Understanding Chimerism Ratios: Predictors of Outcomes

By Elaine S. DeMeyer, RN, MSN, AOCN®, BMTCN® - Last Updated: October 4, 2022

Understanding allogeneic stem cell transplantation (SCT) is becoming more complicated with advanced technology like testing genetic markers to confirm engraftment chimerism. Oncology nurses can help patients understand beyond the fundamental “count recovery” to the more advanced concepts of “immune reconstitution” and “chimerism” by mastering these topics themselves.

How Does Allogeneic SCT Fight Disease?

The allogeneic SCT process includes 2 main components: 1) conditioning regimens and 2) immunologic response. First, a conditioning regimen—chemotherapy and/or total body irradiation—is given to kill any remaining tumor cells and suppress recipient alloreactivity against the donor cells to allow for engraftment. Second, an immunologic response is anticipated when the donor cells react against the host’s malignant tissue. This phenomenon is called graft-versus-tumor effect, formerly graft-versus-leukemia.

What Is Engraftment Chimerism?

The term “chimerism” refers to the state of being a chimera, or an individual, organ, or part consisting of tissues of diverse genetic constitution. In Greek mythology, chimera refers to a fire-breathing she-monster with a lion’s head, a goat’s body, and a serpent’s tail. Oncology nurses need to be aware that this might be the image conjured by patients or their caregivers when explaining “chimerism” in SCT.

Engraftment chimerism goes beyond just looking at engraftment of neutrophils, erythrocytes, and thrombocytes (i.e., white cells, red cells, platelets). It is not only looking at the blood counts but also the donor–recipient DNA composition of the marrow. Chromosomal analysis from a bone marrow biopsy or sometimes peripheral blood is critical to identify the origin of the new marrow. The DNA can be the donor, the patient, or a mixture. Mixed chimerism occurs when there is a mix of donor and recipient cells (also called the residual host or patient cells). Using reduced-intensity conditioning regimens and T-cell depletion of the graft can result in higher states of mixed chimerism.

How Do Transplant Teams Assess Chimerism?

Routine monitoring of chimerism helps the team see how many blood cells are produced by the donor’s stem cells. Several different techniques, such as sorted T cells (CD3+) and leukemia lineage cells (CD13+, CD33+, and CD19+) or bone marrow CD34+ stem cells (BM-CD34+SC), are used to assess chimerism.

Transplant teams assess the donor-to-recipient DNA ratio for engraftment chimerism at different time frames (e.g., 30 days, 90 days, 1 year). A “good chimerism” depends on the time frame and what is being measured: whole blood and T-cell chimerism or even natural killer cells. The optimal percentage of chimerism on specific days (e.g., donor chimerism 83% on Day +14) for different patient populations is unclear. In time, the goal is for only the donor cells to be populating the patient’s marrow, or 100% donor chimerism.

What Is the Importance of Chimerism?

Chimerism is an essential predicator for patient outcomes—relapse, measurable residual disease (MRD), GVHD, and graft rejection. According to a study published in Bone Marrow Transplantation, researchers found that mixed chimerism is a robust predictor of relapse. This study assessed BM-CD34+SC and whole peripheral blood in 261 allogeneic SCT recipients with myeloid malignancies. Most patients received a matched related transplant (n = 145) followed by a haploidentical (n = 65) and matched unrelated graft (n = 51). BM-CD34+SC chimerism at 3 months post-transplant was shown to be a robust marker to predict relapse after allogeneic SCT for myeloid disease. Chimerism levels could be a surrogate marker to aid in decision making regarding post-transplant relapse prevention measures, such as maintenance therapy decisions.

Oncology nurses need to understand the clinical relevance of chimerism because chimerism ratios not only help predict outcomes but also guide treatment decisions. For example, if the chimerism level drops (meaning the percentage of patient cells increases), it may indicate graft rejection or failure. In this case, patients may need an intervention, such as a donor lymphocyte infusion, that can push the chimerism level back up to an acceptable level. In addition, oncology nurses can help explain the importance of chimerism monitoring as a diagnostic tool for assessing outcomes, particularly in patients who lack specific markers for tracking residual disease.