Late Effects of Treatment of NHL

Late effects of treatment of non-Hodgkin lymphoma (NHL) have been observed. Impaired fertility may occur after exposure to alkylating agents.[8] For as many as three decades after diagnosis, patients are at a significantly elevated risk of developing second primary cancers, especially the following:[9-12]

Left ventricular dysfunction was a significant late effect in long-term survivors of high-grade NHL who received more than 200 mg/m² of doxorubicin.[8,13]

Myelodysplastic syndrome and acute myelogenous leukemia are late complications of myeloablative therapy with autologous bone marrow or peripheral blood stem cell support, as well as conventional chemotherapy-containing alkylating agents.[10,14-21] Most of these patients show clonal hematopoiesis even before the transplant, suggesting that the hematologic injury usually occurs during induction or reinduction chemotherapy.[16,22,23] A series of 605 patients who received autologous bone marrow transplant (BMT) with cyclophosphamide and total-body radiation therapy (as conditioning) were followed for a median of 10 years. The incidence of a second malignancy was 21%, and 10% of those malignancies were solid tumors.[24]

A study of young women who received autologous BMT reported successful pregnancies with children born free of congenital abnormalities.[25] Late-occurring venous thromboembolism can occur after allogeneic or autologous BMT.[26]

Some patients have osteopenia or osteoporosis at the start of therapy; bone density may worsen after therapy for lymphoma.[27]

Long-term impaired immune health was evaluated in a retrospective cohort study of 21,690 survivors of diffuse large B-cell lymphoma from the California Cancer Registry. Elevated incidence rate ratios were found up to 10 years later for pneumonia (10.8-fold), meningitis (5.3-fold), immunoglobulin deficiency (17.6-fold), and autoimmune cytopenias (12-fold).[28] Similarly, there are impaired humoral responses to COVID-19 virus vaccination in patients with lymphoma who receive B-cell–directed therapies.[29,30]