Background: High dose Melphalan (HDM) and autologous stem cell transplantation (ASCT) is a standard care for Myeloma ≤ 65 years. Studies have demonstrated that depth of response prior to ASCT does not impact outcome post ASCT, e.g. solely depth of response post ASCT matters. However, with improving induction regimens, the questions remains whether patients achieving a deeper response at completion of induction would not perform better post ASCT. ASCT can only be performed in Tunisia if newly diagnosed Multiple Myeloma (NDMM) achieves at least PR; we therefore sought to report the national Tunisian experience. Patients and Methods: NDMM aged ≤65 years received three cycles of Thalidomide (200mg daily) and Dexamethasone, followed by HDM and ASCT.52% received maintenance therapy for 12 months with Thalidomide, from 3 months post transplantation. Non responders to TD induction were salvaged with Lenalidomide or Bortezomib-based regimen. The response was assessed based on IMWG response criteria. The study is performed in ITT. Results: 202 consecutive pts were included between April 2012 and December 2014. The median age was 56 yrs (range, 25-65), sex ratio was 1.R-ISS stage was 3 in 27.5%. 21% had high risk cytogenetic (by Conventional karyotyping and FISH). Renal failure was observed in 17%. ORR after induction was 71% with 12% CR, 17% VGPR. 22% failed to obtain PR following TD induction, and 51% of whom received salvage induction therapy (ST) with 72% that further reached ≥PR after ST. Overall, 141 pts (70%) underwent ASCT, 121 of whom had evidence of chemo-sensitive MM at completion of induction. 16% were transplanted in CR, 22% in VGPR and 62% in PR. At 3 months post-ASCT, the ORR in induction chemo-sensitive MM was 89%: 36% CR, 20% VGPR, and 33% PR. With a median follow-up post-ASCT of 27 months, the OS, PFS and EFS at 27 months were 82%, 60.5% and 56%, respectively. Maintenance treatment was significantly associated with longer PFS only in MM who did not achieve CR (29 versus 9 months, p=0.004). MM with improved response post-ASCT had a significantly longer PFS (39 versus 21 months, p=0.003) and EFS (39 versus 20 months, p=0.002). Importantly, achieving CR before (p=0.03) and after ASCT (p<0.0001) was also predictive for prolonged EFS. Early relapses/progressions (less than 18 months) was the sole predictive factor of adverse OS in our study (p=0.01). In multivariate analysis, ISS stage 3 was the sole independent predictor of induction failure (p=0.003). Importantly, predictive factors of achievement of CR post-ASCT comprised absence of delay farther to 4 months from completion of induction (p=0.006; OR = 4.54) and achievement of at least VGPR status before transplant (p=0,001; OR = 4.09). Conclusion: Achievement of at least VGPR at completion of induction improved response after ASCT and consequently influenced the post-ASCT outcome. Therefore, depth of response matters before and after ASCT, and validates in some extent the concept of induction salvage therapy prior to ASCT for patient not reaching response. Disclosures Leleu: TEVA: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; LeoPharma: Honoraria; Pierre Fabre: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria.
Dear Editor,Lymphoblastic lymphoma (LL) of the mediastinum is a rare tumour accounting for 2 % of non-Hodgkin lymphomas. It is a diagnostic and therapeutic emergency. Positive diagnosis is based on microscopic examination. They are classified as T LL in 85 to 90 % of the cases. Few survival studies have been reported, and our knowledge about these tumours is based on rare case reports and case studies [1]. Our aim was to assess the most relevant factors influencing the survival of patients presenting mediastinal LL.We conducted a retrospective single-centre study over a 16-year period between 2000 and 2015 including all patients presenting mediastinal LL. Patients with other mediastinal lesions were ruled out. Two age groups were identified: the pediatric age lower than 15 years and the adult age superior to 15 years. The tumours were subdivided into localized tumours including stages I and II according to the Ann Arbor classification of lymphoma and disseminated tumours including stages III and IVaccording to the same classification. The nature of the specimen, the gross exam, the microscopic features and the crowding artefacts were recorded. The immunohistochemical study was performed in all cases using a manual method performed by the same technician. The different antibodies included CD3, CD5, CD99, CD1a, CD45, Tdt, Ki-67, CD20, CK, EMA, CD79a, CD15 and CD30 antibodies. A multivariate analysis was performed to compare the sex, the gender and the age in relation to the global survival of the patients using cox model. The SPSS software (version 15.0) was used.Thirty-one T cell LL of the mediastinum were diagnosed. The mean age of the patients was 26 years. A male predominance was noticed with 19 men and 12 women. The global survival was estimated to 85 % at 8 months and 70 % at 12 months with a mean survival of 24 months. The multivariate analysis revealed that the sex was a relevant prognostic factor (p = 0.045). Table 1 illustrates the different results related to the odds ratio, the confidence interval and the p values.This study highlights the bad prognosis of these tumours with a global survival of 24 months versus 43 months in the literature. Many prognostic factors have been reported in the literature [2,3]. The young age is considered as a prognostic factor [4,5]. This was not proved in our study (p = 0.46). The female sex is considered as a prognostic factor either in our study or in the literature review (p = 0.045) [6]. In opposition to the literature, the stage does not seem to play a key role (p = 0.88) [7].Other prognostic factors have been reported in the literature including mir17, mir 19, MYC, bcl2, bcl6 and the c-myc without a real consensus [8,9].Our survival study revealed the prognostic relevance of the gender in LL. The prognostic impact of the subtype of the lymphoma was not highlighted because all the cases diagnosed were of T cell subtype. This fact is concordant to the literature review because the majority of mediastinal LL are of T cell subtype.
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