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  • Prior case reports have described hematological

    2019-05-14

    Prior case reports have described hematological remission in patients with myelofibrosis during treatment with bisphosphonates, but a phase II study investigating the effects of zoledronic CM-272 on patients with myelofibrosis showed responses in only 1 of 16 patients[13]. In conclusion, we report complete hematological response in concert with a partial molecular response in a patient with PV treated with alendronate and simvastatin. Although bisphosphonate monotherapy – as illustrated by Delforge et al. [13] – may rarely be beneficial in the late myelofibrosis stage, the highly remarkable response in our patient on combination therapy with statin and bisphosphonate, possibly exhibiting different but synergistic blocking effects in the mevalonate pathway, is certainly an encouraging stimulus for further experimental and clinical research on the potential role of these “old drugs” in the treatment of MPNs alone or adjuvant to HU, interferon-2a or JAK1/2 inhibitors [3]. Furthermore, a greater response may be expected in the earlier stages of the MPN disease (ET or PV), before the bone marrow becomes fibrotic. Besides, a relatively small number of responders may still be beneficial, when taking into account the relatively low toxicity of these treatments.
    Conflict of interests
    Introduction Recently Zhou et al. developed the new National Comprehensive Cancer Network (NCCN)- International Prognostic Index (IPI) to predict survival in the rituximab era more accurately than the older IPI system [1]. Although reports that used the same prognostic stratification have since been published from various geographic regions, whether these results can be extrapolated to different ethnic populations is unclear. We therefore aimed to validate the NCCN-IPI in the presumably less selected population of Japanese patients with diffuse large B cell lymphoma (DLBCL).
    Materials and methods We included 284 patients who were consecutively diagnosed with DLBCL and treated with first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (r-CHOP), or R-CHOP-like treatment at Kansai Medical University Hospital during 2006–2014 in this retrospective analysis. This study was approved by the Ethics Committee of Kansai Medical University. Patient survival was analyzed with the Kaplan–Meier method, and results were compared by log-rank and Cox proportional hazards models. P<0.05 was considered significant. All statistical analyses were performed using EZR (modified R software, Saitama Medical Center, Jichi Medical University, Saitama, Japan).
    Discussion Although the NCCN-IPI was developed to improve stratification of high-risk patients with DLBCL (i.e., whose 5-year OS<50%), it failed to detect them in our analysis; the HI group had shorter 5-year OS than the high-risk group (Fig. 1 A.). In our institute, most eligible high-risk or HI patients were treated with upfront ASCT, which we assumed would improve their survival. When we excluded these patients from our analysis, the poorer 5-year OS for the HI group compared with the high-risk group was even more pronounced (Fig. 1 B.). As the NCCN-IPI attaches more weight on age in the 4 risk groups, we supposed that its failure to predict outcome in this study was because our patients were older than original cohort; thus prognoses of patients whose high scores were due to age rather than tumor burden (as indicated by LDH or stage) might not be accurately predicted in the NCCN-IPI system. Some reports described results similar to ours, showing that NCCN-IPI failed to accurately predict outcomes for elderly patients [4,7]. Aside from LDH, information about how other important parameters affect NCCN-IPI results have not been published, as far as we know. Hemoglobin [2], albumin [3,4], and CRP [5] have been found to be independent prognostic factors in aggressive lymphoma. As these reported parameters were routinely available in our patients’ records, we analyzed their effects on OS, using multivariate analysis; however, we found only low albumin levels to be a significant predictor of worse 5-year OS. As albumin is usually assessed, quite easily and cheaply in standard blood laboratory tests, and is highly reproducible, it could be an important predictor, and be incorporated into a prognostic index.