CPHON Bone Marrow Transplant and Stem Cell Therapy 2 — Questions and Answers

Question 1: What is the difference between autologous and allogeneic HSCT, and which type carries risk for graft-versus-host disease?

Allogeneic uses donor stem cells and carries GVHD risk; autologous uses the patient's own cells and does not (Correct answer)
Autologous uses donor cells with GVHD risk; allogeneic uses patient's own cells without risk
Both types carry equal GVHD risk
Neither type carries GVHD risk in pediatric patients

Correct answer: Allogeneic uses donor stem cells and carries GVHD risk; autologous uses the patient's own cells and does not

Allogeneic HSCT uses stem cells from a matched donor (sibling, unrelated, or cord blood), and the immunologic mismatch between donor T cells and host tissues is the basis for GVHD. Autologous HSCT uses the patient's own stored stem cells, so GVHD does not occur.

In autologous HSCT, the patient's own hematopoietic stem cells are collected (usually via peripheral blood mobilization with G-CSF), stored, and re-infused after high-dose conditioning chemotherapy. Because the immune cells are self-derived, there is no risk of GVHD. Autologous HSCT is used primarily to allow dose escalation of chemotherapy. In allogeneic HSCT, cells come from a donor (HLA-matched sibling, matched unrelated donor, haploidentical parent, or cord blood). Donor T cells recognizing recipient tissues as foreign cause GVHD — but may also provide a graft-versus-leukemia (GVL) effect.

Question 2: A child receiving allogeneic HSCT develops sudden weight gain, right upper quadrant pain, and jaundice on day 10 post-transplant. Labs show elevated bilirubin and transaminases. The nurse suspects:

Hepatic veno-occlusive disease (VOD/SOS) (Correct answer)
Acute GVHD of the liver
Cytomegalovirus hepatitis
Drug-induced hepatotoxicity

Correct answer: Hepatic veno-occlusive disease (VOD/SOS)

VOD/SOS typically presents in the first 30 days post-transplant with the classic triad of painful hepatomegaly/right upper quadrant pain, fluid retention/weight gain >2%, and hyperbilirubinemia (>2 mg/dL).

Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS) results from injury to hepatic sinusoidal endothelial cells by conditioning chemotherapy. Fibrin deposits obstruct hepatic venules, causing portal hypertension and hepatic dysfunction. The clinical criteria (modified Seattle or Baltimore criteria) include: weight gain >5%, hyperbilirubinemia, and hepatomegaly/right upper quadrant pain — typically by day 30. Severe VOD carries high mortality. Defibrotide (Defitelio) is the only FDA-approved treatment; it acts as an anticoagulant and anti-inflammatory agent at the endothelial level.

Question 3: Which type of donor match provides the best outcomes in pediatric allogeneic HSCT?

10/10 HLA-matched sibling donor (Correct answer)
5/10 haploidentical parent
Unrelated cord blood with 4/6 HLA match
Mismatched unrelated donor

Correct answer: 10/10 HLA-matched sibling donor

A fully HLA-matched sibling donor (10/10 allele-level match) provides the best outcomes with the lowest rates of graft rejection, acute GVHD, and transplant-related mortality.

HLA (human leukocyte antigen) matching is the foundation of allogeneic HSCT donor selection. A 10/10 matched sibling donor (matched at HLA-A, -B, -C, -DRB1, and -DQB1 at the allele level) is the gold standard and associated with the best transplant outcomes—lowest rates of GVHD, graft failure, and transplant-related mortality. Matched unrelated donors (MUD, 10/10) are the next best option. Haploidentical donors (typically a parent) share only 5/10 HLA antigens but have become increasingly viable due to T-cell depletion and post-transplant cyclophosphamide strategies. Cord blood is readily available but associated with slower engraftment.

Question 4: What is the graft-versus-leukemia (GVL) effect, and why is it clinically important in allogeneic HSCT?

Donor T cells attacking residual leukemic cells in the recipient, reducing relapse risk (Correct answer)
Donor cells producing antibodies against leukemia-specific antigens
The conditioning regimen's direct cytotoxic effect on residual leukemia
Recipient NK cells eliminating donor leukemia-contaminated cells

Correct answer: Donor T cells attacking residual leukemic cells in the recipient, reducing relapse risk

The GVL effect refers to donor T and NK cells recognizing and eliminating residual host leukemic cells that express alloantigens, providing an immune-mediated anti-tumor effect that reduces relapse rates.

The graft-versus-leukemia (GVL) effect is a critical therapeutic component of allogeneic HSCT. Donor T lymphocytes and NK cells that react against recipient minor and major HLA antigens also recognize leukemia-specific or leukemia-associated antigens on residual malignant cells, destroying them. GVL is responsible for the lower relapse rates seen after allogeneic vs. autologous HSCT for leukemia. However, GVL is immunologically linked to GVHD — the same donor T cells that eliminate leukemia also attack normal host tissues. Complete T-cell depletion eliminates GVHD but also abolishes GVL, demonstrating this inseparable relationship.

Question 5: Which stem cell source typically results in the fastest neutrophil engraftment following HSCT?

G-CSF mobilized peripheral blood stem cells (PBSC) (Correct answer)
Bone marrow harvest
Umbilical cord blood
Adipose-derived stem cells

Correct answer: G-CSF mobilized peripheral blood stem cells (PBSC)

G-CSF-mobilized peripheral blood stem cells contain the highest CD34+ progenitor cell content, resulting in faster neutrophil and platelet engraftment compared to bone marrow or cord blood.

Peripheral blood stem cells (PBSC) collected via apheresis after G-CSF (and sometimes plerixafor) mobilization contain 10–100 times more CD34+ hematopoietic progenitor cells than a typical bone marrow harvest. This higher progenitor content leads to faster neutrophil engraftment (median ~10–12 days vs. ~18 days for marrow) and platelet engraftment. However, PBSC grafts contain more T cells, which may increase chronic GVHD risk compared to marrow. Cord blood has the slowest engraftment (median 26+ days) due to lower cell dose, but its immaturity results in lower GVHD severity.

Question 6: A child post-allogeneic HSCT is prescribed tacrolimus and methotrexate. What is the primary purpose of this combination?

GVHD prophylaxis by suppressing donor T-cell activation and proliferation (Correct answer)
Prevention of viral reactivation
Promotion of faster engraftment
Treatment of active acute GVHD

Correct answer: GVHD prophylaxis by suppressing donor T-cell activation and proliferation

Tacrolimus (a calcineurin inhibitor blocking IL-2 production) combined with short-course methotrexate (inhibiting T-cell proliferation) is the standard combination for acute GVHD prophylaxis in allogeneic HSCT.

GVHD prophylaxis is given to all allogeneic HSCT recipients to prevent acute GVHD. The standard regimen of tacrolimus (or cyclosporine) plus short-course methotrexate (days +1, +3, +6, +11) is the most widely used approach. Tacrolimus is a calcineurin inhibitor that blocks T-cell activation by inhibiting IL-2 transcription. Methotrexate inhibits proliferating T cells. Together they reduce the frequency and severity of acute GVHD. Monitoring of tacrolimus drug levels and renal function is essential, as toxicity (nephrotoxicity, neurotoxicity, PRES) can occur. Newer approaches include post-transplant cyclophosphamide (PTCy) for haploidentical and mismatched HSCT.

CPHON Bone Marrow Transplant and Stem Cell Therapy 2

What is the difference between autologous and allogeneic HSCT, and which type carries risk for graft-versus-host disease?