Anaplastic large cell lymphoma is a rare type of non-Hodgkin lymphoma that primarily affects T cells. While most cases respond well to conventional chemotherapy, achieving long-term survival rates as high as in 80-90%, a subset of patients require more extensive treatment.
“Anaplastic large cell lymphoma (ALCL) that has relapsed is often treated with autologous or allogeneic hematopoietic cell transplantation (HCT),” said Dr. Monica Thakar in the Fred Hutch Clinical Research Division.
Hematopoietic cell transplantation is an intensive two-step process. It first involves a conditioning treatment that kills the cancerous cells – and severely depletes the immune system. Then, healthy stem cells, either from the patient (autologous HCT) or a donor (allogeneic HCT), are introduced. The stem cells engraft and produce healthy, functional cells to replace problematic ones and recover immune function.
Dr. Thakar explained, “It is most ideal to enter HCT without disease burden to achieve the highest chances of cure. Unfortunately, a subset of patients are not able to achieve this.” The conditioning step aims to kill all cancerous cells to produce the best possible treatment outcome, but in ALCL cases where that isn’t possible, is HCT still an effective treatment?
Dr. Thakar and colleagues investigated this question in a recent study published in Frontiers in Oncology. The retrospective study analyzed the outcomes of 41 ALCL patients who received HCT at Fred Hutch between 1997 and 2020. Of these patients, 22 achieved complete cancer elimination prior to stem cell transplant while 19 received transplant despite continued disease burden. The team also explored whether there were differences in efficacy between autologous and allogeneic HCTs. In the study, 24 patients underwent autologous HCT while 17 received allogeneic HCT. In each case, the treating clinician decided whether to pursue autologous or allogeneic HCT based on myriad disease and individual factors.
The study confirmed that people who reached complete remission from conditioning treatments had better HCT outcomes than those who had persistent disease. The 5-year overall survival rates were 76% and 37%, respectively.
“We also saw that those with persistent disease burden who received allogeneic HCT had better outcomes than would be expected,” indicated Dr. Thakar. There were superior outcomes in the cohort of people who received allogeneic HCT compared to autologous HCT, both among patients who did and did not achieve pre-transplant cancer elimination. The 5-year overall survival for in the allogeneic HCT cohort was 65% compared to 53% for the autologous HCT cohort. Moreover, the response to allogeneic HCT was more durable – patients who received allogeneic HCT had a relapse/disease progression rate of only 29%, compared 55% among patients who received autologous HCT. All allogeneic HCT patients who did progress or relapse did so within the first 6 months after HCT. It seems that once achieved, ALCL remission after allogeneic HCT is long- lasting.
A potential explanation for this is the graft versus tumor (GVT) effect, a phenomenon unique to allogeneic transplants. The idea is that the graft – the immune cells from the healthy donor – attack and kill the cancer cells in the HCT recipient. Any cancer that remains after conditioning is eliminated by fresh, genetically distinct immune cells that are encountering the cancer for the first time.
The information gained in this study may not only influence decisions about whether to perform autologous versus allogeneic HCT, but also how to approach conditioning strategies and treatment guidelines for relapsed ALCL more broadly. Dr. Thakar commented, “These data raise the question of whether, given the apparent susceptibility of this disease to GVT effects, immunotherapy could be used to eradicate residual disease. Also, since GVT is suggested to play such an important role in ALCL, myeloablative conditioning may not be as necessary as it is for other lymphoid-based malignancies. This is particularly important for cancer survivorship and reducing long-term side effects, especially those associated with intensive treatments such as high-dose radiation.” These results may help pave the way to curing difficult-to-treat ALCL with less intense therapies and fewer treatment-related health consequences.
Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium Member Drs. Corinne Summers, Ted Gooley, Rachel Salit, Ann Dahlberg, Marie Bleakley, Mohamed Sorror, Leona Holmberg, Paul Carpenter, Brenda Sandmaier, and Monica Thakar contributed to this research.
The spotlighted research was funded by the American Society of Hematology, Alpha Omega Alpha Carolyn L. Kuckein Student Research Award, and the National Institutes of Health.
Smith NL, Summers C, Gooley T, Shustov A, Salit R, Gardner RA, Dahlberg A, Bleakley M, Sorror ML, Holberg L, Carpenter PA, Sandmaier BM, Maloney D, Thakar MS. 2026. Autologous and allogeneic hematopoietic cell transplantation in children and adults with high-risk anaplastic large cell lymphoma. Frontiers in Oncology. doi: 10.3389/fonc.2026.1785566
Science Spotlight writer Ashley Person is a PhD candidate in the Cohn lab in the Vaccine and Infectious Disease Division at Fred Hutch. She studies how HIV-infected cells persist over time in people living with HIV on long term treatment.