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Haem/Onc > Stem Cell Transplantation, ASPHO > Flashcards

Stem Cell Transplantation, ASPHO Flashcards

1
Q

3 sources?

A

bone marrow, peripheral blood stem cells, cord blood

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2
Q

CD34 cell concentration to get good collection? Use what to get this?

A

> 20 cells/uL…GCSF (with or without chemo), plerixafor (–> peaks 5-11 hours later)

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3
Q

what if have ABO incompat with BONE MARROW donor?

A

need to do RBC depletion for major mismatches…plasma depletion for minor mismatches…PBSC generally have low RBC count so this is less of an issue

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4
Q

Role of cryopreservation?

A

done for autologus collections and cord blood, with DMSO.. smetimes needed for allogenic

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5
Q

what does DMSO do?

A

if you freeze a cell, it’s like a plate in a freezer and it can crack! DMSO –> membrane of cells–> keeps them flexible and less likely to break during freezing and thawing

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6
Q

CHallenge with DMSO?

A

room temp or warmed cells: can be toxic at high concentrations…infuse rapidly when thaw!

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7
Q

for what reason would you cryopreserve cells for allogenic transplant?

A

if cannot give cells to patient within 48-72 hours due to illness, etc–> need to cyropreserve the cells

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8
Q

problme with cyropreservation for AA pts?

A

could lead to increased rejection

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9
Q

sometimes do t-cell depletion, why?

A

decreased risk ofGVHD

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10
Q

2 ways to do t-cell depletion?

A

in vivo and in vitro

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11
Q

in vitro t-cell depeltion: hwo?

A

CD34+ selection OR CD3+ depeltion, CD3+/CD19+ depletion, alpha betaCD3+/19+depletion

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12
Q

problem with CD34 selection?

A

immune recovery very slow because ONLY have CD34 cells in your infusion

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13
Q

in vivo t-cell depletion how?

A

horse ATG
rabbit ATG
alemtuzumab
post-transplant cyclophosphamide

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14
Q

best to collect t-cells when?

A

early on, what high lymphocyte count, not too compromised from chemo

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15
Q

steps in car t cell prep?

A

collection, viral transduction, expansion, cryopreservation, infusion

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16
Q

how do you store stem cells for transplant?

A

fresh cells transpored cool; frozen cells in regulated shippers with continuous temp monitoring

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17
Q

stem cells stored how in lab?

A

liquid nitrogen tanks…viable for 30+ yrs

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18
Q

source for autologous transplant?

A

Peripheral cells!!!

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19
Q

source for allo transplant?

A

usually cord or marrow usually

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20
Q

t-cell count by source?

A

periphreal>BM>cord>t-cell depleted BM/periph

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21
Q

t-cell count affects?

A

time to neutrophil recovery faster with more t-cells…risk of graft rejection higher if few t-cells…gvhd high if lots of t-cells

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22
Q

CD34 count by source?

A

PBSC>BM>cord…higher if do t-cell depletion

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23
Q

early post HCT risk of infections by source?

A

highest in t-cell depleted>cord>BM>periphral

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24
Q

risk of graft rejection by source?

A

cord>BM>peripheral…higher if t-cell depleted

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25
Q

risk of acute GVHD by source?

A

peripheral=BM=cord…low if t-cell depleted

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26
Q

risk of chronic GVHD by source?

A

Peripheral>BM>cord…lower if t-cell depleted

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27
Q

target CD34 dose for BM adn PBSC transplant?

A

> 4-8x10^6 CD34 cells/kg recipient weight

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28
Q

target cells for cord blood transplant?

A

> 4 x 10^7 TNC/kg single unit…if mismatched, want >5 x 10^7…if 2 units, at least 3 x 10^7…more GVHD with 2 units though

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29
Q

if t-cell depleted/haploidentical cells, dose?

A

> 5-20 x 10^6 CD34 cells/kg recippient

also target <1x 10^5 CD3+ cells/kg recipient

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30
Q

allo trnasplant for leukemia: choose pbsc or cord if same match rate?

A

choose cord! don’t like to give unrelated donor peripheral cells in peds for allo

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31
Q

HLA: classes?

A

1 and 2

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32
Q

class I HLA compromised of?

A

A,B,C

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33
Q

class II HLA includes?

A

DR, DP, DQ

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34
Q

HLA antigens found where?

A

short arm of chrom 6

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35
Q

Class I HLA antigens found where?

A

almost all cells except some neurons

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36
Q

class II HLA antigens found where?

A

found on antigen-presenting cells, B cells

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37
Q

do we match for minotr antigens?

A

no

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38
Q

what does it mean to have a 6/6 match?

A

A,B,DRB1 matched

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39
Q

8/8 match=?

A

ABC and DRB1

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40
Q

10/10 match=?

A

ABC, DRB1, DQB1

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41
Q

12/12 match=?

A

A,B,C, DRB1, DQB1, DPB1

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42
Q

donor with respect to age consideration?

A

take the younger one!…most imp after HLA

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43
Q

what is the MOST important consideration for donor?

A

HLA

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44
Q

what the limit for unrelated donor mismatch BM/PBSC?

A

single allele/antigen mismatch…eg: 7/8

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45
Q

cord blood allowsfor waht level of mismatch?

A

4/6…although 6-7/8 better and high cell dose (>5 x 10^7) helps with mismatches

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46
Q

__ is preferred in peds over ___…data esp strong fron what?

A

BM; pbsc; non-malig disorders

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47
Q

PBSC –> ___ engraftment, __ GVHD

A

faster; more

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48
Q

when would you use PBSC?

A

used for high risk procedures (RIC, second trnaplants where need GVL effect)

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49
Q

need what from/to know what about peds donor?

A
  • assent
  • has relationship to recipient
  • review of health conditoins
  • screen fro HIV, HBV, HCV, syphilis, WNV, chagas
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50
Q

blood type matching ___; also want to match for?

A

helps (but not necessary)…CMV if possible

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51
Q

donor to avoid?

A

multiparous females (>1 preg), older female donor, donor who is much smaller than recipient

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52
Q

max volume you can take from donor?

A

20 ml/kg…goal of at least >4 x 10^6 CD34 cells/kg for recipient

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53
Q

ideal cord dose?

A

> 4 x 10^7 TNC/kg…at least 2.5 though!…and need >3 if 2 cords used…outcomes better with 1 cord (less GVHD)

54
Q

best donor?

A

matched sibling

55
Q

2 best donor?

A

matched unrelated donor, 8/8 or 10/10, BM preferred source

56
Q

10/10 unrelated donor is similar to what?

A

single antigen mismatch sibling donor

57
Q

fraternal or identical twin better donor?

A

FRATERNAL…identcal is like an auto transplant

58
Q

reasons to not go forth with trnasplant?

A

-active infection/inflamm
-non-recovery of counts
-non-remission (TLS)
-MRD + (can still do but relapse risk higher)
-pulmonary function <50% FEV1, DLCOc
-LFTs>5x ULN
-Cardiac EF<50%
-GFR<70
-low Karonowsky score
-Psych disorder
some of these issues can be addressed with RIC

59
Q

diff between non myeloablative, RIC, MA conditioning?

A

NMA: counts would eventually recover without transplant
RIC: may or may not eventually recover
MA: you would never recover

60
Q

For AML/MDS, do you use MA or RIC?

A

MA…more relapse with RIC

61
Q

conditioning for AML/RDS?

A

Busulfan-based: Bu/Cy, Bu/Fludarabine, Treosulfan/flu

62
Q

Conditoning for ALL?

A

TBI-based!
decrease relapse by 21%, increase OS by 16% with TBI… give this >1200-13500cGy in 6-8 fractions + cy or VP 16 +/- thiotepa/fludarabine

63
Q

conditoining for HLH?

A

RIC: flu/melphalan +/- thiotepa, bu/cy, treo/flu…and use serotherpay like rATG or campath to reduce GVHD

64
Q

2 conditonsin with reduced prep?

A

FA (sensitive to TBI—> give min TBI, lower dose chemo), SCID (no prep!)

65
Q

which disorders are hard to engraft?

A

SCD/thal

66
Q

all autologous regimens are __ ___, ___ procedures

A

high dose, myeloablative

67
Q

conditoning for NBL?

A

Carbo/Etop/Mel= CEM, tandem procedures

68
Q

condtioning for CNS tumours?

A

Carbo/thio x 3 tandem, carbo/thio/etop x 1

69
Q

conditioning for lymphoma?

A

BEAM (BCNU, Etop, Ara-C/Mel)

70
Q

3 things in SCT that would prolong immune suppression?

A

use of cord blood
use of t-cell depletion
use of ATG

71
Q

if you have prolonged immuen suppression, waht are you at risk for?

A

marked increase risk of viral reactivation/infection (CMV, adeno, EBV)…need surveillance for these!

72
Q

other than prlonged immune suppression, what else increases risk of infection?

A

acute and chronic GVHD, particularly use of and dose of steroids = the critiical RF…best to use doses below 1 mg/kg and every other day

73
Q

HLH pt who received RIC of alemtuzumab/flu/mel has a falling chimerism at day +55 (90 to 70%)…do what?

A

wean immune suppression rapidly and follow the chimerism

74
Q

ways to measure chimerism?

A

FISH if sex mismatch, or short tandem repeats

75
Q

in addition to whole blood chimerism can look at chimerism fo what?

A

t-cell (CD3)

76
Q

if t-cell (or whole blood) chimerism of a normal (t-cell replete) transplant is falling what does this indicate?

A

may be rejecting

77
Q

increased t cell chimerism from recipient in a malig case is associated with waht? what should you do?

A

relapse…wean immune suppression rapidly, consider donor leukocyte infusion

78
Q

if rapid loss of t cell chimerism from recipinet in AA waht is this? do waht?

A

ongoing anti-marrow response; increase immune suppression (exception)

79
Q

if no GVHD after tapering immunosuppression (in case of increased t cell chimerism from recipient in a malig case), do what next?

A

consider DLI

80
Q

5 RFs for graft rejection

A
  • NMA or RIC
  • HLA mismatched donors
  • cord blood/haploidnetial donors
  • non-malig disordrse
  • hyperinflamm/hyperprolif states
  • infetion,viral reactivation
81
Q

how to minimize risk fo graft rejection in NMA or RIC regimens?

A

use PBSC/agents like fludarabine

82
Q

how to min risk of rejection in HLA mimatched donors?

A

avoid donor-specific abs

83
Q

how to min rejection in cord blood/haploidentfical donors?

A

use intense, immunoablative regimens

84
Q

how to min rejection in hyper-inflamm/prolif states?

A

calm down inflamm/prolif

85
Q

how to min rejection in infection/viral reactivation?

A

control infection first, prevent viral reactivation if psosible

86
Q

acute GVHD dx’ed when?

A

usually before day +100, but typically near time of engraftment

87
Q

acute GVHD almost always invovles waht? and can involve what?

A

skin…intestine, liver, lung

88
Q

of stages fo acute GVHD?

A

4

89
Q

describe grading of skin aGVHD

A

1-rash <25%
2-25-50%
3->50%
4-generalized eyrhtroderma with bullae

90
Q

describe liver grading of acute GVHD

A

1- bili 2-3 mg/dl
2- bili 3.1-6
3- bili 6.1-15
5- bili >15

91
Q

describe gut grading of aGVHD

A

1-diarrhea 280-555 ml/m2/d
2-556-883
3->883
4- severe abdo pain

92
Q

aGVHD grading IN GENERAL: how does skin translate?

A

skin grade 1-2–> grade one
skin grade 3–> grade three
skin grade 4- four

93
Q

aGVHD grading in GENERAL: how does liver and gut translate?

A

liver or gut grade 1–> grade two
grade 2-3–> grade three
grade 4-> grade four

94
Q

prevent GVHD how?

A

Calcinurin inhbitor like tacro or cyclosproin…mtx…ssome centres use mmf…others= sirolimus, ATG, pred, post-transplant cyclophos…..ALSO t-cell depletion! rATG, hATG, campath= alemtuzumab, CD34 selection, alpha beta CD3-CD19 depletion

95
Q

t- cell dpletion increases risks of what?

A

infection
rejection
relapse

96
Q

for mild GVHD (rash only), do what?

A

optimize levels of calcineurin inhibitor and give steroids topically

97
Q

if progressive or multisystem GVHD,do what?

A

prednisolone 1-2 mg/kg/day

98
Q

steroid refractory acute GVHD=?

A

no resposne at 3-7 days

99
Q

do waht for steroid-refractory GVHD?

A

ruxolitinib for kids>12, also ECP, etanercept, infliximab, pentostatin…poor prog due to infectious complications

100
Q

cGVHD diagnosed when?

A

usually after day +100

101
Q

list 5 manifestations fo cGVHD

A
  • vitiligo
  • bronchiolitis obliterans
  • vanishing bile ducts
  • esoph strictures
  • fat malabs
  • poikiloderma
102
Q

which SCT patients do best with GVHD?

A
  • younger do better
  • less adv disease do better
  • good karofsky scores do better
  • high plt counts
  • matched sibling
103
Q

tx for cGVHD?

A

pred 1 mg/kg/day…taper to 1 mg every other day over 6 weeks…most kids with more than mild disease require taco/siro/cyclosporine plus other meds…median duration of tx is 2 yrs for respondign patients

104
Q

PTLD highly associated with waht?

A

t-cell depletion

105
Q

4 ways to tx PTLD?

A

lower immune suppression
rituximab
cyclophosphamide
EBV_targeted cytotoxic t-lymphocytes

106
Q

when does VOD present?

A

usually in the first 14 days after transpant, though can be through day +30

107
Q

pathophys of VOD?

A

endothelial damage in hepatic venules–> plt deposition–> hepatic congestion–> cholestasis

108
Q

which treatments are associated with VOD?

A

cy, busulfan, TBI….also sirolimus when used with tacro or cyclophos

109
Q

list 5 signs/sx of VOD

A
  • low plts (plt refractory)
  • increased bili
  • weight gain
  • RUQ pain
  • ascites
  • renal insufficiency
  • pulmonary edema
110
Q

how to tx VOD?

A
  • fluid management: diuresiss, keep fluid neg
  • manage intravasc volume
  • maage renal failure
  • defibrotide
111
Q

pathophys of transplant-associatd thrombotic microangiopathy?

A

endothelial damage from HSCT–> thrombosis nad fibirn depositonin the microcirc, with micoangiopathic HA and plt consuption

112
Q

TA-TMA affects whihc organ mostly? others?

A

kidney…others= GI, neuro

113
Q

How does TMA prseent?

A 
low hgb
low plts
schistocytes
increased LDH
decreased haptoglobin
114
Q

causes/associations fro TMA?

A

calcinuerin inhibitors (esp WITH sirolimus), TBI, high dose busulfan, infections

115
Q

tx TMA how?

A

eculizimab can improve renal function; stop or lower calcineurin inhibitor

116
Q

PRES stands for?

A

posteiror reversible encephalopathy syndrome

117
Q

sx of PRES assocaited with what?

A

malignant hypertension

118
Q

PRES linked to what tx?

A

calcineurin inhibitors

119
Q

when does PRES occur?

A

days 30-100

120
Q

how does PRES present?

A

headache, confuson, seizures, vision loss

121
Q

Dx PRES how?

A

MRI imaging of brain

122
Q

what do you see on MRI for PRES?

A

pattern of enhancement at post circulation

123
Q

tx PRES how?

A
  • control htn

- stop calcineurin inhibitors

124
Q

most common problem 2 years after HCT?

A

relapse

125
Q

list 5 late effects of HCT

A 
cGVHD
relapse
secondary malig
grwoth failure (TBI, CNS rad)
hypot4
gonadal failure
cardiomyoapthy from rad, anthra
126
Q

what’s most dangerous, allo or auto trnasplant?

A

allo

127
Q

GIve two disorders for which HCT can be used as gene therapy

A

Hurlier syndrome

X-linked adrenoleukodystrophy

128
Q

indications for CAR T-cells?

A

-refractory B-ALL or second or higher relapse

129
Q

% of pts who will either lose CARs and have CD 19 + relapse or CD 19 neg relapse?

A

30-35%, usually in first 6 months

130
Q

in adult, CARs also used in?

A

NHL

131
Q

AEs of CARs?

A

CRS, neuro events

Haem/Onc (30 decks)

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