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BMT Drugs Flashcards

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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
Indications for allogenic HCT
-multiple myeloma-not preferred -Hodgkin’s lymphoma-***not preferred*** -DLBCL-no preferred -AML -MDS -ALL -CML, CLL -severe aplastic anemia -SSD
26
Mobilization methods autologous and allogeneic
Autologous: -single agent G-CSF -chemo (***cyclophos or etoposide***) + G-CSF -plerixafor + G-CSF Allogeneic: -single agent G-CSF only
27
Myeloma mobilization
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
28
NHL mobilization
-single agent G-CSF has high failure rate -plerixafor if low CD34+(<10) -chemo based mobilization can be incorporated into planned salvage chemo
29
Which type of conditioning regimen is always used for autologous HCT?
Myeloablative -allogeneic can use all three types depending on the situation- myeloablative is better for young/fit pts
30
Who gets myeloablative conditioning ?
-AML, MDS, ALL, CML -young, low comorbidities ***TBI based in ALL***
31
Who gets reduced intensity or no myeloablative conditioning?
-older, significant comorbidities -prior HCT -CLL, NHL, HL, plasma cell disorders
32
Palifermin
Mucositis prevention for autologous HCT receiving HD-chemo + TBI
33
TBI antiemetics
High risk RT for Emesis 5HT3 + dex on day of and 1 day after
34
Sinusoidal obstruction syndrome prevention
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
35
Sinusoidal obstruction syndrome treatment
Defibrotide 6.25 mg/kg iv Q6h x 21d (max of 60 days) Most commonly occurs in first 3 weeks
36
GVHD prevention: myeloablative MRD or MUD
CNI + MTX +/- ATG ***Consider cyclosporine for related and tacrolimus for unrelated donor***
37
GVHD prevention: non-myeloablative
-CNI + mycophenolate +/- ATG -CNI + post transplant cyclophosphamide
38
GVHD prevention: ***mismatched unrelated*** donor
CNI + MTX + abatacept
39
GVHD prevention: haploidenrical
Tacrolimus + mycophenolate + post transplant cyclophosphamide
40
GVHD prevention: umbilical cord blood
CNI + mycophenolate ***avioid MTX***d/t delayed engraftment ***No ATG!!***
41
Acute GVHD grade 1 (skin only)
-continue or restart immunosuppressant -topical steroid -antihistamine -observation
42
Acute GVHD treatment ***grade II-IV***
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
Steroid refractory acute GVHD
Ruxolitinib-Skin and GI (liver is less likely to respond)
44
chronic GVHD tx
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
Chronic GVHD bronchiolitis obliterates syndrome
Fluticasone + azithromycin + montolukast (FAM) Note: most other pulmonary complicates are treated with steroids
46
Steroid refractory chronic GVHD
Belumosudil, ibrutinib, or Ruxolitinib
47
Bacterial ppx
-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
PJP ppx
-***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
Candida ppx
-***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
Mold ppx, aspergillus ppx
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
HSV and VZV ppx
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
CMV prevention
***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
Tx of thrombotic microangiopathy
-decrease or stop CNI/ sirolimus -change CNI/mTOR-I to other agents -plasma exchange -rituximab, Defibrotide, eculizumab
54
Autologous relapse prevention
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
Allogenic relapse prevention
AML/MDS: consider sorafenib if FLT3-***ITD*** AML (***no Lenalidomide***) ALL ph+: BCR-ABl TKI CML: consider BCR-ABL TKI
56
Late effects monitoring
-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
Secondary cancers
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
BEAM
BCNU (carmustine) Etoposide Cytarabine Melphalan ***For NHL and HL***
59
Define engraftment
ANC > 500 x3 days Plt > 20k w/o transfusion for 7 days
60
Vaccinations
-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
Pros and cons of peripheral blood vs bone marrow Also umbilical cord and haploidentical
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
Goals # of stem cells to collect
2-5 x10^6 CD34+ cells/kg (minimum 2)
63
Plerixafor
Mobilization agent for autologous ADR: diarrhea Often good if <10 CD34+ cells
64
***allogeneic*** RIC/NMA vs MA: which dx states get which?
RIC/NMA: CLL, HL, NHL, plasma cell disorders, prior HCT MA: AML, MDS, ALL, CML
65
NMA v MA risk of graft rejection
Higher risk with NMA (relies on immunosuppression rather than ablation)
66
Conditioning regimens
***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 (
67
Role of ATG
Unclear Guidelines rec for ***matched*** (MUD or MRD) at ***high risk*** of GVHD
68
Is G-CSF used after BMT to reduce neutropenic time
Yes- better evidence for autologous Allogenic- more with cord blood
69
Tx of viruses post HCT
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
Ifosfamide
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
Who do we need GVHD prophylaxis in?
Allogeneic!
72
Dose adjusting tacro and cyclosporin
Scr 2-2.9x BL- 25% dose reduction Scr >3x BL- 50% dose reduction
73
How long to continue tacro or cyclosporine
Begin tapering by 10% per week at day 50-100 if no aGVHD
74
Where does acute GVHD manifest?
Skin, liver, GI Chronic can be other places (often we see fibrosis)
75
Who need sinusoidal obstructive syndrome ppx?
-***Allogenic***- especially if myeloablative -busulfan Others: -pre-existing liver injury -iron overload -ozogamicin -abdominal irradiation -prior HCT
76
HCT late complications
-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
Low level laser therapy
Mucositis from HCT high dose chemo +/- TBI
78
Define Steroid refractory
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
Other respiratory issues
***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
Stem cell mobilization g-CSF and plerixafor dosing
G-CSF- max 10 mcg/kg Plerixaphor: 0.24 mg/kg x1, ~11hours prior to collection (max 4 days)
81
Most common infections after allogenic HCT in first 30-100 days
HHv6, EBV, CMV
82
Preffered donor type
MRD>haploidentical >MUD> UBC>MMUD
83
Infusion of stem cells pearls
-premedication with h1, APAP, steroid for infusion rxn -if cryopreserved beware DMSO toxicity (nausea, bradycardia, garlic smell x24h)
84
Sinusoidal obstructive syndrome
-can be “classical” or “late onset” (>21d) -signs/symptoms: ***2 of the following*** -bili >2 -painful hepatomegaly -Ascites -wt gain >5% pre HCT
85
GVHD ppx- RIC
CNI + mycophenolate + post transplant cyclophosphamide
86
Organs likely to respond to respective second line agents for GVHD
***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
When to give tamiflu
<2 years post HCT- exposure during outbreak 75 bid x5d- tx 75 QD x10-14d- post exp ppx
88
Allo vs auto pros and cons
Autologous: -decreases transplant related mortality Allogenic: -lower relapse rate -graft v host effect -graft free of contaminating tumor cells
89
Carmustine + thiotepa
PCNSL and NHL with CNS dx
90
Thiotepa + busulfan + cyclophosphamide
PCNSL and NHL with CNS dx
91
Most common type of infection in first few weeks after transplant
Gram positive

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