Subpoblaciones de linfocitos T en adultos mayores cubanos con leucemia linfoide crónica / Subpopulations of T lymphocytes in Cuban older adults with chronic lymphoid leukemia

Introducción: la inmunosenescencia está asociada con un mayor riesgo de desarrollo de cáncer. Dentro de las hemopatías malignas que afectan a este grupo de edad, está la leucemia linfoide crónica (LLC), caracterizada por trastornos en la inmunidad adaptativa que incluye las subpoblaciones de linfocitos T. Objetivo: Determinar la frecuencia de las subpoblaciones de linfocitos T en los pacientes adultos mayores con leucemia linfoide crónica evaluados en el Instituto de Hematología e Inmunología de Cuba. Métodos: Se realizó un estudio transversal en 30 adultos mayores con leucemia linfoide crónica. Se cuantificaron los linfocitos TCD3+CD4+ y TCD3+CD8+ en sangre periférica por citometría de flujo. Para la lectura y el análisis de los datos se empleó un citómetro de flujo Beckman Coulter Gallios. Se utilizaron los valores porcentuales, la media y la desviación estándar. Se consideró estadísticamente significativo si p≤0.05. Resultados: Hubo un predominio de hombres que representaron el 56,7 por ciento y del grupo de 70-79 años de edad. No se reportó ningún adulto mayor con LLC con valores altos ni normales de linfocitos TCD3+CD4+. Predominaron los hombres con valores bajos porcentuales de linfocitos TCD3+CD4+, TCD3+CD8+ e inversión del índice CD4/CD8 en relación con las mujeres. Conclusiones: Los adultos mayores con LLC presentan alteraciones en el número de las subpoblaciones de linfocitos T. La acción de estas células en relación al crecimiento de células B malignas aún es desconocido y resulta importante determinar si esto puede reflejar un intento de evasión de las células tumorales al control inmunológico(AU)

Introduction: Immunosenescence is associated with an increased risk of cancer development. Among the malignant hemopathies that affect this age group, it is chronic lymphoid leukemia (CLL), characterized by disorders in adaptive immunity, which include subpopulations of T lymphocytes. Objective: To determine frequency of T lymphocyte subpopulations in older adult patients with chronic lymphoid leukemia evaluated at the Institute of Hematology and Immunology of Cuba. Methods: A cross-sectional study was conducted in 30 older adults with chronic lymphoid leukemia. TCD3+CD4+ and TCD3+CD8+ lymphocytes were quantified in peripheral blood by flow cytometry. A Beckman Coulter Gallios flow cytometer was used to read and analyze the data. The percentage values, the mean and the standard deviation were used. It was considered statistically significant if p≤0.05. Results: There was a predominance of men who represented 56.7 percent and the age group of 70-79 years. No older adults with CLL with high or normal values of TCD3+CD4+ lymphocytes were reported. Men predominated with low percentage values of TCD3+CD4+, TCD3+CD8+ lymphocytes and inversion of the CD4/CD8 ratio in relation to women. Conclusions: Older adult with CLL present alterations in the number of T lymphocyte subpopulations. The role of these cells in relation to the growth of malignant B cells it is unknown and it turns out important to determine if this may reflect an attempt to evade tumor cells from immune control(AU)

Microorganismos aislados de hemocultivos en niños con leucemia y linforma: Seis años de seguimiento / Microorganisms isolated from blood cultures in children with leukemia and lymphoma: six years of follow-up

Las Leucemias y linfomas constituyen las enfermedades oncológicas más frecuentes en pediatría y las bacteriemias representan infecciones graves en estos pacientes. Objetivos: describir los microorganismos aislados de sangre en pacientes con leucemia aguda o linfoma pediátrico; comparar la incidencia de aislamientos según enfermedad de base; detallar las variaciones en la incidencia de dichos aislamientos y la evolución de su resistencia antimicrobiana. Estudio retrospectivo, observacional. Se incluyeron 823 episodios de bacteriemia en 467 pacientes pediátricos, entre julio-2016 y junio-2022, dividido en tres períodos (período-1: años 2016- 2018, período-2: años 2018-2020, período-3: años 2020-2022). Se aislaron 880 microorganismos: 55,3% gram negativos (GN), 40% gram positivos (GP) y 4,7% levaduras. En GN predominaron: enterobacterias (72%) y en GP: estreptococos del grupo viridans (SGV) (34,1%). Se encontró asociación entre LLA-enterobacterias (p=0,009) y LMA-SGV (p<0,001). Hubo aumento de GN entre los períodos 1 y 3 (p=0,02) y 2 y 3 (p=0,002) y disminución de GP entre 2 y 3 (p=0,01). Se registraron los siguientes mecanismos de resistencia: BLEE (16,4%), carbapenemasas: KPC (2,5%); MBL (2,7%) y OXA (0,2%); meticilinorresistencia en Staphylococcus aureus (20%) y estafilococos coagulasa negativos (95%), vancomicina resistencia en Enterococcus spp. (39%), SGV no sensibles a penicilina (44%) y a cefotaxima (13%). Hubo aumento de MBL entre los períodos 1 y 2 (p=0,02) y una tendencia en disminución de sensibilidad a penicilina en SGV entre el 1 y 3 (p=0,058). El conocimiento dinámico y análisis de estos datos es esencial para generar estadísticas a nivel local, fundamentales para el diseño de guías de tratamientos empíricos (AU)

Leukemias and lymphomas are the most common cancers in children and bacteremia is a severe infection in these patients. Objectives: to describe the microorganisms isolated from blood in pediatric patients with acute leukemia or lymphoma; to compare the incidence of isolates according to the underlying disease; and to detail the variations in the incidence of these isolates and the evolution of their antimicrobial resistance. Retrospective, observational study. We included 823 episodes of bacteremia in 467 pediatric patients seen between July-2016 and June-2022, divided into three periods (period-1: 2016- 2018, period-2: 2018-2020, period-3: 2020-2022). A total of 880 microorganisms were isolated: 55.3% were gram-negative (GN), 40% gram-positive (GP) and 4.7% yeasts. In GN there was a predominance of: enterobacteria (72%) and in GP viridans group streptococci (VGS) (34.1%). An association was found between ALL-enterobacteria (p=0.009) and AML-VGS (p<0.001). There was an increase in GN between periods 1 and 3 (p=0.02) and 2 and 3 (p=0.002) and a decrease in GP between 2 and 3 (p=0.01). The following resistance mechanisms were recorded: BLEE (16.4%), carbapenemases: KPC (2.5%), MBL (2.7%), and OXA (0.2%); methicillin resistance in Staphylococcus aureus (20%) and coagulase negative staphylococci (95%), vancomycin resistance in Enterococcus spp. (39%), VGS resistant to penicillin (44%) and to cefotaxime (13%). There was an increase in MBL between periods 1 and 2 (p=0.02) and a decreasing trend in penicillin sensitivity in VGS between periods 1 and 3 (p=0.058). Dynamic knowledge and analysis of these data is essential to generate statistics at the local level, which is fundamental for the design of empirical treatment guidelines (AU)

Paraneoplastic Pityriasis Rubra Pilaris Preceding Leukemia.

ABSTRACT: Pityriasis rubra pilaris (PRP) is a rare, chronic papulosquamous disorder that presents with scaling plaques, palmoplantar keratoderma, and keratotic follicular papules. Typically, there are distinctive unaffected areas referred to as "islands of sparing." Pityriasis rubra pilaris has been associated with various immunodeficient states and malignancies.The authors conducted a literature review using MEDLINE, PubMed, and Google Scholar, documenting all known cases of PRP associated with malignancy; 15 cases were found in the literature. They also present the case of a 49-year-old White man who, prior to referral to dermatology, was seen in urgent care for widespread pruritic rash. Physical examination in the dermatology clinic revealed confluent, scaly erythematous papules coalescing into plaques with island of sparing involving the trunk and upper and lower extremities. Bilateral palms and soles showed hyperkeratosis with fissuring. He was diagnosed with PRP after punch biopsy and began a new course of topical corticosteroid therapy. Hematology was consulted because of abnormal complete blood count results, and he was subsequently diagnosed with chronic lymphoid leukemia.Treatment of PRP is largely based on clinical experience and may involve corticosteroids, immunomodulators, or biologic therapy. The relationship between PRP and malignancy is unknown. Current theories postulate it may be driven by tumor production of functional peptides or antigen cross-reactivity between cancer cells and the skin. This is the second reported case of PRP as a manifestation of leukemia, and the first of chronic lymphoid leukemia. Although not yet understood, the documented relationship between PRP and malignancy prompts screening for cancer in all patients with new-onset PRP.

Case Report: Stepwise Anti-Inflammatory and Anti-SARS-CoV-2 Effects Following Convalescent Plasma Therapy With Full Clinical Recovery.

In these times of COVID-19 pandemic, concern has been raised about the potential effects of SARS-CoV-2 infection on immunocompromised patients, particularly on those receiving B-cell depleting agents and having therefore a severely depressed humoral response. Convalescent plasma can be a therapeutic option for these patients. Understanding the underlying mechanisms of convalescent plasma is crucial to optimize such therapeutic approach. Here, we describe a COVID-19 patient who was deeply immunosuppressed following rituximab (anti-CD20 monoclonal antibody) and concomitant chemotherapy for chronic lymphoid leukemia. His long-term severe T and B cell lymphopenia allowed to evaluate the treatment effects of convalescent plasma. Therapeutic outcome was monitored at the clinical, biological and radiological level. Moreover, anti-SARS-CoV-2 antibody titers (IgM, IgG and IgA) and neutralizing activity were assessed over time before and after plasma transfusions, alongside to SARS-CoV-2 RNA quantification and virus isolation from the upper respiratory tract. Already after the first cycle of plasma transfusion, the patient experienced rapid improvement of pneumonia, inflammation and blood cell counts, which may be related to the immunomodulatory properties of plasma. Subsequently, the cumulative increase in anti-SARS-CoV-2 neutralizing antibodies due to the three additional plasma transfusions was associated with progressive and finally complete viral clearance, resulting in full clinical recovery. In this case-report, administration of convalescent plasma revealed a stepwise effect with an initial and rapid anti-inflammatory activity followed by the progressive SARS-CoV-2 clearance. These data have potential implications for a more extended use of convalescent plasma and future monoclonal antibodies in the treatment of immunosuppressed COVID-19 patients.

Characteristics and outcome according to underlying disease in non-AIDS patients with acute respiratory failure due to Pneumocystis pneumonia.

In the non-AIDS group, several underlying conditions and immune defects could lead to different PCP presentations. This study compared PCP presentation and outcome according to the underlying disease. A secondary analysis of a previously published prospective observational study including 544 PCP patients was done. Only non-AIDS patients were included. Underlying disease was defined as chronic lymphocytic leukemia (CLL), organ transplantation, solid cancer, allogeneic hematopoietic stem cell transplant (AHSCT), other hematological diseases, and immunosuppressive treatment. Clinical characteristics and outcomes were compared between groups. Multiple correspondent analyses compared clinical characteristics at diagnosis. Day 30 mortality was analyzed. Three hundred and twenty-one patients were included in the study. The underlying diseases were hematological malignancy (n = 75), AHSCT (n = 14), CLL (n = 19), solid organ transplant (n = 94), solid tumor (n = 39), and immunosuppressive treatment (n = 57). Compared with other underlying diseases, PCP related to CLL was closer to PCP related to AIDS presentation (long duration of symptoms before diagnosis, high level of dyspnea, and low oxygen saturation at diagnosis). Day 30 mortality was associated with underlying disease, oxygen flow, and shock at ICU admission. PCP presentations may vary according to the underlying reason for immunosuppression. Response to treatment and adjuvant steroid therapy should be analyzed regarding this result.

The preventable burden of work-related ill-health.

Background: The fraction of ill-health overall attributable to occupational conditions has not been extensively evaluated, thus contributing to the perception of a lesser relevance of education and research in occupational health in respect to other fields of medical research and practice. Aims: To assess the relevance of work-related conditions on the aetiology of human ill-health in different health domains. Methods: We extracted the risk estimates associated with heritability and with occupational risk factors for chronic lymphocytic leukaemia (CLL), major depressive disorder (MDD) and long QT syndrome (LQTS) from 13 published international reports. The selection criteria for the eligible studies were: genome-wide studies, or studies of the occupational risk factors associated with one of the three diseases of interest. We calculated and compared the respective population attributable fraction for the combined occupational risk factors, and for heritability. Results: We estimated that occupational risk factors would account for 12% (95% confidence interval (CI) 4-19) of CLL, 11% (95% CI 7-15) of MDD and 10% (95% CI 2-13) of LQTS burden in the general population. The corresponding figures for heritability would be 16% (95% CI 11-22), 28% (95% CI 20-5) and 17% (95% CI 7-27). Conclusions: More efforts in capacity building and research in occupational health are warranted aiming to prevent ill-health and to preserve a productive life for the ageing work population.

Utility of autopsy brain imprint and squash cytology for detection of lymphoma/leukemia emboli in select patients presenting with rapid decline in mental status.

Central nervous system (CNS) hematologic malignancies, whether primary or secondary, are uncommon and their clinical presentations vary. Intravascular lymphoma (IVL) is a very rare, aggressive systemic malignancy that is often difficult to diagnose and susceptible to early CNS involvement. Blast crisis in myeloid leukemias can cause widespread neoplastic emboli. Here, we report two adult patients (72 years and 22 years of age) who presented with altered mental status followed by rapid decline in their conditions leading to death. No prior significant medical history was present for either patient, while acute myeloid leukemia was diagnosed in the younger patient immediately before death. During autopsy, we performed imprint and squash preparations, and frozen sections of representative cerebral cortex, cerebellum, leptomeninges, and the pituitary gland. In the older patient, presence of IVL was readily detected on cytologic preparations. Diffuse involvement of brain vasculature and perivascular parenchyma with acute myeloid leukemia was identified in the other patient. Although examination of the fresh brain is not routinely performed during autopsy, these cases are presented to illustrate that imprint and squash preparations can provide a rapid and reliable provisional autopsy diagnosis in select patients.

Infections Caused by Fusarium Species in Pediatric Cancer Patients and Review of Published Literature.

Fusarium species have emerged as responsible for a broad spectrum of infections, including superficial, locally invasive and disseminated ones, especially in the hospital environment. Since there are few reports of invasive and disseminated fusariosis in children, the aim of this study was to report four cases of nosocomial infection caused by this microorganism in children with cancer hospitalized in a public children's hospital located in Brazil. Two of these patients were female and two were male. All patients presented febrile neutropenia, while three patients had acute lymphocytic leukemia and one patient had Wilms' tumor as underlying disease. In two cases, fungi were isolated from blood and identified as Fusarium oxysporum species complex after phenotypic and genotypic studies, while in two other cases fungi were isolated from skin biopsies and identified as Fusarium solani species complex. One patient died 12 days after the onset of cutaneous lesions. All isolates, after susceptibility testing, presented high levels of minimum inhibitory concentration for itraconazole, voriconazole and amphotericin B. Considering the emergence of filamentous fungi as etiologic agents of nosocomial infections, health professionals should be aware of the problems these infections, especially fungal ones, may cause to debilitated patients.

Oral health status in adult patients with newly diagnosed acute leukemia.

BACKGROUND: The aim of this cross-sectional study was to evaluate the oral health of adult patients with newly diagnosed acute leukemia. METHODS: Patients with initially diagnosed acute myeloid (AML) or lymphocytic (ALL) leukemia and a matched healthy control (HC) group were included. The oral investigation comprised inspection of the oral mucosa; the decayed (D), missing (M), and filled (F) teeth (DMF-T) index; and a detailed periodontal status. Subgingival biofilm samples were analyzed (polymerase chain reaction) for the presence of selected potentially periodontal pathogenic bacteria. Statistical analysis was performed using Fisher's exact test, chi-squared test, and Mann-Whitney U test (significance level α = 5%). RESULTS: Thirty-nine patients with leukemia (AML 26, ALL 13) and 38 HCs were included. Oral mucosal findings were present in 62% of L compared to 0% of HC patients, whereby gingival hyperplasia was the most detected finding. Furthermore, a higher caries prevalence in leukemia patients was shown (D value 3.64 ± 3.98 vs. 0.72 ± 1.72, p < 0.01). The periodontal parameters were poorer in leukemia patients. No substantial differences in microbiological findings of selected bacteria were detected within L group and between L and HC patients. CONCLUSION: The high prevalence of oral diseases supports the demand of an early and consequent dental treatment of leukemia patients, especially considering subsequent therapy.

Extended Follow-up of Patients Treated With Bendamustine for Lymphoid Malignancies.

INTRODUCTION: Bendamustine, typically in combination with rituximab, is an effective treatment for chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma. Despite its acceptable short-term toxicity profile, long-term toxicities are less well established. This study investigated the long-term adverse effects of bendamustine and responses to subsequent treatments. PATIENTS AND METHODS: Charts of 194 patients were retrospectively reviewed; 54% had received prior treatment (76% attained complete response [CR] or partial response [PR]). RESULTS: Patients who did not achieve a CR or PR did not respond well to subsequent treatments. Malignancies following bendamustine were diagnosed in 11% (21) of patients (first line [7] and salvage [14]), including squamous (8) or basal cell (4) skin cancers; prostate cancer (3), renal cancer (3), bladder cancer (2), melanoma (2), lung cancer (1), and histiocytic sarcoma (1). There were no occurrences of therapy-related myelodysplastic syndrome or acute myelogenous leukemia reported. Infections occurred in 63% of patients; however, no deaths were attributable to bendamustine. CONCLUSION: Bendamustine is an effective therapy with limited long-term sequelae in patients with lymphoid malignancies.

Assessing Decision Making Capacity for Do Not Resuscitate Requests in Depressed Patients: How to Apply the "Communication" and "Appreciation" Criteria.

The Patient Self Determination Act (PSDA) of 1991 brought much needed attention to the importance of advance care planning and surrogate decision-making. The purpose of this law is to ensure that a patient's preferences for medical care are recognized and promoted, even if the patient loses decision-making capacity (DMC). In general, patients are presumed to have DMC. A patient's DMC may come under question when distortions in thinking and understanding due to illness, delirium, depression or other psychiatric symptoms are identified or suspected. Physicians and other healthcare professionals working in hospital settings where medical illness is frequently comorbid with depression, adjustment disorders, demoralization and suicidal ideation, can expect to encounter ethical tension when medically sick patients who are also depressed or suicidal request do not resuscitate orders.

Incidence of Myelofibrosis in Chronic Myeloid Leukemia, Multiple Myeloma, and Chronic Lymphoid Leukemia during Various Phases of Diseases.

Pathomorphological study of trephinobiopsy specimens from 129 patients with lymphoproliferative and myeloproliferative diseases was carried out over the course of chemotherapy. Combinations of initial and manifest myelofibrosis (loose network of reticulin fibers and extensive network of reticulin and collagen fibers, respectively) predominated at the debut of chronic myeloid leukemia, chronic lymphoid leukemia, and multiple myeloma. Manifest myelofibrosis was detected in patients with chronic myeloid leukemia without hematological response (failure of normalization of hematological values) and in patients with progressing and relapsing multiple myeloma. Combinations of foci of initial and manifest myelofibrosis were most incident in patients with progressing and relapsing chronic lymphoid leukemia. The incidence of myelofibrosis was higher in patients with multiple myeloma and chronic lymphoid leukemia progression and relapses and in patients with chronic myeloid leukemia without hematological response than at the disease debut and in case of response to chemotherapy. The response to chemotherapy in patients with chronic myeloid leukemia and chronic lymphoid leukemia was associated with a decrease in the incidence of myelofibrosis. In patients with multiple myeloma responding to chemotherapy, the incidence of myelofibrosis did not change in comparison with the disease debut.

Efficacy and safety of vitamin D supplementation in patients with chronic lymphocytic leukemia.

BACKGROUND: Vitamin D (VD) deficiency in chronic lymphocytic leukemia (CLL) is associated with inferior prognosis, shorter time to treatment and worse overall survival. VD deficiency is the first potentially modifiable prognostic factor in CLL. Currently, however, there is a lack of studies concerning VD supplementation in CLL patients. AIM: To evaluate the efficacy and safety of VD supplementation in patients with CLL. METHODS: A 6-month interventional study was conducted in CLL patients with lower serum 25-OH-D3 concentrations (< 30 ng/ml) than currently recommended. Patients with VD insufficiency (20-30 ng/ml) received 2000 IU of cholecalciferol/day, patients with moderate deficiency (10-19.9 ng/ml) received 4000 IU/day, and patients with severe VD deficiency (<10 ng/ml) received 6000 IU/day. RESULTS: In the analyzed group of 13 CLL subjects, only 1 patient had a VD level within the optimal range (30-80 ng/ml), 7 had an insufficient concentration, 4 had moderate deficiency, and 1 had severe deficiency. Secondary hyperparathyroidism was diagnosed in 4 subjects. Cholecalciferol supplementation (mean dose of 3384 ± 1211 IU) was followed by a significant increase in 25-OH-D3 concentration (from 17.3 ± 5.8 to 41.4 ± 17.5 ng/ml; p<0.05) and decrease in PTH (p<0.05). Five patients did not achieve the recommended 25-OH-D3 concentration. Calcium level remained unchanged and no patients developed hypercalcemia. CONCLUSIONS: VD replenishment is safe and can be effectively achieved by means of the employed cholecalciferol dosage in the majority of patients. However, some subjects may require higher doses to obtain the optimal level and immune function.

Púrpura trombótica trombocitopénica inducida por ciclosporina. Estudio de 3 casos / Cyclosporin-induced thrombotic thrombocytopenic purpura. Report of three cases

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Gamma heavy chain disease associated with large granular lymphocytic leukemia: A report of two cases and review of the literature.

OBJECTIVE AND IMPORTANCE: Gamma heavy chain diseases (γHCD) and large granular lymphocyte (LGL) leukemia are two rare lymphoproliferative diseases, respectively with B and T phenotype. Both γHCD and LGL leukemia share some similar clinical features, such as cytopenias, splenomegaly, and recurrent infections. Association of these two diseases is exceptional and suggest pathogenic link. We report two cases of γHCD associated with T-LGL leukemia. CLINICAL PRESENTATION: Patient 1 was a 70-year-old woman, with lymphoplasmacytic lymphoma, refractory to chlorambucil-rituximab treatment. She developed during the follow up a γHCD with T-LGL leukemia, unresponsive to melphalan, thalidomide, and steroids, requiring supportive care. Patient 2 was a 40-year-old man with chronic severe asymptomatic neutropenia, revealing both γHCD and T-LGL leukemia. He is still well without any treatment nor complications, with 7 years follow up. CONCLUSION: Several types of B lymphoproliferative disease are associated with LGL leukemia. Although exceptional, this association of two rare lymphoproliferative disorders, with a different phenotype, does not seem fortuitous.

Angioinvasive opportunistic filamentous mycoses in immunocompromised patients.

Immunocompromised individuals are at greater risk for disseminated fungal infections. Immunocompromised individuals in the community have increased because of medical advances, thereby increasing the incidence and prevalence of opportunistic mycoses. The following case series illustrates the importance of having a high clinical suspicion for skin manifestations concerning for deep fungal infections.