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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
Chronic GVHD Risk Factors -6
 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
26
chronic GVHD can effect virtually any organ. examples? -9
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
27
Mild Chronic GVHD (10% of pts that develop cGVHD) | NOT TESTABLE
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)
28
Moderate Chronic GVHD (30%) | NOT TESTABLE
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
29
Severe Chronic GVHD (60%, 2yr OS 50%) | NOT TESTABLE
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
30
Initial Therapy of Chronic GVHD -MILD
Topical therapy
31
Initial Therapy of Chronic GVHD -MODERATE OR SEVERE -3
 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
32
Topical Therapy for Chronic GVHD - Skin
Topical steroids; topical calcineurin inhibitors; PUVA; UVA; UVB
33
Topical Therapy for Chronic GVHD - Gastro- intestinal
Topical steroids (budesonide or beclomethasone)
34
Topical Therapy for Chronic GVHD - Liver
Ursodiol
35
Topical Therapy for Chronic GVHD - Lung
Inhaled steroids
36
Topical Therapy for Chronic GVHD - Oral
Topical steroids (dexamethasone, prednisolone, clobetasol, fluocinonide) Topical tacrolimus ointment; Topical cyclosporine rinse; topical azathioprine rinse
37
Topical Therapy for Chronic GVHD - Eye
Artificial Tears; topical steroids; topical cyclosporine
38
Topical Therapy for Chronic GVHD - Vaginal
Topical steroids Topical tacrolimus or pimecrolimus
39
2nd Line Therapy of Chronic GVHD -treatment
NO SOC NOT TESTABLE  Patient history with prior therapies  Agents with non-overlapping toxicities  Patient preference
40
2nd Line Therapy of Chronic GVHD - when to consider PROBABLY NOT ON TEST
 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
extracorporeal photopheresis indx -2
skin and lung cGVHD
42
Bacterial px > 100 days (streptococcus pneumoniae) indx and dose -2
 Allogeneic recipients with chronic GVHD (AIII)  Penicillin 500 mg BID or 1000 mg daily
43
Bacterial day 0 – 100 indx and dose -2
 Consider fluoroquinolone with antipseudomonal activity with anticipated neutropenia > 7 days  Levofloxacin (BI) or Ciprofloxacin (BII)
44
Yeast (Candida) Prophylaxis - auto
Prolonged neutropenia and mucosal damage from intense conditioning regimen, graft manipulation, recent purine analog exposure  Fluconazole 400 mg/day conditioning through engraftment
45
Yeast (Candida) Prophylaxis - allo
 Fluconazole 400 mg/day conditioning through day +75 (AI)  Itraconazole (CI)  Micafungin (BI)  Posaconazole (BI)  Voriconazole (BI)
46
Allogeneic Mold Prophylaxis (Aspergillus, Fusarium, Mucor) - PRE ENGRAFTMENT
 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
Allogeneic Mold Prophylaxis (Aspergillus, Fusarium, Mucor) -POST ENGRAFTMENT
 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
VORI VS FLUC for alloHSCT px
NO DIFFERENCE caveat: used aggressive monitoring that most centers don't use
49
Pneumocystis jiroveci Prophylaxis - auto indx - 5
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
Pneumocystis jiroveci Prophylaxis -allo
Engraftment x 6 months after HSCT, longer if patients continue to receive immunosuppressive drugs or have chronic GVHD (AII)
51
how long to continue VZV px in allo?
Routine acyclovir 800 mg PO BID during first year (BI) or 6 months after discontinuation of all immunosuppression (CIII)
52
CMV Prophylaxis
-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
CMV Preemptive Therapy - allo
 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
CMV Preemptive Therapy - auto
Consider monitoring until day + 60 in patients at risk (TBI, alemtuzumab, purine)
55
CMV Pneumonia tx
 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
CMV tx -Enteritis, esophagitis, hepatitis, retinitis, marrow infection
 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
Varicella zoster virus tx
Acyclovir 10 mg/kg q 8 h x 7 -14 days; Valacyclovir
58
Adenovirus tx
Taper / withdrawal immunosuppression more in kids, cord blood tx
59
Human Herpes Virus 6 tx
Ganciclovir, cidofovir, foscarnet have in vitro activity cord blood tx
60
Respiratory syncytial virus tx
Aerosolized ribavirin x 7-10days + IVIG (if LRI)
61
Influenza tx
Oseltamivir 75 – 150 mg BID x 10 days
62
BK virus tx
 Hyperhydration  Taper / withdrawal immunosuppression  Cidofovir for hemorrhagic cystitis
63
Invasive Fungal Infection (IFI) Treatment Candidemia
 Neutropenic: caspofungin / micafungin / liposomal amphotericin x 14 days + resolution of neutropenia (ESPECIALLY IF ON AZOLE)  Non-neutropenic: echinocandin preferred if recent azole exposure
64
Invasive Fungal Infection (IFI) Treatment Candidiasis
 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
IFI Treatment --Invasive Aspergillosis
 Voriconazole (survival advantage at 12 weeks over amphotericin B deoxycholate 71% vs. 58%)  Withdrawal/reduction in corticosteroids  A. terreus should received amphotericin B
66
IFI Treatment --Fusarium
Amphotericin B; voriconazole; posaconazole
67
IFI Treatment --Mucormycosis
Liposomal amphotericin B + echinocandin x 3 weeks, then posaconazole 200 mg PO QID
68
recommended vax - all 6mo later except MMR is 24 mo -8
PCV, TDap, haem inf, meningococcal, polio, hep B, influenza, MMR
69
Sinusoidal Obstruction Syndrome Veno-Occlusive Disease (VOD) - incidence and presentation
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
Sinusoidal Obstruction Syndrome Veno-Occlusive Disease (VOD) - Prevention
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
Sinusoidal Obstruction Syndrome Veno-Occlusive Disease (VOD) - Treatment
supportive care defibrotide (compassionate use only)
72
Can you give a live vaccine to someone with GVHD?
NO
73
what is last immune cell to fully reconstitute?
CD4 T cell
74
Transplant Associated Thrombotic Microangiopathy (TMA) - incidence and presentation -4
2.5-25%; median survival ~ 39% thrombocytopenia; microangiopathic hemolysis (schistocytes, inc LDH, inc indirect bilirubin, dec haptoglobin) renal dysfunction; neurologic complications
75
Transplant Associated Thrombotic Microangiopathy (TMA) -treatment -4
best supportive care decrease or discontinue calcineurin inhibitor and/or sirolimus Plasma exchange – response rates of 40-60% Rituximab – case reports
76
pulmonary sx - Idiopathic Pneumonia Syndrome
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
pulmonary sx - Diffuse Alveolar Hemorrhage
onset: Day 12 - 19 sx: Shortness of breath, hypoxia, cough tx: Methylprednisolone 2 mg/kg/day OR 1 g/m2/day
78
pulmonary sx - Periengraftment respiratory Distress Syndrome
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
pulmonary sx - Bronchiolitis Obliterans Organizing Pneumonia
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
pulmonary sx - Bronchiolitis Obliterans
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
Renal Complications - onset and presentation
6-12 months after HSCT ``` idiopathic, but may also be TMA, glomerulonephritis, nephrotic syndrome, radiation nephritis ```
82
Renal Complications - Treatment (for hypertension and CKD) mgmt
ACEI ARB
83
secondary cancer screening - if TBI and chest irradiation
mammography at age 25 or 8 years after radiation, which ever is later, no later than age 40
84
secondary cancer screening - Chronic GVHD
screen for oral / pharyngeal cancer
85
Treatment of Late Complications - oral
 Discontinue medications that cause oral dryness  Artificial saliva substitutes, sugar – free candy/ gum  Sialogogues (pilocarpine / cevimeline); oral hygiene
86
Treatment of Late Complications - C/V
 Hypertension – manage per JNC 7  Hyperlipidemia – manage per NCEP III  Diabetes – insulin for short-term use; sulfonylurea, metformin and sitagliptin
87
Treatment of Late Complications -Thyroid
Thyroid hormone replacement (levothyroxine)
88
Treatment of Late Complications - Male hypogonadism
If symptomatic (low libido, erectile dysfunction, fatigue, bone loss) and low testosterone may use testosterone replacement
89
Treatment of Late Complications - Primary ovarian failure
 Vaginal hypoestrogenism – topical estrogen / lubricant  Hormone replacement therapy until age of normal menopause – estradiol + cyclic medroxyprogesterone (35yo different risk profile than 55yo)
90
Treatment of Late Complications - Skeletal Complications -osteoporosis - PREVENTION -4
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
Treatment of Late Complications - Skeletal Complications - osteoporosis - TREATMENT -3
Bisphosphonate Hormone replacement therapy if deficient 2nd line: teriparatide, denosumab, raloxifene
92
Treatment of Late Complications - Iron Overload -4
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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