (e.g., hepatitis A, cytomegalovirus, Epstein-Barr virus); Bordetella pertussis infection
high LDH?
The elevated lactate dehydrogenase level also suggests the rapid proliferation of cells as seen in a neoplastic disorder
leukemic hiatus?
The peripheral smear did not show a morphological progression from blasts to mature forms. This observation is called the leukemic hiatus and suggests the blasts are autonomous suggesting a neoplastic process rather than an response to inflammation which would show the progression of elements of the granulocytic series
infant myeloid leukemia is associated with propensity to extramedullary disease in the what
skin and CNS
extremely high platelets are consistent with what
transient myeloproliferative disorder
Transient myeloproliferative disorder originally thought to only occur in patients with trisomy 21
Clinically appears identical to acute myeloid or acute megakaryocytic leukemia
The only distinguishing factor is the spontaneous resolution of all the hematological abnormalities, usually by 12 weeks of age
The skins rashes of true infant leukemia have been described as only nodular
true leukemia–> accumulation of leukemic cells in the skin!
CD34
stem cell associated antigen
CD45
pan-leukocyte antigen
CD41
megakaryocyte associated antigen
CD33
a myeloid antigen
CD117
a early myeloid antigen
median age of diagnosis of transient myeloproliferative disorder
7days
A 3 y/o boy presents to the clinic with pallor, bruising and intermittent fever for the past 3 weeks.
Physical exam reveals no cause for his fever or pallor.
hemoglobin 6.8 low
WBC 1800 low
2% neuts 98% lymphocytes
bone marrow aspirate–> myeloblasts
leukemia!
the initial presentation was pancytopenia that mimicked aplastic anemia
50% of children with ALL and 20-30% with AML present with WBC
A 13 y/o girl presented with malaise and intermittent fever for 1 week. She had bilateral 2-3 cm nontender anterior cervical nodes and splenomegaly. EBV titers were equivocally high. A presumptive diagnosis of mononucleosis was made and laboratory studies were drawn.
hemoglobin 10.5 low WBC 135,000 high platelets 40,000 low LDH 4500 high Uric acid 11 mg very high (cell turnover)
24hrs later
WBC differential- 95% blasts
lymphoblastic leukemia
Flow cytometry is positive for CD2 and
CD7 and identifies the T-cell origin of this acute lymphoblastic leukemia subtype
Case 2 is typical of high risk ALL
High Risk ALL presents with rapid onset, high tumor burden due to marked leukocytosis with lymphadenopathy and/or hepatosplenomegaly and mediastinal disease
About 20 % of patients with WBC > 50,000 will have this presentation
Sometimes the presentation is thought to be mononucleosis
A 5 y/o girl presents with intermittent bilateral leg and wrist pain and fever as high as 103° F of 3 weeks duration. Physical exam is normal with the exception of the limp.
hemoglobin 10.9 low MCV 77 WBC 4100 Diff- 21% neuts 79% mature lymphocytes platelets 190,000 ESR 35 (elevated sed rate)
A diagnosis of juvenile rheumatoid arthritis is made and she is started on aspirin therapy. There is improvement over the next 2 days but then the pain worsens and she refuses to bear weight. A 2 week trial of naproxen provided no relief, Images of the wrists and legs were normal. Further testing was done.
LDH- 1200
uric acid 6.9
bone marrow aspirate -pre b cell lymphoblasts
Leukemia
The presentation with bone pain and fever occurs more commonly in the younger child
Fever is secondary to cytokine release from lymphoblasts but could also indicate a life threatening infection due to neutropenia
The bone pain is secondary to marrow expansion
These patients will frequently have normal range WBC
Elevated LDH and uric acid levels suggest a malignant process
most common pediatric cancer
ALL -acute lymphoblastic leukemia
accounting for 25% of all cancers in children < 15 years of age
peak incidence of ALL
2-5 yrs of age
more common in males
what are the genetic syndromes associated with leukemias
Down syndrome-15-20 fold increase
Fanconi syndrome
Klinefelter syndrome
Shwachman-Diamond syndrome
WBC greater than 200,000 run the risk of what
microemboli to brain or lungs suggesting a stroke or PE
more commonly seen in AML
Respiratory distress, cough and facial edema suggest what?
superior vena cava syndrome due to mediastinal compresion of the airway or major vessels in ALL
how does AML sometimes present that is life threatening
DIC
what is in the differential diagnosis for leukemia non malignant conditiions
Aplastic anemia Juvenile rheumatoid arthritis Viral infection —Infectious mononucleosis —Cytomegalovirus Autoimmune thrombocytopenic purpura Autoimmune pancytopenia/Evan syndrome Sepsis Leukemoid reaction —Pertussis —Acute infectious lymphocytosis Langerhans cell histiocytosis Osteomyelitis Hypersplenism Megaloblastic anemia
what is in the differential diagnosis of leukemia (malignancies)
Neuroblastoma
Retinoblastoma
Rhabdomyosarcoma
how is the diagnosis of leukemia made definitively in a child
not JUST peripheral smear and WBC
bone marrow samples for morphology
flow cytometry and cytogenetics are necessary for diagnosis and to determine appropriate therapy
CSF is obtained to verify CNS leukemia is not present-this study must be done under optimal conditions (sedation, ultrasound guidance) to prevent a traumatic tap that introduce leukemic cells into the CNS
what is the survival rate of children with ALL and AML
80-90% of children with ALL and 50% with AML are cured
what are the lower risk factors for leukemia
age 1-9
low to normal WBC at diagnosis
hyperdiploidy (>50 chromosomes/cell)
higher risk factors for leukemia
age>10,
infants with high WBC and
those with mature B cell leukemia
hypodiploidy
t9;22
following induction of ALL, therapy for ALL lasts how long..
when are CNS prophylactics given ?
2-3 years
2 for girls
3 for boys
therapy in the first 6-12 months are more aggressive
Patients with bad prognostic indicators receive more aggressive intensified therapy
CNS prophylactics provided in all treatment regiments-mostly intrathecal chemotherapy
general therapeutic concepts for AML
dramatically different than ALL
extremely intensive chemo for about 1 year
if available Bone marrow transplant from antigen identical sibling (found only 20% of time) is optimal
what are the morbidities of leukemia treatment
infection!!!
management of fever is critical
Constant immunosuppressive therapy depresses lymphocyte function during therapy and for 3-12 months after therapy is completed
Live virus vaccines are CONTRINDICATED
what are the tumor lysis syndrome characteristics?
uric acid
renal function
potassium
phosphate
● Release of intracellular uric acid, potassium, and phosphate from rapid
turnover of malignant cells
● Usually precipitated by chemotherapy, but can occur before
● Most often with high tumor burden or T-cell leukemia
● Components of tumor lysis: —Hyperuricemia —Renal precipitation can progress to acute renal failure —Hyperkalemia —Can progress to fatal arrhythmia —Hyperphosphatemia/Hypocalcemia —Increased phosphate can cause hypocalcemia and renal precipitation can progress to renal failure
how do you manage tumor lysis syndromes
Hydration and diuresis!!
supplemental potassium
treat hyperkalemia emergently if necessary
decrease uric acid with allopurinol or urate oxidase
consider oral phosphate binders
initiate dialysis for acute renal failure
transfer urgently to a pediatric oncology tertiary care center
