High Incidence of tMDS in Elderly Lymphoma Patients Subjected to Radioimmunotherapy

Conventional therapies with cytotoxic agents for disseminated NHL are associated with a high risk of therapy related myeloid neoplasm (tMN). The latency period between exposure to this agents and development of tMN ranges from one to 10 years.

Radioimmunotherapy (RIT) uses monoclonal antibodies, specifically binding to antigens of tumor cells, as a carrier for the radioisotope. The radiation is delivered not only to the antibody –bound tumor cell, but also neighboring cells.

In the years 2005–2011 radioimmunotherapy with ibritumomab tiuxetan was used in 102 patients with FL (during consolidation therapy), MCL (as consolidation of the first-line treatment and after achieving PR in the first- or second-line therapy), DLBCL and MCL (in the HDT supported by auto-SCT). 5 patients (4,9%) ( 4 with MCL/ 1 with FL) subjected to RIT developed tMDS. All patients with MCL in previous treatment were exposed to alkylating agents, antymetabolites and inhibitors of II topoisomerase. All patients had hypoplastic bone marrow year after RIT.

Median time to diagnosis of tMDS after treatment with RIT was 2,3 years. 4/5 during 6 month transformed into tAML. In peripheral blood of all patients anemia, thrombocytopenia or pancytopenia was observed. All patient in histophatology had dysplastic changes in 3 hematopoetic lines with 5% blast cells, without elevated percentage of ring sideroblasts. Each patient had typical for tMDS complex abnormalities with monosomy of chromosome 5 or 7, or abnormalities of this chromosome [table 1]. Three of this patients was treated with azacitidine, one of this patients was prepared to RIC allo BMT but developed tAML and died during induction therapy. All patients received supportive care.

The development of secondary hematological malignancies (tMDS and tAML) after RIT is very closely related to the drugs applied in the induction treatment especially purine analogues. Higher incidence of tMDS in patients with MCL confirm the relationship of occurrence of secondary MDS and AML after radioimmunotherapy with the earlier use of purine analogs (fludarabine) and cumulative damage to bone marrow cells rather than exclusively associated with administration of RIT.

No relevant conflicts of interest to declare.