Post Transplant Issues

What are some cardiac disease diagnosed in transplant patients?

• Cardiomyopathy

• HF

• Pericarditis

• Arrythmias

What kind of chemotherapies or medications can cause cardiac disease?

• HD Cytoxan

• HD Melphalan

• Tacrolimus / Cyclosporine / Sirolimus

What blood test can indicate HF?

BNP lab (brain natriuretic peptide)

(1)_________ is the most common post-transplant bacterial infection. That can cause:

• (2)____________

• (3)____________

(1) Streptococcus pneumoniae

(2) Pneumonia

(3) Meningitis

• Vancomycin resistant (1) __________

• Methicillin-resistant (2)_______________

• Multidrug-resistant (3)________________

(1) Enterococci

(2) Staphylococcus aureus

(3) Pseudomonas aeruginosa

• __________ is the most common viral infection post transplant

CMV

Viral influenza can be treated with (1)__________ and (2)_________

(1) Oseltamivir

(2) Zanamivir

• (1)__________ fungal is the most common fungal infection post transplant and can be found in ___________

• (2)__________ is the most common late invasive fungal infection and can be found in __________

• (3) __________ also is considered a serious post-transplant infection.

(1) Candida / oral mucosa

(2) Aspergillosis / sinuses and lungs

(3) Mucormycosis

Inactivated Vaccines

1. _________________

   • Can be given ________ post transplant

2. _________________

   • Can be given ________ post transplant

3. _________________

   • Can be given ________ post transplant

   • This is to prevent (a)_________, (b)_________, ©____________, (d)__________

4. _________________

   • Administer to patients who are _____________

5. _________________

   • Give one dose after ______ months

6. _________________

   • May administer __________ months post transplant

1. Pneumococcal

   • 6 months

2. DTap (Diptheria, Tetanus, and Pertussis)

   • 6 months

3. Haemophilus influenza Type B

   • 6 months

   • (a) Pneumonia

   • (b) meningitis

   • © Epiglottis

   • (d) Bacteremia

4. Hepatitis B

   • HBV-negative

5. Meningococcus

   • 6 months

6. Influenza

   • 4 months

Live Virus Vaccines

1. ________________

2. ________________ = _________ vaccines

3. Both can be given _______ months post transplant

4. Both are limited to ____________ individuals

1. Measles, mumps, and rubella (MMR)

2. Zoster = Shingles

3. 24

4. immunosuppressions

What are the ocular complications associated with GVHD?

• Dry eye syndrome (keratoconjunctivitis sicca)

• Retinal microvasculopathy

• Conjunctival disease

• Cataract

• Opportunistic infections

What are the preventions and treamtents for ocular disease associated with GVHD?

• (1) ______________

• (2) ______________

• (3) ______________

• (4) _______________ and (5)____________ environement

(1) Cyclosporine eye drops

(2) Tacrolimus

(3) Corticosteroids

(4) humid, (5) low temperature

What are the musculoskeletal complications assosciated with GVHD?

• Osteoporosis

• Avascular Necrosis (AVN)

• Osteomyelitis

• AVN of the bone is a painful and deliberating condition that develops when (1)___________ to the bone is disrupted.

• Affects mostly the (2)_______ and (3)______

• Risk factors:

  • (4)_______________

  • (5)_______________

  • (6)_______________

  • (7)_______________

  • (8)_______________

(1) blood supply

(2) hips, (3)knees

(4) History of GVHD

(5) Older age

(6) TBI

(7) Steroids use

(8) Primary diagnosis of leukemia

Treatments for osteoporosis and AVN include:

• (1) __________ and (2) ___________ supplements

• (3)__________________

(1) calcium, (2) vitamin D

(3) biphosphonate

• Osteomyelitis can be (1)_____________, (2)___________ and may be (3)________

• Treatment consists of aggressive management of various drug combinations

(1) bacterial

(2) fungal

(3) lethal

What is a secondary graft failure?

The loss of donor cells after initial engraftmenth

Which medication can induce ADH which cause SIADH?

Vincristine

Which chemotherapy can cause hyponatremia?

HD Cytoxan

Hypokalemia

• Potassium level is less than (1) ______ mEq/L

• Possible causes:

  • Decreased (2)_______

  • Drugs including (3)________ or (4)______________

  • Increased in (5)____________

  • (6)_____________________

• Complications:

  • (7)________________

  • (8)________________

  • (9)_________________

• Treatment is (10)_______________

(1) 3

(2) intake

(3) diuretics, (4) amphotericin B

(5) GI output

(6) Renal dysfunction

(7) Generalized weakness

(8) Muscle cramps

(9) Arrythmias

(10) Potassium chloride

Hyperkalemia

• Potassium level is greater than (1)______ mEq/L

• Possible causes:

  • (2)____________

  • (3)____________

  • (4)____________

  • (5)____________

  • (6)____________

• Symptoms:

  • D (7)______________

  • E (8)______________

  • A (9)______________

  • T (10)_____________

  • H (11)_____________

• Treatment:

  • (12)_____________

  • (13) __________ and (14)__________

  • (15)______________

  • (16)_______________

  • (17)_______________ for cardiac emergency

(1) 5

(2) Acute Renal Failure

(3) Sepsis

(4) TLS

(5) Medications

(6) Dehydration

(7) Decreased HR

(8) Early Muscle Twitching

(9) Arrhythmia (peaked T waves)

(10) Tummy issues (N/V)

(11) Hypotension

(12) Furosemide

(13) Glucose and (14) IV insulin

(15) Sodium bicarb

(16) Sodium polysterene sulfonate → promote potassium loss in feces

(17) Calcium gluconate

Hypernatremia Symptoms:

• F (1)___________

• R (2)__________

• I (3)___________

• E (4)__________

• D (5)__________

(1) Flushed skin

(2) Restlessness

(3) Increased urine output

(4) Edema

(5) Dry mucous membrance

What is the normal range for calcium level?

8.7 - 10.2

Hypercalcemia

• Possible causes:

  • Bone (1)________

  • (2)

• Symptoms:

  • B (3)____________

  • A (4)____________

  • C (5)____________

  • K (6)____________

  • M (7)____________

  • E (8)____________

• Treatments:

  • Main treatment is (9)__________

  • (10)______________

  • (11)______________

(1) reabsorption

(2) Hyperparathyroidism

(3) Bone pain

(4) Arrhythmias

(5) Cardiac arrest

(6) Kidney stones

(7) Muscle weakness

(8) Excessive urination

(9) Hydration

(10) Dialysis

(11) Biphosphonate

Hypocalcemia

• Possible causes:

  • Decreased (1)_________

  • (2)_______________

• Symptoms:

  • (3)_______________

  • (4)_______________

  • (5)_______________

  • (6)_______________

• Treatments:

  • (7)_____________ if asymptomatic

  • (8)______________ if symptomatic

(1) intake

(2) Renal dysfunction / TLS

(3) Headache

(4) Muscle cramping

(5) Tingling, numbness

(6) Arrhythmias

(7) Calcium carbonate

(8) Calcium gluconate

How to calculate ANC?

ANC = (% bands + % neutrophils) x total WBC

Gram positive organisms include:

• (1)______________

• (2)______________

• (3)______________

(1) Staphylococcus

(2) Enterococcus

(3) Streptococcus

Gram negative organisms include:

• (1)_________

• (2)_________

• (3)_________________

(1) E. Coli

(2) Klebsi

(3) Pseudomonas aeruginosa

• Vancomycin-resistant Enterococcus (VRE) should be evaluated (1)________ and (2)__________

• 4 antibiotics that are approved for VRE are:

  • (3)__________

  • (4)__________

  • (5)__________

  • (6)__________

(1) pre-transplant

(2) weekly

(3) Quinupristin

(4) Dalfopristin

(5) Linezolid

(6) Daptomycin

HSV can reacts with __________

mucositis

• Ganiciclovir for CMV should be discontinued before (1)_________ and after (2)___________ since it lowers (3)________

• CMV should be tested (4)__________ for 60 days

• What are other treatments for CMV?

(1) transplant

(2) engraftment

(3) immune system

(4) weekly

(50) Foscarnet and valacyclovir

Adenovirus can cause:

• (1)______________

• (2)______________

• (3)______________

(1) Hemorrhagic cystitis

(2) Pneumonia

(3) Hepatitis

Graft failure is a term used to describe lack of ______ recovery at day 28 for myeloablative transplant.

neutrophil

Symptoms of engraftment syndrome:

(1)____________

(2)____________

(3)____________

Laboratory findings:

(4) Elevated ________

(5) Elevated ________

(6) Elevated ________

(7) Decreased ________

(1) Fever

(2) Rash

(3) Pulmonary edema

(4) Creatinine

(5) Bilirubin and hepatic transaminases

(6) C-reactive protein

(7) Albumin

What is platelets normal range?

150,000 - 400,000

What is thrombocytopenia?

Low platelet counts

What is idiopathic thrombocytopenia purpura (ITP)?

The immune system mistakenly attacking and destroys platelets

What is Thrombotic thrombocytopenia purpura?

A rare but serious blood disorder that involves the formation of small blood clots (thrombi) throughout the body's small blood vessels. These clots can limit or block blood flow to vital organs such as the brain, kidneys, and heart, leading to a variety of severe symptoms and complications.

What is Hemolytic Uremic Syndrome?

Commonly triggered by a bacterial infection, particularly with Shiga toxin-producing Escherichia coli (STEC) following food contamination. This toxin damages the blood vessels in the kidneys, leading to clot formation.

What is diffuse alveolar hemorrhage?

A condition characterized by bleeding into the alveoli of the lungs, often resulting from various underlying causes such as autoimmune diseases, infections (Aspergillus species pneumonia), or drug reactions. Symptoms may include cough, shortness of breath, and hemoptysis.

What is the life span of platelets?

8-10 days

What is the life span of erythrocytes?

120 days

What is the primary indicator for transplant outcome?

Absolute Lymphocyte Counts (ALC)

Grading Scales for Oral Mucositis

• Grade 0: no changes

• Grade 1: soreness with erythema

• Grade 2: soreness with erythema and ulceration; ability to eat solid foods

• Grade 3: soreness with erythema and ulceration; ability to eat liquid food

• Grade 4: soreness with erythema and ulceration; cannot eat.

Hypogeusia

a reduced ability to taste certain flavors, often experienced by patients after transplantation.

Dysgeusia

a distortion of the sense of taste, commonly reported by transplant patients, leading to unpleasant taste sensations.

Ageusia

the complete loss of taste sensation, frequently observed in transplant patients.

What is Post-Transplant Lymphproliferative Disorders (PTLD)?

1. A complication after transplant where some WBCs (especially B cells) grow too much and and may turn into lymphoma

2. This happens because the immune system is weakened by anti-rejection drugs → can’t control viruses like Epstein-Barr virus that normally stay quiet in the body.

   • If EBV is present → can affect B cells → make them grow out of control → PTLD

3. Who gets it more often:

   • People who never had EBV and get a transplant from someone who has

   • Children

   • Those who have a lot of immunosuppressive medication

   • People who had T cell removing treatments (ATG/Campath)

4. Symptoms:

   • Fever that doesn’t go away

   • Swollen lymph nodes

   • Tiredness and weight loss

   • Cough

5. Diagnosis:

   • Blood test → check for EBV viral load

   • CT or PET scan for swollen lymph nodes

   • Biopsy

6. Treatment:

   • Lower immune meds

   • Rituximab → kills B cells (often bad ones)

   • Chemo

What are the biomarkers to detect CRS in CAR-T?

• Increased C-reactive protein (CRP)

  • A substance your liver makes in response to inflammation in the body

• Increased Ferritin (can rise wit h inflammation)

What are the treatments for graft failure in allo transplant?

• Discontinue as many myelosuppresive medications as possible

• Treat infectious process if present

• Administration of cytokines:

  • Erythropoetin

  • Eltrombopag

  • GCSF

• Donor lymphocyte infusions (DLIs) may be considered

What are some medications that can cause graft failure?

• Trimethoprim-sulfamethoxazole

• Valganciclovir

• Mycophenelate mofetil

Primary Graft Failure vs Graft Rejection

Primary Graft Failure:

• No initial engraftment

• No/low donor chimerism from start

• Diagnosed by day +28 to +42

• Causes: poor graft, inadequate conditioning, residual immunity, drugs

• Requires second transplant

Graft Rejection:

• Initial engraftment → later loss

• Initial good chimerism → declines

• Happens weeks–months post-transplant

• Causes: immune rejection, viral reactivation, poor immunosuppression

• Managed with DLI or immune adjustment

Mnemonic:
GF → Never takes
Rejection → Takes, then lost

What does Ex vivo and In vivo Y cell-depleted transplant mean?

• Ex Vivo = outside of the body

  • CD 34 selection = T cells collected and processed in lab

  • Low GVHD but slow immune recovery

• In Vivo = inside the body

  • ATG / CAMPATH

1. What is GVHD?

2. Define:

   • Acute GVHD

   • Chronic GVHD

   • Hyperacute GVHD

   • Overlap GVHD

1. Donor cells attacking host cells

2. Definition:

   • Acute GVHD = occurs within 100 days after transplant

   • Chronic GVHD = occurs beyond 100 days after transplant

   • Hyperacute GVHD = occurs 7-14 days after the infusion

     • A severe form of acute GVHD

     • Treatment is high-dose steroids

   • Overlap GVHD = has features of acute and chronic GVHD

- Prognosis is more severe then chronic GVHD

Feature	Acute GVHD	Chronic GVHD
Timing	Usually within first 100 days post-HSCT	Usually after 100 days post-HSCT
Cause	Donor T-cell activation against host antigens	Immune dysregulation and fibrosis-driven
Onset	Abrupt, can be early or late-onset	Gradual, progressive
Affected Organs	Mainly: Skin, Liver, GI	Can affect almost any organ
Skin	Maculopapular rash, may progress to desquamation	Sclerosis, depigmentation, lichen planus-like lesions
GI	Watery diarrhea, abdominal cramping, anorexia	Dry mouth, esophageal webs, strictures
Liver	↑ Bilirubin, transaminases (cholestasis)	Cholestasis or hepatitis, less acute rise
Eyes	Rare	Dry eyes, keratoconjunctivitis sicca
Mouth	Rare	Dry mouth, ulcers, lichenoid changes
Lungs	Rare	Bronchiolitis obliterans (BO)
Joints/Fascia	Not involved	Contractures, restricted range of motion
Hair/Nails	Rare	Hair loss, nail dystrophy
Pathophysiology	T-cell cytokine storm → direct tissue damage	Chronic inflammation + fibrosis
Diagnosis	Clinical + biopsy of skin/GI/liver	Clinical + NIH criteria
Treatment	Steroids + immunosuppression (e.g. tacrolimus)	Steroids + other agents (e.g. ruxolitinib, ECP)
Prognosis	Varies—can be life-threatening	Chronic condition, long-term disability risk

3 stages of GVHD

Stage	What happens	Simple idea
Stage 1: Activation of host tissues	Conditioning (chemo/radiation) damages host tissues → cells release inflammatory signals (cytokines).	Tissues get inflamed — they "call for help."
Stage 2: Donor T cell activation	Donor T cells see the inflamed host as "foreign" → become activated → expand.	Donor T cells wake up and attack.
Stage 3: Target tissue damage	Activated donor T cells and other immune cells attack skin, gut, liver. More inflammation occurs.	Donor T cells damage the body (GVHD symptoms).

Why does intense or myeloablative conditioning and TBI have a higher incidence of GVHD?

Myeloablative conditioning (including TBI) increases GVHD risk because it causes more tissue damage and inflammation, which activates donor T cells to attack the recipient’s body.

Risk factors of GVHD:

1. Matched unrelated and mismatched related

2. Intense or myeloablative conditioning and TBI

3. Peripheral blood

4. ABO mismatch

5. Female donors to male recipients

6. Parous female donors

7. Donors previously transfused

8. An older donor

Staging and Grading for Acute GVHD

Stage	Skin (% BSA Rash)	Liver (Total Bili, mg/dL)	GI (Diarrhea mL/day)
0	None	< 2	None
1	< 25%	2–3	500–1000 mL/day
2	25–50%	3.1–6	1001–1500 mL/day
3	> 50%	6.1–15	1501–2000 mL/day (or severe pain)
4	Generalized bullous / desquamation	> 15	> 2000 mL/day (or ileus)

🎖 Grade	✨ Description
⭐ Grade I	Skin stage 1–2 only
⭐⭐ Grade II	Skin stage 3 OR liver 1–2 OR GI 1
⭐⭐⭐ Grade III	Liver 3 OR GI 2–3
⭐⭐⭐⭐ Grade IV	Skin 4 OR liver 4 OR GI 4 (ileus)

Sinusoidal Obstruction Syndrome (SOS) or VOD

• Life-threatening condition that can lead to multi organ failure.

• Damage to liver sinusoids (smallest blood vessels in liver) → they become blocked → blood backing up in liver → liver congestion and dysfunction → portal hypertension develops → fluid leaks out → liver swelling

• Key risk factors:

  • HD Busulfan or Cytoxan

  • TBI

  • Prior chemo or HSCT

  • Pre-existing liver disease

  • Younger age

  • Tacrolimus or Sirolimus

  • Iron overload

• Signs and symptoms:

  • Classic triad:

    • Weight gain

    • Hepatomegaly

    • Jaundice

  • Ascites

  • Right upper quadrant pain

  • Rising in bilirubin levels

• Diagnosis:

  • At least 2 or more of the classic triad symptoms within 30 days after transplant.

  • Bilirubin equal or greater than 2 mg/dl

• Prevention: Ursodiol

• Treatment: Defibrotide is the only approved treatment for severe SOS

  • Improve endothelial cell function

  • Reduces clotting in liver sinusoids

  • Fluid management and pain control

• Monitor for bleeding given that coagulopathy occurs with SOS

Typhlitis (Neutropenic Enterocolitis)

• Rare but life-threatening complication

• Abdominal pain, fever, bloody diarrhea, nausea