Hematology, transfusion and cell therapy最新文献

Background and objectives: Stem cell mobilization is a well-known procedure to harvest hematopoietic stem cells for autologous stem cell transplantation in certain hematologic diseases. Numerous studies have been conducted to identify risk factors for poor mobilization but there are no studies that identify good mobilizers. In our hospital, we decided to explore good mobilizers, defining them as those with ≥40 CD34⁺ cells/μL on Day +4 in order to start early apheresis.

Material and methods: A descriptive retrospective study was performed at Hospital Universitari Son Espases. A total of 198 patients mobilized with doses of around 10 µg/kg of granulocyte colony-stimulating factor (G-CSF) every 12 h were analyzed for autologous collection between January 2015 and September 2022. Fifty patients who had ≥40 CD34⁺ cells/μL on Day +4 started early apheresis; the rest continued mobilization as planned. Success was defined as obtaining over 2.5 × 10⁶ CD34⁺ cells/kg in a single apheresis.

Results: The necessary number of CD34⁺ cells/kg to perform an autologous stem cell transplantation was reached in a single apheresis session in 62 % of patients with ≥40 CD34⁺ cells/μL in peripheral blood. A cutoff of 102 CD34⁺ cells/μL on Day +4 was shown to have the best success rate (94 %). In an analysis of success, age, previously failed mobilization and having one or more adverse factors for bad mobilization were statistically significant.

Conclusion: Patients considered as good mobilizers were matched with our factors of poor mobilization, revealing that most patients (79 %) had none or only one risk factor for poor mobilization. Apheresis on Day +4 in good mobilizers was shown to be an effective alternative to reduce mobilization duration and decrease the amount of granulocyte-colony stimulating factor administered.

The German Hodgkin Study Group developed the escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) protocol as a treatment strategy for advanced-stage Hodgkin's lymphoma. In Brazil, as well as in other countries, procarbazine has been replaced with dacarbazine due to the limited availability of procarbazine. The Hematology Center at Irmandade da Santa Casa de Misericórdia in São Paulo adopted and modified the escalated BEACOPP protocol, substituting prednisone with dexamethasone and incorporating two different doses of dacarbazine: 375 mg/m²/day on Day 8 or the original dose of 250 mg/m²/day on Days 2 and 3. This adjustment was made in response to the anticipated toxicity profile. This study aimed to compare the two different doses in the protocols (375 mg/m²/cycle versus 500 mg/m²/cycle) administered to patients with advanced Hodgkin's lymphoma in similar periods. This retrospective study analyzed the data of 31 patients at a single center in Brazil from 2019 to 2021. Seventeen of the 31 patients received 500 mg/m²/cycle (500 Group), while 14 received 375 mg/m²/cycle (375 Group). At the end of the protocol, 71% of the patients in the 375 Group and 76% in the 500 Group achieved complete remission. On analyzing the number of cycles that patients presented with febrile neutropenia, the 500 Group had three times more events (17.9%) than the 375 Group (6.09% - p-value = 0.04). In the 500 Group, 47.1% needed to change the protocol to ABVD (doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine) due to toxicity. In this limited cohort from a single public center in Brazil, the use of 375 mg/m² of dacarbazine per cycle of the modified escalated BEACOPP protocol emerged as a safer strategy, maintaining treatment efficacy without compromising response in patients with advanced Hodgkin's lymphoma.

Background: Neuroblastomas account for 8-10 % of all cancer diagnoses among children. Most patients present with advanced, high-risk disease and 90 % are less than five years old. The burden of morbidity and mortality is high and is quantifiable by measures of health-related quality of life (HRQL). Measuring quality of life in under five-year-old children is a particular challenge that has been met with the development of the Health Utilities Pre-School (HuPS) instrument. Quality of life studies in children with cancer are scarce in low- and middle-income countries and are usually conducted at a single center, thus limiting any conclusions drawn. This pilot study aimed to assess the health-related quality of life of children at the time of diagnosis of high-risk neuroblastomas.

Method: This prospective cross-sectional multicentric study assessed the quality of life of children with high-risk neuroblastoma. The Health Utilities Pre-School instrument was applied to under five-year-olds, and the related Health Utilities Index Mark 3 instrument to over five-year olds.

Main results: Eleven patients participated in this study. There was a high burden of morbidity at diagnosis, often equating to severe disability, indicative of states of health with scores worse than being dead in two under five-year-old children.

Conclusion: The results of the current study will help to set research priorities for subsequent investigations and provide a basis to improve supportive care for children with high-risk neuroblastoma.

The first step in innovation is to identify a problem of real relevance and systematically address it to deliver a sophisticated and viable solution. Disruptive innovation is a process where technology, products, or services are transformed or replaced by a better innovative solution. This superiority must be perceived by users as being more accessible, simple, or convenient. Patient Blood Management (PBM) suggests the notion of the timely application of evidence-based medical and surgical concepts designed to maintain hemoglobin concentration, optimize hemostasis and minimize blood loss thus improving patient outcomes, that is, they are aimed at changing patient care, assisting healthcare professionals in disease treatment and cure as well as risk reduction. Thus, innovation in PBM is a new frontier to be pursued. The management of patient's blood and preparation for surgical procedures is an enormous challenge that helps minimize anemia and control blood loss during hospitalization, ensuring they are discharged in adequate clinical conditions. Until 2016, there was no standard definition or classification for the severity of intraoperative bleeding or hemostasis. The development of a PBM program when combined to the development of a bleeding scale such as the validated Intraoperative Bleeding (VIBe) Scale, represents a new solution that balances perioperative blood loss and more importantly, enables a critical cultural change which can be useful to help surgeons communicate anticipated hemostatic needs throughout a case and therefore enhance efficiency leading to better outcomes.

Introduction: Plasma cell quantification in bone marrow is important for diagnosis, prognosis, and treatment of plasma cell diseases. It can be performed by several methods such as aspiration, imprint and flow cytometry, and biopsy.

Objectives: To compare plasma cell counts at diagnosis of plasma cell diseases using different methods.

Methods: An observational study was carried out of laboratory results of adult patients with plasma cell diseases, who underwent aspiration, imprint cytology, flow cytometry (CD38, C138) and biopsy in a single institution between January 2015 and May 2021. The intraclass correlation coefficient was used to assess agreement between different methods with results stratified into three groups: <10%; 10-59% and ≥60% of infiltration.

Results: Sixty-seven cases were studied: 59.7% were men with a median age of 70 (range: 32-85) years. The diagnoses were multiple myeloma in 61%, gammopathy of undetermined significance in 25.4%, smoldering myeloma in 6% and other plasma cell dyscrasias in 7.6%. Less than 10% infiltration was found in 32 (47.7%), 35 (52.2%), 44 (65.7%) and 25 (37.3%) of patients, respectively by aspiration, imprint cytology, flow cytometry and biopsy. Infiltration ≥60% was detected in 7 (10.4%), 4 (6.0%), 2 (3.0%) and 21 (31.3%) cases, respectively. There was disagreement between the results in 37 (55.2%) of patients. Of these, 28 had greater infiltration in biopsies. The concordance (Kappa index) of biopsy with aspiration, imprint and flow cytometry was 0.501, 0.408 and 0.17; of aspiration with imprint and flow cytometry, it was 0.738 and 0.541 and between imprint and flow cytometry, it was 0.573%.

Conclusions: Only aspiration and imprint cytology results agreed. Biopsy showed greater infiltrations than the other methods, but aspiration, and imprint and flow cytometry provided additional data in the diagnosis and thus should also be performed.

Objective: Bacteremia is a serious complication in patients undergoing allogeneic hematopoietic stem cell transplantation. The aim of this study was to determine the frequency, epidemiological profile, and risk factors of bacteremia early after allogeneic hematopoietic stem cell transplantation.

Methods: An observational descriptive retrospective study was conducted in patients who received transplants between January 2016 and December 2021. Early bacteremia was defined as blood stream infection occurring between Day 0 and Day 100 after transplantation.

Results: Forty episodes of early bacteremia occurred in 36/245 transplanted patients. Fifteen episodes (37.5%) were due to gram-positive bacteria and 25 (62.5%) to gram-negative bacteria. The most frequent species isolated were coagulase negative staphylococci (CoNS) in gram-positive bacteremia (n = 8/15), and Klebsiella species (8/25) and Pseudomonas species (8/25) in gram-negative bacteremia. Twenty-nine episodes of bacteremia (72.5%) occurred during the first 30 days after transplantation with a median time of nine days (range: 0-90 days). Coagulase negative staphylococci were methicillin-resistant in 75% of cases, the only Staphylococcus aureus isolated was methicillin-resistant. All gram-positive bacilli were penicillin-resistant. Gram-negative bacilli were multidrug resistant in 61.5% of cases. In multivariate analysis, bone marrow as source of graft (p-value = 0.02) and cytomegalovirus reactivation (p-value = 0.02) were significantly associated with an increased risk of bacteremia. Mortality attributable to bacteremia was 2.8%. The one-year overall survival was not significantly different between those with and without bacteremia.

Conclusions: Bacteremia was more frequent within the first 30 days after transplantation indicating the crucial role of neutropenia. An increase in multidrug resistant gram-negative bacteremia was noted.

Background: Providing quality supportive therapy for children with cancer is essential to reduce the high mortality rates in low- and middle-income countries. Febrile neutropenia is the most common life-threatening complication of cancer in children. The objective of this study was to evaluate the long-term effectiveness of the 'Golden Hour' intervention in reducing the time to administer antibiotics and its impact on clinical outcomes in a Mexican hospital.

Methods: A comparative study of children with febrile neutropenia who attended the emergency department at the Hospital Universitario "Dr. José Eleuterio González" was performed between January 2017 and December 2022. In May 2019, this center joined the collaborative 'Mexico in Alliance with St. Jude' project. An adapted improvement program was developed based on the implementation of an algorithm comprising institutional guidance, supplies kit, standardization of sample processing, training of healthcare providers, and patient education. The time to antibiotic administration was compared with clinical outcomes between the historical control and post-intervention groups.

Results: A total of 291 patients were included, 122 in the pre-intervention period and 169 in the intervention period. Only 5.7 % of the pre-intervention group received the first dose of antibiotics within 60 min of presenting to the emergency department compared to 84.6 % in the intervention group (p-value <0.000). The median times to antibiotic administration in the pre-intervention and post-intervention periods were 269.4 and 50.54 min, respectively (p-value <0.000). Clinical deterioration and admission to the pediatric intensive care unit decreased significantly from 6.6 % to 2.3 % (p-value = 0.03).

Conclusions: Sustainability of the quality improvement project 'Golden Hour' in low- to mid-income countries demonstrated high effectiveness in reducing time to antibiotic administration among children with febrile neutropenia and improved clinical outcomes over three years of implementation.

The introduction of tyrosine kinase inhibitors has revolutionized the treatment of chronic myeloid leukemia vastly improving the prognosis and clinical outcome of most patients. It was estimated that approximately 40-50 % of patients treated with imatinib will require treatment with a second-generation or third-generation tyrosine kinase inhibitor to achieve an optimal response. The treatment duration, increased patient survival, and aging of the population receiving tyrosine kinase inhibitors raise concerns as to long-term toxicities, such as an elevated cardiovascular risk and a higher rate of comorbidities. Ponatinib is a highly potent third-generation tyrosine kinase inhibitor that was shown to be effective in patients with a wide range of ABL mutations, including T315I. The use of ponatinib is associated with significant vascular toxicity, including peripheral arterial occlusive disease, ischemic heart disease, cerebrovascular accidents, and venous thromboembolism. This review discusses the vascular toxicity of ponatinib and presents a comprehensive panel of tests for the evaluation of patients requiring ponatinib therapy. Moreover, the management of patients with cardiovascular risk factors who receive ponatinib is discussed. Finally, the strategy for establishing the optimal dose of ponatinib in patients with chronic myeloid leukemia is described.

Introduction: The scenario of adult patients with acute lymphoblastic leukemia treated in Brazil has not been well described yet.

Methods: Four hundred patients diagnosed with acute lymphoblastic leukemia from 1981 to 2019, registered in the Brazilian lymphoma and leukemia association (ABRALE) or their caregivers were interviewed by telephone to evaluate patient-reported perceptions of diagnosis, treatment and adverse effects.

Results: Overall, 203 were male with a mean age of 15.7 years and median follow-up of 6.2 years. Main presenting symptoms were fever (39 %), bleeding/ecchymosis (38 %), intense fatigue (30 %), and musculoskeletal pain (28 %). The proportion of patients diagnosed within one week of symptoms onset differed between public (17.9 %) and private healthcare (31.1 %; p-value = 0.019). Additionally, diagnostic difficulties were higher in public care: 35 % versus 22.6 % (p-value = 0.034). Only 36 patients were able to report their treatment protocols; from a list of eight reported protocols, the most common were the Brazilian Childhood Cooperative Group for Treatment of Acute Lymphoblastic Leukemia in Children (GBTLI - 10/27.8 %) and Berlin-Frankfurt-Münster (BFM - 8/22.2 %). Seventy patients (17.5 %) required treatment modification, 37.1 % due to severe adverse effects; 21.7 % received short treatment duration (≤6 months) and 16 % proceeded to allogeneic hematopoietic stem cell transplantation with 17/64 (27 %) reporting difficulties in this step, characterized as >3 months delay. Indication for transplantation was related to minimal residual disease and cranial radiotherapy; 41.7 % reported treatment-related adverse effects (range: 1-6), in particular: mood disorders (26.3 %), neurologic deficit (13.8 %), cognitive/memory impairment (12 %), and lung disease (15 %). Risk factors for adverse effects were age, indication of transplantation and living in a large city. Treatment disparities such as diagnostic and transplantation delays remain challenges in these patients.

Conclusions: Urgent interventions are needed to optimize healthcare and reduce adverse effects, especially in adolescent and young adult patients.