THERAPY-RELATED MYELOID NEOPLASM IN NON-HODGKIN LYMPHOMA SURVIVORS

Abstract

Background: Relatively little information on secondary cancers is available for Non-Hodgkin lymphoma (NHL) treated patients as treatments have been less effective compared to those for Hodgkin Lymphoma. Recently, evolving chemotherapy (CHT) in combination with monoclonal antibodies, sometime supplemented with radiotherapy (RT) have improved survival outcome of NHL patients and the use of autologous and allogeneic bone marrow transplantation for relapsed patients have further improved long term survival for some histological subtypes. As a results of these advances secondary malignancies are becoming an important issue in NHL survivors.

Design and Methods: In the last few years, our group performed 4 researches about second neoplasms in NHL survivors: (1) Secondary malignancies after treatment for indolent NHL; (2) Secondary malignancies after treatment for Diffuse Large B Cell Lymphoma (DLBCL); (3) Meta analysis on the risk of second malignancies in NHL survivors; (4) Incidence of  second myeloid malignancies (SMyM) in patients treated for NHL, evaluated on Modena Cancer Registry (MCR) database.

Results: In the first study we analyzed 563 patients with indolent NHL enrolled in Gruppo Italiano Studio Linfomi (GISL) trials from 1988 to 2003; results showed that, after a median follow-up of 62 months, 39 patients (6.9%) developed secondary cancer (12 Myelodisplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML), and 27 solid tumours). The cumulative incidence (CI) of secondary cancer at 12 years was 10.5%.

In the second paper we considered 1280 patients with DLBCL enrolled in GISL trials from 1988 to 2003; with a median follow-up of 51 months 48 patients (3.8%) developed a second cancer (8 MDS/AML, 5 other hematologic malignancies and 35 solid tumours). The CI of second cancer was 8.2% at 15 years.

The third research consist in a meta-analysis in which we carried out an electronic search seeking articles investigating the risk of second malignant neoplasm (SMN) after NHL treatment; we have found 1,521 papers and after selection we considered 19 studies available for our aims. Our results indicated that NHL patients experienced a higher risk for SMN (1.88-fold increased risk) than the general population, in particular the standardized incidence risk (SIR) for secondary AML was 11.07.

In province of Modena in the period 2000-2008 we found that the SIR  to develop a second tumor after NHL was 1.63 and it grew up for second haematological malignancies (SIR 1.99). As concern the incidence of MDS and/or AML in Modena province on MCR we found a total of 9 NHL with SMyM (3 AML and 6 MDS) with a higher risk than expected (SIR 8.8, 95% CI: 4.0-16.6), in particular the SIR for secondary AML was 5.7.

Conclusions: Overall our results observed either in patients enrolled in clinical trials or on database from hospital and population registry showed an increased risk to develop a second tumour in CHT/RT-treated patients. By meta-analysis, more impressive results have been observed considering only SMyM . Data from MCR confirm the trend for NHL treated to be at higher risk to develop SMN and in particular SMyM .

In conclusion patients treated for NHL are at increased risk to develop secondary neoplasm. Thus for NHL survivors a long term monitoring should be considered  with a follow-up longer than five years as usually.