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Hematology RC Editable > Transplant > Flashcards

Transplant Flashcards

1
Q

Four risk factors for cGVHD

A

Higher degree of HLA mismatching
Older age of donor and/or recipient
Female donor into male recipient
Alloimmunization of the donor (history of pregnancy, transfusions)
PB graft
Prior acute GVHD
EBV or CMV seropositivity (donor and/or recipient)
Previous splenectomy
Administration of donor lymphocyte infusions

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2
Q

Features of VOD/SOS

A

Modified Seattle criteria (for diagnosis) – any 2 of (within 20d of HSCT):
Bilirubin >34
Hepatomegaly or RUQ pain
Weight gain due to fluid (>2% baseline body weight)

Balitmore Criteria (for diagnosis):
Bilirubin >34 within 21 days of HCT
plus at least two of the following:

●Hepatomegaly
●Ascites
●Weight gain >5% of baseline body weight

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3
Q

Treatment of VOD

A
  1. Supportive – salt restriction, stop hepatotoxins
  2. Defibrotide (especially if younger and auto-SCT)-reduce endothelial cell activation and increase ec-induced fibrolysis, increase plasminogen and decrease VWF and PAI-1.
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4
Q

What is VOD? What are the risk factors?

A

VOD: Damage to endothelial cells, sinusoids, and hepatocytes in area around hepatic venules–> leading to scarring and hepatic dysfunction. Usually a consequence of the conditioning regime in transplant.

RFs: prior hepatic damage, heavily pretreated before transplant, prolonged and high busulfan level, TBI >10-12Gy, allo>auto

Others: carmustine, gemtuzumab/inotuzumab, iron overload, older age, high level of mismatch.

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5
Q

Characteristics of MHC class I vs class II antigens.

A

Class I
Present on surface of all nucleated cells
Mainly interact with cytotoxic T cells (CD8)
Encoded by HLA-A, B and C genes
Responsible for graft rejection and clearance of endogenous antigens
Self-antigens

Class II
Present on APC (macrophages, B cells, DC)
Mainly interact with helper T cells CD4
Encoded by HLA-D genes DP, DQ, DR
Responsible for graft rejection and clearance of exogenous antigens
Non-self antigens

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6
Q

Pre-engraftment, Post-engraftment, Late/chronic
Bacterial:
Viral:
Fungal:

A

0-30 days (preengraftment)
Bacterial – gram- and +
Fungal – candida
Viral – HSV, RSV

31-60 days (early postengraftment)
Bacterial – listeria, legionella, TB
Fungal – aspergillus, candida, PCP
Viral – CMV (pneumonia, enteritis), EBV, HHV-6, resp viruses

> 61 days (late postengraftment, >100d)
Bacterial – encapsulated
Fungal – PCP
Viral – VZV, EBV (PTLD)

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7
Q

Name the stem cell source you would use for AA and justify your reasoning

A

Bone marrow collection from a 10/10 familial match, (If syngenetic twin BM, can use PB b/e GVHD is minimal).
Decreased rate of GVHD from this (ideally want no GVHD in aplastic anemia transplants)
No need for graft Vs Tumor effects.

HCT both restores the supply of hematopoietic stem/progenitor cells and replaces the immune system that is responsible for depleting them.

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8
Q

Name 3 reasons for and 3 reasons against cord blood transplants.

A

For:

  1. Quick TAT (one week vs URD up to 3 months)
  2. Don’t need full HLA (greater HLA disparity allowed with no further increase in GHVD rate)
  3. Less GVHD
  4. Expanded donor base

Against:

  1. Low-cell dose (usually need 2 cord units)
  2. Slow engraftment
  3. Increased risk of infection (due to slow engraftment)
  4. Higher risk of rejection = non-immunologic rejection i.e. graft failure
  5. No ability for DLI or second infusion for graft failure.
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9
Q

Name 3 reasons for and 3 reasons against MUD transplants.

A

For:

  1. Increased graft-vs-disease effect
  2. Donor availability > MUD (70% will have donor)
  3. Able to do DLI if graft failure.

Against

  1. Increased GVHD
  2. Long TAT
  3. Higher graft failure
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10
Q

Name 3 reasons for and 2 reasons against Syngeneic transplants.

A

For:

  1. No need for IST
  2. No GVHD
  3. Donor readily available

Against
1. No graft vs. tumor effect–>high rates of relapse

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11
Q

Name 2 reasons for and 3 reasons against halpo-identical transplants.

A

For:

  1. Almost all pts will have a donor (child, parent, sibling).
  2. Able to do DLI or top-up infusion

Against:

  1. Need for signifiant IST (need to deplete T cells donor product)
  2. High infection risk
  3. Highest graft failure 10-15%
  4. High acute GVHD
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12
Q

5 medications associated with difficult stem cell collection

A
  1. Lenalidomide
  2. Fludarabine
  3. Melphalan
  4. Cisplatin
  5. Chlorambucil
  6. Carmustine
  7. Hyper-CVAD
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13
Q

2 side effects specific for cyclosporine vs tacrolimus

A

Both drugs: nephrotoxicity, HTN, neurotoxicity (tremor, seizures), metabolic abN (hyperlipiedemia, hyperuricemia, hyperk, hypoMg), Increased risk of malignancy (skin squamous cell CA)

Cyclosporine :gingival hyperplasia, hirsutism, PRES

Tacrolimus: Diabetes, HoCM, alopecia, neuro symptoms (HA, tremor).

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14
Q

Explain a CAR-T cell.

A

Aphereised autologous T-cells are transduced with a retro or lenti viral vector containing a construct that codes for a chimeric antigen receptor for a target of interest (eg. CD19).

A CAR is a construct that consists of an antigen-specific end that is bound to a linker, costimulatory domain (CD28 or 41-bb), which is then linked to an intracellular cCD3 domain. CAR then binds the target of interest, which triggers intracellular signals that produce cell-dependent cytotoxicity.

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15
Q

What is the main toxicity of CAR T cells?

What is the main treatment for that toxicity?

A

What is the main toxicity of CAR T cells?
Cytokine release syndrome - Immune activation leading to elevation of numerous cytokines (IL-6, INF gamma, IL10, others). Clinically see constitutional symptoms, fevers, hypotension, and in severe cases multiorgan failure.

Other: neurotoxciy (confusion, seizure, myoclonus, cerebral edema), allergic reactions, “on target, off tumor” effects (eg- normal B cell lymphopenia in CD19 CAR-T cells)

What is the main treatment for that toxicity?
Steroids (dexamethason 10-20mg q6-12hr)
Anti-IL6 → Tocilizumab 8mg/kg
Supportive care, including pressors if needed

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16
Q

MOA of Plerixafor

A

Reversible CXCR4 antagonist that allows the release of stem cells from the marrow by disrupting the interaction of CXCR4 with SDF-1.

Plerixafor-mobilized SCs have a higher proportion of cells in the growth phase, primitive CD34+CD38s, B and T lymph, dendritic and NK cells–> better able to repopulate the marrow.

SE: GI (diarrhea), injection site rxn

In contrast, CXCR2 mediates release of neutrophils from BM

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17
Q

Four causes of hemolytic anemia after allogeneic bone marrow transplant for aplastic anemia (d+62)?

A
  1. ABO incompatible transplant
  2. PNH clone
  3. Drug induced MAHA from antibiotics or TAC
  4. Post transplant TMA
  5. Passenger lymphocyte syndrome
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18
Q

A donor is having difficulty mobilizing with G-CSF. What two other strategies would you recommend to improve yield?

A

Plerixafor

Chemomobilization-Cyclophosphamide

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19
Q

What are four clinical features of CMV infection?

A
  1. Fever
  2. Cytopenias
  3. Lymphocytosis
  4. Hepatitis
  5. Pneumonitis (CMV pneumonia)
  6. Gastroenteritis
  7. Uveitis/retinitis
  8. CMV encephalitis

Tx: at first detection of CMV viremia start ganciclovir or valganciclovir to prevent the above complications. (foscarnet and cidofovir can be used but are more nephrotoxic)

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20
Q

2 common viral infection reactivations after transplant and their treatments

A
  1. Parvovirus B19–>pRCA. Decrease immunosuppression, IVIG and EPO
  2. CMV—>ganciclovir or foscarnet
  3. HHV-6 (usually not clinically significant)
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21
Q

What is passenger lymphocyte syndrome and in which types of solid organ transplant are they most common?

A

PLS occurs when viable donor B-lymphocytes are passively transferred to the recipient within the allograft and form antibodies that result in complement-mediated red blood cell destruction of the recipient . Most commonly, it is in the setting of minor ABO mismatches,

small bowel>heart-lung>liver>kidney

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22
Q

What is the presentation and treatment for passenger lymphocyte treatment?

A

Hemolysis is abrupt several days after Tx (1-3 weeks).
Elevated hemolysis markers (DAT +, RBC specific Ab to donor antigen).

Tx:usually self limited (lymphs have short survival) within 3 months, can give pRBC of organ donor (if ABO compatibility).

If refractory—> inc IST, IVIG, red cell exchange or PLEX (to remove donor’s lymphocytes Abs)

23
Q

3 types of PTLD

A
  1. Infectious mononucleosis-like PTLD
  2. Florid follicular hyperplasia
  3. Polymorphic PTLD
  4. Monomorphic PTLD
  5. Classic Hodgkin lymphoma-like PTLD

1+2 reduction of IST usually enough, #3 radiation, single agent ritux

24
Q

5 things on your DDx in post transplant dyspnea with bilateral infiltrates

A
  1. TACO/cardiogenic pulmonary edema
  2. TRALI
  3. Infectious process- Bacterial, fungal, viral (CMV pneumonitis) pneumonia
  4. Engraftment syndrome
  5. Idiopathic pneumonia syndrome
  6. ARDS from conditioning chemo
  7. Diffuse alveolar haemorrhage

BOS-late complication, obstructive PFTS, no pulm infiltrates, if bx proven, diagnostic of cGVHD.

25
Q

Clinical features of engraftment syndrome

A

Two main criteria (Spitzer, Miolino–>look up)

Common:

  • noninfectious fever (>38.3°C)
  • maculo-papular rash (looks like AGVHD)
  • diffuse pulmonary opacities
  • Hypoxemia
  • diarrhea

Less common:
Weight gain/edema, hepatic and renal dysfxn, encephalopathy.

26
Q

Prognostic factors for cGVHD (CIBMTR criteria)

A

Pre-transplant
Donor characteristics:
-Sex (female –>male)
-Type of donor (MUD)

Recipient characteristics:

  • age
  • disease status prior to Tx
  • GVHD proph (cyca + MTX combo)
  • Karnofsky performance status
Post Tx/time of cGVHD appearance
Time from transplant? (= 5 months, >5months)
Is it worsening?
Hx of acute GVHD?
Plt?
bili?
27
Q

What are five risk factors for poor stem cell mobilization?

A
  1. Use of particular agents- fludarabine, lenolidaminde, busulfan
  2. Older age
  3. Refractory disease at collection
  4. Hypocellular bone marrow (heavily pre-treated)
  5. Prior radiation

CHIP and DM2 are also risk factors for poor collection. .

28
Q

3 genes (clonal hematopoiesis) often affected in aging even in the absence of hematologic malignancy?

A

ASXL1, DMNT3A, TET2 (others TP53, PPM1D can be seen in pts previously exposed to cytotoxic agents).

These mutations have been show to contribute to inflammation, CVD (increased MI and stroke), hematologic malignancy and worse outcomes in solid-organ neoplasm.

29
Q

What are the 4 functions of the hematopoetic niche or microenvironment?

A
  1. Regulation of stem cell self-renewal
  2. Control of the number of stem cells, a parameter that is regulated in part by specific extracellular matrix proteins, such as osteopontin, a negative regulator of HSC number.
  3. Coordinated regulation of proliferation and differentiation of HSCs (issues here lead to MDS or MPN)
  4. Cell localization, a process that is important in the context of harvesting stem cells by mobilization into the blood or delivery of transplanted HSCs to enable engraftment.
30
Q

What is linkage disequilibrium from a transplant perspective?

A

The concept that alleles occur together with a greater frequency than would be expected by chance. Linkage disequilibrium is more frequently observed between loci that are in close proximity (eg, between HLA-B and -C and HLA-DRB1 and -DQB1).

31
Q

What are the 3 intrinsic properties that define hematopoietic progenitor cells? (hint: some of these overlap with the features of the BM microenvironment)

A
  1. Extensive proliferative capacity
  2. Pluripotency (the ability to differentiate into all blood cell types)
  3. Self-renewal capacity (the ability to replace the cells that became progressively committed to differentiation).
32
Q

What is the definition of a hematopoietic progenitor cell? (hint, 3 key features)

A
  1. Ability to form multilineage colonies in semisolid soft agar medium
  2. Ability to form colony-forming units after being maintained in culture for a minimum of 5 weeks
  3. Ability to provide long-term (>4 months) repopulation of all blood lineages.
33
Q

What are the 5 phases of SCT and associated days pre/post transplant?

A

Phase 1=conditioning (day -10 to 0)
Phase 2=cytopenia (day 0 to engraftment, usually 10-28 days)–>infxn, diarrhea, mucositis
Phase 3=early recovery (engraftment +7) –>engraftment syndrome + acute GVHD
Phase 4= early convalescent (day +30- 6-12 months)–>increased infxn risk despite count recovery. Late effects of conditioning can manifest- pneumonitis, BOS, PTLD.
Phase 5=late convalescent (beyond 12 months)–>chronic GVHD, secondary malignancy, cataracts, CVD.

34
Q

What plt and ANc counts define engraftment?

A

Anc >0.5 AND plt >20 for 3 consecutive days

35
Q

HHV-6 frequently reactivates after allogeneic HSCT and can cause what 2 major complications

A
  1. Encephalitis
  2. Aplasia
  3. Interstitial pneumonia
  4. Idiopathic pneumonia syndrome
36
Q

Rash develops following conditioning in a SCT pt, it is especially noted around the skin folds and high sweat areas. What is the cause?

A

Thiotepa

37
Q

3 risk factors for development of stomatitis?

A

Usually develops 5-7 days after conditioning.

  1. Intensity of conditioning regimen
  2. Poor oral hygiene
  3. Extensive prior therapy
  4. chemo + rad

Prevention: ice chips when melphalan infusing, recombinant keratinocyte growth factor (palifermin) in the setting of TBI.

38
Q

What is idiopathic pneumonia syndrome (IPS)? When does it occur post transplant? RFs? What is the treatment?

A
  • Restrictive pattern of PFTs, multilobar infiltrates (must r/o infxn/pulm edem, DAH etc).
  • Occurs within 21 days of Tx (mortality 30-70%). UTD says The median time to onset is 63 days.
  • RFs: TBI, carbamustine, bleo, more common in auto!
  • Tx:supportive +/- corticosteroids, entanercept (TNF alpha blocker)
39
Q

3 drug classes that can cause neurologic toxicity post transplant.

A

Neuro toxicity in Tx usually within first 100 days, allo»auto.

  1. Calcineurin inhibitors (PRES, h/a, tremor)
  2. Busulfan (Szs, use phenytoin proph)
  3. Fludarabine (dose dependent cog toxicity and sensory impairment).
40
Q

What are 3 skin features which are diagnostic of skin cGVHD?

A
  1. Lichen planus–like sclerosis
  2. Morphea-like features
    3 Lichen sclerosis–like features
    4 Piokiloderma
41
Q

Chronic effects of HSCT which should be screened for?

A
  1. Endocrine (growth, fertility, thyroid dysfxn)
  2. MSK (OP/osteopenia, AVN, decreased ROM from cGVHD)
  3. Psychosocial concerns (school or work peformance)
  4. Secondary malignancy (SCC, melanoma, PTLD)
42
Q

3 RFs for PTLD development?

A
  1. MUD or mismatched donor
  2. in vitro or in-vivo T cell depleted grafts
  3. Highly immunosuppressive conditioning or GVHD proph
  4. Age >40
43
Q

What is the major risk side effect of donor lymphocyte infusion?

A

Acute GVHD and marrow aplasia, incidence is 50% usually 32 to 42 days post infusion (mortality 3-10%)

44
Q

Relapsed APL, when to use auto vs allo?

A

Auto- if in molecular remission (ie. no detectable PML:RARA)

Allo- NOT in molecular remission, or if they relapse after auto (rare)

45
Q

What are 3 co-stimulatory domains used in second generation CAR-T cells

A
  1. CD28
  2. OX40
  3. 4-1BB
46
Q

What are 4 risk factors for CRS in CAR-T?

A
  1. High tumor burden (sig BM involvement, bulky disease, organ involvement)
  2. Thrombocytopenia
  3. High ferritin level
  4. Higher CAR-T cell dose
  5. Lymphodepletion with fludarabine
  6. Bulk CD8+ T-cell selection
47
Q

Median day of onset and duration of CRS and ICANS in CAR-T?

A

CRS
Median day of onset: Day 2
Median duration: 7 days

ICANs
Median day of onset: day 6
Median duration: 13 days

48
Q

Risk factors for passenger lymphocyte syndrome?

A
  1. Blood group O to A transfer
  2. Sensitizing events (pregnancy, transfusion)
  3. Cyclosporine use
  4. Infection in the post transplant period
49
Q

What are the Billingham’s criteria for GVHD to happen?

A

3 criteria must be met in order for GVHD to occur
An immunocompetent graft is administered, with viable and functional immune cells
The recipient is immunologically different from the donor – histo-incompatible
The recipient is immunocompromised and therefore cannot destroy or inactivate the transplanted cells

50
Q

4 Hematologic findings in cGVHD:

A
  1. Thrombocytopenia (ITP)
  2. Anemia (AIHA)
  3. Eosinophilia
  4. Lymphopenia
  5. Hypo or hypergammaglobulinemia
51
Q

What are 4 things that predict the severity of CHRONIC GVHD?

A

Number of organs involved
Extent of organ involvement
Degree of mismatch
Older age at transplant

52
Q

2 non-heme conditions in which AUTO SCT is used?

A
  1. Scleroderma
  2. MS

Heme: MCL, HL, MM, DLBCL

53
Q

What are two toxicities of DMSO other than nausea and vomiting?

A 
Bradycardia, arrhythmias
Neurotoxicity, leukoencephalopathy, seizure, coma, stroke
Diffuse alveolar hemorrhage
Acute kidney injury
Respiratory depression

Hematology RC Editable (28 decks)

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