OBJECTIVES

A common chemotherapy regimen in Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV⁺ PTLD) following solid organ transplants is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). This study describes the available evidence for long-term consequences, therapy-related complications that persist or arise after treatment, associated with any components of CHOP.

METHODS

Long-term consequences from any components of CHOP were identified from the Children’s Oncology Group Long-Term Follow-Up Guidelines (COG LTFU). Cited references were screened; eligibility was based upon reporting data for one or more of the 14 identified COG LTFU long-term consequences along with pre-specified criteria (English, systematic review, randomized controlled trial n>100, observation study n>100, case series n>20). Relevant data were extracted and synthesized.

RESULTS

Of the 61 studies, 66% were retrospective cohort studies, 28% were in the US, 36% were in the EU, and 95% had pediatric patients. Follow-up duration ranged from 2 to 26.5 years. No study focused specifically on the CHOP regimen. Only 10 studies reported the time to onset of complications.

Long-term consequences of components of CHOP observed in >3 studies included cardiac toxicity (n=14), hormone deficiencies or infertility (n=14), acute myeloid leukemia (n=7), osteonecrosis (n=6), and urotoxicity/ bladder malignancy (n=4). Majority of the studies evaluated consequences to anthracycline or alkylating agents while 15% evaluated corticosteroids. All three product classes had a dose dependent risk of these long-term consequences. Other key risk factors included age, gender, primary cancer diagnosis, and radiation. There was limited evidence (≤3 studies) on the impact to reduced bone mineral density, mental health disorders, socioeconomic issues, fatigue/ sleep, dental abnormalities, Raynaud’s phenomenon, neuropathy, cataract, and quality of life effects.

CONCLUSIONS

Patients exposed to anthracycline, alkylating, or corticosteroid agents have a dose dependent risk of cardiac toxicity, infertility, secondary leukemia, osteonecrosis, and bladder cancer. Safe and effective EBV⁺ PTLD treatments that potentially avoid these long-term consequences are urgently needed.