• 2018-07
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  • 2019-09
  • br Discussion This observation reports an unusual associatio


    Discussion This observation reports an unusual association of LEMS with LGL leukemia occurring in the same patient, and clearly shows that both diseases benefited from LGL leukemia therapy. Methotrexate and steroids rapidly induced hematological complete remission associated with disappearance of RA and neurological symptoms. Anti-N Sildenafil mesylate titers progressively decreased. Indeed, correlations have already been shown between the anti-N titer evolution and the disease activity in longitudinal studies on single patients. Moreover, patient did not display any resurgence of LEMS over the time. This observation supports the hypothesis that LEMS could be considered as a paraneoplastic manifestation of LGL leukemia. Since T-regulatory cells protein expression pattern had been shown to be different in some LEMS patients, we can hypothesize that LEMS occurrence could be linked to a specific immunoregulatory system deregulation in the context of LGL leukemia. To our knowledge, this is the first ever described association of LEMS with LGL leukemia, whereas it has been reported in other lymphoproliferative diseases such as multiple myeloma, Hodgkin lymphoma, or even in myeloproliferative ones, such as chronic myeloid leukemia. About half of the patients presenting with LEMS have a SCLC. For 94% of these patients, LEMS manifestations are usually present 6 months before the SCLC diagnosis. Our patient underwent regular chest CT scan which were always non-contributive. He did not develop any pulmonary symptoms over the 9 years following LEMS diagnosis. LEMS has been described in association with at least 6 cases of prostatic carcinoma, which all had some neuroendocrine and/or small cells features. In our patient, histopathology concludes to a localized adenocarcinoma, without any neuroendocrine or small cell feature. Hormonotherapy was efficacious on the PSA-value, improving neither LEMS manifestations nor anti-N VGCC antibodies values. Anti-N antibodies value even increased. Prostate irradiation was performed with good efficacy on PSA-value, without any impact on the LEMS.
    Myelodysplastic syndrome (MDS) is a group of clonal bone marrow disorders with increased risk for leukemic transformation. Aside from allogeneic stem cell transplantation, the currently approved treatments for MDS, including growth factors, lenalidomide and hypomethylating agents, are not curative and have short response duration. Further, after failure of hypomethylating agents, the median survival is very short-lived, only 4.3 months with similar 25% risk of progression to acute myeloid leukemia, by one report. Another large study including 435 patients with high risk MDS that failed hypomethylating therapy demonstrated a median overall survival of 5.6 months and a two-year survival probability of only 15%. Of note, lack of hematologic response to previous hypomethylating therapy was one of the factors associated with poor outcome. Clofarabine is a second generation purine nucleoside analog that was tested in MDS both intravenously (IV) and orally. The IV route (15mg/m vs. 30mg/m daily for five days every 4ā€“8 weeks) was administered in-house and was significantly myelotoxic. Only a median of two consolidation cycles were administered resulting in a median survival of 7.4 months. Since oral clofarabine has a bioavailability of 50% and could be administered in the ambulatory setting, it was tested in three different doses (20, 30 and 40mg/m daily for five days every 4ā€“8 weeks). A median of one consolidation cycle was administered to 31% of the patients with dose reduction in 74% of them due to infectious complications and prolonged myelosuppression. The median survival was 9.2 months. Most patients received the treatment in the ambulatory setting but 53% received growth factor support at some point and 50% developed infectious complications requiring hospitalization. We hypothesized that protracted low-dose oral clofarabine will be more efficacious and less toxic and designed a phase I (Iā€“144208, NCT01003678) trial to determine the safety and maximum tolerated dose of low-dose oral clofarabine daily for five days in a 28-day cycle. The initial dose was 1mg as a fixed dose. Eligibility criteria included adult patients with intermediate- or high-risk MDS per the International Prognostic Scoring System Score (IPSS) who may have received up to two prior therapies andhad adequate hepatic and renal function. The study was prematurely terminated by the company and we report here our experience with one patient on trial.