Patients with secondary acute myeloid leukemia undergoing allogeneic stem-cell transplant have inferior outcomes than de novo acute myeloid leukemia regardless minimal residual disease level by flow cytometry.

Secondary acute myeloid leukemia (s-AML) patients have a poor prognosis and currently the only curative therapy is allogeneic stem-cell transplant (HSCT). However, we do not yet know whether transplantation is sufficient to reverse the poor prognosis compared to de novo AML patients. We analyzed survival after HSCT comparing a cohort of 58 patients with s-AML versus 52 de novo patients who were transplanted between 2012 and 2020. Patients with s-AML had worse event-free survival (EFS) (p = 0.001) and overall survival (OS) (p < 0.001) compared to de novo AML due to an increased risk of relapse (p = 0.06) and non-relapse mortality (p = 0.03). The main difference in survival was observed in patients who achieved complete remission (CR) before HSCT (EFS p = 0.002 OS and <0.001), regardless minimal residual disease (MRD) by |multiparametric flow cytometry cohorts. In patients transplanted with active disease (AD), the prognosis was adverse in both s-AML and de novo AML groups (EFS p = 0.869 and OS p = 0.930). After excluding patients with AD, we stratified the cohort according to conditioning intensity, noticing that s-AML who received MAC had comparable outcomes to de novo AML, but the survival differences remained among reduce intensity conditioning group. In conclusion, transplanted s-AML patients have worse survival among patients in CR before HSCT, regardless of MRD level by flow cytometry compared to de novo AML. MAC patients had similar outcomes irrespective of leukemia ontogeny.

Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients.

Outcomes for patients with hematologic malignancy infected with COVID-19 have not been aggregated. The objective of this study was to perform a systematic review and meta-analysis to estimate the risk of death and other important outcomes for these patients. We searched PubMed and EMBASE up to 20 August 2020 to identify reports of patients with hematologic malignancy and COVID-19. The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included risk of intensive care unit admission and ventilation in hospitalized patients. Subgroup analyses included mortality stratified by age, treatment status, and malignancy subtype. Pooled prevalence, risk ratios (RRs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Thirty-four adult and 5 pediatric studies (3377 patients) from Asia, Europe, and North America were included (14 of 34 adult studies included only hospitalized patients). Risk of death among adult patients was 34% (95% CI, 28-39; N = 3240) in this sample of predominantly hospitalized patients. Patients aged ≥60 years had a significantly higher risk of death than patients <60 years (RR, 1.82; 95% CI, 1.45-2.27; N = 1169). The risk of death in pediatric patients was 4% (95% CI, 1-9; N = 102). RR of death comparing patients with recent systemic anticancer therapy to no treatment was 1.17 (95% CI, 0.83-1.64; N = 736). Adult patients with hematologic malignancy and COVID-19, especially hospitalized patients, have a high risk of dying. Patients ≥60 years have significantly higher mortality; pediatric patients appear to be relatively spared. Recent cancer treatment does not appear to significantly increase the risk of death.

TRBC1 expression assessed by flow cytometry as a novel marker of clonality in cutaneous αß T-cell lymphomas with peripheral blood involvement.

The TRBC1 evaluation is a useful, simple, and fast flow cytometry tool for the assessment of αß T-cell clonality in the blood of patients suspicious of mycosis fungoides and Sézary syndrome.

Comparative Review of the Current and Future Strategies to Evaluate Bone Marrow Infiltration at Diffuse Large B-Cell Lymphoma Diagnosis.

Diffuse large B-cell lymphoma (DLBCL) requires a complete staging at diagnosis that may have prognostic and therapeutic implications. The role of bone marrow (BM) biopsy (BMB) is controversial in the era of nuclear imaging techniques. We performed a comparative review of 25 studies focused on BM evaluation at DLBCL diagnosis, including at least two of the following techniques: BMB, flow cytometry, and positron emission tomography (PET-FDG). The report about BM involvement (BMi), diagnostic accuracy, and prognostic significance was collected and compared among techniques. A concordance analysis between BMB, FCM, and PET was also performed, and we deeply evaluated the implications of the different types of BMi: concordant by LBCL or discordant by low-grade B-cell lymphoma for both BMB and FCM, and focal or diffuse uptake pattern for PET. As a main conclusion, BMB, FCM, and PET are complementary tools that provide different and clinically relevant information in the assessment of BMi in newly diagnosed DLBCL.

Primary Cardiac Aggressive B-Cell Lymphoma Affecting Right Ventricle and Acute Cardiovascular Events: Multidisciplinary Approach.

Primary cardiac lymphoma (PCL) is extremely rare. A few reviews comprise the available evidence. We present the case of a 70-year-old man who was immunosuppressed as a result of a previous liver transplant and who presented with PCL. This case highlights the cardiovascular issues that clinicians may face in PCL management and the importance of a multidisciplinary team approach.

Survival after allogeneic transplantation according to pretransplant minimal residual disease and conditioning intensity in patients with acute myeloid leukemia.

Background: The measurement of minimal residual disease (MRD) by multiparametric flow cytometry (MFC) before hematopoietic stem cell transplantation (HSCT) in patients with acute myeloid leukemia (AML) is a powerful prognostic factor. The interaction of pretransplant MRD and the conditioning intensity has not yet been clarified. Objective: The aim of this study is to analyze the transplant outcomes of patients with AML who underwent HSCT in complete remission (CR), comparing patients with positive MRD (MRD+) and negative MRD (MRD-) before HSCT, and the interaction between conditioning intensity and pre-HSCT MRD. Study design: We retrospectively analyzed the transplant outcomes of 118 patients with AML who underwent HSCT in CR in a single institution, comparing patients with MRD+ and MRD- before HSCT using a cutoff of 0.1% on MFC, and the interaction between conditioning intensity and pre-HSCT MRD. Results: Patients with MRD+ before HSCT had a significantly worse 2-year (2y) event-free survival (EFS) (56.5% vs. 32.0%, p = 0.018) than MRD- patients, due to a higher cumulative incidence of relapse (CIR) at 2 years (49.0% vs. 18.0%, p = 0.002), with no differences in transplant-related mortality (TRM) (2y-TRM, 19.0% and 25.0%, respectively, p = 0.588). In the analysis stratified by conditioning intensity, in patients who received MAC, those with MRD- before HSCT had better EFS (p = 0.009) and overall survival (OS) (p = 0.070) due to lower CIR (p = 0.004) than MRD+ patients. On the other hand, the survival was similar in reduced intensity conditioning (RIC) patients regardless of the MRD status. Conclusions: Patients with MRD+ before HSCT have worse outcomes than MRD- patients. In patients who received MAC, MRD- patients have better EFS and OS due to lower CIR than MRD+ patients, probably because they represent a more chemo-sensitive group. However, among RIC patients, results were similar regardless of the MRD status.

Early Cellular and Humoral Responses Developed in Oncohematological Patients after Vaccination with One Dose against COVID-19.

Individuals with oncohematological diseases (OHD) may develop an impaired immune response against vaccines due to the characteristics of the disease or to its treatment. Humoral response against SARS-CoV-2 has been described to be suboptimal in these patients, but the quality and efficiency of the cellular immune response has not been yet completely characterized. In this study, we analyzed the early humoral and cellular immune responses in individuals with different OHD after receiving one dose of an authorized vaccine against SARS-CoV-2. Humoral response, determined by antibodies titers and neutralizing capacity, was overall impaired in individuals with OHD, except for the cohort of chronic myeloid leukemia (CML), which showed higher levels of specific IgGs than healthy donors. Conversely, the specific direct cytotoxic cellular immunity response (DCC) against SARS-CoV-2, appeared to be enhanced, especially in individuals with CML and chronic lymphocytic leukemia (CLL). This increased cellular immune response, developed earlier than in healthy donors, showed a modest cytotoxic activity that was compensated by significantly increased numbers, likely due to the disease or its treatment. The analysis of the immune response through subsequent vaccine doses will help establish the real efficacy of COVID-19 vaccines in individuals with OHD.

Diffuse follicular lymphoma variant with a typical diagnostic pattern and an unusually aggressive clinical presentation.

Diffuse follicular lymphoma (FL) variant is a rare condition that shows distinctive clinical, morphological, immunophenotypic, and molecular features that distinguish it from classical FL. Diffuse FL variant is characterized by a predominantly diffuse growth pattern, absence of the t (14;18) IGH/BCL2 translocation, CD23 expression, and presence of 1p36 deletion. Gene mutations involving STAT6 have been reported, with nuclear expression of STAT6 and phosphorylated STAT6 detected by immunohistochemistry. Patients frequently present with inguinal node involvement and low clinical stage. We describe the case of an 80-year-old female diagnosed with diffuse FL variant, presented with a classic diagnostic pattern and an unusual aggressive clinical onset.

Early detection of lysosomal diseases by screening of cases of idiopathic splenomegaly and/or thrombocytopenia with a next-generation sequencing gene panel.

Lysosomal diseases (LD) are a group of about 70 rare hereditary disorders (combined incidence 1:5000) in which diverse lysosomal functions are impaired, impacting multiple organs and systems. The first clinical signs and symptoms are usually unspecific and shared by hundreds of other disorders. Diagnosis of LD traditionally relies on performing specific enzymatic assays, if available, upon clinical suspicion of the disorder. However, the combination of the insidious onset of LD and the lack of awareness on these rare diseases among medical personnel results in undesirable diagnostic delays, with unchecked disease progression, appearance of complications and a worsened prognosis. We tested the usefulness of a next-generation sequencing-based gene panel for quick, early detection of LD among cases of idiopathic splenomegaly and/or thrombocytopenia, two of the earliest clinical signs observed in most LD. Our 73-gene panel interrogated 28 genes for LD, 1 biomarker and 44 genes underlying non-LD differential diagnoses. Among 38 unrelated patients, we elucidated eight cases (21%), five with LD (GM1 gangliosidosis, Sanfilippo disease A and B, Niemann-Pick disease B, Gaucher disease) and three with non-LD conditions. Interestingly, we identified three LD patients harboring pathogenic mutations in two LD genes each, which may result in unusual disease presentations and impact treatment. Turnaround time for panel screening and genetic validation was 1 month. Our results underline the usefulness of resequencing gene panels for quick and cost-effective screening of LDs and disorders sharing with them early clinical signs.

Bone marrow infiltration by flow cytometry at diffuse large B-cell lymphoma NOS diagnosis implies worse prognosis without considering bone marrow histology.

BACKGROUND: The significance of discrepant findings between histology (BMB) and flow cytometry (FC) in bone marrow (BM) examination at diffuse large B-cell lymphoma (DLBCL) diagnosis is uncertain. METHODS: We performed a 5-year retrospective single-center study of patients diagnosed by DLBCL not otherwise specified (n = 82), divided into three groups according to BM infiltration at diagnosis: BMB-/FC- (75.6%), BMB+/FC+ (13.4%), and BMB-/FC+ (11%). RESULTS: Median infiltration by FC analysis of the BMB-/FC+ group was 0.8% and if we considered BM infiltration as positive in all cases, 4/9 would be upstaged. Median follow was 33 months. Event-free survival (EFS) after 18 months was 82, 23, and 27% for BMB-/FC-, BMB-/FC+, and BMB+/FC+, respectively (p < .001). After 18 months of observation, OS was 87, 46, and 55% for BMB-/FC-, BMB-/FC+, and BMB+/FC+, respectively (p = .001). In multivariate analysis (BM infiltration vs. cell-of-origin according to Hans algorithm and standard IPI), BM infiltration was independently associated with EFS (HR: 1.94, 95% CI: 1.3-2.9) and overall survival (HR: 1.69, 95% CI: 1.1-2.7). CONCLUSION: In summary, minimal BM infiltration, detected by FC but not by BMB, has same prognostic implications than overt BM infiltration and should be considered as extranodal involvement regardless the infiltration quantity.