CPHON Bone Marrow Transplant and Stem Cell Therapy 1 — Questions and Answers

Question 1: A pediatric patient undergoing allogeneic hematopoietic stem cell transplant (HSCT) develops a skin rash, diarrhea, and elevated bilirubin 3 weeks post-transplant. The nurse recognizes this as which complication?

Acute graft-versus-host disease (aGVHD) (Correct answer)
Engraftment syndrome
Veno-occlusive disease
Cytomegalovirus colitis

Correct answer: Acute graft-versus-host disease (aGVHD)

Acute GVHD classically presents within 100 days of allogeneic HSCT with involvement of skin (maculopapular rash), GI tract (diarrhea, cramping, nausea), and liver (elevated bilirubin, alkaline phosphatase).

Acute graft-versus-host disease (aGVHD) occurs when donor T lymphocytes recognize the recipient's tissues as foreign and mount an immune attack. It typically presents within the first 100 days post-transplant. Classic target organs are skin (maculopapular rash starting on the palms and soles), GI tract (profuse watery or bloody diarrhea, nausea, vomiting, abdominal cramping), and liver (hyperbilirubinemia, elevated liver enzymes). Severity is graded I–IV based on extent of organ involvement. First-line treatment is high-dose systemic corticosteroids.

Question 2: Which conditioning regimen used prior to HSCT is associated with the highest risk of veno-occlusive disease (VOD)/sinusoidal obstruction syndrome?

Myeloablative conditioning with busulfan and cyclophosphamide (Correct answer)
Reduced intensity conditioning with fludarabine
Non-myeloablative conditioning
Standard chemotherapy without radiation

Correct answer: Myeloablative conditioning with busulfan and cyclophosphamide

High-dose busulfan combined with cyclophosphamide in myeloablative conditioning regimens causes the most significant hepatic sinusoidal endothelial cell injury, leading to VOD/SOS.

Hepatic veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (SOS), results from injury to hepatic sinusoidal endothelial cells caused by high-dose conditioning chemotherapy—particularly busulfan. Myeloablative conditioning with busulfan/cyclophosphamide or busulfan/cyclophosphamide/TBI carries the highest risk. VOD is characterized by painful hepatomegaly, fluid retention/weight gain (ascites), hyperbilirubinemia, and impaired hepatic function. Defibrotide is used for treatment; ursodeoxycholic acid is used for prophylaxis.

Question 3: What is the primary purpose of the preparative (conditioning) regimen given before HSCT?

To eradicate residual malignancy and create marrow space for donor cells (Correct answer)
To prevent graft-versus-host disease
To stimulate stem cell mobilization in the donor
To induce remission from active disease

Correct answer: To eradicate residual malignancy and create marrow space for donor cells

The conditioning regimen serves the dual purpose of destroying residual malignant cells (eradication) and creating immunosuppression and physical space in the bone marrow to allow engraftment of donor hematopoietic stem cells.

The conditioning regimen (also called the preparative regimen) is administered in the days immediately preceding HSCT infusion. It achieves three primary goals: (1) eliminates residual malignant or abnormal hematopoietic cells; (2) creates physical space in the bone marrow cavity (myeloablation); and (3) provides sufficient immunosuppression to prevent rejection of donor cells. Myeloablative regimens completely destroy the patient's hematopoietic system, while reduced-intensity and non-myeloablative regimens provide less myelosuppression, relying more on immunosuppression. The choice depends on disease type, patient fitness, and donor match.

Question 4: A child 6 months post-allogeneic HSCT develops dry eyes, oral mucosal changes, joint contractures, and skin tightening. This clinical picture is most consistent with:

Chronic graft-versus-host disease (cGVHD) (Correct answer)
Late cytomegalovirus end-organ disease
Post-transplant lymphoproliferative disorder
Drug-induced scleroderma

Correct answer: Chronic graft-versus-host disease (cGVHD)

Chronic GVHD is a multi-system inflammatory and fibrotic disorder occurring after 100 days post-transplant, resembling autoimmune connective tissue diseases with features of scleroderma, Sjögren's, and lichen planus.

Chronic graft-versus-host disease (cGVHD) is the most common long-term complication of allogeneic HSCT. It can affect virtually any organ system, with clinical features similar to autoimmune diseases: sicca syndrome (dry eyes/mouth), oral lichen-planus-like lesions, skin sclerosis, esophageal strictures, bronchiolitis obliterans (lung), joint contractures, and liver disease. The 2014 NIH consensus criteria classify cGVHD as mild, moderate, or severe based on organ involvement. First-line treatment is corticosteroids, with ruxolitinib approved for steroid-refractory cGVHD.

Question 5: What is engraftment, and what laboratory finding confirms that it has occurred following HSCT?

Recovery of donor-derived hematopoiesis, confirmed by absolute neutrophil count (ANC) ≥500/µL for 3 consecutive days (Correct answer)
Disappearance of GVHD symptoms
Platelet count above 100,000/µL
Return of pre-transplant immunoglobulin levels

Correct answer: Recovery of donor-derived hematopoiesis, confirmed by absolute neutrophil count (ANC) ≥500/µL for 3 consecutive days

Engraftment is defined as the successful establishment of donor hematopoietic stem cells in the recipient's bone marrow, with the primary indicator being an ANC of ≥500/µL (some use ≥500 for 3 days or ≥1000 for 1 day).

Engraftment refers to the establishment and proliferation of donor hematopoietic stem cells within the recipient's bone marrow, leading to restoration of blood cell production. The standard definition is achievement of an ANC ≥500/µL on three consecutive days (or ≥1000 for one day, depending on institutional protocol). Platelet engraftment typically follows neutrophil engraftment and is defined as platelets ≥20,000 or ≥50,000/µL without transfusion support for three consecutive days. Chimerism studies (measuring percentage of donor vs. recipient DNA) confirm donor origin of engrafted cells.

Question 6: Which infection is of greatest concern during the pre-engraftment phase of HSCT (days 0–30) when the patient is profoundly neutropenic?

Bacterial and fungal infections (Correct answer)
Herpes zoster (VZV)
Cytomegalovirus (CMV) end-organ disease
EBV-associated lymphoproliferative disorder

Correct answer: Bacterial and fungal infections

During profound neutropenia in the pre-engraftment phase, bacterial (gram-positive and gram-negative) and invasive fungal infections (Aspergillus, Candida) pose the greatest immediate threat to life.

The pre-engraftment phase (days 0–30) is characterized by severe neutropenia, breached mucosal barriers (from conditioning), and central line access—all risk factors for bacterial sepsis and invasive fungal infection. Gram-positive bacteria (from skin/central lines) and gram-negative bacteria (from gut translocation) are the most common causes of febrile neutropenia. Invasive mold infections (Aspergillus) and candidiasis are major fungal threats. CMV, VZV, and EBV-PTLD become more prominent in the early post-engraftment (CMV) and late (VZV, EBV-PTLD) phases.

CPHON Bone Marrow Transplant and Stem Cell Therapy 1

A pediatric patient undergoing allogeneic hematopoietic stem cell transplant (HSCT) develops a skin rash, diarrhea, and elevated bilirubin 3 weeks post-transplant.
The nurse recognizes this as which complication?