Haematopoetic Stem Cell Transplant

Question 1

Haematopoietic Stem Cell Transplant (HSCT)
Q. preparation
Q. Types
Q. Risks and advantages of each type

Answer 1

Overview:
* Potentially curative treatment for hematologic malignancies.

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Pre-HSCT Preparation:
* Requires myeloablative conditioning:
-Destroys endogenous bone marrow cells
- Involves chemotherapy ± total body irradiation (TBI)

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Types (based on source of stem cells):
1. Peripheral blood stem cells
2. Bone marrow
3. Umbilical cord

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Types (based on donor source):

1. Autologous HSCT:
   
   • Patient’s own stem cells collected during remission.
     *Advantages:
   • No GVHD (graft-versus-host disease)
     -Lower treatment-related mortality
   *Disadvantages:
   - Risk of reintroducing tumor cells
   - Higher rate of disease relapse
2. Allogeneic HSCT:
   
   • Stem cells from related or unrelated donor.
   • Requires immunosuppression
   • Risks:
     
     • GVHD
     • Higher treatment-related mortality
     • Intensive immunosuppression and myeloablation required

Question 2

Complications of Haematopoietic Stem Cell Transplant (HSCT)

Answer 2

General Complications:
1. Infection
2. Graft-versus-host disease (GVHD)
3. Graft failure
4. Engraftment syndrome
5. Veno-occlusive disease
6. Thrombotic thrombocytopenic purpura (TTP)
7. Diffuse alveolar hemorrhage
8. Idiopathic pneumonic syndrome
9. PTLD (Post-transplant lymphoproliferative disorder)
10. PRES (Posterior reversible encephalopathy syndrome)

Question 3

Infectious Complications by Time Period:

Answer 3

1. Pre-engraftment phase (<30 days post HCT):
   
   • Neutropenia → bacterial infections common
   • Most ICU admissions occur in this phase
   • Common: gram-negative infections (e.g., E. coli), Staph, Strep, Enterococcus
2. Early post-engraftment (30–100 days):
   
   • Cell-mediated immunity impaired
   • Viral and fungal infections dominate
   • Examples: CMV, Pneumocystis, Aspergillus
3. Late post-engraftment (>100 days):
   
   • Impaired humoral + cell-mediated immunity
   • Hypogammaglobulinemia
   • Increased risk of:
     
     • Viral infections
     • Mycobacterial infections

• CMV prophylaxis has decreased CMV incidence
  
  • PJP infections less common with prophylaxis
  • Fungal infections like Aspergillus and Candida still prevalent

Question 4

Graft Failure
* Q. Definition
* Q.Causes
Q.Associations
Q. management

Answer 4

Definition:
* Failure to establish engraftment

Causes:
* Inadequate stem cell infusion
* Infection
* GVHD

Associations:
* ↑ Risk of infection
* ↑ Transplant-related mortality

Management:
* G-CSF (Granulocyte-colony stimulating factor)
* Stem cell reinfusion
* Consider second HSCT

Question 5

Engraftment Syndrome
* Q. Mechanism
* Q. Timing
* Q.clinical features
* Q.Management
* Q.Special features

Answer 5

Overview:
* Capillary leak syndrome
* Peak incidence: 5–7 days post autologous HSCT

Mechanism:
* Release of cytokines & neutrophils

Clinical Features:
* Fever
* Erythematous rash
* Non-cardiogenic pulmonary oedema
* Liver dysfunction (↑ LFTs)
* Transient encephalopathy

G-CSF Use:
* May increase incidence
* If syndrome occurs, G-CSF should be stopped immediately

Management:
* Supportive care
* Steroids

Question 6

Graft-versus-Host Disease (GVHD)
#Pathophysiology
#Risk factors.

Answer 6

Pathophysiology:
* Occurs when donor marrow recognizes host tissue as foreign → triggers immune response
* Most common in allogeneic transplant
* Incidence: 30–50%
# ↑ risk with:
* HLA mismatch
* Inadequate immunosuppression
* Advanced donor age
* Peripheral blood stem cell source (more WBCs)

Question 7

Onset

GVHD cont..
Acute GVHD

Answer 7

Acute GVHD
* Onset: 7–28 days post-transplant
* Most commonly affects:
1. Skin → maculopapular rash
2. GI tract → diarrhoea
3. Liver → intrahepatic cholestasis

Diagnosis:
* Confirmed by skin/rectal/liver biopsy(see foot note)

Management:
* First-line: IV methylprednisolone ± additional immunosuppressants
* Prophylaxis: Steroids + Cyclosporin or MMF

Clinical Grading

• Grading based on number + severity of organ involvement

Biopsy: dysmorphic small bile ducts
vacuolisation of epidermis- foll by separation from dermis
- crypt cell degeneration in rectal biopsy

Question 8

Timimg

GVHD cont..
Chronic GVHD

Answer 8

Chronic GVHD
* Multisystem dysimmune syndrome; onset >100 days post-transplant
* Can be limited or extensive

Organ Involvement:
* Skin: Scleroderma-like changes
* Lung: Bronchiolitis obliterans
* Salivary glands: Xerostomia
* Eyes: Sicca keratitis
* Neuromuscular: Polymyositis, Myasthenia gravis
* Liver: Hepatitis, cirrhosis

Tt- Difficult- increasing doses of immunosuppression.

Question 9

Veno-Occlusive Disease (VOD)

Q.#pathophysiology

Q.#Clinical Features

Q.#Risk factors

Q.#investigations

Q.#Management

Q.#Prophylaxis

Q.#Prognosis

Answer 9

Also known as: Sinusoidal Obstruction Syndrome

Clinical Triad (typically within 3 weeks post-HSCT):
* Painful hepatomegaly
* Ascites
* Jaundice

Other Features:
* Weight gain
* Hepatorenal syndrome (HRS)
* Encephalopathy

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Risk Factors:
Myeloablative conditioning regimens
- Especially with Busulfan,
Cyclophosphamide
- Pre-existing liver dysfunction
- Repeat HSCT

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Investigations:
* Abdominal Doppler ultrasound: shows reversed or reduced portal blood flow
* Liver biopsy (if needed for confirmation)

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Management / Prophylaxis:
* Supportive care
* Prophylaxis: Ursodeoxycholic acid, Defibrotide (mucoprotectant)
* Advanced cases: consider TIPS, antithrombotics, or fibrinolytics

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Pathophysiology:
Endothelial injury from:
* Toxic metabolites
* Alkylating agents
* Radiation

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Prognosis:
* Severe VOD is associated with >85% mortality

Question 10

PRES

Q.Clinical features

Q. Association

Q. Management

Answer 10

Posterior Reversible Encephalopathy Syndrome (PRES)

Features:
* Confusion
* Headache
* Visual loss
* Seizures

**Association:
* Often occurs post-HSCT
* Commonly linked to immunosuppressants, especially cyclosporin

Management:
* Treat underlying cause (e.g., adjust immunosuppression)

Question 11

TTP

Q.Cause

Q.Clinical features

Q. Mx

Answer 11

Thrombotic Thrombocytopenic Purpura (TTP)

Cause:
* Endothelial injury from chemotherapy or transplant-related stress

Pentad of Features:
1. Fever
2. MAHA (microangiopathic haemolytic anaemia)
3. Thrombocytopenia
4. Renal failure
5. Neurological involvement

Note: HUS (hemolytic uremic syndrome) presents similarly but lacks fever & neurological signs

Management:
* Plasmapheresis
* Broad-spectrum antibiotics
* High-dose steroids

Question 12

Diffuse Alveolar Haemorrhage (DAH)

Answer 12

Overview:
* Injury to pulmonary endothelial lining from toxins/radiation
* Occurs within 30 days of transplant

Clinical Features:
* Fever, dyspnoea, cough
* CXR: Diffuse infiltrates (non-specific)
* Haemoptysis-Rare
* BAL: progressively bloodier aliquots, presence of haemosiderin-laden macrophages

Management:
* High-dose steroids

Question 13

Idiopathic Pneumonia Syndrome (IPS)

Answer 13

• Affects ~3 wks post-HSCT
  
  • Presents with diffuse pulmonary infiltrates
  • No identifiable infection
  • Risk factors: pre-transplant radiation, chemotherapy, GVHD, Allogenic Tx

Management:
* Supportive

Question 14

Post-Transplant Lymphoproliferative Disorders (PTLD)

Q. Pathophysiology

Q.Risk factors

Q.Treatment

Answer 14

Pathophysiology:
* Uncontrolled EBV-infected B cell proliferation
* Due to T-cell immune suppression

Risk Factors:
* Previous EBV exposure
* T-cell depleted transplant
* Aggressive immunosuppression

Treatment:
* Reduce immunosuppression(increase risk of GVHD)
* Anti-B cell monoclonal antibodies (Rituximab)
* Infusion of donor T-cells
*IVIg