leukocyte disorders pt 1 Flashcards
A procedure in which a hole is drilled into the bone to allow for aspiration of the cellular contents of the bone marrow
Bone Marrow Aspiration and Biopsy
indications for bone marrow aspiration and biopsy
- diagnosis, staging, and therapeutic monitoring of bone marrow disorders
- unexplained elevation or decrease in any hematologic cell line
- i.e anemia, leukocytosis - lymphoma, solid tumor
- evaluation of iron metabolism & stores when routine testing is inadequate
- fever of unknown origin
- unexplained splenomegaly
CI of bone
marrow aspiration/biopsy
-
severe bleeding disorders
- hemophilia, Disseminated Intravascular Coagulation (DIC) - thrombocytopenia is not a CI
consider platelet transfusion if plt count <20,000 prior to procedure
testings for bone marrow aspiration/biopsy
histology
cytogenetic testing
flow-cytometry
for a bone marrow aspiration/biopsy, you must avoid:
any area with signs of infection, injury or excessive overlying adipose tissue
what is the preferred site for bone marrow aspiration and biopsy
posterior iliac crest
- No major blood vessels or organs
- Easily accessible and less risky site
what site do you use for aspiration only
- tibia (under general anesthesia)
- MC site used in infants < 12 m - sternum (between 2nd and 3rd ICS)
- reserved for only >12 yrs old and morbidly obese
a malignant disorder often as a result of chromosomal translocation
Acute Lymphoblastic Leukemia (ALL)
lymphoblast cell mutation results in: (4)
- rapid cell proliferation/self-renewal
- reduction in normal cell proliferation
- block in cell differentiation
- increase resistance in cell apoptosis
Accumulation of abnormal lymphoblasts in the BM causes what?
-
suppress normal hematopoiesis
- anemia
- thrombocytopenia
- neutropenia -
accumulate in other organs
- meninges, gonads, thymus, liver, spleen, and lymph nodes
What environmental agents are linked to increased risk
of ALL
- In utero radiation exposure
- Chemicals - pre/postnatal exposure (questionable)
- pesticides, tobacco, alcohol, nitrites, chemotherapy - High birth weight - increased insulin-like growth factor (IGF-1)
- Lack of exposure to infections in the first few weeks/months of life
ALL is MC in what demographic?
children
males
White
Most deaths from ALL occur in ?
adults
MC presenting symptom of ALL
fever
s/s of ALL related to bone marrow infiltration
-
neutropenia
- secondary infections most often seen with ANC < 500/µL; severe infection with < 100/µL -
anemia
- fatigue, dizziness, palpitations, exertional dyspnea, pallor -
thrombocytopenia
- petechiae, ecchymosis, occult and gross blood loss
s/s of ALL Related to organ infiltration
- lymphadenopathy
- bone pain
- early satiety (splenomegaly)
- mediastinal mass
- chest pain, dysphagia, or dyspnea
- swelling of the neck, face, and upper limbs - painless testicular swelling/mass
s/s of leukostasis from ALL leads to what?
- inadequate circulation
- HA, altered mental status, blurred vision, dyspnea, priapism
- increased risk of intracranial hemorrhage - risk persists for at least 1 week after reduction of WBC
what is the initial work up for ALL
- CBC
- decreased RBC, platelet and neutrophils
- WBC may be normal, high or low - Complete Metabolic Panel (CMP) - kidney/liver function
- Blood Cultures - if signs of infection
- Initial Imaging
- CXR - r/o pneumonia as a source of infection, assess for signs of mediastinal mass
- CT/MRI Brain (without contrast) - if neurologic s/s are present or leukostasis is suspected
what additional work ups could you do for ALL
- Peripheral smear - pancytopenia with circulating lymphoblasts
- LDH - ↑ due to tissue destruction
- CT chest w contrast - assess lymphadenopathy, further assess mediastinal mass
- CSF Analysis
- (+) lymphoblast cells - with spinal infiltration of dz. -
Flow-cytometry
- ALL cells will express CD19 antigens and (+/-) CD10 antigens
- A lack of mature T-cell markers most of the time -
Bone Marrow Aspiration & Biopsy
- definitive diagnosis - > 20% lymphoblasts (WHO classification)
management for ALL in EVERY pt
- Refer to hematology/oncology
- Screen and treat for active infections in febrile patients
- ALL treatment begins with
- induction chemotherapy
- CNS prophylaxis followed by
- post-remission therapy with or without stem cell transplantation
pancytopenia with circulating lymphoblasts on peripheral blood smear
is the hallmark of
ALL
what is Induction Chemotherapy and its goal?
- Multi-drug chemotherapy over the course of 4-6 weeks
- Initiated in the hospital
- Complete remission achieved at 65-85%
- Goal: remission induction
why is CNS prophylaxis vital for ALL
Intrathecal therapy is vital during all stages to prevent CNS recurrence
what is the ALL management of post-remission therapy for young pts with tolerable effects of chemo
- Consolidation/Intensification therapy
- readministration of induction regimen or other high dose chemotherapeutic agents after normal hematopoiesis is restored
- Duration: usually for 4-8 months
- Goal: increases time of remission
— Small numbers of leukemic lymphoblasts will remain in the bone marrow after induction therapy
— Recurrence and therapeutic resistance can occur if therapy isn’t continued - Maintenance/Continuation Therapy
- A less intensive regimen weekly and/or daily for 2-3 years
what is the ALL management of post-remission therapy for older patient or unable to tolerate SE of chemo
- Allogeneic Stem Cell Transplantation
- Stem cells are collected from a matching donor
- Patient receives intensive chemotherapy prior to transplant to ensure destruction of as many cancer cells as possible.
what is the tx for leukostasis from ALL
- prophylaxis for tumor lysis syndrome
- IV hydration
- hypouricemic agents - emergent chemotherapy
- leukapheresis
the cure rate of ALL is higher in what demographic of pts
children - 90%
adults - 50%
relapse of ALL is MC when
within first 2 years
if a pt presented with:
1. No chromosomal abnormalities
2. Age younger than 39 years
3. White blood cell (WBC) count of < than 30,000/μL
4. Complete remission within 4 weeks
what is their prognosis
Good prognostic criteria
if a pt that has ALL presented with:
1. Chromosomal abnormalities
2. Age older than 60 years
3. Precursor B-cell WBCs with WBC count > than 100,000/μL
4. Failure to achieve complete remission within 4 weeks
what is their prognosis
bad prognostic criteria
a malignant lymphoid neoplasm that is characterized by the accumulation of long-lived, functionally incompetent, small mature B cells
Chronic Lymphocytic Leukemia (CLL)
- dysfunction in the maturation of the B-cell
- results in B-cells that are unable to respond to immunologic stimulation
What is the MC form of leukemia in the US
Chronic Lymphocytic Leukemia (CLL)
CLL is MC in what demographic
elderly
90% occur after age 50; median age of onset is 72 y/o
white
male
clinical presentation of CLL
- slow onset - may be found incidentally
- lymphadenopathy - MC
- recurrent infections (pneumonia, HSV, HZV)
- hepatosplenomegaly (HSM) - upper abdominal discomfort/fullness and early satiety
- s/s of anemia/thrombocytopenia - found later in course of disease
isolated absolute lymphocytosis is the hallmark for what malignancy?
CLL
persists for > 3 months
if a peripheral smear showed (+) smudge cells and prolymphocytes, what type of malignancy do they have?
CLL
what is the work up for CLL
- CBC
- peripheral smear - smudge cells + prolymphocytes
- CMP
- Peripheral blood via flow cytometry - confirms diagnosis
- confirms the presence of various abnormal B-lymphocyte surface antigens - Bone marrow aspiration/biopsy -
not always required to make diagnosis
what is the Staging CLL: Revised Rai staging system
- Low risk
- Stage 0: Lymphocytosis aline
— lymphocyte > 15000/μL, and > 40% lymphocytes in the bone marrow - Intermediate risk
- Stage I: Lymphocytosis - enlarged node(s)
- Stage II: splenomegaly or hepatomegaly or both - High risk
- Stage III: Anemia (hemoglobin level < 11.0 g/dL) - Stage IV: Thrombocytopenia (platelets < 100,000/μL)
if a pt is considered at the “low risk” stage (Asx) of CLL, what is their management?
observation
indication of tx for CLL is ?
symptomatic disease!!
1. Initial “high risk” stage
2. Progressive symptomatic “intermediate risk” staging
- worsening fatigue, symptomatic lymphadenopathy, anemia, or thrombocytopenia
otherwise, just observation!!
tx/management for CLL (symptomatic)
- multidrug chemotherapy
- Growth factors - utilized to decrease duration of neutropenia following chemotherapy - Allogeneic stem cell transplant
- reserved for patients who are not controlled with standard therapies - Splenectomy - for refractory splenomegaly and pancytopenia
complications with CLL
- Obstructive lymphadenopathy - compressing on internal organs
-
Transformation into aggressive large cell lymphoma (Richter Syndrome)
- weight loss, fevers, night sweats, muscle wasting, increasing hepatosplenomegaly and lymphadenopathy - Autoimmune hemolytic anemia or thrombocytopenia
what makes a good prognosis with CLL
- Low risk stage - average survival 10-15 years
- Intermediate/high risk
- 2 year survival is > 90%,
- 5-year survival is > 70%
A malignant disease of the bone marrow resulting from an arrest in the early development of myeloid precursors
Acute Myelogenous Leukemia (AML)
pathophys of Acute Myelogenous Leukemia (AML)
- rapid proliferation of myeloblast without differentiation
- resistant to apoptosis
- accumulation of myeloblasts in marrow, blood, spleen, liver
- reduction of normal hematopoiesis
Myelodysplastic Syndrome (MDS) is the MC risk factor for what malignancy?
Acute Myelogenous Leukemia (AML)
it is a progressive cytopenias that occur over months to years
causes of acute myelogenous leukemia (AML)
- myelodysplastic syndrome (MDS) (MC risk factor)
- congenital/genetic disorders
- Trisomy 21
- Bloom’s syndrome
- Fanconi anemia - environmental exposures
- radiation, smoking, benzene⁴, soot, creosote, inks, dyes, tanning solution, coal dust - Chemotherapeutic agents
what is the epidemiology of acute myelogenous leukemia (AML)
~70y/o
white
males
developed countries
if a pt is experiencing bone marrow failure, what might be the presentation
amenia, neutropenia, thrombocytopenia
if a peripheral smear showed auer rod, what is that indicative of ?
acute myelogenous leukemia (AML)
work up for AML
- CBC - decreased RBC, platelet and neutrophils
- WBC may be normal, high or low - Peripheral smear
- predominantly blasts seen
- Auer rod - eosinophilic needle-like inclusion in the cytoplasm of myeloblasts (Confirmation) - CMP
- LDH
- BM - hypercellular, predominant blasts
- Flow Cytometry
- imaging
- LP - sx only
work up for AML
- CBC
- decreased RBC, platelet and neutrophils
- WBC may be normal, high or low - Peripheral smear
- Auer rod - CMP
- Blood Cultures - if signs of infection
- Lactic dehydrogenase level (LDH) -↑ with tissue destruction
- Bone Marrow - hypercellular, predominant blasts
- Flow Cytometry
- imaging studies
- brain MRI/CT - indicate for neurologic symptoms (leukostasis) - lumbar puncture - for sx pt ONLY
- to look for leukemic (myeloblast) cells
- only for sx pt only bc CNS infiltration is rare
what differentiates AML from ALL by detecting myeloid antigens on cell surface
flow cytometry
what confirms the presence of AML?
auer rods in peripheral smear
management for acute myelogenous leukemia (AML)
- induction: multi-drug chemo
- post-remission therapy - standard chemo and/or stem-cell replacement
- allogeneic preferred - CNS involvement
- intrathecal chemo w/wo local radiation - leukostasis
- emergent chemotherapy, leukapheresis and prevention of tumor lysis syndrome
- disorder characterized by dysregulated production and uncontrolled proliferation of mature and maturing granulocytes with normal differentiation
- results from a single specific genetic mutation
Chronic Myeloid Leukemia (CML)
the philadelphia chromosome is the hallmark for which disorder?
Chronic Myeloid Leukemia (CML)
translocation t(9:22), also known as philadelphia chromosome, is a result in a genetic defect known as ?
bcr/abl
produces overactive tyrosine kinase (TK) activity
- TK is responsible for controlling cell growth, differentiation, metabolism and apoptosis
epidemiology of CML
55y/o or middle aged
etiology of CML
exposure of ionizing radiation
unknown otherwise
what are the 3 phases of CML
- First phase: chronic - WBC’s differentiate
- mostly found incidentally
- chronic for 3-5 years if left untreated - Second phase: accelerated - additional cytogenetic abnormalities occur
- Third “blast” phase: terminal blast crisis - immature myeloid cells rapidly proliferate (fatal)
what is often the first symptom pts present with CML
fatigue and weight loss
pruritus, diarrhea, flushing, gastrointestinal ulcers seen with elevated basophils due to overproduction of ?
histamine
clinical presentation of CML
- fatigue and weight loss (MC)
- fever of unknown origin, bone pain, marked splenomegaly
- signs of acute leukemia
what is the MC PE finding for CML
splenomegaly
work up for CML
- CBC
- chronic phase - granulocytosis with marked increase in mature neutrophils,
- accelerated phase - reduced platelets, RBC - Peripheral Smear
- chronic phase - confirmation of CBC findings
- accelerated phase - peripheral blast cells, promyelocytes visualized - Leukocyte Alkaline Phosphatase (LAP)
- low LAP = resistance to apoptosis - CMP
- Bone Marrow Aspiration/Biopsy
- hypercellular with increased granulocyte cells and their progenitors
- Blast phase: >20% blasts - Polymerase chain reaction (PCR)
- can be performed on blood or marrow aspirate
- identifies bcr/abl DNA segment (aka Philadelphia Chromosome)
management of chronic phase with CML
- Standard therapy: tyrosine kinase inhibitor - single drug chemotherapy
- targets abnormal bcr-abl protein
- inhibits the cancer cells “addiction” to tyrosine kinase
- results in CML cell death = healthy cells less affected compared to standard chemotherapy
what are the goals and course expectations with management of standard therapy with CML
- Hematologic remission - ~3 months
- normal CBC and physical exam - Cytogenetic remission - 3-6 months
- normal chromosome returns - Molecular remission - ~12 months
- negative PCR of bcr/abl - Continue for 2 years
tx for accelerated/blast phase of CML
- TKI + multidrug chemotherapy
- consider allogeneic stem cell transplantation
- indicated if lack of response to TKI
what are the signs of chronic turning into accelerated phase of CML?
- progressive splenomegaly
- inadequate decrease in granulocytes
- blast cells and promyelocytes in peripheral smear
- anemia, basophilia, thrombocytopenia
- new cytogenetic abnormalities or myelofibrosis (bone marrow bx)
a neoplastic proliferation of plasma cells producing an overproduction of nonfunctional monoclonal immunoglobulins
Multiple Myeloma (MM)
pathogenesis of Multiple Myeloma (MM)
is preceded by what disorder?
- Monoclonal Gammopathy of Undetermined Significance (MGUS)
- from abnormal plasma cell response to antigenic stimulation
risk factors for multiple myeloma
- older age, immunosuppression, and environmental exposures
- radiation, benzene, organic solvents, herbicides, and insecticides
epidemiology of multiple myeloma
- ~65y/o
- Males
- african americans > caucasian/hispanics > asian/pacific islanders
pathophys of multiple myeloma
- diminished hematopoiesis
- Neoplastic plasma cells are monoclonal = lack of adequate immunoglobulin response to infection
- increase osteoclastic activity, bone tumor formation and hypercalcemia
- M-proteins - harmful to the kidneys, nerves etc
- plasmacytomas
if a pt presents with bone pain in the axial skeleton via back, what is the possible diagnosis?
multiple myeloma
Skeletal system - MC in the axial skeleton
- bone pain - MC presenting symptom in the back, hips, ribs
clinical presentation of multiple myeloma
- Skeletal system - MC in the axial skeleton
- bone pain - MC presenting symptom in the back, hips, ribs
- spinal cord compression = back pain, weakness, numbness, or dysesthesias in the extremities
- pathologic fracture
- hypercalcemia (from skeletal destruction) - Bone marrow
- anemia, neutropenia, thrombocytopenia - Renal
- impaired function/failure, proteinuria, oliguria - Neuro
- radiculopathy or neuro deficits
- peripheral nerve compression - MC median nerve (Carpal Tunnel Syndrome) -
Plasmacytomas
- bleeding, obstruction
- aerodigestive tract (MC), orbital, ear canal, cutaneous, gastric, rectal, prostatic, and retroperitoneal
work up for multiple myeloma
- CBC - pancytopenia
- Peripheral blood smear
- RBC rouleaux formation - CMP
- Bone marrow aspiration/biopsy
- monoclonal plasma cells - Serum protein electrophoresis (SPEP)
- (+) paraprotein (M-protein) - 24 hour urine collection with urine protein electrophoresis (UPEP)
- (+) Bence Jones protein - Quantitative immunoglobulin levels
- suppression immunoglobulins (IgG, IgA, IgM - imaging
- x-rays - complete skeletal survey - MC seen in skull, spine, long bones
- CT scan - for monitoring
- MRI spine - assess spinal nerve compression
if a peripheral smear presents with RBC rouleux formation, what is it indicative of ?
multiple myeloma
how can you determine the prognosis/”tumor burden” of multiple myeloma
beta-2 microglobulin
high = more burden
which disease is incurable
multiple myeloma
Goal of treatment: prolong life, reduce complications and improve symptoms
hem/onc will manage multiple myeloma how?
- Initial induction therapy - triple agent chemotherapy
- Chemotherapy is followed by autologous stem cell transplant (reserved for younger patients)
- Localized radiation - palliative for bone pain related to tumor formation
complications with multiple myeloma? tx for each
- pathologic fractures
- stabilize the bone and irradiate the lesion - vertebral body collapse
- vertebroplasty/kyphoplasty - spinal cord compression
- IV steroids
- radiation
- consult neuro for surgical intervention - Bone disease/Hypercalcemia
- bisphosphonates (for sx pts with good renal function) - anemia
- EPO for persistent anemia - renal impairment
- plasmapheresis to remove M-proteins
what is the only known curative therapy for CLL
Allogeneic stem cell transplant
