ALBERT

Description: Introduction: Outcome in allogeneic HSCT varies widely depending on disease type, stage, stem cell source, HLA-matched status and conditioning regimen. IFI is a possible complication of HSCT and a prior IFI increases the patient's risk for transplant related mortality due to the possibility of reactivation of the fungal infection. This study aimed to evaluate the impact of a previous IFI history on transplant outcome Methods: We retrospectively collected the clinical data of patients considered eligible for allogeneic HSCT during 2014 at the Rome Transplant Network (RTN), a JACIE accredited metropolitan transplant program established in Rome since 2006. The observation of patients was continued until 31 December 2015. The diagnosis of IFI were defined as possible, probable and proven as established by European Organization for Research and treatment of Cancer. Results: Twenty-one (37%) out of 57 eligible patients had an IFI episode before transplant: 6 of the episodes were proven, 4 probable and 11 possible. Overall, 10 (47%) pneumonia, 4 (19%) gastroenteritis, 3 sinusitis, 2 candida sepsis, 1 meningitis and 1 cutaneous abscess were registered. Five out of 21 patients (23%) died before HSCT versus 2 of 36 patients (5%) without previous documented IFI, [OR 5.31 95% CI 0.93- 30.40 , p value 0.06 Fisher Test], . A larger percentage of patients with past IFI waited HSCT over 6 months from the date of eligibility in comparison with those without previous IFI [43% vs 30% ; OR 1.87 95% CI 0.54-6.40 , p value 0.5 Yates test]; Sixteen (57%) out of 28 dead patients in the pre-transplant period have had a previous IFI episode vs 5(17%) out of patients alive [OR 6.4, 95% CI 1.89-21.68, p value: 0.004 Yates Test]. In the post-transplant period, only 6% of patients with a past IFI, experienced an engraftment in a time of 〈 15 days, vs 30% of patients without past IFI [OR 4.86 CI 95% 0,5-43,2, p value 0,2 Yates test]. In the post-transplant period, a IFI was diagnosed in 13 (26%) patients; ten (76%) out of 13 patients had a past IFI versus 9 (24%) of the patients without IFI.. [OR 7.87, CI 95% 1,8-34,2, p value 0,005 Yates test].Among the dead HSCT patients, those who had a previous IFI had a lower median survival [160 days (range 22- 480)] compared to patients without a previous IFI who died [196.5 days period (range 20-820)]. Conclusions: A previous IFI episode in the pre transplant period slow the accessibility to the transplant, adversely affects the engraftment, and is significantly associated with increased post-transplant mortality Disclosures No relevant conflicts of interest to declare.

Description: Acute leukemias (AL) of ambiguous lineage are a heterogeneous group of high-risk leukemias characterized by co-expression of myeloid and lymphoid markers. In this study, we identified a distinct subgroup of immature acute leukemias characterized by a broadly variable phenotype, covering acute myeloid leukemia (AML M0 or M1), T/myeloid mixed phenotype acute leukemia (T/M MPAL), and early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Rearrangements at 14q32/BCL11B are the cytogenetic hallmark of this entity. In our screening of 915 hematological malignancies, there were 202 AML and 333 T-cell Acute Lymphoblastic Leukemia (T-ALL) (58 ETP, 178 non-ETP, 8 T/M MPAL, 89 not otherwise specified). We identified 20 cases of immature leukemias (4% of AML and 3,6% of T-ALL) harbouring four types of 14q32/BCL11B translocations: t(2,14)(q22.3;q32) (n=7), t(6;14)(q25.3;q32) (n=9), t(7;14)(q21.2;q32) (n=2) and t(8;14)(q24.2;q32) (n=2). The t(2;14) produced a ZEB2-BCL11B fusion transcript, while the other three rearrangements displaced transcriptionally active enhancer sequences close to BCL11B without producing fusion genes. All translocations resulted in the activation of BCL11B, a regulator of T-cell differentiation associated with transcriptional corepressor complexes in mammalian cells. The expression of BCL11B behaved as a disease biomarker, which was present at diagnosis but not in remission. Deregulation of BCL11B co-occurred with variants at FLT3 and at epigenetic modulators, most frequently DNMT3A, TET2 and/or WT1 gene. Transcriptome analysis identified a specific expression signature, with significant downregulation of BCL11B targets, and clearly separating BCL11B positive AL from AML, T-ALL, and ETP-ALL. Remarkably, ex-vivo drug sensitivity profile identified a panel of compounds with effective antileukemic activity.