Week 2 Flashcards
1
Q
t/f- JAK2 inhib can be used for HSCT patient
t/f- inhib of jak/stat causes increase chance of replase
A
T - blocks T cell proliferation …used for GVHD!!
False - does not
2
Q
clinical pres of AML
A
INC MYELOBLASTS»_space; dec everything downstream
- low grade fever/infection (pt interview = flu!) – low mature WBC
- fatigue/palpitations roaring in ears - low RBC
- bruising and bleeding - low platelets
3
Q
T/F - hyperviscocity of blood is feature of AML
A
TRUE… why they get visionchanges, dyspnea and roaring in ears
4
Q
how do we diagnose AML?
A
bone marrow biopsy - see >20% blasts
and test for myeloidbladt markers (MPO+, auer bodies)
5
Q
what test do we do to distinguish good vs bad prognosis in AML?
A
Good: t(15, 17); t(8,21), Inv16
Poor: chrom 5, 7, 8, complex
Intermediate: Normal karyotype
6
Q
good or bad prognosis in AML:
- chr 5,7,8 complex
- t(15,17)
- normal karyoptyr
- inv 16
- t(8,21)
A
Good: t(15, 17); t(8,21), Inv16
Poor: chrom 5, 7, 8, complex
Intermediate: Normal karyotype
7
Q
T/F - majority of AML patients have normal karyoptyr which had more favorable prognosis than translocations like t(15,17)
A
false - is most common, but trans actually have GOOD prognosis
8
Q
- *principles of AML therapy
- give ____ as induction therapy , when?»_space;> follow up eith BM biopsy» then do ____ if CR and _____ if not CR
- when do we do transplant?
A
induce with a month of anthracycline araC (if active disease)
-then consolidate ALL! with high dose AraC
CR = residual leukemia burden just below the level of detection Cure = CR beyond 5 years
- if low risk»_space; consolidate and observe
- if high risk» consolidate and transplant (esp if relapse)
9
Q
we use retinoic acid and arsenic for ____ leukemia
A
acute promyelocytic leukemia
10
Q
T/F - relapse AML has dismal prognosis in young and old patients
A
true
11
Q
dx? 62 year old F presents with fatigue, RBC is 8, WBC is 21K, smear shows abnormal promyelocytes with primary granules. Neutrophil count is low. BM biopsy shows esterase+, myeloperoxidase+, t(15,19) mutation
A
AML»_space; specifically acute promyelocytic leukemia
12
Q
what is difference between allogenic and autologous HSCT?
A
allo = from someone else (1/2 match dad/mom/sib) , stranger or cord blood
auto = own stem cells
13
Q
what are indications for BM transplant in AML patient?
A
- if patient relapses
- or if patient at high risk and doesn’t respond
- *do risk startification during first block of induction treatment»_space; still have cancer 2 weeks later?»_space; then consolidate with another hig hdose ArC then»_space; TRANSPLANT
14
Q
what are indications for hematopoteic stem cell transplant (big 3) - are they mostly allo or auto
A
MYELOMA #1 - almost all auto
NHL #2 - mostly auto
AML #3 - mostly allo
others less common = ALL, Hodgkins, MDS, CML
15
Q
what is first step for HSCT:
- preparative regimen
- stem cell collection
- insurance approval
- engraftment
A
-insurance approval! and establish indication obv
16
Q
GVHD occurs ____(after stem cell infusion or after engraftment)
A
AFTER ENGRAFTMENT ! before that there are no T cells ! becuase stem cells haven’t grafted into BM and started differentiationg
17
Q
describe GVHD… what are acute v. chronic signs?
APC is from ____(host or donor)
T cells are from ____(host or donor)
A
GVHD = when donor T cells attack patient tissue (recognize antigens»_space; IL-12»_space; Th1»_space; IFN-gam + IL2»_space; NK and and CTL »_space; KILLL!
Acute = liver damage (big belly), skin (rash, no hair) and GI Chronic = arbritary > 100 days post engraftment = SKIN (rash, necrosis), oral ulcers, DRY EYES and DRY MOUTH, TIGHT skin/muscles/joints
18
Q
are following pre- or post-engraftment complications:
- neutropenic fevers and sepsis
- nausea vomitting, mucositis
- anorexia
T/F- liver toxicity is common pre-engraftment complication
A
- all PRE
- liver/kidney/lungs are NOT common
19
Q
T/F - GVHD is number 1 cause of death in HSCT patients
A
FALSE. its #2 .. behind “primary disease” (~40-50%)
GVHD and infection are tied #2/#3 - around ~15%
20
Q
JAK2 kinase inhibitors block ____ cell activation in GVHD patient
A
T-cell
21
Q
how do we “prepare” patient prior to HSCT (chemo, radiation, immunotherapy?)
A
-chemo +/- whole body radiation
22
Q
HSCT permits ____(chemotherapy, immunotherapy) in allogenicc patient and ______ therapy in autogenic patient
A
chemotherapy in auto +/- immuno (TNF-alpha inhib) in allo
23
Q
ENGRAFTMENT??
- need ___ and ____ adhesion molecules
- how do we “measure”
A
- homing of stem cells into bone marrow (occurs ~10 days post infusioN) … so for 1st ten days NO IMMUNE CELLS (need to tranfuse platelts, RBC, everything)
- VLA-4 and CD34
MEAURE - via chromosomes and variable # tandem repeats (VNTR) … basically a PCR band to make sure donor = host
24
Q
are each part of innate or adaptive
- granulocytes
- NK
- T cells
- dendritic
T/F - innate immune system shaped by pathogen exposure
A
all innate except T
-innate NOT shaped by pathogen exposure,l only adaptive
25
--describe path from naiive B to plasma cell (follicular, mantle, naive, plasma cell)
--and where (blood, germinal center, mantle zone, marginal zone, bone marrow)
in blood: naive >>
in Mantel zone: mantle >>
in germinal center: follicular B-blast >> CENTROBLAST (BIG)
in marginal zone: monocytoid or centrocyte >> PLASMA (BM)
N>M>F>C> P
26
CD20 is target for _______ heme cancers
B-cells! esp the lymphomas
27
dx? 70 F presents with recurrent infection and fatigue, RBC low, cervical lymphadenopathy, elevated WBC, platelets normal, smear shows spherocytes and smudge cells, biopsy shows diffuse uniform pattern
- AML
- CML
- ALL
- CLL
- hodgkin lymphoma
- non-hodgkin lymphoma
CLL = SMEAR!
28
T/F - CLL median age of diagnosis is 40-50
| T/F - more common in african americans
false - 72 median
| false - cauc > AA
29
antibody production is ____(+/-/0) in CLL and risk of infection is ____(+/-/0)
- increased
| - increased (becuase antibodies ARENT GOOD!)
30
- CBC and smear findings in CLL
- diagnosis of CLL requires >5000/ncl CLL lymphocytes in _______(periphery, marrow, LN) that are ______(polyclonal or monoclonal)
- increased WBC, smudge cells on blood smear
| - CIRCULATING! cells with CLL MONOCLONAL IMMUNOPHENOTYPE (kappa/lambda ratio NOT 3:1)
31
- rouleux on periph smear indicates _____
| - smudge cell on periph smear indicates _____
- myeloma
| - CLL
32
dx? 58 yeara old onset of severe lumbar pain, tender to palp, has been tried lately, WBC low, hemoglobin low, platelet borderline low, Calcium high, globulin high, serum protein electrophoresis shows IgGk paraprotein spike 4.8
plasma cell MYELOMA >> back pain cuase eating away at bone, would expect lytic lesions on x-ray
33
where do you find the plasma cells in myeloma (periphery, lymph nodes, marrow)
MARROW!!! see lots of plasma cells, may see in periphery too
34
- -how does MM present
| - -how is it diagnosed (3 things)
- fatigue (low RBC), bone pain, renal dysfunction (50%), hypercalcemia (25%), recurrent infections (low WBC)
- presence of M-protein in serum (>3gm, 97% of patients) presence of clonal bone marrow plasma cells, presence of tissue organ damage (inc Ca2+ , renal insufficiency, anemia, lytic bone lesions = CRAB)
35
difference between MM and smoldering
both = M protein and clonal bone marrow plasma cells
smoldering = NO CRAB (Ca2+ , renal, anemia, bone pain/lesions) ie, asymptomatic
36
what is MGUS? precursor of ______
- monoclona lgammopathy of undetermined significance = increased serum protein with M-spike on SPEP w/out organ damage found in MM
- -MYELOMA
37
what are values of following for MM, smoldering M, MGUS:
- marrow plasma cells (> or 3 or ,3)
- organ damage (CRAB, absent/present)
MM = >10%, >3, CRAB yes
SM = >10, >3, CRAB NO
MGUS =
38
T/F - B-cell lymphocytosis at increased risk of CLL and MGUS patients at increased risk of myeloma
FALSE
- B cell >> CLL (1%)
- MGUS >> myeloma
39
primary AL amyloidsis is associatd with _____ cancer
multiple myeloma ... cranking out free light chains that are depositing in the tissues
40
difference between non-hodgkin and hodgkin
- -malignant cells
- -present (age, painful or painless lymphadenopathy where?)
- -B- symptoms??
- -importance of staging
NON - malig lymphoid cells (usually B - small or large) , painless lymphadenopathy in late adulthood , limited importance
HODGE = REED-STERNBERG, painless lymph "" in YOUNG ADULTS (B symptoms = weight loss,fever, night sweats), STAGING IMPORTANT
41
T/F - extranodal involvement is RARE in BOTH hodgkin and non-hodgkin
FALSE - rarely extranodal in HODGKINS (except HIV), often extranodal / diffuse in non-hodgkins
42
____ lymphoma (HL, NHL) spreads hematogenously while ______ spreads continuously
HODGKIN = CONTIGUOUS lymph nodes >> one lymph node after the other(all up in the axilla or neck for ex)
NON = diffuse ... can get swollen lymphs all over
43
T/F - reed-sternberg cells are uncommon in the swollen lymph nodes of HL patient
TRUE ... like finding a needle in haystack ... so dx can be tricky
44
HL can secrete ____ and ____ (ILs) leading to Anemia and eosinophilia
Il-6 >> hepcidin >> anemia of chronic inflammation
| IL-5 >> esosiophilia >> ITCHY
45
high LDH can signal _____
- hemolytic anemia
| - fast growing cells (ex - good marker in HL)
46
***staging of ANN ARBOR for HL (I - IV)
- what stage would person with enlarged R cervical lymph nodes and L axilla nodes
- what stage would be patient be with enlarged R axilla nodes, plus spleen and bone marrow involvement
- I - 1 lymph node region or site >> easy radiation port ~90% survival
- II - 2 lymph node regions on SAME SIDE of diaphragm ~90% survival
- III - involvement on BOTH sides of diaphragm ~80% survival
- IV - EXTRANODAL involvement (diffuse involvement of 1 extralymphatic organ likE SPLEEN) ~ 65%
47
what is localized vs disseminated therapy for HL (chem done for ____ , extended field XRT. done for ____ )
localized (stage I-III) = extended XRT and combo chemo + XRT if more than one area affected (ex - axilla and neck)
disseminated (stage IV) - combo chemo
48
T/F - ann arbor staging for HL is important. for prognosis but not for treatment (all treated the same)
FALSE - not treated the same if disseminated just have to do. chemo no radiation
49
T/F - NHL has bimodal distribution but most cases present in early adulthood
FALSE, thats HL!
NHL - incidence rises throughout life, usually seen in LATE ADULTHOOD
50
T/F - HIV strongly increases risk of NHL and HL
TRUE
51
T/F - autoimmune disorders like RA and Sjorgens are at increased risk of NHL
TRUE ... AD + AD treatments (Immunesupression)
esp marginal zone
52
Dx? 74 year old chinese M presents with neck mass, painless to palpation, WBC is is High, LN biopsy shows many mitotic figures and starry sky apperance
burkitts... probably from EBV virus
53
* **understand difference in behavior of 3 grades of NHL (low, intermediate and high grade)
* *what grade is each:
- follicular
- burkitts
- diffuse large B cell
- mantle cell
- marginal
INDOLENT (lowgrade = FOLLICULAR, MARGINAL) - decreased apoptosis, survive mopnths to years even decades without chemo, can't cure - usually just watch
AGGRESSIVE (intermediate grade = DIFFUSE LARGE, MANTLE) - diffuse large B cell
HIGHLY-AGGRESSIVE (high grade = BURKITTS!!) - survive only days to weeks without chemo, need chemo stat!
*>>50% cure rate for intermed and high, but cant cure low-grade paradoxically
54
* **what is most common form of NHL
| - is it low/intermediate/high grade (ie indolent or aggressive)
- diffuse large B-cell - clinically HIGHLY aggressive (high-grade)
- present in adult adulthood with enlarging LN or extranodal mass
55
- what is IPI?
| - person with score of 1 vs. 5 will have _____(better or worse survival)
- INTERNATIONAL PROGNOSTIC INDEX for NHL
| - basically just ANN ARBOR stage with other markers (age,performance status (how well ur doing in life, LDH LEVEL)
56
* understand 8,14 and 14,18 translocations
- what genes involved
- what cancers do they lead to
8,14 = c-myc (14) = oncogene promoting cell-growth (G>S transition) = BURKITTS
14,18 = BCL2 (18) = anti-apoptosis = FOLLICULAR LYMPHOMA (~85% of cases has t(14,18))
57
T/F- don't need to treat asymtomatic follicular or marginal celllymphoma
TRUE ! both are low-grade / indolent
* just observe asymptomatic low-grades
* *can treat with rituximab if symptomatic
58
T/F - treat majority of low-grade (indolent) lymphomas with rituximab +/- radiation
FALSE ... majority just WATCH if asymtomatic low-grade
59
mycosis fungoidies associated with _______ cancer
Cutaneous T cell lymphoma
| -present with slowly progressive plaquey skin lesions of varying shape all over body
60
dx? 9 year old immigrant from ethiopia present with ulcerated jaw mass that has doubled in size over past week, biopsy shows high proliferation and lymphocytes
***what translocation associated with this dx?
BURKITTS ... t(8,14) = cMyc
61
T/F- Burkitt's lymphoma is more common in HIV+ population
TRUE
62
translocation / mutatiion associated with follicular lymphoma?
t(14,18) = BCL2 >> anti-apoptosis
63
What are we worried if WBC is low and you have a fever? (gram +, neg, anaerobe)
what would we use: 1st gen ceph, 3rd gen ceph, macrolide, vancomyocin
YES.- worried that you are immunosuppressed ... like PSEUDOMONAS in the blood
1st cover gram negative >> 3rd + generation ceph, peper, zosin
Then add gram + or add anerobe coverage if abdominal pain
64
What (in general) do myelosupressive and immunosupressive treatments target? What bugs are they THEN at risk for (bacteria vs intracellular)
T/F - AML is mostly immunosupressive therapy?
ALL - immunosupressive ... Parts are myelosupressive
AML - mostly myelosupressive So FALSE
myelosupressive >> targets PMN >> BACTERIA INFECTION!
immunosupressive >> lymphocytes >> INTRACELLULAR
65
T/F - can you be neutropenic with WBC of 100K
T/F - should treat with fever even if WBC is low
YES... becuase if they are just a bunch of blasts (Acute leukemias) then functioanlly neutripenic
TRUE
66
what drugs would we use to cover
- gram +
- gram -
- anaerobes
SKIN/MOUTH >> cover GRAM + >> cephalosporin (3rd or higher) or synthetic peniccilin (peper) >> VANCOMYOCIN (if worried about MRSA) >> linezolid (last line)
ANY FEVER+NEUTROPENIA (esp if GI tract) >> cover GRAM NEG - 3rd + generation ceph, peper, zosin
MOUTH/Abscess/GI >> cover ANAEROBE >> clinda (above diaphragm) or flagil (below diaph
67
SIRS vs sepsis
SIRS
–Systemic symptoms
Sepsis
–Overwhelming bacterial infection leading to shock
68
what is definition of SHOCK?
What is main difference between compensated vs. decompensated (mental status? HR? BP?)
-inadequate tissue perfusion (not enough nutrients and o2 to cap beds) >> acidsosi, anerobic metabolism etc
COMPENSATED = normal mental status, normal BP, high BP
DECOMPENSATED - mental status change, BP dropping, high HR that is slowing
69
what are SIGNS OF COMPENSATED SHOCK:
- mental status
- urine output
- BP
- HR
- pulse pressure (normal, wide, narrow)
```
Elevated HR
●Widened pulse pressure
●Normal to high BP
●Possibly cool extremities
●Normal mental status
●Decreased urine output
```
70
18 year old AML presents with fever and low neutrophils, has high HR, low BP, OK mental status, no urine output. What is most accurate descriptioN:
- bactermia
- SIRS
- decompensated shock
- compensated shock
decompensated
71
findings in tumor lysis syndrome
- ___(Hyper or hypo)kalemia
- ______ phosphatemia
- _____calcemia
- ______Uricemia
- HYPERKALEMIA = b/c tumor cells are fragil and dying >> dump intracellular contents which is HIGH IN K
- HYPERPHOSPHATEMIA = see above (high PO4 inside cells)
- HYPOCALCEMIA =
- HYPERURICEMIA = becuase of high cell turnover >> DNA spilled out >> end of purine degradation pathway = URIC ACID
72
dx? patient with ALL presents with muscle spasms, heart failure, seizures, arrythmias, pH is low
Rx ?
TUMOR LYSIS SYNDROME >> HYPOcalcemia (spasm, HF, seizure) and HYPERKALEMIA (arrythmia)
Rx - HYDRATEEEE!!!! and give ORALL Calcium! (oral not IV becuase that can drop PTH >> make high phosphate worse)
73
name 2-3 complications of tumor lysis syndrome
- hyperkalemia >> acidosis, arrythmia
- hypocalcemia >> seizure, spasm (facial twitch),
- hyperuricemia >> gout, renal FAILURE
74
Tumor lysis sydrome leads to renal failure becuase of ______(high/low) ______(phosphate, calcium, sodium, potassium)
-high phosphate and uric acid
75
what is rx of tumor lysis syndrome (not LO)
Always
●IV fluids 2x maintenance
*FIX ELECTROLYTE IMBALANCES PRESENT.
Old way
●Allopurinol (orally)
●Inhibits Xanthine Oxidase
New way
●Urate Oxidase (Rasburicase)
76
- hyperleukocytosis is WBC greater than ____(50k, 100k, 200k, 500K)
- start seeing symptoms though around _____
- >100
| - >200
77
***list name 2-3 complications of WBC of 350K
- ARDS
- hemorrage / thrombosis / stroke (if >200)
- tumor lysis syndrome (>300)
78
most WORRISOME dx? 21 year old with T-cell Leukemia presenting with cough, dysphagia, orthopenia and edema
MEDIASTINAL MASS!
79
***why is mediastinal mass life-treatening ?
T/F - should intubate IMMEDIATELY if susepcted even before x-ray in order to save life
- obsturction of airway!!
- FALSE - can NOT save with intubation (still obstructied) so put on heart/lung bypass and TREAT with MEDS IMMEDIATELY (don't sedate)
80
**spinal cord compression symtoms
T/F - hurts to palpation
T/F - uncommon but serious complication in leukemia/lymphoma
-BACK PAIN (>90%) or kid that STOPS WALKING
(crescent mass extending to foramen)
-keep in ddx ALWAYS if new tumor (WBC or other like sarcoma)
- TRUE
- FALSE ... seen in lik 5% of newly diagnosed patients
81
T/F - the current survival rate is over 80% for all pediatric cancers
--what is the MOST and LEAST fatal?
TRUE - yay!
- most fatal is AML
- least fatal is hodgkin's
82
T/F - An individual is a cancer survivor from the time of diagnosis through the balance of his or her life.
T/F - Family members, friends and caregivers are also impacted by the survivorship experience and are therefore included in this definition.
TRUe and TRUE
83
name 2-3 late effects of childhood cancer
- growth impairmment
- fertility
- cardiac toxicity, decline in pulm, liver fxn
- subsequent cancers (SCC)
84
what is most common subsequent neoplasm in childhood cancer survival?
NOn-melanoma skin cancers!
-others = breast > thyroid > CNS > Sarcoma > melanoma (6%)
85
which of following is more likely in childhood cancer survival vs regular population:
- breast
- thyroid
- bone
- melanoma
ALL ... basicalaly increased risk of LOTS of cancers
one of the lowest OR (1.8) was actually lymphoma
86
what is highest risk factor for subsequent caner in childhood survival (XRT, chemo, imunosupressive drugs?)
XRT - 5-7 OR
no XRT - 2-4 OR
ALL - 4-5 OR
87
T/F- subsequent complicaitons in childhood cancer survival is similar in both M and F
FALSE ... Female have more complications (breast cancer, ovarian failure biggies)
88
-________ chemo drugs affects fertility
-alkylating agent (cyclophosmaide and procarbazine main 2 !)
89
T/F - cyclophosphamide affects both M and F fertility in childhood cancer survivals
T/F - radiation dose affects female fertility but not M fertility
- TRUE
| - FAlSE (affect both)
90
T/F - hodgkin disease has one of highest childhood cancersurvival rates but are one of most at risk population for long-term complications
TRUE
91
T/F- childhood cancer survivals are at least 5 times more likely to have stroke, heart attack and CHF than sibilings
TRUE
92
T/F - the occurance of late effects in adult survivors of childhood cancer survivals tapers with age then starts to plateau after about 30 years after dx (ie, once you're 30 years out... are they still at risk or no?)
FALSE --- late effect probs ocntinue to increase with time and does NOT appear to plateau
93
how do you tell if you have inborn TTP (mutations) vs. aquired TTP
-mixing with normal !
-- if mix and get SMALLER vWF polymers = inborn ADAMS13 mutation
--if NO CHANGE = antibody destruction of ADAMS13
*same idea as hemophilia vs antibody
94
T/F - TTP presents with CNS dysfunction (ex - altered mental status)
TRUE
95
* **criteria for DIC
- activation of _____(primary, secondary, both)
- activation of _____
- decreased _______
- and ____________
```
Criteria
--Activation of coagulation
Primary
Secondary
--Activation of fibrinolysis
--Consumption of factors and inhibitors
--Evidence of end organ damag
Not organ specific like HUS and TTP
```
96
causes of DIC (MOTS)
M - malignancy
O - obstetric (abruption, eclamsia) = amniotic fluid has TONS of TF
T - trauma (and burns)
S - sepsis *** most common ***
97
T/F- ARDS is more frequent in patients with DIC
T/F - DIC correlates with severity of trauma but not with severity of sepsis
true
false - correlates with both
98
T/F - DIC characterized by microthrombi in every organ system of the body
T
99
what is INR?
standardized PT (since measured differently at dif instutitons)
100
T/F- PT and aPTT not useful in diagnosing DIC
T/F - D-dimer is specific for DIC but not sensitive
TRUE ... can be very variables, prolonged 50-60%, shortenedi n 40-50%
FALSE - sensitive (#1 screening test)
101
fibrin split products vs. D-dimer
- -factor 13 : adds series of bonds betwee ncollagen monomers between ___ and ____ (2 D's , 2 E's or between D and E)
- -this bond _____ (is or is NOT) cleaved by plasmin
T/F - both are usually elevated in DIC
FSP = know plasmin is activated and thats IT
Factor 13 - adds series of bonds between D and E that plasmin can NOT cleave
-if you see D-dimer = collagen monemrs bound by factor 13 bonds (that plasmin can't cleave) = tells you fibrin activated in clot long enough that F13 cross-linked it and then plasmin ate it
TRUE - both are elevated
102
* **list criteria for transfusion in DIC
- -FFP if ______
- -cryopercipitate if_____
- -platelets if _______
- -fibrinolytics if ______
- -frozen flesh plasma (if PT/PTT elevated)
- -cryoprecipitate (to keep fibrinogen > 100)
- -platelets (keep >50K)
- -fibrinolytics - NOT recommeneded (will bleed out)
103
______ (FSP or D-dimer) tells you plasmin is activated while ______ (FSP or D) tells you thrombin and plasmin activated
- FSP = plasmin only
| - D-dimer = plasmin and thrombin activated
104
what would you infuse into pattient (FFP, cryoprecipitate, platelets) with DIC with:
- -normal PT/PTT , 100K platelets, 50 fibrinogen
- -elevated PT, 25K platelets, fibrinogen 150
- -elevated PTT, 75K plates, fibrinogen of 85
--cryo only (fibro
