Post-Transplant Cyclophosphamide (PTCy) for GVHD Prophylaxis

By Elaine S. DeMeyer, RN, MSN, AOCN®, BMTCN® - Last Updated: July 14, 2022

Oncology nurses need to understand various graft-versus-host disease (GVHD) risk reduction strategies for their patients receiving stem cell transplants (SCTs), including the use of post-transplant cyclophosphamide (PTCy). With more knowledge and a better understanding of PTCy, nurses can improve their communication and help to alleviate any patient or caregiver concerns.

How Does PTCy Work?

PTCy is alkylating chemotherapy given after SCT to cause the death, or apoptosis, of specific T cells—the mature T lymphocytes—responsible for GVHD. Although PTCy kills all the donor bone marrow cells, it does not destroy the stem cells. These stem cells contain high levels of the enzyme aldehyde dehydrogenase (ALDH) that protects them from the toxic effects of PTCy. They can then repopulate the bone marrow with hematopoiesis including the red blood cells, white blood cells, and platelets.

This chemotherapy selectively kills the T cell subsets responsible for GVHD while preserving the T cells that provide the immunologic graft-versus-tumor (GVT) effect. It may not eliminate GVHD but may lower its severity. Of course, there is a delicate balance between enough GVHD to cause GVT without significant GVHD complications.

GVT was originally called GVL (graft-versus-leukemia), but the term expanded to be more inclusive of other diseases besides leukemia. The alloreactive T cells are responsible for GVT persist after PTCy. The same donor T cells that attack the patient’s organs also kill any remaining tumor cells, thus, the term “GVT.” Therefore, patients with GVHD have a lower risk of their cancer recurring because of the GVT effect than do patients who do not experience GVHD. Bottom line, mild GVHD can be good.

How Is PTCY Given?

PTCy is just part of a GVHD “prevention cocktail” of agents. It is usually given in combination with a calcineurin inhibitor (CNI)—tacrolimus or cyclosporin, or sometimes substituted with sirolimus. The antimetabolite mycophenolate mofetil (MMF) that inhibits T-cell replication may also be part of the combination strategy.

Intravenous PTCy is given on Day +3 and Day +4 after the stem cell infusion and is typically dosed as 50 mg/kg of ideal body weight. Because cyclophosphamide chemotherapy breaks down into an acrolein metabolite that can cause hemorrhagic cystitis, prevention is critical. Therefore, mesna must start 30 minutes before the PTCy, along with aggressive hydration to prevent bladder irritation. Mesna is a detoxifying agent that binds and neutralizes acrolein to protect the bladder lining.

What Is the Status of Research on PTCy?

PTCy successfully prevents severe acute and chronic GVHD after allogeneic SCT. It was first used in human leukocyte antigen (HLA) haploidentical (haplo), or half match, SCT. More recently, it has had widespread adoption in mismatched unrelated donor SCT with exploration in HLA-matched donors. For example, a small retrospective study of PTCy in acute myeloid leukemia showed a lower incidence of acute GVHD in patients receiving HLA-identical donor SCT than in haplo donor SCT.

To compare studies of PTCy, clinical trial outcomes must be carefully defined. Several trials use GVHD-free, relapse-free survival as the primary goal and overall survival as a secondary endpoint. GRFS means a decreased use of steroids and all their complications. In addition, without GVHD, patients often have a higher quality of life and the ability to do activities of daily living.

How Can Nurses Explain PTCy to Patients?

Patients and their caregivers may have concerns about receiving chemotherapy after the SCT. They may think that chemotherapy can damage these new cells, so oncology nurses need to educate patients on the rationale for PTCy use. They must clearly explain that this chemotherapy DOES NOT damage the donor cells, but it DOES kill some types of white blood cells, called T cells, that cause GVHD. For more curious patients, you may need to explain that it only kills specific T-cell subsets.

Patients receiving SCT need to feel that they are active participants in their care. Effective patient teaching, such as information about PTCy, can reduce anxiety and promote patient safety and involvement. The terms and treatment in SCT are complex, requiring ongoing patient education and communication.

References:

Mystery Explained: How a Common Chemo Drug Thwarts Graft Rejection in Bone Marrow Transplants

Mechanisms of Graft-versus-Host Disease Prevention by Post-transplantation Cyclophosphamide: An Evolving Understanding

Post-Transplantation Cyclophosphamide After HLA Identical Compared to Haploidentical Donor Transplant in Acute Myeloid Leukemia: A Study on Behalf of GETH-TC

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