Mutations Associated With Myeloid Neoplasms Risk Post-Stem Cell Transplant

Author(s):

Patients with TP53/PPM1D mutations in their stem cell product had an increased risk of myeloid neoplasms in patients with Hodgkin lymphoma undergoing autologous stem cell transplant.

There was a 4.17-fold higher hazard of non-relapse mortality in patients with Hodgkin lymphoma who have TP53 and/or PPM1D mutations.

While autologous stem cell transplantation is a potentially curative option for relapsed or refractory Hodgkin lymphoma, certain characteristics in the transplant product may carry a risk of developing a potentially life-threatening myeloid neoplasm from the procedure, according to recent research published in the Journal of Clinical Oncology.

A group of researchers analyzed targeted DNA sequencing in 321 patients with Hodgkin lymphoma who underwent a peripheral blood stem cell transplantation. Forty-six patients experienced clonal hematopoiesis, which is the acquisition of mutations in leukemia-associated genes. Clonal hematopoiesis, according to study author Dr. Smita Bhatia, increases a patient’s risk of leukemia and cardiovascular events.

“Presence of [clonal hematopoiesis] in the [peripheral blood stem cell transplantation] process was an independent predictor of therapy-related myeloid neoplasms,” the researchers wrote.

Study findings showed that the presence of TP53 and/or PPM1D mutations — both of which can lead to clonal hematopoiesis — in the stem cells being transplanted led to a 7.29-fold increased risk of treatment-related myeloid neoplasm. In fact, all patients with a TP53 mutation discovered in the stem cells developed a myeloid neoplasm, compared to those without clonal hematopoiesis-related mutations.

Additionally, findings showed that in patients with TP53 and/or PPM1D mutations, there was a 4.17-fold higher hazard of non-relapse mortality (death from a cause other than cancer relapse).

“Based on these findings, if health care providers find TP53 or PPM1D mutations in the stem cell produce that is being prepared for infusion for autologous transplantation, they should discuss alternative therapeutic options, such as allogeneic [bone marrow transplant],” Bhatia, Director, Institute for Cancer Outcomes and Survivorship, Gay and Bew White Endowed Chair in Pediatric Oncology, Distinguished Professor and Vice Chair, Dept. of Pediatrics, School of Medicine at the University of Alabama at Birmingham, said in an interview with CURE®.

An autologous stem cell transplant is when a patient’s own healthy cells are collected and then infused back into the patient. Conversely, a hematopoietic stem cell transplant (also known as a bone marrow transplant) involves taking a donor’s cells and infusing them into the patient with cancer, according to the National Institutes of Health.

“Autologous peripheral blood stem cell transplantation serves as a potentially curative option for patients with relapsed/refractory Hodgkin lymphoma. Unfortunately, therapy-related myeloid neoplasm is a life-threatening complication, and has a dismal prognosis,” Bhatia said.

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