Long-Term Toxicity after Non-Myeloablative Conditioning Regimens Using Total Body Irradiation

Area of Science:

• Hematology
• Oncology
• Transplantation Medicine

Background:

• Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for various hematologic malignancies and non-malignant conditions.
• Total body irradiation (TBI) is a component of conditioning regimens used prior to HSCT to eliminate residual disease and immunosuppress the recipient.
• Non-myeloablative conditioning regimens aim to reduce toxicity compared to traditional myeloablative regimens, but long-term outcomes require thorough evaluation.

Purpose of the Study:

• To evaluate the long-term health risks and toxicities following allogeneic HSCT that utilizes non-myeloablative conditioning with TBI.
• To compare the incidence and severity of long-term toxicities between patients receiving non-myeloablative TBI-based conditioning and those receiving myeloablative TBI-based conditioning.

Main Methods:

• A retrospective analysis included adult patients undergoing non-myeloablative allogeneic HSCT with TBI-based conditioning between 1995 and 2020.
• Long-term toxicities were defined as events occurring or persisting beyond 6 months post-transplant and graded using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
• Competing risk analysis using the Fine-Gray model assessed the risk of organ-specific toxicities, with outcomes compared to a historical cohort receiving myeloablative TBI.

Main Results:

• The study analyzed 174 non-myeloablative HSCT recipients and 378 myeloablative HSCT recipients, with a median follow-up of 7.4 years.
• At 5 years, cumulative incidences of pulmonary, cardiac, renal, and thyroid toxicities were comparable between non-myeloablative and myeloablative groups.
• While the risk of secondary malignancy was not significantly different, non-myeloablative recipients showed a higher incidence of other endocrine toxicities (3.1% vs 8.8%, P=.04).

Conclusions:

• Non-myeloablative conditioning regimens, even with reduced TBI doses, confer a significant risk of long-term medical conditions.
• The incidence of several long-term toxicities in non-myeloablative HSCT recipients was comparable to those undergoing myeloablative HSCT.
• These findings underscore the importance of long-term surveillance for diverse toxicities in allogeneic HSCT survivors, irrespective of conditioning intensity.