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BCOP > BMT supportive > Flashcards

BMT supportive Flashcards

1
Q

plt engraftment

A

> 20 without transfusions

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2
Q

mucositis risk factors -4

A

Melphalan, Etoposide, TBI 12-14 Gy; methotrexate

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3
Q

mucositis prevention -3

A

 Good oral hygiene: saline or sodium bicarbonate

 Ice chips: beneficial in patients receiving melphalan

 Palifermin: beneficial in autologous patients receiving TBI/cyclophosphamide/etoposide (NOT STUDIED WITH BEAM)
% patients with Grade 3/4 mucositis
 duration of Grade3/4mucositis
 opioidinfusions&totalparenteralnutrition

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4
Q

Palifermin is NOT BENEFICIAL -3

A
  1. Multiple myeloma patients with melphalan 200 mg/m2
  2. Allogeneic HSCT patients in bu/cy pts (some evidence to use for cy/tbi but should not be test question)
  3. BEAM
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5
Q

acute GVHD risk factors -6

A

 HLA disparity
 HLA matched unrelated donors (HR 1.66)
 HLA mismatched related donors (HR 1.74)
 HLA mismatched unrelated donors (HR 2.0)
 Source & dose of stem cells
 peripheral blood > bone marrow > ?cord blood
 Increased CD34+ associated with increased
GVHD
 Older age of host or donor
 Conditioning regimen
 Higher dose of TBI increased risk of acute
GVHD
 TBI containing regimen vs. no TBI (HR 1.49)
 Sex mismatch
 Highest with parous females donating to males
 Female donor and male recipient (HR 1.14)
 CMV infection - cause-and-effect unclear

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6
Q

protective acute GVHD risk factors - 2

A

 Conditioning regimen
 Antithymocyte globulin is protective (HR 0.77)

 Diagnosis of CML (HR 0.87)

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7
Q

Acute GVHD Prevention -5

A

Donor selection - best histocompatible match

Single agent immunosuppression (not used much)
 Cyclophosphamide; cyclosporine; methotrexate

Combination immunosuppression
 Cyclosporine + Methotrexate 
 Tacrolimus + Methotrexate 
 Cyclosporine + Mycophenolate 
 Tacrolimus + Sirolimus

T-cell depletion – in vivo or ex vivo

Palifermin – negative trial

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8
Q

acute GVHD px - MRD

csa + MTX vs fk +MTX

A

CSA + MTX

-better OS 57 vs 47 even though worse aGVHD

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9
Q

acute GVHD px - MUD

csa + MTX vs fk +MTX

A

FK + MTX

-same OS, less aGVHD

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10
Q

Does replacing MTX with MMF in combo with CSA or FK work?

A

NO

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11
Q

MTX in acute GVHD ADR -2

A

mucositis

delays engraftment

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12
Q

CLL and cord blood SCT’s use MMF for aGVHD px. why is that?

A

delayed engraftment

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13
Q

why use single agent cyclophos for aGVHD px?

A

reduced cGVHD to 10% at 2 years

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14
Q

ADR comparison:

Siro + FK vs FK + MTX

A

more rapid engraftment and less mucositis with siro

more VOD and thrombotic microangiopathy

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15
Q

Cyclosporine aGVHD px ADR -3

A

Nephrotoxicity

Neurotoxicity

Trough level 150-450 ng/mL

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16
Q

Tacrolimus aGVHD px ADR -3

A

Nephrotoxicity

Neurotoxicity

Trough level 5-20 ng/mL (5-10 ng/mL with sirolimus)

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17
Q

Sirolimus aGVHD px ADR -3

A

TMA

Hepatotoxicity

Trough level 3-12 ng/mL

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18
Q

Mycophenolate aGVHD px ADR -3

A

GI toxicity

Myelosuppression

? AUC; trough levels don’t correlate in all HSCT trials

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19
Q

Methotrexate aGVHD px ADR -3

A

Mucositis

Delayed engraftment

Dose reduce or hold in renal or hepatic dysfunction; fluid collections; severe mucositis

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20
Q

Initial Treatment of Acute GVHD -3

A

 Grade I - Skin Only (less than 25%)
 Initially manage with topical corticosteroids

 Grade II – IV
 Methylprednisolone 2 mg/kg/day
 CR in 25-40% of patients; ORR 50%
 Taper by 10%/week after 1-2 weeks if patient responds (typically 6-12 weeks of therapy)

 Grade I or II GVHD
 Retrospective data suggests 1 mg/kg/day is effective (minimize toxicity)

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21
Q

Combination Initial Therapy for Acute GVHD - no benefit -3

A

 Anti-thymocyte globulin, Daclizumab, Infliximab

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22
Q

Combination Initial Therapy for Acute GVHD - possible benefit -3

A

Beclomethasone (BDP) in stage 1, isolated gut GVHD
- more rapid steroids

Mycophenolate – based on BMT CTN 0302 Trial
CR = 60%; OS at 9 months 64%
 Higher CR and OS than Etanercept, Denileukin diftitox, and Pentostatin (CR 26-53% and OS 47-49%)

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23
Q

Steroid Refractory Acute GVHD definition -3

A

 Progression after 3 days of methylprednisolone
 No change after 7 days of methylprednisolone
 Incomplete response after 14 day

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24
Q

Steroid Refractory Acute GVHD treatment

A

no standard of care (unlikely test question)

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25
Q

Chronic GVHD Risk Factors -6

A

 Prior grade III-IV acute GVHD (HR 1.42)

 HLA disparity between host and donor
 MUD (HR 1.3)
 MMRD (HR 1.24)
 MMUD (HR 1.57)

 Peripheral blood > bone marrow (HR 1.74)

 Older age of host or donor

 Sex mismatch
 Female : male (HR 1.37)

 Donor leukocyte infusion

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26
Q

chronic GVHD can effect virtually any organ. examples? -9

A
  1. dry eyes
  2. mucositis
  3. nail dystrophy
  4. skin
  5. deep muscle / joint
  6. liver
  7. lung - bronchiolitis obliterans
  8. autoimmune
  9. endocrine / metabolic
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27
Q

Mild Chronic GVHD (10% of pts that develop cGVHD)

NOT TESTABLE

A

Involves only 1 or 2 organs/sites (except the lung) with no clinically significant functional impairment (maximum score of 1 in all affected organs/ sites)

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28
Q

Moderate Chronic GVHD (30%)

NOT TESTABLE

A

Involves at least 1 organ/site with clinically significant but no major disability (maximum score of 2 in any affected organ/ site OR 3 or more organs/sites with no clinically significant functional impairment (max score of 1 in all affected organs/sites) OR a lung score of 1

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29
Q

Severe Chronic GVHD (60%, 2yr OS 50%)

NOT TESTABLE

A

Indicates major disability caused by cGVHD – score of 3 in any organ site. A lung score of 2 or greater will also be considered severe cGVHD

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30
Q

Initial Therapy of Chronic GVHD -MILD

A

Topical therapy

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31
Q

Initial Therapy of Chronic GVHD -MODERATE OR SEVERE -3

A

 Prednisone 1 mg/kg/day- taper to every other day (NOTE NOT BID)

 Prednisone + calcineurin inhibitor (not strong evidence)
 May benefit patients with platelet < 100 x 109/L

 Prednisone + other agents is not beneficial
 No benefit to addition of mycophenolate, thalidomide, hydroxychloroquine

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32
Q

Topical Therapy for Chronic GVHD - Skin

A

Topical steroids;

topical calcineurin inhibitors;

PUVA;

UVA;

UVB

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33
Q

Topical Therapy for Chronic GVHD - Gastro- intestinal

A

Topical steroids (budesonide or beclomethasone)

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34
Q

Topical Therapy for Chronic GVHD - Liver

A

Ursodiol

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35
Q

Topical Therapy for Chronic GVHD - Lung

A

Inhaled steroids

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36
Q

Topical Therapy for Chronic GVHD - Oral

A

Topical steroids (dexamethasone, prednisolone, clobetasol, fluocinonide)

Topical tacrolimus ointment;

Topical cyclosporine rinse;

topical azathioprine rinse

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37
Q

Topical Therapy for Chronic GVHD - Eye

A

Artificial Tears;

topical steroids;

topical cyclosporine

38
Q

Topical Therapy for Chronic GVHD - Vaginal

A

Topical steroids

Topical tacrolimus or pimecrolimus

39
Q

2nd Line Therapy of Chronic GVHD -treatment

A

NO SOC
NOT TESTABLE

 Patient history with prior therapies

 Agents with non-overlapping toxicities

 Patient preference

40
Q

2nd Line Therapy of Chronic GVHD - when to consider

PROBABLY NOT ON TEST

A

 Progression or new clinical manifestations on prednisone 1 mg/kg/day x 2 weeks

 No improvement despite treatment for 4-12 weeks

 Unable to taper prednisone < 1 mg/kg/day within 3 months or symptoms worsen during a taper < 0.5 mg/kg/day

 Inability to tolerate therapy

41
Q

extracorporeal photopheresis indx -2

A

skin and lung cGVHD

42
Q

Bacterial px > 100 days (streptococcus pneumoniae) indx and dose -2

A

 Allogeneic recipients with chronic GVHD (AIII)

 Penicillin 500 mg BID or 1000 mg daily

43
Q

Bacterial day 0 – 100 indx and dose -2

A

 Consider fluoroquinolone with antipseudomonal
activity with anticipated neutropenia > 7 days

 Levofloxacin (BI) or Ciprofloxacin (BII)

44
Q

Yeast (Candida) Prophylaxis - auto

A

Prolonged neutropenia and mucosal damage from intense conditioning regimen,

graft manipulation,

recent purine analog exposure

 Fluconazole 400 mg/day conditioning
through engraftment

45
Q

Yeast (Candida) Prophylaxis - allo

A

 Fluconazole 400 mg/day conditioning through day +75 (AI)

 Itraconazole (CI)

 Micafungin (BI)

 Posaconazole (BI)

 Voriconazole (BI)

46
Q

Allogeneic Mold Prophylaxis (Aspergillus, Fusarium, Mucor) - PRE ENGRAFTMENT

A

 Prolonged neutropenia
 higher with cord blood or BMT
 lower with peripheral blood and RIC transplant
 Risk is higher with prolonged neutropenia prior to HSCT

 Prophylaxis
 micafungin 50 mg (BI)

47
Q

Allogeneic Mold Prophylaxis (Aspergillus, Fusarium, Mucor) -POST ENGRAFTMENT

A

 Immunodeficiency caused by GVHD and its treatment
 higher risk include MUD, MMRD, and haploidentical

 Prophylaxis
 posaconazole 200 mg PO TID (BI)
 Alternative: voriconazole 200 mg PO BID (BII)

48
Q

VORI VS FLUC for alloHSCT px

A

NO DIFFERENCE

caveat: used aggressive monitoring that most centers don’t use

49
Q

Pneumocystis jiroveci Prophylaxis - auto indx - 5

A

Hematologic malignancies,

intense conditioning regimens,

graft manipulation (t-cell depletion),

recent purine analog therapy (BIII),

—engraftment x 3 to 6 months after HSCT (CIII), OR longer if ongoing immunomodulatory therapy (ex. imides in MM)

50
Q

Pneumocystis jiroveci Prophylaxis -allo

A

Engraftment x 6 months after HSCT, longer if patients continue to receive immunosuppressive drugs or have chronic GVHD (AII)

51
Q

how long to continue VZV px in allo?

A

Routine acyclovir 800 mg PO BID during first year (BI) or 6 months after discontinuation of all immunosuppression (CIII)

52
Q

CMV Prophylaxis

A

-No OS improvement

Ganciclovir 5 mg/kg/ dose IV BID x 5-7 days,
then once daily through day 100- start at engraftment (AI)

53
Q

CMV Preemptive Therapy - allo

A

 Ganciclovir 5 mg/kg/ dose IV BID 2 wk; or x 7 days+5 mg/kg/daily x2 wks; may go thru day 100

54
Q

CMV Preemptive Therapy - auto

A

Consider monitoring until day + 60 in patients at risk (TBI, alemtuzumab, purine)

55
Q

CMV Pneumonia tx

A

 Ganciclovir 5 mg/kg/dose IV BID x 21 days + IVIG 500 mg /kg IV QOD x 21 days (NOTE: ADDED IVIG)

 Maintenance x several weeks; longer if immunosuppression must be continued

56
Q

CMV tx -Enteritis, esophagitis, hepatitis, retinitis, marrow infection

A

 Ganciclovir 5 mg/kg/dose IV BID x 14-21 days or until resolution of process

 Maintenance x several weeks; longer if immunosuppression must be continued

57
Q

Varicella zoster virus tx

A

Acyclovir 10 mg/kg q 8 h x 7 -14 days;

Valacyclovir

58
Q

Adenovirus tx

A

Taper / withdrawal immunosuppression

more in kids, cord blood tx

59
Q

Human Herpes Virus 6 tx

A

Ganciclovir, cidofovir, foscarnet have in vitro activity

cord blood tx

60
Q

Respiratory syncytial virus tx

A

Aerosolized ribavirin x 7-10days + IVIG (if LRI)

61
Q

Influenza tx

A

Oseltamivir 75 – 150 mg BID x 10 days

62
Q

BK virus tx

A

 Hyperhydration

 Taper / withdrawal immunosuppression

 Cidofovir for hemorrhagic cystitis

63
Q

Invasive Fungal Infection (IFI) Treatment Candidemia

A

 Neutropenic: caspofungin / micafungin / liposomal amphotericin x 14 days + resolution of neutropenia (ESPECIALLY IF ON AZOLE)

 Non-neutropenic: echinocandin preferred if recent azole exposure

64
Q

Invasive Fungal Infection (IFI) Treatment Candidiasis

A

 Neutropenic: liposomal amphotericin / caspofungin

 Non-neutropenic: echinocandin preferred if recent
azole exposure; moderate to severe illness; at high
risk for infection due to C. glabrata or C. krusei

65
Q

IFI Treatment –Invasive Aspergillosis

A

 Voriconazole (survival advantage at 12 weeks over amphotericin B deoxycholate 71% vs. 58%)

 Withdrawal/reduction in corticosteroids

 A. terreus should received amphotericin B

66
Q

IFI Treatment –Fusarium

A

Amphotericin B; voriconazole; posaconazole

67
Q

IFI Treatment –Mucormycosis

A

Liposomal amphotericin B + echinocandin x 3 weeks, then posaconazole 200 mg PO QID

68
Q

recommended vax - all 6mo later except MMR is 24 mo -8

A

PCV, TDap, haem inf, meningococcal, polio, hep B, influenza, MMR

69
Q

Sinusoidal Obstruction Syndrome Veno-Occlusive Disease (VOD) - incidence and presentation

A

9-18%; mortality rate of severe VOD with supportive are alone was 84%

bilirubin > 2 mg/dL;
weight gain > 2-5% of baseline; hepatomegaly/right upper quadrant pain;
ascites

70
Q

Sinusoidal Obstruction Syndrome Veno-Occlusive Disease (VOD) - Prevention

A

reduced intensity conditioning

target dosing of busulfan to AUC < 1500 Mol/min

ursodiol 12 mg/kg/day (myeloablative only) RR 0.34 (CI 0.17-0.66)

71
Q

Sinusoidal Obstruction Syndrome Veno-Occlusive Disease (VOD) - Treatment

A

supportive care

defibrotide (compassionate use only)

72
Q

Can you give a live vaccine to someone with GVHD?

A

NO

73
Q

what is last immune cell to fully reconstitute?

A

CD4 T cell

74
Q

Transplant Associated Thrombotic Microangiopathy (TMA) - incidence and presentation -4

A

2.5-25%; median survival ~ 39%

thrombocytopenia;
microangiopathic hemolysis (schistocytes, inc LDH, inc indirect bilirubin, dec haptoglobin)
renal dysfunction;
neurologic complications

75
Q

Transplant Associated Thrombotic Microangiopathy (TMA) -treatment -4

A

best supportive care

decrease or discontinue calcineurin inhibitor and/or sirolimus

Plasma exchange – response rates of 40-60%

Rituximab – case reports

76
Q

pulmonary sx - Idiopathic Pneumonia Syndrome

A

onset: Day 20-50
sx: Pneumonia, dyspnea, fever, non-productive cough, hypoxia
tx: Methylprednisolone 2 mg/kg/day THEN taper + Etanercept x 8 doses

77
Q

pulmonary sx - Diffuse Alveolar Hemorrhage

A

onset: Day 12 - 19
sx: Shortness of breath, hypoxia, cough
tx: Methylprednisolone 2 mg/kg/day OR 1 g/m2/day

78
Q

pulmonary sx - Periengraftment respiratory Distress Syndrome

A

onset: Day 4-7 post engraftment
sx: Fever, cough, dyspnea, rash, weight gain, edema
tx: Supportive care, Discontinue filgrastim, Prednisone 1 mg/kg/day THEN rapid taper

79
Q

pulmonary sx - Bronchiolitis Obliterans Organizing Pneumonia

A

onset: Before day 100 (2-12 months)
sx: Fever, dry cough, shortness of breath
tx: Prednisone 1 mg/kg/day, tapered over 3-6 months

80
Q

pulmonary sx - Bronchiolitis Obliterans

A

onset: 7-15 months
sx: Dry cough, dyspnea, wheezing; (NO fever)
tx: Prednisone 1-1.5 mg/kg/day taper over 6-12 months

81
Q

Renal Complications - onset and presentation

A

6-12 months after HSCT

idiopathic, 
but may also be TMA, 
glomerulonephritis, 
nephrotic syndrome, 
radiation nephritis
82
Q

Renal Complications - Treatment (for hypertension and CKD) mgmt

A

ACEI

ARB

83
Q

secondary cancer screening - if TBI and chest irradiation

A

mammography at age 25 or 8 years after radiation, which ever is later, no later than age 40

84
Q

secondary cancer screening - Chronic GVHD

A

screen for oral / pharyngeal cancer

85
Q

Treatment of Late Complications - oral

A

 Discontinue medications that cause oral dryness

 Artificial saliva substitutes, sugar – free candy/ gum

 Sialogogues (pilocarpine / cevimeline); oral hygiene

86
Q

Treatment of Late Complications - C/V

A

 Hypertension – manage per JNC 7

 Hyperlipidemia – manage per NCEP III

 Diabetes – insulin for short-term use; sulfonylurea, metformin and sitagliptin

87
Q

Treatment of Late Complications -Thyroid

A

Thyroid hormone replacement (levothyroxine)

88
Q

Treatment of Late Complications - Male hypogonadism

A

If symptomatic (low libido, erectile dysfunction, fatigue, bone loss) and low testosterone may use testosterone replacement

89
Q

Treatment of Late Complications - Primary ovarian failure

A

 Vaginal hypoestrogenism – topical estrogen / lubricant

 Hormone replacement therapy until age of normal
menopause – estradiol + cyclic medroxyprogesterone (35yo different risk profile than 55yo)

90
Q

Treatment of Late Complications - Skeletal Complications -osteoporosis - PREVENTION -4

A

Calcium 1200 mg / day + Vitamin D 800-2000 IU daily
 LABS (25 hydroxyvitamin D > 30 ng/mL)

Weight bearing exercise

fall prevention

smoking cessation

91
Q

Treatment of Late Complications - Skeletal Complications - osteoporosis - TREATMENT -3

A

Bisphosphonate

Hormone replacement therapy if deficient

2nd line: teriparatide, denosumab, raloxifene

92
Q

Treatment of Late Complications - Iron Overload -4

A

Treatment considered if ferritin > 2500 ng/mL or
hepatic iron > 7 mg/g dry weight

Goal ferritin < 500 – 1000 ng/mL

Phlebotomy if hematocrit > 38%

Deferoxamine, deferiprone, deferasirox may be considered although there is no evidence in HSCT patients and significant risk of toxicity

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