Leucemia aguda de fenotipo mixto: presentación de un caso pediátrico de Perú / Acute leukemia of mixed phenotype: presentation of a pediatric case from Peru

Introducción: Las leucemias agudas de linaje ambiguo representan un grupo heterogéneo de leucemias sin una clara diferenciación del linaje celular. Constituyen alrededor de 2 a 5 por ciento del total de leucemias agudas. Objetivo: Describir un caso de leucemia aguda de fenotipo mixto (LAFM) en un paciente pediátrico de 4 años de Lambayeque, Perú. Presentación del caso: Se evaluó una muestra de sangre periférica de un niño de 4 años de edad, cuyo inmunofenotipo por citometría de flujo evidenció una población, correspondiente al 94 por ciento de la celularidad total, de linajes mieloide compatible con diferenciación a linaje neutrófilo y en menor medida a monocítica/célula dendrítica (CD123 intenso), con expresión de mieloperoxidasa (MPO) y CD33 intensos; CD13, CD64 y CD66c parcial; y expresión de marcadores de linaje linfoide B (CD19 y CD22 intensos). Este fenotipo obliga a descartar la t(8;21), y anomalías del gen MLL. Por los mencionados hallazgos, la presente leucemia fue clasificada como leucemia aguda de fenotipo mixto, B/Mieloide. Conclusiones: Se concluyó como una leucemia aguda de fenotipo mixto B/Mieloide, con la peculiar inclinación del linaje mieloide hacia neutrófilos y en menor medida hacia monocítica/célula dendrítica(AU)

Introduction: Acute leukemias of ambiguous lineage represent a heterogeneous group of leukemias without a clear differentiation of the cell lineage. They constitute about 2 to 5 percent of all acute leukemias. Objective: To describe a case of acute leukemia of mixed phenotype (LAFM) in a 4-year-old pediatric patient from Lambayeque, Peru. Case presentation: A peripheral blood sample from a 4-year-old boy was evaluated, whose immunophenotype by flow cytometry showed a population, corresponding to 94 percent of total cellularity, of myeloid lineages compatible with differentiation to neutrophil lineage and in less to monocytic/dendritic cell (CD123 high), with expression of myeloperoxidase (MPO) and CD33 high; CD13, CD64 and CD66c partial; and expression of B lymphoid lineage markers (CD19 and CD22 high). This phenotype requires ruling out the t (8; 21), and abnormalities of the MLL gene. Due to the aforementioned findings, the present leukemia was classified as acute leukemia of mixed phenotype, B/Myeloid. Conclusions: It was concluded as an acute leukemia of mixed phenotype B/Myeloid, with the peculiar inclination of the myeloid lineage towards neutrophils and to a lesser extent towards monocytic/dendritic cell(AU)

Pericarditis and myocarditis long after SARS-CoV-2 infection: a cross-sectional descriptive study in health-care workers

BackgroundCardiac sequelae of past SARS-CoV-2 infection are still poorly documented. We conducted a cross-sectional study in health-care workers to report evidence of pericarditis and myocarditis after SARS-CoV-2 infection. MethodsWe studied 139 health-care workers with confirmed past SARS-CoV-2 infection (103 diagnosed by RT-PCR and 36 by serology). Participants underwent clinical assessment, electrocardiography, laboratory tests including immune cell profiling and cardiac magnetic resonance (CMR). Pericarditis was diagnosed when classical criteria were present, and the diagnosis of myocarditis was based on the updated CMR Lake-Louise-Criteria. ResultsMedian age was 52 years (IQR 41-57), 100 (72%) were women, and 23 (16%) were previously hospitalized for Covid-19 pneumonia. At examination (10.4 [9.3-11.0] weeks after infection-like symptoms), all participants presented hemodynamic stability. Chest pain, dyspnoea or palpitations were observed in 58 (42%) participants; electrocardiographic abnormalities in 69 (50%); NT-pro-BNP was elevated in 11 (8%); troponin in 1 (1%); and CMR abnormalities in 104 (75%). Isolated pericarditis was diagnosed in 4 (3%) participants, myopericarditis in 15 (11%) and isolated myocarditis in 36 (26%). Participants diagnosed by RT-PCR were more likely to still present symptoms than participants diagnosed by serology (73 [71%] vs 18 [50%]; p=0.027); nonetheless, the prevalence of pericarditis or myocarditis was high in both groups (44 [43%] vs 11 [31%]; p=0.238). Most participants (101 [73%]) showed altered immune cell counts in blood, particularly decreased eosinophil (37 [27%]; p<0.001) and increased CD4-CD8-/loT{beta}-cell numbers (24 [17%]; p<0.001). Pericarditis was associated with elevated CD4-CD8-/loT{beta}-cell numbers (p=0.011), while participants diagnosed with myopericarditis or myocarditis had lower (p<0.05) plasmacytoid dendritic cell, NK-cell and plasma cell counts and lower anti-SARS-CoV-2-IgG antibody levels (p=0.027). ConclusionsPericarditis and myocarditis with clinical stability are frequent long after SARS-CoV-2 infection, even in presently asymptomatic subjects. These observations will probably apply to the general population infected and may indicate that cardiac sequelae might occur late in association with an altered (delayed) innate and adaptative immune response. The trial is registered with ClinicalTrials.gov, number NCT04413071 Research in contextO_ST_ABSEvidence before this studyC_ST_ABSVery little evidence exists describing long cardiac sequelae after SARS-CoV-2 infection. Although pericarditis and myocarditis are the two most frequent cardiac manifestations observed after a viral infection, as of May 13, 2020, the peer-reviewed literature was limited to isolated case reports of myocarditis and pericarditis during the COVID-19 hospitalization phase and to a retrospective observation in 26 recovered patients with COVID-19 pneumonia presenting cardiac complaints during hospitalization, revealing the presence of myocardial oedema in 14 (54%) patients and late gadolinium enhancement in 8 (31%) patients. These small size case series, limited to hospitalized RT-PCR patients with COVID-19 pneumonia, are insufficient to generalize conclusions about the true prevalence of pericardial and myocardial long involvement after SARS-CoV-2 infection. In addition, no study has investigated the immunological consequences of SARS-CoV-2 infection in the settings of pericarditis and myocarditis. Added value of this studyTo our knowledge, this is the largest cohort of subjects (N=139) --even for other common viruses-- with clinical, electrocardiographic, laboratory and CMR imaging evaluations, to assess pericardial and myocardial involvements after SARS-CoV-2 infection. The strength of this study is the addition of non-hospitalized participants and also the inclusion of participants diagnosed of past SARS-CoV-2 infection through serology. Contrary to previous studies, women are well represented. We found a prevalence of pericarditis or myocarditis up to 40% cases; pericarditis coexisted with some degree of concurrent myocardial inflammation in 11% cases. Study participants who were previously hospitalized for COVID-19 pneumonia and patients who received antiviral (hydroxychloroquine, lopinavir-ritonavir) or anti-inflammatory (high-dose glucocorticoids and anti-interleukin treatments) treatments, and who were on chronic drug treatment with statins, were less likely to develop pericarditis or myocarditis. The clinical assessment of the participants showed clinical stability without any patient presenting severe pericardial effusion, heart failure or left ventricular dysfunction. We provide new data on seropositive subjects; although RT-PCR participants were more likely to still present symptoms than participants diagnosed by serology, the prevalence of pericarditis, myocarditis or myocarditis, almost three months after the initial viral prodrome, was high in both groups. In-depth investigation of the distribution of multiple major and minor populations of immune cells in blood showed high frequency of altered immune profiles after SARS-CoV-2 infection. The altered immune cell profiles identified partially mimic abnormalities previously reported during active infection together with others described here for the first time, with unique patterns associated with pericardial and/or myocardial injury. Nonetheless, we also described altered immune profiles in participants without pericardial and myocardial manifestations. Whether these later alterations are due to persistence of tissue damage in other organs affected by SARS-CoV-2, such as the lung, or they reflect normal post-infection immune recovery mechanisms, remains to be investigated. Implications of all the available evidenceAt present, there is much interest in the long-term sequelae of COVID-19. It is intriguing that pericarditis and myocarditis were observed so long after SARS-CoV-2 infection and also in some presently asymptomatic subjects, in association with notably altered immune cell profiles in blood. These observations will probably apply to the general population infected and may indicate that cardiac sequelae might occur late, paving the way for a better understanding the immune mechanisms involved. Thus, our study may have health-care consequences given the widespread diagnosis of SARS-CoV-2 infection in population-based seroprevalence studies.

Maturation-associated immunophenotypic abnormalities in bone marrow B-lymphocytes in myelodysplastic syndromes.

Recent studies concerning the pathophysiology of myelodysplastic syndromes (MDS) have shown evidences for the existence of complex interactions between hematopoietic stem cells and the bone marrow (BM) microenvironment. We analyzed the B-lymphocyte maturation in BM of patients with MDS. For this purpose, 41 newly-diagnosed patients were analyzed. Enumeration and characterization of CD34+ and CD34- B-cell precursors and mature B-lymphocytes was performed using multiparameter flow cytometry. BM from eight transplant donors and six orthopedic surgery patients were used as controls. CD34+/CD45(lo) B-cells were found in 17/22 patients with RA/RARS and in 5/13 with RAEB. In patients with RAEB-t and CMML no CD34+ B-cell precursors could be detected. A positive correlation was found between CD34+ and CD34- B-cell precursors (r=0.52). CD34+ B-cell precursors presented an inverse correlation with BM percentage of blasts and peripheral leukocytes and a positive one with hemoglobin. Asynchronous antigen expression (CD19+/CD79a- cells) was found in 7/11 cases of RA/RARS and 6/18 cases of RAEB in which this phenotype was examined. Abnormal patterns of expression for at least one antigen was found in 91% of RA/RARS cases and in 74% of RAEB. Underexpression of TdT and CD79a were the most frequent abnormalities. Our results present evidences of an abnormal B-cell maturation in MDS. This may be an evidence that B-lymphocytes are derived of the abnormal clone. But it may also be the consequence of influences of abnormalities of BM microenvironment leading to an impaired commitment and maturation of the B-cell line in MDS. Studies performed with purified well-characterized B-cells may further elucidate these abnormalities.