Hematologic Malignancies Flashcards
5 types of leukemia
- chronic lymphocytic leukemia
- chronic myelogenous leukemia
- acute myelogenous leukemia
- actue lymphoblastic leukemia
- acute promyelocytic leukemia
4 types of lymphoma
- Hodgkin’s Lymphoma
- Non-Hodgkin’s lymphoma
- Follicular lymphoma
- Diffuse large B-cell lymphoma
Hem. malignancy not leukemia or lymphoma
multiple myeloma
How common are hematologic malignancies
not very
what cell type are most hem. malignancies in?
B cells, not T cells
Chronic lymphocytic leukemia (CLL)
- risk factors
- runs in families
- herbicides
- viruses (HTLV I & II and Epstein- Barr)
- Not radiation or alkylating agents
**not really sure what the exact cause is still…
Chronic lymphocytic leukemia (CLL)
Clinical presentation
- 25% asymptomatic, often high WBC found on CBC run for something else
If symptomatic
- lymphadenopathy
- splenomegaly
- hepatomegaly
Chronic lymphocytic leukemia (CLL)
in general, what is happening
So many lymphocytes in marrow compromises the ability to make other cells (anemic)
Chronic lymphocytic leukemia (CLL)
- lab presentation
- WBC > 100,000
- Hgb < 11
- Platelets <100,000
Chronic lymphocytic leukemia (CLL)
- Dx criteria
- Absolute lymphocyte count of => 5,000/mm3
- Lymphocytes are monoclonal (all come from the same malignant stem cell)
- Low levels of surface immunoglobulins
- Bone marrow is min 30% lymphocytes
- Rule out other causes of lymphocytosis (mono, pertussis, toxo)
what is the purpose of staging in hematology and oncology
- standardize descriptions of disease state
- provides prognostic info to help discussions with pt
Chronic lymphocytic leukemia (CLL)
Staging - list two kinds, what are they based on
- Rai classification
- Binet classification
- both reflect tumor burden
Chronic lymphocytic leukemia (CLL)
Rai classification: what happens as go from stage 1 to 5
- months of survival decrease if untreated
Chronic lymphocytic leukemia (CLL)
- Rai 5 stages
0 lymphocytosis I lymphocytosis adenopathy II Lymphocytosis, hepatomegaly or splenomegaly III Lymphocytosis, anemia IV thrombocytopenia
Chronic lymphocytic leukemia (CLL)
Binet staging
A - lymphocytosis and =< 3 enlarged nodal groups
B - lymphocytosis and >3 enlarged nodal groups
C - lymphocytosis, anemia, or thrombocytopenia
What are common maladies associated with Chronic lymphocytic leukemia (CLL) (3)
- autoimmune hemolytic anemia (most common)
- immune thrombocytopenia
- infections
Anemia in CLL and AHA
Anemia will show up in AHA but isn’t considered when staging CLL because it is not due to the CLL
Why is CLL at greater risk for infection?
Lack of surface immunoglobulins
most common cause of death in people with CLL is infection
How true is the statement “CLL is an indolent disease associated with a 10 to 20 year clinical course with death unrelated to CLL”
< 30% of the time
What are good prognostic sx in CLL
- Low Rai or Binet clinical stage
- Nodular findings on bone marrow study (vs. interstitial which is worse)
- Lymphocyte doubling >12 months
- Mutated Vh genes
- ZAP-70 negativity
- Chromosome 13q14
- CD38 negativity
Chronic lymphocytic leukemia (CLL)
Treatment indications
- fever, night sweats
- weight loss
- progressive anemia
- thrombocytopenia
- progressive/painful splenomegaly
- progressive/bulky lymphadenopathy
- rapidly increasing lymphocytosis
- autoimmune cytopenias (low platelets or anemia)
**might not treat right away if pt is asymptomatic
Chronic lymphocytic leukemia (CLL)
- evidence for early treatment
- curable?
- what drives treatment?
- no evidence for early therapy
- not curable (except with stem cell transplant that can be used on people who have tried and failed treatment and dx is still progressing)
- tx is sx driven
Chronic lymphocytic leukemia (CLL)
- Treatment
- Alkylators
- Prednisone
- Imbruvica
- monoclonal antibodies
- lots of others
Chronic Myelogenous Leukemia (CML)
- blood smear
- Lots of immature cells in peripheral smear
- These cells should be in blood marrow
- won’t see a lot of blasts unlike leukemia
Chronic Myelogenous Leukemia (CML)
- median age range at presentation
- what increases incidence
- male vs. female
- how most often found?
- 45 to 55, middle age disease
- incidence increases with age (12-30% >60 yo)
- M>F
- 50% dx by routine lab test
Chronic Myelogenous Leukemia (CML)
- clinical presentation
- 50% asymptomatic!
- fatigue, weight loss, abdominal fullness
- palpable splenomegaly common
Chronic Myelogenous Leukemia (CML)
- lab findings
- abnormal differential
- leukocytosis
- thrombocytosis
- anemia
- basophilia
Chronic Myelogenous Leukemia (CML)
- three phases
- chronic phase
- accelerated (advanced phase)
- blast crisis (advanced phase)
Chronic Myelogenous Leukemia (CML)
- chronic phase: duration, lab findings, associated issue
median 5-6 years stabilization
- elevated WBC
- elevated platelets
- anemic
Chronic Myelogenous Leukemia (CML)
- Accelerated phase: duration, lab finding
- 6-9 months
- lots of basophils on peripheral smear
Chronic Myelogenous Leukemia (CML)
- blast crisis: duration, lab finding
- 3-6 months survival
- surplus of myeloblasts in peripheral smear (>30%)
Chronic Myelogenous Leukemia (CML)
- caused by what
- philadelphia chromosome (9 & 22) also known as Bcr-Abl
- activates tyrosine kinase which makes cell immortal.
- causes transformation of hematopoietic progenitor into malignant clone
- first malignancy where specific abnormality was found that causes the disease
What disease(s) is Philadelphia chromosome found in?
- CML: almost 100%
- ALL adult and pediatric
- AML
- found less often in ALL and AML
Chronic Myelogenous Leukemia (CML)
- new treatment type
Tyrosine kinase inhibitors - if can inhibit tyrosine kinase, will shut down cell and it will die
What are the two acute leukemias
- AML (acute myelogenous leukemia)
- ALL (acute lymphoblastic leukemia)
What lab finding is only found in AML?
Auer Rods (little sticks coming off the granule into the cytoplasm)
AML vs. ALL
- which one common in childhood, which in adults
- 90% adult leukemia is AML
- 80% childhood leukemia is ALL
When does incidence of ALL decrease?
after age 9
when does incidence of AML increase?
- with age
- 30% after age 60
Male or female more likely to get AML
males - as infant and elderly
What causes AML/ALL
- Radiation,
- viruses?
- benzene, toluene, other chemicals
- drugs: alkylators, arsenicals, etc
- Hereditary: Bloom’s syndrome (AML)
- Fanconi’s anemia (AML)
- Trisomy 21: AML and ALL
- Siblings - 5X risk among siblings, 25% risk with monozygotic twins
AML and ALL
- sx
- fatigue, fever, weight loss
- HA
- Cranial nerve palsies (chin and facial numbness), obstipation
- bone pain and abdominal fullness from splenomegaly more common in ALL
- bone pain common in kids
AML & ALL
- PE findings
- pallor, petechia, purpura (from thrombocytopenia)
- sternal pain, lymphadenopathy, hepatosplenomegaly (ALL > AML)
- meningismus (stiff neck) (ALL>AML)
- flame hemorrhage in fundus exam
- gingival enlargement
- bleeding/DIC
Initial work up for leukemia
- H&P
- CBC, PT/PTT, Fibrinogen
- Bone marrow aspiration/biopsy
- morphology: determine what cell line dealing with
- cytochemistry
- immunophenotyping
- FISH (older cytogenetics) to look at DNA
- HLA-typing: Human lymphocyte antigen typing to find stem cell donors.
- Cardiac scan to help with medication selection
- FLT-4. a molecular mutation. If have, bad news
When is a bone marrow exam appropriate for leukemia?
> 20% blasts
Three cytogenetic findings in leukemia
- Auer rods = AML
- Terminal transferase (TdT) = ALL
- Peroxidase = AML
what anemia is most commonly found in leukemia?
hypoproliferative
normochromic
normocytic
WBC findings in leukemia
leukocytosis 60%
leukopenia 25%
normal 15%
thrombocytopenia 90%
what happens when treat a malignant tumor (findings in blood)
the tumor cells lyse and dump:
- k+ (cardiac arrhythmia)
- uric acid (kidney failure)
- creatine
- PO4 up and mg down which causes musculoskeletal problems
When check CSF?
- Always with ALL (might wait until “count” goes down)
- AML if signs or symptoms present
AML
- what used to stage?
“FAB”
french-american-british
M0-M7
What is a good prognosis for AML
- WBC < 39,000
- LDH - normal (reflection of cell turnover)
- translocations 8;21
- M4 with eosinophils
- Inv 16
- (15;17)
AML bad prognosis
- secondary leukemia (ex. breast cancer)
- Myelodysplastic syndrome
- CD34 + blasts
- p-glycoprotein positive
- MDR gene (multidrug resistent gene)
Myelodysplastic syndrome
- usually in older its who show up with abnormal CBC, pancytopenia, possibly thrombocytopenia
- some will evolve into acute leukemia which is worse than de novo
Three stages of leukemia treatment
- induction
- consolidation
- maintenance
- post-remission therapy
Induction - leukemia treatment
induce a remission via chemotherapy
Consolidation - leukemia treatment
Once in remission, keep getting chemotherapy. May be same drug used in induction at same level of intensity or less intense level
Maintenance - leukemia treatment
After induction and consolidation, want to maintain that remission. Mandatory in treatment of ALL (3-5 years)
Post remission therapy - leukemia treatment
can be maintenance, can be something like a stem cell transplant (depending on how favorable or unfavorable the cancer is at that point)
5 Meds used to for AML induction and consolidation
- Daunomycin + cytarabine (Ara-C)
- Idarubicin + Cytarabine (Ara-C)
- High dose Ara-C
- Gemtuzumab ozogamicin (monoclonal antibody)
- Vyxeos
SWOG 9034
Not sure exactly but I think some sort of study that links mortality of leukemia to whether they are considered favorable, intermediate, or unfavorable.
- favorable 60% are expected to live 5 years
- unfavorable 20% are expected to live 5 years
Acute promyelocytic leukemia (APL)
- treatment
- completely different from other myeloproliferative diseases.
- don’t miss: the treatment is very effective!
- transretinoic acid and arsenic (the chinese reported these work and western world keeps thinking they are crazy)
what is a common problem associated with Acute promyelocytic leukemia (APL)
DIC
Who first described lymphoma? when?
Thomas Hodgkin in 1832
Who made first definitive and thorough microscopic description of lymphoma?
Sternberg and Reed
Hodgkin’s vs. non-Hodgkin’s lymphoma - which is more common
NHL by a lot
What origin are most lymphomas?
B-cell origin
Three types of NHL
- diffuse large B - cell
- Follicular
- Other NHL
Hodgkin’s Lymphoma
- how common
- men vs. women
- less common in what race
- does it run in families?
- uncommon
- M > F
- less common in african americans
- does run in families
Hodgkin’s Lymphoma
- Age of incidence
- likely cause?
- bimodal: young and old people
- childhood happens in underdeveloped countries
- likely related to virus, maybe Epstein barr?
Hodgkin’s Lymphoma
- what cells are found in peripheral smear?
- Reed-sternberg cells aka Owl Eyes
- arise in lymph nodes
- germinal centre b-cells
what is the cellular composition of enlarged lymph nodes in Hodgkin’s lymphoma?
- most are recruited lymphocytes (polyclonal reactive lymphoid cells)
- only a minority of cells are malignant (unlike other cancer tumors when most of the cells are malignant)
What are the 5 types of Hodgkin’s lymphoma
- Nodular sclerosis
- Mixed cellularity
- Lymphocyte-rich
- Lymphocyte depleted or not depleted
- Nodular lymphocyte-predominant (controversy if Hodgkin or NHL)
** all treated essentially the same way except #5, all have slightly different prognoses
What are the three main components of the lymphatic system
- lymphocytes
- lymphoid organs
- lymphocyte circulation
What are the 6 lymphoid organs?
- bone marrow
- thymus
- lymph nodes
- spleen
- tonsils, adenoids
- digestive and respiratory tract
What system is used to stage Hodgkin’s Lymphoma
Ann-Arbor staging
stages 1-4
Stage 1 Hodgkin’s Lymphoma
- localized disease
- single lymph node region
- single organ outside the lymph nodes
Stage 2 Hodgkin’s Lymphoma
Two or more lymph node regions near each other (on the same side of the diaphragm)
Stage 3 Hodgkin’s Lymphoma
Two or more lymph node regions above and below the diaphragm
Stage 4 Hodgkin’s Lymphoma
- widespread disease
- multiple organs (liver and bone marrow most common)
- with or without lymph node involvement
What determines how treat Hodgkin’s lymphoma
staging of the disease
How treat Hodgkin’s lymphoma in stages 1 and 2
- Radiation
- Unless have B symptoms, then might get radiation and chemo
Hodgkin’s lymphoma B symptoms
feel ill
night sweats
weight loss
How treat Hodgkin’s lymphoma in stages 3 and 4
- chemotherapy
what is moving into front line therapy for How treat Hodgkin’s lymphoma
monoclonal antibodies
Non-Hodgkin’s lymphoma (NHL)
- S&S
- enlarged lymph nodes
- general symptoms (weight loss, fatigue, night sweats, fever, severe itching)
- less than 20% of pts have general sx at onset
Non-Hodgkin’s lymphoma (NHL)
- risk factors
- environmental - chemicals and high-dose radiation
- immunosuppression (biologics, AIDS, post-organ transplant)
- viral and bacterial infections (HTLV-1, EBV, H pylori)
- inherited - small %
**cause is unknown
Non-Hodgkin’s lymphoma (NHL)
- how is it related to age
incidence increases with age
Non-Hodgkin’s lymphoma (NHL)
- dx
- Biopsy (FNA, excisional/incisional, bone marrow, LP)
- Laboratory testing
- Imaging (chest x-ray, CT, MRI, PET)
why is FNA not a great way to dx NHL
only know it is lymphoma, not whether HL or NHL…
What labs would run to dx NHL
- CBC
- Chem panel
- Liver panel
- LDH (would be elevated in rapidly dividing tumor)
Three types of NHL B-cell neoplasms
- Indolent - slow growing, CLL + small lymphocytic leukemia
- Aggressive - diffuse large b-cell most common
- Very aggressive - precursor B cell and Burkitt
3 factors that influence treatment of Lymphoma
- Grade (growth rate and aggressiveness)
- Cell type
- Stage (extent of spread)
What system used to grade NHL?
Ann Arbor, same as HL
What is difference between staging of HL and NHL?
HL: stage determines prognosis, stepwise progression through each stage
NHL: prognosis determined by cell type, diff biological behavior of diff cells, no stepwise progression like HL
Indolent lymphoma - treatment and reaction
- slow progression
- responds well to initial treatment,
- chronic disease with periods of relapse
Aggressive lymphoma - progression, how easy to treat
- rapid progression
- easier to cure
Types of lymphoma treatment
- radiation (early stage indolent)
- Chemo (advanced stage)
- Chemoradiation (early stages)
Three common lymphomas1
- follicular
- diffuse large b-cell
- Hodgkin’s
Follicular lymphoma
- which type
- response to treatment
- cell or origin
- most common type of indolent
- frequency stage 4 when dx (already spread to lymph node)
- often asymptomatic
- not curable but treatable for a long time
- cell of origin is germinal center B cell
How treat follicular lymphoma
- defer tx if asymptomatic
- chemo if symptomatic
- over time can become more aggressive and turn into diffuse large b-cell lymphoma…
Diffuse large B-cell lymphoma
- which type
- cell of origin
- sx?
- treatment
- treatment success
- most common type of “aggressive” lymphoma
- cell or origin: germinal center B-cell
- usually symptomatic
- should offer treatment
- 60-70% cured after monoclonal antibody drug therapy
Multiple Myeloma (MM) - peripheral smear
- perinuclear pallor
- multiple nuclei in single cell
- way too many plasma cells
Multiple Myeloma (MM) - x-ray findings
- fractures (duh)
- dark areas/mottling of bone
- changes from plasma cells which dissolve the bone
- lytic lesions
Plasma cell dyscrasias 6 types
- multiple myeloma
- smoldering myeloma
- solitary plasmacytoma of bone
- monoclonal gammopathy of unknown significance (MGUS)
- amyloid
- Waldenstrom’s macroglobulinemia
Smoldering myeloma
too many plasma cells but no end organ damage yet
Solitary plasmacytoma of bone
- one area of plasma cells forms a tumor “plasmacytoma”
- can treat with radiation
Monoclonal gammopathy of unknown significance (MGUS)
- prob all myelomas arise from MGUS but not all MGUS become MM
- as age, get monoclonal changes,
Amyloid plasma cell dyscrasias
plasma cells make abnormal immunoglobulins and light chains (deposited in tissues, kidneys, heart, liver)
Waldentstrom’s Macroglobulinemia
IgM: huge molecule that causes hyper viscosity of blood.
Multiple Myeloma (MM)
- what does NOT cause
- what might cause
- what race most common in
- m vs. f
- appears to develop from what
- NOT radiation, solvents, paints, pesticides
- NO epidemiological clusters
- maybe human herpes virus
- 2X incidence in AA
- M > F
- appears to develop from MGUS
End organ damage critera
CRAB
- Calcium (high)
- Renal (Failure)
- Anemia
- Bone (disease)
How test for CRAB
- chem panel for calcium, kidney fn, anemia
- metastatic skeletal survey for bones (series of x-rays to look at every bone in the body OR PET scan but more $$)
Multiple Myeloma (MM) - two staging systems
- Durie-Salmon staging system
2. International Staging System (ISS)
Multiple Myeloma (MM) - Durie-Salmon staging system stage I
All of the following:
- Hgb > 10 g/dL
- normal serum calcium
- bone x-ray normal/solitary bone plasmacytoma
- low M protein production
- urine light chain M-component on electrophoresis
Multiple Myeloma (MM) - Durie-Salmon staging system stage II
Not stage I or III
Multiple Myeloma (MM) - Durie-Salmon staging system stage III
One or more of the following:
- Hgb <8.5 g/dL
- serum ca >12 mg/dL
- advanced lytic bone lesions
- high M protein production rates
- Bence Jones protein >12 g/24 hours
Multiple Myeloma (MM)
ISS
- how common
- response to therapy and prognosis stage 1-3
- less common than Durie-Salmon
- stage 1 has better response to therapy and more fav prognosis than Stage II and III
Treatment of Multiple Myeloma (MM)
- Alkalators
- steroids
- immunomodulating agents (Thalamide was first)
- proteosome inhibitors
- monoclonal antibodies
- autologous stem cell transplantation
KAR-T Cells
- Pre-B cell ALL and <25 yo
- diffuse large b-cell lymphoma
- maybe MM and solid tumors in future
Kar-T cell tx
- separate T cells from blood
- send to NJ where mix T cells with virus which sticks in receptor that looks at part of the B cell malignancy
- cells back to pt
- new T cells recognize B cell and kills it, T cells live for years and will kill new emergences of disease in future
- will be IgG dependent for life bc all B cells are dead (downside)
In summary…
- what is common about all hematologic disorders
- non specific sx of fatigue, weight loss, fever
In summary…
- what should do with even mild CBC abnormalities
pay attention! Evaluate
In summary…
- what type of lymph node needs attn
persistent >1 cm
In summary…
- how treatable are hematologic disorders
usually highly treatable which means missing one is really bad…
