Patients with an age-related blood condition undergoing autologous stem cell transplantation (ASCT) for lymphoma are at greater risk of adverse outcomes, reports a new study published in the Journal of Clinical Oncology.
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Clonal hematopoiesis of indeterminate potential (CHIP) is a condition with greater prevalence in individuals aged older than 70 years in which somatic mutations are present in blood cells or bone marrow. Up until now, there had been no studies of the implications of CHIP in patients with cancer who have received cytotoxic therapy.
Researchers led by Christopher J Gibson, MD, department of medical oncology, Dana-Farber Cancer Institute (Boston, MA), conducted a study involving patients with CHIP undergoing ASCT for lymphoma. The study consisted of whole-exome sequencing on pre- and post-ASCT samples from 12 patients with Hodgkin lymphoma or non-Hodgkin lymphoma who developed therapy-related myeloid neoplasm as a result of ASCT. Researchers also performed targeted sequencing on autologous stem-cell products from 401 patients with non-Hodgkin lymphoma between 2003-2010 who underwent ASCT. Assessed outcomes included the effect of CHIP at the time of ASCT on therapy-related myeloid neoplasm, cause-specific mortality, and overall survival (OS).
In the targeted sequencing cohort, 120 patients (29.9%) had CHIP at the time of ASCT. These patients were more likely to experience therapy-related myeloid neoplasm (10-year cumulative incidence, 14.1% vs 4.3% for those with and without clonal hematopoiesis, respectively; P = .002). These patients also had significantly inferior OS compared with the other patients in the cohort (10-year OS, 30.4% vs 60.9%, respectively; P < .001). Six of the patients in the exome sequencing cohort had detectable pre-ASCT mutations that were also found in the therapy-related myeloid neoplasm.
Researchers concluded that CHIP at the time of ASCT for patients with lymphoma is directly related to increased risk of therapy-related myeloid neoplasm and inferior survival. Further prospective evaluations are suggested to validate the effects of ASCT on patients with lymphoma, along with alternatives to ASCT for the treatment of patients with CHIP. – Zachary Bessette