Primary cutaneous plasmablastic lymphoma revealing clinically unsuspected HIV infection

Abstract: Plasmablastic lymphoma is a rare subtype of diffuse large B-cell lymphoma more frequently diagnosed in immunosuppressed patients, mainly HIV-infected. Primary cutaneous plasmablastic lymphoma is extremely rare, and in this patient it was the first clinical manifestation of unsuspected HIV-infection

Sorafenib plus intensive chemotherapy in newly diagnosed FLT3-ITD AML:a randomized, placebo-controlled study by the ALLG.

Sorafenib maintenance improves outcome after hematopoietic cell transplant (HCT) for patients with FLT3-ITD acute myeloid leukemia (AML). Although promising outcomes have been reported for sorafenib plus intensive chemotherapy, randomized data are limited. This placebo-controlled, phase 2 study (ACTRN12611001112954) randomized 102 patients 18-65 years (2:1) to sorafenib vs placebo (days 4-10) combined with intensive induction; idarubicin 12mg/m2 days 1-3 plus cytarabine 1.5g/m2 twice daily on days 1,3,5,7 (18-55 years) or 100mg/m2 days 1-7 (56-65 years), consolidation therapy, followed by maintenance treatment for 12 months (post-HCT excluded) in newly diagnosed FLT3-ITD AML. Four patients were excluded from modified intention-to-treat final analysis (3 not dosed and 1 later found to be FLT3-ITD negative). Rates of complete remission (CR)/CR with incomplete hematologic recovery (CR/CRi) were high in both arms (sorafenib 78%/9%, placebo 70%/24%). With 49.1 months median follow-up, the primary endpoint of event-free survival (EFS) was not improved by sorafenib (2-year EFS 47.9% vs 45.4%)(hazard ratio [HR] 0.87;95% confidence interval [CI] 0.51-1.51, p=0.61). Two-year overall survival (OS) was 67% in the sorafenib arm and 58% in the placebo arm (HR 0.76; 95% CI 0.42-1.39). For patients transplanted in first remission, 2-year OS was 84% and 67% in the sorafenib and placebo arms, respectively (HR 0.45;95% CI 0.18-1.12, p=0.08). In exploratory analyses, FLT3-ITD measurable residual disease negative status (<0.001%) post-induction was associated with improved 2-year OS (83% vs 60%) (HR 0.4;95% CI 0.17-0.93, p=0.028). In conclusion, routine use of pre-transplant sorafenib plus chemotherapy in unselected patients with FLT3-ITD AML is not supported by this study

Molecular MRD is strongly prognostic in patients with NPM1-mutated AML receiving venetoclax-based nonintensive therapy

Assessment of measurable residual disease (MRD) by quantitative reverse transcription polymerase chain reaction is strongly prognostic in patients with NPM1-mutated acute myeloid leukemia (AML) treated with intensive chemotherapy; however, there are no data regarding its utility in venetoclax-based nonintensive therapy, despite high efficacy in this genotype. We analyzed the prognostic impact of NPM1 MRD in an international real-world cohort of 76 previously untreated patients with NPM1-mutated AML who achieved complete remission (CR)/CR with incomplete hematological recovery following treatment with venetoclax and hypomethylating agents (HMAs) or low-dose cytarabine (LDAC). A total of 44 patients (58%) achieved bone marrow (BM) MRD negativity, and a further 14 (18%) achieved a reduction of ≥4 log10 from baseline as their best response, with no difference between HMAs and LDAC. The cumulative rates of BM MRD negativity by the end of cycles 2, 4, and 6 were 25%, 47%, and 50%, respectively. Patients achieving BM MRD negativity by the end of cycle 4 had 2-year overall of 84% compared with 46% if MRD was positive. On multivariable analyses, MRD negativity was the strongest prognostic factor. A total of 22 patients electively stopped therapy in BM MRD-negative remission after a median of 8 cycles, with 2-year treatment-free remission of 88%. In patients with NPM1-mutated AML attaining remission with venetoclax combination therapies, NPM1 MRD provides valuable prognostic information

Outcomes of non-myeloablative allogeneic stem cell transplant in older patients with acute myeloid leukaemia in first remission

The benefits of non-myeloablative stem cell transplant in older patients with acute myeloid leukaemia are unclear. We compare the long-term outcomes of this regimen in those aged 55-65 years in first remission with a chemotherapy only cohort that achieved durable morphologic remission. Five-year overall survival was similar (32% vs 33%, P = 0.90), as was relapse-free survival (23% vs 20%, P = 0.37). There was a trend for decreased relapse that was balanced against increased non-relapse mortality with transplantation

Evaluation of T-cell clonality by anti-TRBC1 antibody-based flow cytometry and correlation with T-cell receptor sequencing

Flow cytometry (FC) incorporating the T-cell receptor β constant chain-1 (TRBC1) has been recently proposed as a new standard in T-cell clonality assessment. While early studies demonstrated high sensitivity in samples with conspicuous tumour burden, performance in real-world samples, including those with low tumour burden and correlation with molecular methods has been limited. We evaluated TRBC1-FC performance and correlated the results with high-throughput TRB sequencing and a targeted next-generation sequencing gene panel. Our cohort consisted of 90 evaluable samples from 57 patients. TRBC1-FC confirmed T-cell clonality in 37 out of 38 samples (97%) that were involved in a mature T-cell neoplasm (MTCN). T-cell clonality was also identified in nine samples from patients lacking a current or prior diagnosis of MTCN, consistent with the emerging entity T-cell clonality of uncertain significance. TRBC-FC was polyclonal in all samples and negative for disease involvement by standard pathology assessment. However, correlation with TRB sequencing in 17 of these samples identified two cases that harboured the known clonal sequence from index testing, indicating the presence of measurable residual disease not otherwise detected. Our study provides real-world correlative validation of TRBC1-FC, highlighting the strengths and limitations pertinent to its increasing implementation by general diagnostic laboratories