Risk of second malignant neoplasms after cyclophosphamide-based chemotherapy with or without radiotherapy for non-Hodgkin lymphoma

Abstract

Relatively little information is available on quantitative risks of therapy-induced second malignant neoplasm (SMN) in patients with non-Hodgkin lymphoma (NHL). A nested case-control study was conducted in a cohort of 3412 patients treated for NHL between 1990 and 2006, including 118 patients with SMN and 472 controls. Risks of leukemia/lung/breast/colorectal and bladder cancer were higher in NHL compared with the general population. A higher risk of leukemia was restricted to patients given a cumulative dose of cyclophosphamide more than 11 250 mg/m(2). However, no significant association was found between SMN risk with rituximab, fludarabine, anthracyclines, epipodophyllotoxins and platinum, respectively. In combined modality treatment, involved-field radiation therapy (IFRT) had a higher risk for second solid cancers as compared to involved-nodal radiation therapy (INRT). For patients receiving radiation doses exceeding 40 Gy, the risk of lung cancer and breast cancer was increased. In conclusion, we found that cyclophosphamide-based therapy increased the risk of SMN in NHL. Leukemia risk was linked with high-dose cyclophosphamide. A received larger radiation field or higher radiation dose also could be an important risk factor for the development of SMN.

Effect of rituximab on malignancy risk in patients with ANCA-associated vasculitis

“…There is emerging evidence that regulatory B cells are the main mediators of this mechanism 30. In humans, the hypothesis that rituximab enhances the antitumour immune response is supported by the trend towards a lower risk of developing a second primary malignancy in patients with non-Hodgkin's lymphoma treated with rituximab-containing chemotherapy compared with patients treated with chemotherapy that does not include rituximab 31 32. However, clarification of the effects of B-cell depletion on antitumour immunity in humans requires further investigation.…”

Second cancers in patients with chronic lymphocytic leukemia who received frontline fludarabine, cyclophosphamide and rituximab therapy: distribution and clinical outcomes

“…[ 4,13 ] Cyclophosphamide is known to have weaker carcinogenicity compared to other alkylating agents however high dose cyclophosphamide based therapies increases the risk of second cancers in patients with CLL and Non-Hodgkin’s lymphoma. [ 14,15 ] Skin cancers which developed after therapy with fludarabine in patients with CLL were reported to be more aggressive, with higher growth rate, recurrence and distant metastasis. [ 16 ] Cheson et al compared the number of observed to the expected second cancers in 724 relapsed refractory patients with CLL who were treated with fludarabine for a median follow up of 7.4 years.…”

Therapy-related myelodysplastic syndromes, or are they?

“…There has been conflicting data whether radiotherapy adds to the leukemia risk associated with chemotherapy in patients treated with combined modality treatment. In non-Hodgkin lymphoma, there was no correlation between radiation and risk of developing leukemia [32].…”

“…T-AML/ MDS was a major contributor to the increased risk of second cancers in these patients compared to the general population [57]. In NHL, a cumulative dose of cyclophosphamide of 11,250 mg/m2 or higher was associated with increased risk of t-MDS/AML compared to a matched NHL cohort (odds ratio: 7) [32].…”