Leukemia, Lymphoma and Multiple Myeloma Flashcards
What are the functions of neutrophils?
Target bacteria and fungi
What are the functions of eosinophils?
Target larger parasites and modulate allergic inflammatory responses
What are the functions of basophils?
Release histamines for inflammatory responses
What is cytopenia?
Reduction in mature blood cells
What is pancytopenia?
Deficiency in all 3 cellular components
Difference between leukopenia and leukocytosis
Leukopenia is a decrease in WBCs below 4.5 K/mcL
Leukocytosis is an increase in WBCs above 10K
What is leukemia?
Cancer of the blood forming tissues (bone marrow and lymphatic system) with high numbers of WBCs
What is the most common acute leukemia in adults?
Acute myeloid leukemia
More in males (median age 65) and Caucasians
What is acute myeloid leukemia?
Accumulation of leukemic blasts in the bone marrow and peripheral blood (always abnormal if here) and reduced production of normal cells
What environmental factors can lead to AML?
Chemicals, radiation, smoking, chemotherapy drugs
What genetic abnormalities will make you consider AML?
Trisomy 21, Fanconis anemia (bone marrow failure), familial RUNX1 mutations (activates genes that control development of blood cells)
What complications of pancytopenia are seen in the presentation of AML?
Anemia, neutropenia, thrombocytopenia (bleeding), ophthalmic changes (hemorrhage or white plaques)
What will you see on a bone marrow aspiration and biopsy in AML?
Blast forms over 20% of cells (might be less if there are cytogenetic abnormalities tho)
*used for diagnosis!
What are some diagnostic tests for AML?
CBC with dif (cytopenia and blasts over 20%)
Auer rods on peripheral smear
Metabolic panel (elevated creatinine and liver function tests, altered electrolytes- increased Ca and K)
Elevated uric acid and LDH (due to tumor burden and high cell turnover)
What is the normal value of absolute neutrophil count?
2500-7500 (multiply WBC count by % neutrophils)
What is neutrophilia defined as?
ANC over 10,000
Due to stress/trauma, cancer, demargination, meds (corticosteroids), poison
When would you see neutropenia?
Chemo, radiation, blood related cancer, overwhelming infection, meds (PCN, ibuprofen)
What are auer rods?
Clumps of azurophilic granule material that forms elongated needles in leukemic blasts
*pathognomonic of myeloblasts
Can be seen in others than AML too
What tx do you do for AML?
Induction is chemotherapy to eradicate most leukemic cells and then consolidation to destroy the remaining ones (stem cell transplant)
Then maintenance
When is the prognosis for AML unfavorable?
Over 60, history of exposure and history of myelodysplasia
What is myelodysplastic syndrome?
Cytopenia (reduced number of blood cells) due to ineffective hematopoiesis
May progress to AML
What kinds of tx are used for myelodysplastic syndrome?
Hematopoietic growth factors to help blood cells grow and mature
Immunomodulatory agents to regulate immune function
Hypomethylating agents
Immunosuppressive therapy
What are the goals of tx for myelodysplastic syndrome?
Minimized cytopenias, maintain quality of life and delay onset of leukemic transformations
What is tumor lysis syndrome?
When there is massive tumor cell lysis and it releases potassim, phosphate, nucleic acids etc
Causes of tumor lysis syndrome
Initiation of cytotoxic therapy (12-24 hrs after) for lymphomas or acute lymphoblastic leukemia
Spontaneous
What are the manifestations of tumor lysis syndrome?
Hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia
What can tumor lysis syndrome lead to?
Renal failure, ECG changes, seizures, tetany
What is the tx for tumor lysis syndrome?
Prevention mostly (basically stop anything it can become)
Fluids, diuresis
Frequent monitoring of blood levels
Meds to treat manifestations
What is chronic myeloid leukemia?
Uncontrolled production of mature and maturing granulocytes (mostly neutrophils) due to the abnormal BCR-ABL1 fusion gene from 9 and 22
What is the risk factor of CML?
Ionizing radiation
Slight males, median age 50
Common signs/symptoms of CML?
A lot are asymptomatic (20-50%) and only seen on routin blood tests
Fatigue, splenomegaly, bleeding episodes, B sxs (fever, weight loss, night sweats)
What are the 3 phases of CML?
Chronic, accelerated, blast
What is the chronic phase of CML?
Most are diagnosed here with better prognosis and asymptomatic
WBC>100,00
<10% blood or BM are blast cells
What is the accelerated phase of CML?
10-19% blood or BM cells are blasts
Progressively impaired neutrophil differentiation
See flu-like sxs
What is blast crisis phase of CML?
Resembles AML with 20% of blood/BM cells being blasts
Fatigue, fever, extramedullary blasts, splenomegaly
What does tx of CML depend on?
The stage at diagnosis
What kinds of tx are there for CML?
Tyrosine kinase inhibitors, monoclonal antibodies, chemotherapy, allogenic stem cell transplant (possible cure)
What are complications of CML?
Tumor lysis syndrome, hyperleukocytosis or hyperviscosity syndrome
What is hyperleukocytosis?
WBC > 100,000/mcl
Medical emergency that may need leukapheresis
Decreased tissue perfusion
What are sxs of hyperviscosity syndrome?
Spontaneous bleeding from mucous membranes, visual disturbances, neurologic sxs, HA, vertigo, seizures, coma
CML and multiple myeloma
How do you treat hyperviscosity syndrome?
Leukapheresis or plasma exchange
What is the most common cancer in children and teens?
Acute lymphoblastic leukemia
Peak incidence 2-5 yrs old
More males (whites and hispanics)
What genetic conditions do you see acute lymphoblastic leukemia with?
Down syndrome, neurofibromatosis type 1, bloom syndrome
Most common clinical features of ALL
Fever, fatigue, bruising, pallor, hepatosplenomegaly, LAD
testicular mass is rare
What lab findings might you see in ALL?
Lymphoblasts on peripheral blood smear and BM
Cytopenias (neutropenia, anemia, thrombocytopenia)
Elevated LDH
What types of tx can be used in ALL?
Chemotherapy, monoclonal antibodies, oral tyrosine kinase inhibitors
Complete response in 98% of kids with chemo
When is there an 85% 5 year prognosis for ALL?
Younger than 35, favorable cytogenetics, absence of CNS disease at dx and B cell vs T cell phenotype
What do you use the bone marrow biopsy to see in ALL?
Shape
Immunophenotype (70-80% b cell and 15-17% t cell)
Cytogenetics/ chromosomal abnormalities
What is chronic lymphocytic leukemia?
Chronic lymphoid neoplasm with a progressive accumulation of functionally incompetent B cell lymphocytes
When is CLL most common?
70 yrs, males and caucasians
What is the most common finding at dx of CLL?
Organomegaly (LAD, spleno, hepato)
What is the most common non-lymphoid organ affected by CLL?
Skin (leukemia cutis)
What is the indolent stage of CLL?
Usually asymptomatic
Lymphocytosis on peripheral blood and BM
B sxs
What is the advanced stage disease in CLL?
Rapidly progressive and terminal
Anemia, b sxs
Atypical infections
Death secondary to infection, bleeding, cachexia
What tests help you diagnosis CLL?
CBC with diff (B lymphocytes >5000 microL)
Flow cytometry of peripheral blood (clonality of B lymphocytes)
Bone marrow aspirate and biopsy (lymphocytes >30%)
Lymph node biopsy (infiltrate with mature, small lymphocytes)
When do you see a significantly shorter survival rate for CLL?
When lymphocyte doubling time is less than 12 mos
How you treat asymptomatic and early stage 1 CLL?
Observe
What are options of tx for pts with symptoms of CLL?
Chemotherapy, immunotherapy (monoclonal antibodies), radiation, splenectomy
What are lymphomas?
Cancers that begin in the lymphocytes
Where are lymphocytes?
Lymph nodes, spleen, thymus, bone marrow, tonsils, adenoids
Risk factors of Hodgkins lymphoma
Socioeconomic status, immunosuppression, autoimmune disorders, family hx (genetic susceptibility or common environmental exposure)
What is Hodgkins lymphoma characterized by?
Enlargement of lymph nodes, spleen, liver
Reed-Sternberg cells (multinucleated B cells)- popcorn cells
What is a very common etiology of Hodgkins lymphoma?
EBV (40-50%)
When is hodgkins lymphoma most common?
15-34, peak in 20s and after 50
Rare under 5
Slight male
What are some clinical features of Hodgkins lymphoma?
Painless LAD (cervical most common), mediastinal mass, sever pain response after alcohol, B symptoms, fatigue, pruritus but no rash
Ann Arbor staging of Hodgkins lymphoma
I: 1 lymph node area of lymphoid organ
II: 2+ groups of lymph nodes on same side of diaphragm
III: lymph nodes on both sides of diaphragm
IV: distant spread
X: bulky disease or mediastinal mass
What can chemo and radiation as tx for lymphoma lead to?
Another cancer or heart disease
Treatment for Hodgkins lymphoma
Combo chemo (curative most cases)
Often combine with radiation (bulky disease or relapse)
Stem cell transplant if more severe
What are considerations of hodgkins lymphoma?
Secondary malignancy, CAD, pulm dysfunction, infertility, hypothyroidism, diabetes, psychosocial issues
What diseases are associated with non-hodgkin lymphoma?
HIV, autoimmune diseases, inflammatory GI disease
Age: 66
What are clinical features of NHL?
Painless, persistent LAD
Mediastinal mass
Extralymphatic sites (GI, skin, bone, BM, adm)
B sxs in high grade disease
What are the b symptoms?
Fever, weight loss, night sweats
When is NHL considered aggressive?
Rapidly growing mass
B sxs
Elevated LDH and uric acid
1/3 curable with chemo
What are indolent NHL?
LAD, hepatomegaly, splenomegaly, cytopenias
What diagnostic tests can you do for NHL?
Biopsy (lymph nodes over 2 cm best) CT or PET/CT to see areas of involvement Bone marrow aspiration and biopsy Cerebral spinal fluid, pleural/peritoneal fluid Splenectomy
How do you treat indolent NHL with 1-2 nodes?
Radiation only
How do you treat aggressive or high grade NHL?
Chemo, immunotherapy, autologous stem cell transplant
What is multiple myeloma?
Malignancy of plasma cells that proliferate in the bone marrow, can form tumors and secrete paraproteins (abnormal Ig fragments)
What does protein electrophoresis do for multiple myeloma?
Blood or urine
Shows paraproteins as different bands
Provides an early indication of malignant condition
Can see an m-spike
Common clinical presentation of multiple myeloma
Fatigue, bone pain, weight loss, weakness, back pain
What diagnostic studies are used for multiple myeloma?
Anemia-rouleaux formation (RBCs stacked like coins)
Hallmark: monoclonal spike on protein electrophoresis
Bence-jones proteins in urine
Xrays of axial skeleton that show lytic lesions and osteoporosis
CRAB (calcium >10.5, renal insufficiency, anemia, bone lesions)
Txs for multiple myeloma
REFER Combo chemo Vertebroplasty or balloon kyphoplasty IV bisphosphonates (prevent loss of bone mass) Autologous hemopoeitic cell transplant
