Indice de comorbilidad específico para trasplante alogénico de células progenitoras hematopoyéticas: cohorte retrospectiva de niños y adolescentes con enfermedad maligna / Specific comorbidity index for allogeneic hematopoietic stem cell transplantation: a retrospective cohort of children and adolescents with malignancies

Introducción: Entre las variables que afectan el riesgo de mortalidad relacionada (MRT) al trasplante alogénico de células progenitoras hematopoyéticas (TACPH) se incluyen las comorbilidades previas. Los índices de comorbilidad (IC) buscan mejorar la predicción de eventos combinando factores de riesgo independientes. Objetivos: 1) evaluar el uso de la versión breve y adaptada para niños, adolescentes y adultos jóvenes con enfermedad maligna del índice de comorbilidad específico para trasplante alogénico de células progenitoras hematopoyéticas (smyHCT-CI ); 2) evaluar el uso de los biomarcadores ferritina y albúmina en un índice de comorbilidad ampliado (smyHCT-CIa). Población y métodos: Diseño: cohorte retrospectiva. Periodo 2017- 2022. A cada p se le asignó nuevos puntajes utilizando el smyHCT-CI y el smyHCT-CIa. Los p se clasificaron en grupos de riesgo (GR) bajo (puntaje 0), intermedio (1-2) y alto (>3) con cada índice. Se comparó el n° de p asignado a cada GR grupo de riesgo y la MRT en cada grupo al usar el HCT-CI, el smyHCTCI y el smyHCT-CIa. Resultados: n 75. Frecuencia de p por GR según cada indicador (IC95): HCT-CI bajo 36 (25-47), intermedio 57 (56-69), alto 7 (1-12); smyHCT-CI: bajo 48 (37-59), intermedio 33 (23-44), alto 19 (10-27); smyHCT-CIa: bajo 43 (31-54), intermedio 36 (25-47), alto 21 (12-31). MRT por GR según indicador (IC95): HCT-CI: bajo 6,8 (14-28), intermedio 20,9 (9-33), alto 17,9 (0-55); smyHCT-CIa bajo 12,5 (1-24), intermedio 18,5 (4-33), alto 31,2 (9-54). Conclusión: El smyHCT-CI permitió identificar mejor los pacientes con mayor comorbilidad y riesgo de MRT. La ferritina resultó un biomarcador útil en la estimación del riesgo de MRT (AU)

Introduction: Variables affecting allogeneic hematopoietic stem cell transplantation (HCT) related mortality risk (TMR) include prior comorbidities. Comorbidity indices (CI) aim to improve event prediction by combining independent risk factors. Objectives: 1) to evaluate the use of the brief and adapted version of the HCT-specific comorbidity index for children, adolescents and young adults with malignancies (ymHCT-CI); 2) to evaluate the use of the biomarkers ferritin and albumin in an expanded comorbidity index (expanded ymHCT-CI). Population and methods: Design: retrospective cohort. Period 2017- 2022. Each patient was assigned new scores using the ymHCTCI and expanded ymHCT-CI. The p were classified into low (score 0), intermediate (1-2) and high (>3) risk groups (RG) with each index. The number of patients assigned to each RG and the TMR in each group were compared using the HCTCI, the ymHCT-CI, and the expanded ymHCT-CI. Results: n 75. Frequency of patients per RG according to each indicator (95%CI): HCT-CI low 36 (25-47), intermediate 57 (56-69), high 7 (1-12); ymHCT-CI: low 48 (37-59), intermediate 33 (23-44), high 19 (10-27); expanded ymHCT-CI: low 43 (31-54), intermediate 36 (25-47), high 21 (12-31). TMR by RG according to indicator (95%CI): HCT-CI: low 6.8 (14-28), intermediate 20.9 (9-33), high 17.9 (0-55); expanded ymHCT-CI low 12.5 (1-24), intermediate 18.5 (4-33), high 31.2 (9-54). Conclusion: ymHCT-CI allowed better identification of patients with higher comorbidity and risk of TMR. Ferritin proved to be a useful biomarker to estimate TMR risk (AU)

Utilidad del lavado broncoalveolar para la detección microbiológica, y factores asociados, en receptores de trasplante de precursores hematopoyéticos: estudio de cohorte retrospectivo / Usefulness of bronchoalveolar lavage for microbiological detection and asssociated factors in hematopoietic stem cell transplant receivers: a retrospective cohort study

INTRODUCCIÓN: Las opacidades pulmonares en receptores de trasplante de precursores hematopoyéticos (TPH) representan un desafío diagnóstico y son una causa de morbimortalidad. Existen grandes discrepancias con respecto a la sensibilidad diagnóstica del lavado broncoalveolar (LBA), sus complicaciones, y los factores asociados a la identificación microbiológica. OBJETIVO: Conocer la utilidad del estudio microbiológico del LBA en el diagnóstico, modificación de la conducta médica y estimar las complicaciones y mortalidad asociada al procedimiento, en receptores de TPH con opacidades pulmonares. PACIENTES Y MÉTODOS: Estudio de cohorte, retrospectivo, en adultos receptores de TPH a los que se les realizó una broncoscopía con LBA por presentar opacidades pulmonares, en el Hospital Italiano de Buenos Aires entre el 01/01/2011 y el 31/12/2020. RESULTADOS: De los 189 procedimientos analizados, en 79 se logró un hallazgo microbiológico (41,8%) y 122 permitieron modificar la conducta médica (64,6%). En 11 casos se observaron complicaciones graves dentro de las 12 horas (5,8%) de efectuado el LBA. La mortalidad intrahospitalaria fue de 16,8% (N = 21/125). El valor de neutrófilos en sangre previo al LBA (p = 0,037) y la presencia de nódulos pulmonares como lesión tomográfica predominante (p = 0,029) se asociaron independientemente al hallazgo microbiològico global. CONCLUSIONES: Nuestra investigación apoya la realización del LBA como herramienta diagnóstica en pacientes que reciben un TPH y presentan opacidades pulmonares.

BACKGROUND: Lung opacities are a cause of morbimortality in bone marrow transplant patients, and represent a diagnostic challenge. There are large discrepancies regarding the diagnostic sensitivity of bronchoalveolar lavage (BAL), its complications, and the factors associated with microbiological detection. AIM: To know the usefulness of the microbiological study of BAL in the diagnosis, in the modification in medical behavior and to estimate the complications and associated mortality of this diagnostic procedure in patients transplanted with hematopoietic progenitor cells with pulmonary opacities. METHODS: Retrospective cohort study in bone marrow transplant adult patients who underwent bronchoscopy with BAL due to lung opacities at Hospital Italiano de Buenos Aires between 01/01/2011 and 12/31/2020. RESULTS: Of the 189 BAL analyzed, 79 presented a microbiological detection (41.8%) and 122 allowed to modify the medical behavior (64.6%). Severe complications were observed within 12 hours after the procedure in11 cases (5.8%). In-hospital mortality was 16,8% (N = 21/125). The value of blood neutrophils prior to bronchoalveolar lavage (p = 0.037) and the presence of pulmonary nodules as the predominant tomographic lesion (p = 0.029) were independently associated with global microbiological detection. CONCLUSION: Our research supports the performance of BAL as a diagnostic tool in bone marrow transplant patients with lung opacities.

Riesgo de mortalidad en infecciones invasivas por Mucor SPP. en niños con enfermedades hemato-oncológicas: revisión sistemática / Mortality risk of invasive Mucor spp. infections in children with cancer: A systematic review

Los estudios sobre la infección fúngica invasiva (IFI) por Mucor spp. en pacientes pediátricos con patología hematooncológica, son de baja solidez científica, lo que dificulta conocer en profundidad sus características y evolución. Con el objetivo de analizar la evolución fatal de esos pacientes, se llevó a cabo esta revisión sistemática (RS). Material y métodos: La búsqueda bibliográfica se realizó con fecha 23 de marzo de 2023, en las principales bases de datos (Medline (a través de Pubmed), Embase (a través de Embase-Elsevier), The Cochrane Library (a través de Wiley), Cinahl (a través de Ebsco HOST), SCI-EXPANDED, SciELO (a través de la WOS) y Scopus (a través de Scopus-Elsevier), libre (mediante el motor Google) y revisando las citas de los artículos incluidos. Resultados: Se rescataron 1393 artículos, de los cuales se descartaron 1386 por diversas razones. Mediante el análisis de los textos completos, finalmente se incluyeron 7 estudios. Todos los estudios eran series de casos (nivel 4). La mediana de la frecuencia de muerte observada fue de 36,6% (Q1 20% - Q347%). Conclusiones: Esta RS mostró en niños con patología hemato-oncológica, que la mortalidad por IFI por Mucor spp. alcanzó a casi un tercio de los pacientes (AU)

Studies on invasive fungal infection (IFI) by Mucor spp. in pediatric patients with cancer have a low level of evidence, which makes it difficult to elucidate its characteristics and progression. To analyze the fatal outcome of these patients, this systematic review (SR) was conducted. Material and methods: A literature search was carried out on March 23, 2023, in the following main databases (Medline (via Pubmed), Embase (via Embase-Elsevier), The Cochrane Library (via Wiley), Cinahl (via Ebsco HOST), SCI-EXPANDED, SciELO (via the WOS) and Scopus (via Scopus-Elsevier). Additionally, a complementary search was carried out using free search engines (such as Google) and by reviewing the references of the included articles. Results: A total of 1393 articles were retrieved, of which 1386 were excluded for various reasons. After a thorough analysis of the full-text articles, 7 studies were ultimately included in the review. All studies were case series (level 4). The median observed death rate was 36.6% (IQR, 20% - 47%). Conclusions: This SR showed that in children with hematological-oncological disease, mortality due to IFI by Mucor spp. affected almost one third of the patients (AU)

Clinical development of chimeric antigen receptor-T cell therapy for hematological malignancies / 中华医学杂志(英文版)

Cellular therapies have revolutionized the treatment of hematological malignancies since their conception and rapid development. Chimeric antigen receptor (CAR)-T cell therapy is the most widely applied cellular therapy. Since the Food and Drug Administration approved two CD19-CAR-T products for clinical treatment of relapsed/refractory acute lymphoblastic leukemia and diffuse large B cell lymphoma in 2017, five more CAR-T cell products were subsequently approved for treating multiple myeloma or B cell malignancies. Moreover, clinical trials of CAR-T cell therapy for treating other hematological malignancies are ongoing. Both China and the United States have contributed significantly to the development of clinical trials. However, CAR-T cell therapy has many limitations such as a high relapse rate, adverse side effects, and restricted availability. Various methods are being implemented in clinical trials to address these issues, some of which have demonstrated promising breakthroughs. This review summarizes developments in CAR-T cell trials and advances in CAR-T cell therapy.

Challenges and optimal strategies of CAR T therapy for hematological malignancies / 中华医学杂志(英文版)

Remarkable improvement relative to traditional approaches in the treatment of hematological malignancies by chimeric antigen receptor (CAR) T-cell therapy has promoted sequential approvals of eight commercial CAR T products within last 5 years. Although CAR T cells' productization is now rapidly boosting their extensive clinical application in real-world patients, the limitation of their clinical efficacy and related toxicities inspire further optimization of CAR structure and substantial development of innovative trials in various scenarios. Herein, we first summarized the current status and major progress in CAR T therapy for hematological malignancies, then described crucial factors which possibly compromise the clinical efficacies of CAR T cells, such as CAR T cell exhaustion and loss of antigen, and finally, we discussed the potential optimization strategies to tackle the challenges in the field of CAR T therapy.

Second allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning and donor changes in relapsed hematological malignancies after the first allogeneic transplant / 中华血液学杂志

Objective: The purpose of this study was to assess the safety and efficacy of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning (RIC) in patients with hematological malignancies who had relapsed after the first allo-HSCT. Methods: Between April 2018 and June 2021, 44 patients with hematological malignancies (B-ALL 23, T-ALL/T-LBL 4, AML15, and MDS 2) were enrolled and retrospectively examined. Unrelated donors (n=12) or haploidentical donors (n=32) were used. Donors were replaced in all patients for the second allo-HSCT. Hematological and immunological germline predisposition genes and hematopoietic and immune function tests were used to select the best-related donor. Total body irradiation (TBI) /fludarabine (FLU) -based (n=38), busulfan (BU) /FLU-based (n=4), total marrow irradiation (TMI) /FLU-based (n=1), and BU/cladribine-based (n=1) were the RIC regimens used. For graft versus host disease (GVHD) prevention, cyclosporine, mycophenolate mofetil, short-term methotrexate, and ATG were used. Eighteen (40.9%) of 44 patients with gene variations for which targeted medications are available underwent post-transplant maintenance therapy. Results: The median age was 25 years old (range: 7-55). The median interval between the first and second HSCT was 19.5 months (range: 6-77). Before the second allo-HSCT, 33 (75%) of the patients were in complete remission (CR), whereas 11 (25%) were not. All patients had long-term engraftment. The grade Ⅱ-Ⅳ GVHD and severe acute GVHD rates were 20.5% and 9.1%, respectively. Chronic GVHD was found in 20.5% of limited patterns and 22.7% of severe patterns. CMV and EBV reactivation rates were 29.5% and 6.8%, respectively. Hemorrhage cystitis occurred in 15.9% of cases, grade Ⅰ or Ⅱ. The 1-yr disease-free survival (DFS), overall survival (OS), and cumulative recurrence incidence (RI) rates of all patients were 72.5% (95% CI, 54.5%-84.3%), 80.6% (95% CI, 63.4%-90.3%), and 25.1% (95% CI, 13.7%-43.2%), respectively, with a median follow-up of 14 (2-39) months. There were eight deaths (seven relapses and one infection). The rate of non-relapse mortality (NRM) was only 2.3%. The CR patients' 1-yr RI rate was significantly lower than the NR patients (16.8% vs 48.1%, P=0.026). The DFS rate in CR patients was greater than in NR patients, although there was no statistical difference (79.9% vs 51.9%, P=0.072). Univariate analysis revealed that CR before the second allo-HSCT was an important prognostic factor. Conclusion: With our RIC regimens, donor change, and post-transplant maintenance therapy, the second allo-HSCT in relapsed hematological malignancies after the first allo-HSCT is a safe and effective treatment with high OS and DFS and low NRM and relapse rate. The most important factor influencing the prognosis of the second allo-HSCT is the patient's illness condition before the transplant.

Efficacy and safety of secondary allogeneic hematopoietic stem cell transplantation in 70 patients with recurrent hematologic malignancies after transplantation / 中华血液学杂志

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.

Infección por SARS-COV-2 en pacientes con neoplasias hematológicas y trasplantes / SARS-COV-2 infection in patients with hematological malignancies and transplants

Resumen La infección por SARS-CoV-2 en pacientes con neoplasias hematológicas y trasplantes de células progenitoras hematopoyéticas (TCPH) puede ser grave y con importante mortalidad. Llevamos a cabo un estudio prospectivo y observacional que tuvo como objetivo describir las características clínicas, epide miológicas y la evolución de la infección por SARS-CoV-2 en pacientes con neoplasias hematológicas y TCPH. Se incluyeron 20 pacientes adultos con una mediana de edad de 58 años y una mediana de score de Charlson de 3. Las infecciones fueron de adquisición comunitaria y nosocomial en el 60% y 40% respectivamente, y el 30% de los pacientes tenía antecedente de contacto con una persona infectada por SARS-CoV-2. El 65% pre sentó infiltrados pulmonares, mayormente con patrón de vidrio esmerilado en la tomografía computarizada de tórax. Casi la mitad de los pacientes tuvo enfermedad grave y crítica, y una alta proporción recibió plasma de convalecientes como tratamiento. Presentaron complicaciones e infecciones hospitalarias el 20% y 15% respec tivamente, y tuvieron una mediana de días de internación prolongada. La mortalidad a 30 días fue del 10%. La infección por SARS-CoV-2 en nuestra población tuvo considerable impacto clínico y epidemiológico.

Abstract. SARS-CoV-2 infection in patients with hematological malignancies and hematopoietic stem cell transplants (HSCT) can be severe and with significant mortality. We carried out a prospective and observational study to describe the clinical and epidemiological characteristics and outcome of SARS-CoV-2 infection in patients with hematological malignancies and HSCT. Twenty adult patients were included with a median age of 58 years and a median Charlson score of 3. Infections were community-acquired and nosocomial in 60% and 40%, respectively, and 30% of the patients had a history of contact with a SARS-CoV-2 infected person. Sixty-five percent had pulmonary infiltrates, mostly with a ground-glass pattern on CT scan. Almost half of the patients had a severe and critical illness, and a high proportion received convalescent plasma as treatment. Twenty percent and 15% had complications and hospital infections, respectively, and had prolonged hospitalization expressed as median days of it. The 30-day mortality was 10%. SARS-CoV-2 infection in our population had a considerable clinical and epidemiological impact.

CAR T-cell immunotherapy: a powerful weapon for fighting hematological B-cell malignancies / 医学前沿

The current standard of care in hematological malignancies has brought considerable clinical benefits to patients. However, important bottlenecks still limit optimal achievements following a current medical practice. The genetic complexity of the diseases and the heterogeneity of tumor clones cause difficulty in ensuring long-term efficacy of conventional treatments for most hematological disorders. Consequently, new treatment strategies are necessary to improve clinical outcomes. Chimeric antigen receptor T-cell (CAR T) immunotherapy opens a new path for targeted therapy of hematological malignancies. In this review, through a representative case study, we summarize the current experience of CAR T-cell therapy, the management of common side effects, the causative mechanisms of therapy resistance, and new strategies to improve the efficacy of CAR T-cell therapy.

Effect of KIR/HLA receptor-ligand mode on prognosis of single unrelated cord blood transplantation in patients with hematological malignancies / 中华血液学杂志

Objective: To explore the impact of the natural killer cell immunoglobulin-like receptor/human leukocyte antigen (KIR/HLA) receptor-ligand model in single unrelated cord blood transplantation (sUCBT) . Methods: Between July 2012 and June 2018, 270 patients with malignant hematologic diseases receiving single-unit UCBT were divided into two groups. Group 1 (n=174) patients lacked a C-ligand for inhibitory KIR on UCB NK cells (patients homozygous C1/C1 or C2/C2) . Group 2 (n=96) patients expressed both C ligands for inhibitory KIR in the receptor (patients heterozygous C1/C2) . Results: A total of 270 patients (146 males, 124 females) with a median age of 13 years (1-62) were included in this retrospective study. All patients received a myeloablative conditioning regimen (without ATG) . The ratio of neutrophil engraftment for group 1 and 2 were both 98.9%, the median time of neutrophil engraftment for group 1 and 2 was 16 (10-41) days vs 17 (11-33) days (P=0.705) . The ratio of platelet engraftment was 88.5% for group 1 and 87.5% for group 2, the median time of platelet engraftment was 35 (11-113) days vs 38.5 (13-96) days (P=0.317) . The cumulative incidence of Ⅱ-Ⅳ acute GVHD in 100 days was 38.7% (95%CI 31.4%-45.9%) for group 1 and 50.0% (95%CI 39.6%-59.6%) for group 2 (P=0.075) , but multivariate analysis showed that HLA-C ligand absence was an independent protective factor for Ⅱ-Ⅳ acute GVHD after transplantation (P=0.036) . Patients in absence of a C-ligand for inhibitory KIRs (Group 1) showed a lower relapse rate than patients with both C-ligands (group 2) : 17.7% (95%CI 11.7%-24.9%) vs 22.7% (95%CI 4.4%-32.2%) after 3 years (P=0.288) . The median follow-up time was 742 (335-2 512) days. The 3-year OS was 72.1% for group 1 and 60.5% for group 2 (P=0.079) . There was no statistically significant difference between the two groups in 3-year disease-free survival [64.9% (95%CI 56.2%-72.3%) vs 55.4% (95%CI 44.4%-65.0%) (χ(2)=3.027, P=0.082) ]. Non-relapse mortality for group 1 was 12.1% (95%CI 7.7%-17.4%) and for group 2 was 16.7% (95%CI 10.0%-24.8%) (P=0.328) . Conclusion: Patients lacking a KIR-ligand of HLA group C1 or C2 had a lower incidence of grades Ⅱ-Ⅳ acute GVHD after sUCBT.

Parte I. Requerimientos básicos de infectología para hospitales que atienden pacientes hemato-oncológicos: ambiente hospitalario, protocolos diagnósticos y arsenal terapéutico. Fundamentación / Basic requirements of facilities for hospitals that treat hemato-oncological patients: hospital environment, diagnostic protocols and therapeutic arsenal

Resumen La atención de pacientes con cáncer, incluyendo los receptores de trasplantes de precursores hematopoyéticos, plantea numerosos desafíos para los hospitales que deben proveer ambientes seguros, en que se logre aminorar al máximo posible la exposición a patógenos que generan morbilidad y mortalidad. Al mismo tiempo deben contar con protocolos establecidos que permitan realizar un estudio racional de las posibles etiologías infecciosas que pueden presentar estos pacientes. A su vez, deben asegurar la existencia de un arsenal terapéutico adecuado, junto a algoritmos de tratamiento oportuno, actualizado según guías consensuadas y efectivo según la infección sospechada o confirmada. En este artículo se introducen algunos de los argumentos que sustentan estos requerimientos que luego se desarrollan en tres artículos sucesivos dedicados al ambiente hospitalario, protocolos diagnósticos y arsenal terapéutico.

The care of cancer patients, including recipients of hematopoietic stem cell transplantation, has numerous challenges for hospitals that must provide safe environments in which exposure to pathogens that generate morbidity and mortality is reduced at maximum. At the same time, they must have established protocols that allow a rational study of the possible infectious etiologies and the existence of an adequate therapeutic arsenal together with timely treatment algorithms, updated according to consensus guidelines and effective according to the suspected or confirmed infection. This article introduces some of the arguments that support these requirements, then that are developed in three successive articles dedicated to the hospital environment, diagnostic protocols and therapeutic arsenal.

Incidência e risco de quedas em pacientes tratados por neoplasias hematológicas na Unidade de Hematologia Intensiva / Incidence and risk of falls in patients treated for hematologic malignancies in the Intensive Hematology Unit / Incidencia y riesgo de caídas en pacientes tratados por neoplasias hematológicas en Unidad Hematología Intensiva

Objetivo: determinar a incidência e a taxa de risco de quedas em pacientes adultos tratados por neoplasias hematológicas na Unidade de Hematologia Intensiva de um hospital de referência. Método: corresponde a um estudo observacional retrospectivo. Foram avaliados 101 pacientes. A ocorrência de quedas foi obtida a partir do registro da unidade e as variáveis preditivas do modelo Hendrich II foram coletadas: sexo, presença de tontura ou vertigem, confusão mental, problemas de eliminação, depressão, uso de benzodiazepínicos, uso de anticonvulsivantes e o teste Get up and Go. Resultados: dois eventos de quedas foram relatados em 101 pacientes (incidência de 1,98% em um período de 1,5 ano). Usando o ponto de corte cinco do Modelo Hendrich II, identificou-se que 30 pacientes (29,7%) apresentaram risco de queda no primeiro dia de hospitalização, 41 (40,6%) ao meio e 38 (37,6%) no momento da alta hospitalar. Conclusões: pacientes tratados por neoplasias hematológicas apresentaram baixa incidência e alto risco de quedas durante a hospitalização.

Objective: to determine the incidence and rate of risk of falls in adult patients treated for hematologic malignancies in the Intensive Hematology Unit of a reference hospital. Method: this is a retrospective observational study. A total of 101 patients were evaluated. The occurrence of falls was obtained from records of the unit and the predictive variables of the Hendrich II model were collected, namely: sex, presence of dizziness or vertigo, mental confusion, elimination problems, depression, use of benzodiazepines, use of anticonvulsants, and the Get up and Go test. Results: two fall events were reported in 101 patients (incidence of 1.98% over a 1.5-year period). Based on the cut-off point 5 of the Hendrich II Model, 30 patients (29.7%) were at risk of fall at the moment of hospital admission, 41 (40.6%) in the middle of the hospitalization period, and 38 (37.6%) at the moment of hospital discharge. Conclusions: patients treated for hematological malignancies presented low incidence and high risk of falls during hospitalization.

Objetivo: determinar la incidencia y la tasa de riesgo de caídas en pacientes adultos tratados por neoplasias hematológicas en la Unidad de Hematología Intensiva de un hospital de referencia. Método: corresponde a un estudio observacional retrospectivo. Se evaluaron 101 pacientes. La ocurrencia de caídas se obtuvo del registro de la unidad y las variables predictivas del modelo Hendrich II fueron recopiladas: sexo, presencia de mareos o vértigo, confusión mental, problemas de eliminación, depresión, uso de benzodiacepina, uso de anticonvulsionantes y la prueba Get up and Go. Resultados: dos eventos de caídas fueron reportados en 101 pacientes (incidencia de 1,98% en un período de 1,5 años). Utilizando el punto de corte 5 del Modelo Hendrich II, fue identificado que 30 pacientes (29,7%) tenían riesgo de caída al ingreso hospitalario, 41 (40,6%) en la mitad y 38 (37,6%) al egreso hospitalario. Conclusiones: los pacientes tratados por neoplasias hematológicas presentaron una incidencia baja y un alto riesgo de caídas durante la hospitalización.

Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Elderly / Consenso Brasileiro de Nutrição em Transplante de Células-Tronco Hematopoiéticas: Idosos

ABSTRACT The Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Elderly was elaborated by nutritionists, nutrologists and hematologists physicians from 15 Brazilians reference centers in hematopoietic stem cell transplantation, in order to emphasize the importancy of nutritional status and the body composition during the treatment, as well as the main characteristics related to patient's nutritional assessment. Establishing the consensus, we intended to improve and standardize the nutritional therapy during the hematopoietic stem cell transplantation. The Consensus was approved by the Brazilian Society of Bone Marrow Transplantation.

RESUMO O Consenso Brasileiro de Nutrição em Transplante de Células-Tronco Hematopoiéticas: Idoso foi elaborado com a participação de nutricionistas, médicos nutrólogos e médicos hematologistas de 15 centros brasileiros referência em transplante de células-tronco hematopoiéticas, com o objetivo de salientar a importância do estado nutricional e da composição corporal durante o tratamento, bem como as principais características relacionadas à avaliação nutricional do paciente. As intenções, ao se estabelecer o consenso, foram aprimorar e padronizar a terapia nutricional durante o transplante de células-tronco hematopoiéticas. O consenso foi aprovado pela Sociedade Brasileira de Transplante de Médula Óssea.

Fatores na admissão à unidade de terapia intensiva associados à readmissão em pacientes onco-hematológicos graves: estudo retrospectivo de coorte / Admission factors associated with intensive care unit readmission in critically ill oncohematological patients: a retrospective cohort study

RESUMO Objetivo: Determinar os fatores na admissão associados a readmissões na unidade de terapia intensiva em pacientes onco-hematológicos. Métodos: Estudo retrospectivo de coorte utilizando a base de dados de uma unidade de terapia intensiva de um hospital oncológico terciário. Os participantes foram 1.872 pacientes onco-hematológicos graves admitidos à unidade de terapia intensiva entre janeiro de 2012 e dezembro de 2014, e que sobreviveram e receberam alta da unidade. Utilizamos análises univariada e multivariada para identificar os fatores de risco na admissão associados com readmissões mais tarde à unidade de terapia intensiva. Resultados: Dos 1.872 que sobreviveram e receberam alta da unidade de terapia intensiva, 172 (9,2%) pacientes foram readmitidos após terem recebido alta da unidade. Os pacientes readmitidos tinham enfermidade mais grave, quando comparados aos do grupo que não foi readmitido, além de taxa de mortalidade hospitalar mais elevada (32,6% versus 3,7%, respectivamente; p < 0,001). Na análise multivariada, os fatores de risco independentes para readmissão à unidade de terapia intensiva foram: sexo masculino (OR: 1,5; IC95%: 1,07 - 2,12; p = 0,019), cirurgia de emergência como causa da admissão (OR: 2,91; IC95%: 1,53 - 5,54; p = 0,001), maior tempo de permanência no hospital antes da transferência para a unidade de terapia intensiva (OR: 1,02; IC95%: 1,007 - 1,035; p = 0,003) e ventilação mecânica (OR: 2,31; IC95%: 1,57 - 3,40; p < 0,001). Conclusão: Nesta coorte de pacientes onco-hematológicos foram identificados alguns fatores de risco associados à readmissão na unidade de terapia intensiva, a maioria não passível de intervenção. A identificação dos fatores de risco na alta da unidade de terapia intensiva pode ser uma abordagem promissora.

ABSTRACT Objective: The purpose of our study was to determine the admission factors associated with intensive care unit readmission among oncohematological patients. Methods: Retrospective cohort study using an intensive care unit database from a tertiary oncological center. The participants included 1,872 critically ill oncohematological patients who were admitted to the intensive care unit from January 2012 to December 2014 and who were subsequently discharged alive. We used univariate and multivariate analysis to identify the admission risk factors associated with later intensive care unit readmission. Results: One hundred seventy-two patients (9.2% of 1,872 oncohematological patients discharged alive from the intensive care unit) were readmitted after intensive care unit discharge. The readmitted patients were sicker compared with the non-readmitted group and had higher hospital mortality (32.6% versus 3.7%, respectively; p < 0.001). In the multivariate analysis, the independent risk factors for intensive care unit readmission were male sex (OR: 1.5, 95% CI: 1.07 - 2.12; p = 0.019), emergency surgery as the admission reason (OR: 2.91, 95%CI: 1.53 - 5.54; p = 0.001), longer hospital length of stay before intensive care unit transfer (OR: 1.02, 95%CI: 1.007 - 1.035; p = 0.003), and mechanical ventilation (OR: 2.31, 95%CI: 1.57 - 3.40; p < 0.001). Conclusions: In this cohort of oncohematological patients, we identified some risk factors associated with intensive care unit readmission, most of which are not amenable to interventions. The identification of risk factors at intensive care unit discharge might be a promising approach.

Salvaged single-unit cord blood transplantation for 26 patients with hematologic malignancies not in remission

Treatments for patients with hematologic malignancies not in remission are limited, but a few clinical studies have investigated the effects of salvaged unrelated cord blood transplantation (CBT). We retrospectively studied 19 patients with acute leukemia, 5 with myelodysplastic syndrome (MDS with refractory anemia with excess blasts [RAEB]), and 2 with non-Hodgkin's lymphoma who received 1 CBT unit ≤2 loci human leukocyte antigen (HLA)-mismatched after undergoing myeloablative conditioning regimens between July 2005 and July 2014. All of them were in non-remission before transplantation. The infused total nucleated cell (TNC) dose was 4.07 (range 2.76-6.02)×107/kg and that of CD34+ stem cells was 2.08 (range 0.99-8.65)×105/kg. All patients were engrafted with neutrophils that exceeded 0.5×109/L on median day +17 (range 14-37 days) and had platelet counts of >20×109/L on median day +35 (range 17-70 days). Sixteen patients (61.5%) experienced pre-engraftment syndrome (PES), and six (23.1%) patients progressed to acute graft-versus-host disease (GVHD). The cumulative incidence rates of II-IV acute GVHD and chronic GVHD were 50% and 26.9%, respectively. After a median follow-up of 27 months (range 5-74), 14 patients survived and 3 relapsed. The estimated 2-year overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) rates were 50.5%, 40.3%, and 35.2%, respectively. Salvaged CBT might be a promising modality for treating hematologic malignancies, even in patients with a high leukemia burden.

Laser terapia no controle da mucosite oral: um estudo de metanálise / Laser therapy in oral mucositis control: a meta-analysis

OBJETIVO: Realizar uma metanálise da eficácia da laser terapia (LT) na prevenção damucosite oral (MO) em pacientes submetidos à oncoterapia. MÉTODOS: Foi realizada uma busca nas bases de dados MEDLINE, LILACS e Cochrane, utilizando as palavras-chave "laser therapy" e "oral mucositis". Os estudos de caso-controle incluídos foram submetidos à análise do odds ratio (OR), cujo ponto de corte para a estatística foi MO grau > 3. Os cálculos foram realizados com o programa BioEstat 5.0, utilizando a análise estatística de Efeito Aleatório de DerSimonian-Laird. RESULTADOS: Doze estudos foram incluídos na revisão sistemática. A metanálise de sete deles evidenciou que a LT em pacientes submetidos à oncoterapia é aproximadamente nove vezes mais eficaz na prevenção de MO grau > 3 do que empacientes sem o tratamento com laser (OR: 9,5281; intervalo de confiança de 95% 1,447-52,0354, p = 0,0093). CONCLUSÃO: Esses dados demonstraram efeito profilático significativo de MOgrau > 3 nos pacientes submetidos à LT. Estudos com maior tamanho amostral são necessários para melhor avaliação do efeito profilático de MO grau > 3 por LT.

OBJECTIVE: To conduct a systematic review and meta-analysis of the effectiveness of Laser Therapy in the prevention of oral mucositis (OM) in patients undergoing oncotherapy. METHODS: To this systematic review and meta-analysis a search was performed in MEDLINE, LILACS and Cochrane using the keywords "laser therapy" and "Oral mucostitis." The casecontrol studies included were submitted to odds ratio (OR) analysis, which the cut-off point for statistic calculation was OM grade > 3. We carried out a meta-analysis by BioEstat 5.0, using the Random Effect DerSimonian-Laird statistical analysis. RESULTS: Twelve (studies were included in this systematic review, and the meta-analysis of seven of them showed that LT in patients undergoing oncotherapy is approximately nine times more effective in the prevention of OM grade > 3 than in patients without laser treatment (OR: 9,5281, confidence interval 95% 1,447-52,0354, p = 0,0093. CONCLUSION: These data demonstrated significant prophylatic effect of OM grade > 3 in patients undergoing LT. Further studies, with larger sample sizes, are needed for better evaluation of the prophylatic effect of OM grade > 3 by LT.

Bacteriemias por bacilos Gram negativos multirresistentes en neutropénicos febriles con enfermedades hematológicas / Bacteremia due to multiresistant Gram-negative bacilli in febrile neutropenic patients with hematological diseases

Las infecciones por bacilos Gram negativos multiresistentes (BGN-MR) son frecuentes en nuestro hospital. Presentan limitadas opciones terapéuticas e importante impacto en la morbimortalidad y costos. Objetivo: analizar los factoes de riesgo y evolución de las bacteriemias por BGN-MR en pacientes neutropénicos febriles con patologías hematológicas. Materiales y métodos: estudio prospectivo, descriptivo y observacional de los factores de riesgo para BGN-MR en la población descripta. Se realizó análisis univariado y multivariado de variables clínicas, epidemiológicas, microbiológicas y evolutivas. Resultados: El 27 % de los episodios de neutropenia y fiebre cursaron con bacteriemias por BGN, 42 % de ellos fueron producidos por BGN-MR. En el análisis univariado, dichas bacteriemias se asociaron al uso previo de antibióticos; a las bacteriemias de brecha y neutropenias mayores a 7 días. En el análisis multivariado la bacteriemia de brecha mantuvo su significancia estadística (P<0,001; OR: 5,17; IC 95 % 2,1-12,7). Acinetobacter spp fue el BGN-MR más frecuentemente aislado incluso en los pacientes fallecidos. No se detectó el foco en el 45,9 % de los episodios. Los tratamientos inadecuados fueron significativamente más frecuentes en los pacientes con BGN-MR y la mortalidad tanto global como atribuible también se asoció significativamente al tratamiento inadecuado de las bacteriemias por BGN-MR (P<0,04;RR: 2,46;IC 95 % 1,03-5,9 y P< 0,014; RR: 3,02; IC 95 % 1,22-0,45 respectivamente). Conclusiones: Las bacteriemias por BGN-MR son frecuentes en la población estudiada en especial los que han recibido ATB previo y en las que surgen intratratamiento ATB. Recibieron con mayor frecuencia tratamiento empírico inadecuado, lo que se asoció a mayor mortalidad...

Bacterial infections by multiresistant Gram-negative bacilli (BGN-MR) are an increasing problem in our hospital with a major impact on morbidity, mortality and costs. Objective: to analize risk factors and outcome in bacteremia due to multiresistant Gram-negative bacilli in febrile neutropenic patients with hematologic diseases. Material and Methods: We conducted a prospective, descriptive and observational study to describe the risk factors and outcome of BGN-MR bacteremia in these patients. Results: Twenty seven percent of neutropenia and fever episodes had Gram-negative bacilli bacteremia and 42 % of them were caused by BGN-MR. Previous use of antibioteics, breakthrough bacteremia and prolonged neutropenia (<7 days) were significant in univariate analysis. In multivariate analysis only breakthrough bacteremia was significant (P< 0.001; OR 5,17;IC 95 % 2.1-12.7). Acinetobactersppp was the most common BGN-MR isolated in blood-stream infections and in patients who died. The source of infections was unknown in 45,9 % of the episodes. Inadequate empirical therapy was most common in BGN-MR bacteremia and it was associated with increased overall and attributable mortality (P<0.04; RR: 2.46; IC 95 % 1.03-5.9 y P<0.014; RR: 3.02; IC 95 % 1.22-7.45). Conclusions: BGN-MR was frequent in neutropenic patients with hematological diseases specially in those exposed to antibiotics and in breakthroug bacteremia. Inappropiate antimicrobial therapy was common and is associated with adverse outcome...

Análisis de la mortalidad en enfermedades Hemato-oncológicas malignas en pediatría en hospitales públicos de Argentina / Analysis of Mortality due to Hemato-Oncological Pediatrics Malignancies in Public Hospitals in Argentina

INTRODUCCIÓN: En Argentina, la mortalidad por enfermedades malignas en edad pediátrica ocupa un lugar relevante y sus causas todavía no han sido estudiadas en el país. OBJETIVO: Analizar las tasas, causas y etapas de los fallecimientos relacionados con neoplasias en centros públicos seleccionados, desde enero de 2000 a diciembre de 2010. MÉTODOS: Se analizaron las historias clínicas de los pacientes fallecidos por cáncer en centros registrados en el Registro Oncopediátrico Hospitalario Argentino (ROHA) y en los registros individuales de los servicios de Hemato-Oncología. Se clasificaron las causas de mortalidad, la etapa en la cual se produjo el óbito y su relación con el tratamiento o con la patología de base. Se pesquisaron las causas de comorbilidad y las demoras en el diagnóstico y tratamiento. RESULTADOS: En 13 centros se analizó exitosamente un promedio >70...

INTRODUCTION: In Argentina, the mortality of pediatric malignant diseases occupies an important place causes have not yet been studied in the country. OBJECTIVE:To analyze mortality rates, causes and moment of death related to neoplasias in selected public centers from January 2000 until December 2010. METHODS: The analysis was conducted in clinical records of patients who died due to cancer. The cases were registered in the Argentine Hospital Oncopediatric Registry (ROHA)and by different registries belonging to hemato-oncological departments. Mortality causes were classified according to the phase of therapy when the event occurred and the relation shipof death with the treatment or underlying disease. Causes of comorbility and delays in diagnosis/treatment were also analyzed. RESULTS: In 13 centers, more than 70...

Allogeneic haematopoietic stem cell transplantation: The Army hospital experience.

Background. We analysed the results of allogeneic haematopoietic stem cell transplantation (HSCT) in various genetic disorders, bone marrow failures and haematological malignancies done from 2002 to 2010 at the Army Hospital, Research and Referral, Delhi. Methods. A total of 119 matched-related allogeneic- HSCTs (allo-HSCTs) were done in 114 patients (men 76, women 38) aged between 2 and 60 years. Peripheral blood stem cells (n=75) and bone marrow (n=43) were used as the source of stem cells. Results. The overall survival was 62.3% (71/114) at a median follow-up of 34 months. Graft versus host disease (GVHD) was seen in 42 (36.8%) patients; grade III/IV acute GVHD in 17 (15%) and chronic GVHD in 24 (21%) patients. There were 4 (3.5%) graft rejections and one nonengraftment. The overall mortality was 37.7% (n=43) and the main causes of death were GVHD (32%), infections (26%), relapse (23%) and regimen-related toxicity (11%). Conclusion. Our results are comparable to published data in most disease conditions. With improvements in GVHD prophylaxis and better supportive care, we need to further reduce our mortality and morbidity.