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Background

In some clinical situations, for which RCT are rare or impossible, the majority of the evidence comes from observational studies, but standard estimations could be biased because they ignore covariates that confound treatment decisions and outcomes.

Methods

Three observational studies were conducted to assess the benefit of Allo-SCT in hematological malignancies of multiple myeloma, follicular lymphoma and Hodgkin's disease. Two statistical analyses were performed: the propensity score (PS) matching approach and the inverse probability weighting (IPW) approach.

Results

Based on PS-matched samples, a survival benefit in MM patients treated by Allo-SCT, as compared to similar non-allo treated patients, was observed with an HR of death at 0.35 (95%CI: 0.14-0.88). Similar results were observed in HD, 0.23 (0.07-0.80) but not in FL, 1.28 (0.43-3.77). Estimated benefits of Allo-SCT for the original population using IPW were erased in HR for death at 0.72 (0.37-1.39) for MM patients, 0.60 (0.19-1.89) for HD patients, and 2.02 (0.88-4.66) for FL patients.

Conclusion

Differences in estimated benefits rely on whether the underlying population to which they apply is an ideal randomized experimental population (PS) or the original population (IPW). These useful methods should be employed when assessing the effects of innovative treatment in non-randomized experiments.

As the replication pattern of leukemogenic PTLVs possesses a strong pathogenic impact, we investigated HTLV-2 replication in vivo in asymptomatic carriers belonging into 2 distinct populations infected by the same HTLV-2b subtype. They include epidemically infected American blood donors, in whom HTLV-2b has been present for only 30 years, and endemically infected Bakola Pygmies from Cameroon, characterized by a long viral endemicity (at least few generations). In blood donors, both the circulating proviral loads and the degree of infected cell proliferation were largely lower than those characterizing asymptomatic carriers infected with leukemogenic PTLVs (HTLV-1, STLV-1). This might contribute to explain the lack of known link between HTLV-2b infection and the development of malignancies in this population. In contrast, endemically infected individuals displayed high proviral loads resulting from the extensive proliferation of infected cells. The route and/or the duration of infection, viral genetic drift, host immune response, genetic background, co-infections or a combination thereof might have contributed to these differences between endemically and epidemically infected subjects. As the clonality pattern observed in endemically infected individuals is very reminiscent of that of leukemogenic PTLVs at the pre-leukemic stage, our results highlight the possible oncogenic effect of HTLV-2b infection in such population.