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BCOP- Joey > BMT Drugs > Flashcards

BMT Drugs Flashcards

1
Q

Abatacept (orencia)

A

Selective T-cell costimulation blocker- binds CD80 and CD86

-10 mg/kg IV day before transplant, then on days 5, 14, and 28
-to prevent GVHD in combo with CNI and MTX in mismatched unrelated donor

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2
Q

Antithymocyte globulin equine (Atgam)

A

Immunosuppressant

-can be given for steroid refractory acute GVHD tx
-can do test ID dose to assess for anaphylaxis

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3
Q

Antithymocyte globulin rabbit (Thymoglobulin)

A

Immunosuppressant

-can be given as part of conditioning regimen for GVHD prevention

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4
Q

Belumosudil (Rezurock)

A

Rock2 inhibitor

-steroid refractory chronic GVHD after 2 prior lines of therapy
-DDI with PPIs- increase dose to BID

-skin, GI, joint, **eyes, oral, liver, lungs **

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5
Q

Busulfan (Busulfex, Myleran)

A

Alkylating agent

-daily or Q6h
-used in myeloablative and reduced intensity regimens
-IV most common but can use PO (inter patient variability with PO)
-can use TDM
-seizure ppx with keppra
-DLTs: pulmonary fibrosis, hepatotoxicity, mucositis
-caution in pulmonary dysfunction
-sinusoidal obstruction syndrome -ursodiol ppx
-pharmacokinetic monitoring
-Q6h IV: AUC goal 3.9-6.2
-daily iv: AUC goal 14.8-24.6
-DDI- azoles, APAP, metronidazole (all increase busulfan)- avoid APAP/met 72h before and after, also phenytoin
-hepatic metabolism via enzymatic conjugation with glutothione

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6
Q

Carmustine (BiCNU)

A

Alkylating agent

-in BEAM regimen (often used in autologous for lymphoma)
-can cause infusion rxn, HA, perioral paradthesia, flushing d/t etoh in formulation- doses >150 mg/m2 (give APAP, HM, or BZD to mitigate)
-pulmonary toxicity >450 mg/m2- give steroids pred 1mg/kg/d
-renal elimination
-avoid drugs that can cause disulfiram like rxn d/t etoh content

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7
Q

Cyclophosphamide (Cytoxan)

A

Alkylating agent

-used in mx drug regimens
-hemorrhagic cystitis if high doses
-cardio toxicity >150 mg/kg (at ~10days)- monitor w/ ECG
-also used in GVHD ppx
-hepatotoxicity

DI: Give before busulfan and thiotepa

Busulfan and phenytoin increase cyclo metabolism to toxic metabolites

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8
Q

Cyclosporine (Gengraf, Neoral)

A

Calcineurin inhibitor

-commonly used for pts with aplastic anemia
-used to prevent and tx GVHD
-renal toxicity, hypomagnesemia, hyperkalemia, and HTN
-rarely causes PRES (posterior reversible encephalopathic syndrome)
-many DDIs including letermovir and 3A4 substrates
-200-300 ng/mL
-IV:PO 1:4 (sandimmune), 1:2-3 (modified)

Hirtuism (unlike tacrolimus)

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9
Q

Cytarabine

A

Pyramidine analog

-used in BEAM conditioning regimen
-DLT: neurotoxicity (but most transplant regimens are no high dose- they are usually <1g/m2/dose)

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10
Q

Etoposide (toposar)

A

Topo-II inhibitor

-commonly used in mx drug regimens
-if undiluted it can cause hypotension and precipitation so give with high volume of fluid
-metabolic acidosis- large amount of etoh
-DLT: mucositis
-3A4 substrate- interactions!

-metabolized in liver then renally excreted, 1/3 renally excreted unchanged
-renal elimination increases with hepatic impairment

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11
Q

Fludarabine (Fludara)

A

Purine analog

-common drug used in mx regimens
-watch for renal impairment and potential CNS toxicity- esp 40-100 mg/m2/d or total 200 mg/m2 with accumulation (happens ~2 months later)
-immunosuppressive (like cyclophos) so it’s good for NMA regimens

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12
Q

Ibrutinib (imbruvica)

A

BTK inhibitor

-CLL
-used to tx steroid refractory chronic GVHD (less evidence than ruxolitinib and belumosudil)
-DDI with azoles that are dose adjusted specifically based on indication
ADRs: cardiac toxicity (afib, HTN), bleeding (hold for surgery), arthralgia/myalgia, transient lymphocytosis)

cGVHD: skin, oral, GI

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13
Q

Letermovir (Prevymis)

A

Antiviral

-prevents clinically significant CMV in allogenic recipients who are CMV positive (R+)
-Started after HCT and continued through day 100
-dose adjust if given with cyclosporin

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14
Q

Maribavir (Livtencity)

A

Antiviral

-post transplant refractory CMV infection- refractory to IV ganciclovir
-given for 8 weeks

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15
Q

Melphalan (Alkeran, Evomela)

A

Alkylating agent

-most commonly used in autologous regimens for myeloma
-short stability
-given with cryotherapy (ice chips chewed) to prevent mucositis
-VOD
-renal elimination

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16
Q

Methotrexate

A

Antimetabolite

-used to prevent GVHD
-typically 4 doses beginning day +1 in mini-doses (can omit 4th dose if hemorrhagic mucositis)
-no dose adjustment for DDI and no leucovorin since mini-doses
-mucositis
-delayed engraftment

Decrease by 50% for scr >2x BL, LFT>200, or bili >5

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17
Q

Motixaforide (Aphexda)

A

CXCR4 antagonist

-autologous stem cell mobilization in combo with G-CSF

Premedicate with H1 and H2 and leukotriene receptor blocker to prevent hypersensitivity rxn

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18
Q

Mycophenolate mofetil (Cellcept)

A

Immunosuppressant

-used instead of MTX in reduced intensity or non-myeloablative regimens to prevent GVHD
-less commonly used drug for GVHD prevention by depleting T-cells

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19
Q

Omidubicel-onlv (Omisirge)

A

Nicotinamide-modified allogeneic hematopoietic progenitor cell therapy

-used for expansion of umbilical cord blood cells leading to decreased time to neutrophil and plt recovery

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20
Q

Ruxolitinib (Jakafi)

A

JAK inhibitor

-used to tx steroid refractory GVHD
-dose adjust for crcl, plt, and bilirubin
-no adjustment needed for posaconazole, voriconazole, or fluconazole for the GVHD indication

ADR: myelosuppression, infxns (CMV), edema, LFTs, hemorrhage, HLD, high triglycerides

cGVHD: skin, oral, GI, liver, lung, MSK

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21
Q

Sirolimus (Rapamune)

A

mTOR inhibitor

-used to prevent GVHD
-can be used as immunosuppressant when pts develop TMA/MAHA with calcineurin inhibitors
-long t1/2 so monitor trough once weekly
-3A4 substrate- Dec from azoles
-DI with statins- rhabdo
-Increased risk of VOD
-thrombotic microangiopathy
-3-14 ng/mL

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22
Q

Tacrolimus (Prograf)

A

Calcineurin inhibitor

-used to prevent and tx GVHD
-renal toxicity, hypomagnesemia, hyperkalemia, and HTN
-requires TDM
-rarely causes PRES (posterior reversible encephalopathic syndrome)
-many DDIs as it is a 3A4 substrate
-5-15 ng/mL (5-10 if given with sirolimus)
-IV:PO 1:3-4

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23
Q

Thiotepa (Tepadina)

A

Alkylator

-used in CNS penetration in auto and allo conditioning regimens (good if leptomeningeal or parenchyma involvement)
-hyperpigmentation-excreted in sweat- BID skin cleansing during and x48h after therapy. Change linens
-DLTs: mucositis, neurotoxicity
-give after cyclophosphamide (prevents activation of cyclophosphamide

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24
Q

Indications for autologous HCT

A

-multiple myeloma
-Hodgkin’s lymphoma
-DLBCL
-systemic sclerosis

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25
Q

Indications for allogenic HCT

A

-multiple myeloma-not preferred
-Hodgkin’s lymphoma-not preferred
-DLBCL-no preferred
-AML
-MDS
-ALL
-CML, CLL
-severe aplastic anemia
-SSD

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26
Q

Mobilization methods autologous and allogeneic

A

Autologous:
-single agent G-CSF
-chemo (cyclophos or etoposide) + G-CSF
-plerixafor + G-CSF

Allogeneic:
-single agent G-CSF only

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27
Q

Myeloma mobilization

A

Single agent G-CSF 10-16 mcg/kg/d if all of the following
-no more than 1 prior line of chemo
-no prior Melphalan
-no more than 4 cycles lenolidamide and wait 2-4 weeks after last dose

-Use plerixafor if low CD34+ (<10)
-if prior lenalidomide:
-collect after no more than 2-4 cycles
-can use G-CSF + chemo + plerixafor

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28
Q

NHL mobilization

A

-single agent G-CSF has high failure rate
-plerixafor if low CD34+(<10)
-chemo based mobilization can be incorporated into planned salvage chemo

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29
Q

Which type of conditioning regimen is always used for autologous HCT?

A

Myeloablative

-allogeneic can use all three types depending on the situation- myeloablative is better for young/fit pts

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30
Q

Who gets myeloablative conditioning ?

A

-AML, MDS, ALL, CML
-young, low comorbidities

TBI based in ALL

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31
Q

Who gets reduced intensity or no myeloablative conditioning?

A

-older, significant comorbidities
-prior HCT
-CLL, NHL, HL, plasma cell disorders

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32
Q

Palifermin

A

Mucositis prevention for autologous HCT receiving HD-chemo + TBI

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33
Q

TBI antiemetics

A

High risk RT for Emesis

5HT3 + dex on day of and 1 day after

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34
Q

Sinusoidal obstruction syndrome prevention

A

Ursodiol 12 mg/kg/day through days 1-30 (or 1-90)

Risk fx: allogeneic, myeloablative, busulfan, ozogamicin, pre-existing liver injury, iron overload

Avoid hepatotoxins, APAP, azoles, progestins, estrogens

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35
Q

Sinusoidal obstruction syndrome treatment

A

Defibrotide 6.25 mg/kg iv Q6h x 21d (max of 60 days)

Most commonly occurs in first 3 weeks

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36
Q

GVHD prevention: myeloablative MRD or MUD

A

CNI + MTX +/- ATG

Consider cyclosporine for related and tacrolimus for unrelated donor

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37
Q

GVHD prevention: non-myeloablative

A

-CNI + mycophenolate +/- ATG
-CNI + post transplant cyclophosphamide

38
Q

GVHD prevention: mismatched unrelated donor

A

CNI + MTX + abatacept

39
Q

GVHD prevention: haploidenrical

A

Tacrolimus + mycophenolate + post transplant cyclophosphamide

40
Q

GVHD prevention: umbilical cord blood

A

CNI + mycophenolate

avioid MTXd/t delayed engraftment
No ATG!!

41
Q

Acute GVHD grade 1 (skin only)

A

-continue or restart immunosuppressant
-topical steroid
-antihistamine
-observation

42
Q

Acute GVHD treatment grade II-IV

A

Continue/restart/increase immunosuppressant

AND

-skin/lower GI/liver: MP 1-2 mg/kg/d (use lower end for grade II)

grade II upper GI only:
-budesonide or beclomethasone + pred/MP 0.5-1 mg/kg/day

OR
Sirolimus ALONE (instead of steroids) for standard risk aGVHD

43
Q

Steroid refractory acute GVHD

A

Ruxolitinib-Skin and GI (liver is less likely to respond)

44
Q

chronic GVHD tx

A

Mild: topical steroid or pred 1 mg/kg/d

Mod-severe: pred 1 mg/kg/d this is lower than acute GVHD

Notice, not normal grading system like with aGVHD

45
Q

Chronic GVHD bronchiolitis obliterates syndrome

A

Fluticasone + azithromycin + montolukast (FAM)

Note: most other pulmonary complicates are treated with steroids

46
Q

Steroid refractory chronic GVHD

A

Belumosudil, ibrutinib, or Ruxolitinib

47
Q

Bacterial ppx

A

-FQ day 0-30 (auto and allo)
-PCN: day >100 for allogeneic with chronic GVHD on immunosuppressive-CHRONIC NOT ACUTE, ALLO not auto (don’t get tripped up)

48
Q

PJP ppx

A

-allogeneic through 6 months or longer if on immunosuppressive
-consider for autologous if heme ca, intensive conditioning, graft manipulation, or recent purine analog
-start at engraftment (could cause delayed engraftment if started right away)
-GVHD tx with steroid 20+ pred equivalents x4+wk

49
Q

Candida ppx

A

-allogeneic: fluconazole 400 mg/d through at least day 75 (if low risk for mold infection)
-consider for autologous if prolonged neutropenia, mucosal damage (mucositis)graft manipulation, or recent purine analog
-can also use echinocandin
-remember to use mold agent instead of GVHD on tx

50
Q

Mold ppx, aspergillus ppx

A

Mold:
allogeneic
-cord blood, haploidentical, bone marrow, prolonged neutropenia prior to HCT, prior IFI or GVHD on tx (use posaconazole) (DOESNT MATTER IF ACUTE V CHRONIC-unlike PCN)
-azole or echinocandin through duration of neutropenia or immunosuppressant tx
-mold active azoles include, posa, vori, isavu

Aspergillus:
-If allo and high risk aspergillus: posa or vori until at least day 75
-risk fxs: MMUD, UCB, haplo, prolonged neutropenia, GVHD on tx, exposed, prior aspergillus infxn, active heme ca

51
Q

HSV and VZV ppx

A

HSV
-acyclovir for all seropositive allogeneic through duration of neutropenia/mucositis
-consider if seripositive autologous especially if mucositis

VZV
-acyclovir for all HCT for at least 1 year

therefore everyone need acyclovir for at least 1 year

52
Q

CMV prevention

A

all allogeneic
1. Ppx: letermovir 480 mg (240 mg if w/ cyclosporin) for seropositive (R+) AND allogeneic (start day 0 or no later than. Day 28 and continue through day 100)
2. Preemptive: monitor through day 100 and initiate valganciclovir 900 mgPO x14 days then 900 mg daily x1-2 wks- if infxn (for asymptomatic pts with cmv on lab markers)

Treatment:
-ganciclovir, valganciclovor
-foscarnet
-maribavir (oral)

53
Q

Tx of thrombotic microangiopathy

A

-decrease or stop CNI/ sirolimus
-change CNI/mTOR-I to other agents
-plasma exchange
-rituximab, Defibrotide, eculizumab

54
Q

Autologous relapse prevention

A

Multiple myeloma: lenalidomide 10-15 mg QD for at least 2y start 3 months post transplant
bortezomib if can’t take ^

Mantle cell lymphoma: rituximab q8 wk x3 yr- if rituxan sensitive

Follicular lymphoma: rituximab q8 wk x4 doses- if rituxan sensitive

Hodgkin’s lymphoma: Brentuximab (unless already used and refractory) q3 wk x16- if one of the following:
-refractory to initial tx
-relapse <12 months
-extranodal dx at pre-transplant

DLBCL: rituximab is not recommended

CML or ph+ ALL: maybe bcr-abl tki

55
Q

Allogenic relapse prevention

A

AML/MDS: consider sorafenib if FLT3-ITD AML (no Lenalidomide)

ALL ph+: BCR-ABl TKI

CML: consider BCR-ABL TKI

56
Q

Late effects monitoring

A

-ophthalmic exam at 1 yr
-dental exam at 1 yr
-CV risk at 1 yr then annual (lipids, DM)
-renal at 6 mo, 1 yr, then annual
-BP every visit
-thyroid annual
-gyn at 1 yr (women)
-gonadal for men if symptoms
-BMD at 1 yr for all women and allogeneic pts
-avascular necrosis
-secondary cancers

No longer in workbook:
Lfts, Pfts, ferritin

57
Q

Secondary cancers

A

Esophagus: endoscopy if persistent GERD/dysphasia

Oral: annual oral exam

Thyroid: annual exam

Breast: if TBI or chest RT- start screen at age 25 or 8 yr after RT- annual breast exam, mammogram and MRI

Cervix- annual pap and HPV test

Skin- annual skin exam

58
Q

BEAM

A

BCNU (carmustine)
Etoposide
Cytarabine
Melphalan

For NHL and HL

59
Q

Define engraftment

A

ANC > 500 x3 days
Plt > 20k w/o transfusion for 7 days

60
Q

Vaccinations

A

-re-vaccinate 2 years after for live
-inactivated:
-3 months: Covid, hib, PCV13/15/20, polio
-6 months: diptherias, heps, meningitis, hpv
-12 months: PPSV23
-others: flu- 4 mo, zoster 50-70d (autologous only)
-NO LIVE if active immunosuppression and/or GVHD

-recipient no live 4 weeks or inactive 2 weeks before start of conditioning
-Donor* should avoid live for 4 weeks prior to stem cell harvest
Live:
COZY IV RM
Cholera, oral typhoid, zoster (zostavax), yellow fever, intranasal influenza. Varicella, rotavirus, MMR

61
Q

Pros and cons of peripheral blood vs bone marrow

Also umbilical cord and haploidentical

A

Pros:
Peripheral blood
-faster engraftment
-lower graft failure
-ease of collection

Cons:
- higher risk of cGVHD

-umbilical cord is opposite: more graft rejection, but less GVHD
-haploidentical: less graft rejection, more GVHD

62
Q

Goals # of stem cells to collect

A

2-5 x10^6 CD34+ cells/kg (minimum 2)

63
Q

Plerixafor

A

Mobilization agent for autologous

ADR: diarrhea

Often good if <10 CD34+ cells

64
Q

allogeneic RIC/NMA vs MA: which dx states get which?

A

RIC/NMA: CLL, HL, NHL, plasma cell disorders, prior HCT

MA: AML, MDS, ALL, CML

65
Q

NMA v MA risk of graft rejection

A

Higher risk with NMA (relies on immunosuppression rather than ablation)

66
Q

Conditioning regimens

A

MA: high doses of one or more alkylating agent or high dose TBI
RIC:
-<500cGy TBI as single fx or <800cGy as fractionated
-<9 mg/kg PO busulfan
-<140 mg/m2 Melphalan
-<10 mg/kg thiotepa
NMA:
-generally contains low dose TBI (</=200 cGy) and immunosuppressive chemo (Fludarabine, cyclophosphamide)

MA:
-BEAM
-BuCy
-BuFlu
-carmustine + thiotepa
-carbo + etop
-Cyclo/ TBI
-Flu/ TBI
-Flu/Cy/TBI
-Melphalan

RIC:
-Flu/Bu
-Flu/Cy
-Flu/Cy/TBI
-Flu/Cy/thiotepa/TBI
-Flu/Mel

NMA
-Flu/TBI

67
Q

Role of ATG

A

Unclear

Guidelines rec for matched (MUD or MRD) at high risk of GVHD

68
Q

Is G-CSF used after BMT to reduce neutropenic time

A

Yes- better evidence for autologous

Allogenic- more with cord blood

69
Q

Tx of viruses post HCT

A

VZV: Iv acyclovir

Adenovirus: stop immunosuppression and use Cidofovir

Herpes virus 6: ganciclovir, foscarnet, Cidofovir

BK virus: hyper hydrate, decrease immune suppression, Cidofovir +/-probenecid

RSV: aerosolized ribavirin

Flu: neuraminidase inhibitors, tamiflu

70
Q

Ifosfamide

A

DLT is renal toxicity and neurotoxicity

-renal tubular damage can cause fancomi syndrome
-hemorrhagic cystitis occurred with 4-6 weeks of administration

-hepatic metabolism to active metabolite —>renal elimination

-3A4 interactions- pro drug, inducers increase activation to active metabolite, inhibitors decrease activation

71
Q

Who do we need GVHD prophylaxis in?

A

Allogeneic!

72
Q

Dose adjusting tacro and cyclosporin

A

Scr 2-2.9x BL- 25% dose reduction

Scr >3x BL- 50% dose reduction

73
Q

How long to continue tacro or cyclosporine

A

Begin tapering by 10% per week at day 50-100 if no aGVHD

74
Q

Where does acute GVHD manifest?

A

Skin, liver, GI

Chronic can be other places (often we see fibrosis)

75
Q

Who need sinusoidal obstructive syndrome ppx?

A

-Allogenic- especially if myeloablative
-busulfan

Others:
-pre-existing liver injury
-iron overload
-ozogamicin
-abdominal irradiation
-prior HCT

76
Q

HCT late complications

A

-ocular
-oral
-lung
-liver
-cardiac
-renal
-genito-urinary (gyn exam in women at 1 yr and men with symptoms)
-endocrine
-skeletal (BMD at 1 yr for all women and allo HCT)

77
Q

Low level laser therapy

A

Mucositis from HCT high dose chemo +/- TBI

78
Q

Define Steroid refractory

A

aGVHD: progresses after 3-5 days or or doesn’t improve after 5-7 days

cGVHD: progresses after 1-2 weeks or doesn’t improve after 4-8 weeks

79
Q

Other respiratory issues

A

Peri-engraftment respiratory distress syndrome
-discontinue filgrastim
-steroids 1 mg/kg/ day

idiopathic pneumonia syndrome
-Methylpred 2 mg/kg/d x7 d then taper
-eteracept

Diffuse alveolar damage
-steroids 2 mg/kg/d to 1 g/m2/d

bronchiolitus obliteruns organizing PNA
-pred 1 mg/kg/d tapered over 3-6 mo

bronchiolitus obliteruns syndrome
-pred 1-1.5 mg/kg/d taper over 6-12 mo
-FAM

80
Q

Stem cell mobilization g-CSF and plerixafor dosing

A

G-CSF- max 10 mcg/kg

Plerixaphor: 0.24 mg/kg x1, ~11hours prior to collection (max 4 days)

81
Q

Most common infections after allogenic HCT in first 30-100 days

A

HHv6, EBV, CMV

82
Q

Preffered donor type

A

MRD>haploidentical >MUD> UBC>MMUD

83
Q

Infusion of stem cells pearls

A

-premedication with h1, APAP, steroid for infusion rxn
-if cryopreserved beware DMSO toxicity (nausea, bradycardia, garlic smell x24h)

84
Q

Sinusoidal obstructive syndrome

A

-can be “classical” or “late onset” (>21d)
-signs/symptoms: 2 of the following
-bili >2
-painful hepatomegaly
-Ascites
-wt gain >5% pre HCT

85
Q

GVHD ppx- RIC

A

CNI + mycophenolate + post transplant cyclophosphamide

86
Q

Organs likely to respond to respective second line agents for GVHD

A

aGVHD
Ruxolitinib: skin, GI

cGVHD
-Ruxolitinib: skin, GI, oral, liver, lung, MSK
-Belumosudil: skin, GI, oral, liver, lung, eyes, joint/fascia
-ibrutinib: skin, GI, oral

87
Q

When to give tamiflu

A

<2 years post HCT- exposure during outbreak

75 bid x5d- tx
75 QD x10-14d- post exp ppx

88
Q

Allo vs auto pros and cons

A

Autologous:
-decreases transplant related mortality

Allogenic:
-lower relapse rate
-graft v host effect
-graft free of contaminating tumor cells

89
Q

Carmustine + thiotepa

A

PCNSL and NHL with CNS dx

90
Q

Thiotepa + busulfan + cyclophosphamide

A

PCNSL and NHL with CNS dx

91
Q

Most common type of infection in first few weeks after transplant

A

Gram positive

BCOP- Joey (11 decks)

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