Early bacteremia following allogeneic hematopoietic stem cell transplantation without antibiotic prophylaxis: epidemiology and antimicrobial resistance.

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.

An approach to autologous stem cell mobilization: trying to define good mobilizers.

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.

A systematic review of clinical efficacy and safety of cell-based therapies in Alzheimer's disease.

There is presently no disease-modifying therapy for Alzheimer's Disease (AD), which is the most prevalent cause of dementia. Objective: This study aspires to estimate the efficacy and safety of cell-based treatments in AD. Methods: Observing the Joanna Briggs Institute (JBI) methods and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, a systematic search was accomplished in PubMed, Medical Literature Analysis and Retrieval System Online (Medline, via Ovid), Embase; Cochrane, and Cumulative Index of Nursing and Allied Health Literature - CINAHL (via EBSCO) databases up to June 2023. The relevant clinical studies in which cell-based therapies were utilized to manage AD were included. The risk of bias was evaluated using the JBI checklists, based on the study designs. Results: Out of 1,014 screened records, a total of five studies with 70 individuals (including 59 patients receiving stem cells and 11 placebo controls) were included. In all these studies, despite the discrepancy in the origin of stem cells, cell density, and transplant site, safety goals were obtained. The intracerebroventricular injection of adipose-derived stromal vascular fraction (ADSVF) and umbilical cord-derived mesenchymal stem cells (UC-MSCs), the intravenous injection of Lomecel-B, and the bilateral hippocampi and right precuneus injection of UC-MSCs are not linked to any significant safety concerns, according to the five included studies. Studies also revealed improvements in biomarkers and clinical outcomes as a secondary outcome. Three studies had no control groups and there are concerns regarding the similarity of the groups in others. Also, there is considerable risk of bias regarding the outcome assessment scales. Conclusion: Cell-based therapies are well tolerated by AD patients, which emphasizes the need for further, carefully planned randomized studies to reach evidence-based clinical recommendations in this respect.

Atualmente, não há terapia modificadora da doença para a doença de Alzheimer (DA), que é a causa mais prevalente de demência. Objetivo: Este estudo teve como objetivo estimar a eficácia e segurança dos tratamentos baseados em células na DA. Métodos: Observando os métodos do JBI e a declaração PRISMA, uma busca sistemática foi realizada nas bases de dados PubMed, Medical Literature Analysis and Retrieval System Online ­ Medline (via Ovid), Embase, Cochrane e CINAHL (via EBSCO) até junho de 2023. Foram incluídos os estudos clínicos relevantes nos quais terapias baseadas em células foram utilizadas para gerenciar a DA. O risco de viés foi avaliado utilizando os checklists do JBI, com base nos desenhos dos estudos. Resultados: Dos 1.014 registros examinados, foi incluído um total de cinco estudos com 70 indivíduos (incluindo 59 pacientes que receberam células-tronco e 11 controles de placebo). Em todos esses estudos, apesar da discrepância na origem das células-tronco, densidade celular e local de transplante, os objetivos de segurança foram alcançados. A injeção intracerebroventricular de ADSVF e UC-MSCs, a injeção intravenosa de Lomecel-B e a injeção bilateral dos hipocampos e precuneus direito de UC-MSCs não estão relacionadas a quaisquer preocupações significativas de segurança, de acordo com os cinco estudos incluídos. Os estudos também revelaram melhorias nos biomarcadores e resultados clínicos como um desfecho secundário. Três estudos não tinham grupos de controle e há preocupações quanto à semelhança dos grupos em outros. Além disso, há um risco considerável de viés em relação às escalas de avaliação de desfechos. Conclusão: As terapias baseadas em células são bem toleradas por pacientes com DA, o que enfatiza a necessidade de mais estudos randomizados cuidadosamente planejados para alcançar recomendações clínicas baseadas em evidências.

Analysis of apheresis outcomes in a cohort of Chilean patients treated with autologous stem cell transplantation: A single center real-world experience.

Adequate stem cell harvesting is required for autologous hematopoietic transplantation. In deficient mobilizer patients, the collection of stem cells can be challenging because of the impossibility of achieving satisfactory CD34 cell counts with GCSF + - chemotherapy. Plerixafor is a potent and expensive drug that promotes the release of stem cells from the medullary niche to the peripheral blood and allows satisfactory harvests. We performed a retrospective analysis of 370 patients with myeloma and lymphoma harvested at our institution. 99 % of patients achieved satisfactory apheresis using Plerixafor in 45 %. Satisfactory harvests were obtained in patients mobilized with GCSF or plerixafor. In patients who used plerixafor, it was necessary to perform fewer apheresis procedures (P = 0.05). In multivariate analysis, the only factor that predicted the need for plerixafor was the presence of less than 30,000 CD34 / ul on the day of apheresis (OR 0.3. p < 0.001). Since we adopted the plerixafor protocol guided by CD34 counts, the number of patients with harvest failure has decreased. In conclusion, the rational and standardized use of plerixafor favors satisfactory harvest in patients who require autologous transplantation in South-American patients.

Immune reconstitution in rheumatic disease patients after autologous hematopoietic stem cell transplantation.

High-dose conditioning chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) in systemic sclerosis (SSc), lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA), or rheumatoid arthritis (RA) was shown to allow eradication of the abnormal autoimmune compartment and "resetting" of the immune response, all contributing to the observed clinical response. A subset of patients has less favorable clinical outcomes after transplant, as auto-reactive memory cells may escape depletion or the regulatory immune network renewal be incomplete. Conditioning permits non-specific abrogation of the autoreactive T- and B-cell responses and eliminates the autoimmune repertoire. Re-infusion of autologous hematopoietic stem cells shortens the leucopenia duration and contributes to both hematologic and immune reconstitutions. After engraftment and neutrophil recovery, the first phase of immune reconstitution is characterized by clonal expansion of residual memory lymphocytes in response to early antigen stimulation and/or lymphopenia-induced proliferation. Renewal of the immune repertoire follows through exportation of de novo generated thymic-derived naïve T cells and bone marrow-derived naïve B cells, expansion of the regulatory network, and a shift from a pro-inflammatory to a more auto-tolerant profile. We review the well-described mechanisms of immune resetting and their relative contribution to disease control according to the transplantation regimen and the underlying rheumatic diseases.

Newborn screening for inborn errors of immunity: The status worldwide.

Background: Newborn screening (NBS) for the early detection of inborn errors of immunity (IEI) has been implemented in a few countries. The objective of this study was to verify the situation and define obstacles to the implementation of NBS worldwide. Methods: A questionnaire was developed by the Inborn Errors of Immunity Committee of the World Allergy Organization (WAO) with 17 questions regarding NBS for IEI in the physician's workplace, NBS test type, problems hindering NBS implementation, reimbursement for IEI therapy, presence of a national IEI registry, referral centers, molecular diagnosis, hematopoietic stem cell transplantation centers, gene therapy, and immunoglobulin replacement therapy. The survey was sent by email once a week to doctors and others associated with WAO and the main immunology societies worldwide as a Google Form™ to be completed during September and October 2021. Results: Two hundred twenty-nine questionnaires were completed, of which 216 (94.3%) were completed by physicians. One hundred seventy-six (76.8%) physicians were both allergists and immunologists. The agreement between allergists/immunologists and non-allergists/non-immunologists for the question "Is there NBS for IEI in the country you work in?" was good (κ = 0,64: 95% CI 0.55-0.69). Ninety-eight (42.8%) participants were from Latin America, 35 (15.3%) from North America, 29 (12.6%) from Europe, 18 (7.9%) from Africa, 44 (19.2%) from Asia, and 5 (2.2%) from Oceania. More than half the participants (n = 124, 54.2%) regularly treated patients with IEI, followed by occasional treatment (n = 77, 33.6%), or never (n = 28, 12.2%). Of the respondents, 14.8% reported that their countries performed NBS for IEI, whereas 42.2% reported their countries did not. T-cell receptor excision circles was the most widely used technique in some countries, with 75 (59.9%) for the diagnosis of NBS for IEI, followed by combined use with kappa deleting-recombination excision circles. Only 13 participants (10.3%) underwent neonatal exon screening in their respective countries. Financial and technical issues were among the major obstacles to the implementation of NBS for IEI. Conclusions: This pilot study showed that few countries have implemented NBS for IEI, despite the presence of immunology referral centers and the availability of hematopoietic stem cell transplantation and intravenous immunoglobulin replacement therapy. The findings highlight the difficulties, mainly financial and technical, hindering wide application of NBS. Sharing experiences, technologies, and resources at the international level can help overcome these difficulties.

Photobiomodulation minimizes taste changes during hematopoietic cell transplantation: A randomized clinical trial.

Prevention and treatment protocols for taste changes observed during hematopoietic cell transplantation (HCT) are not well-established. The purpose of this study was to assess the efficacy of photobiomodulation (PBM) in relieving taste changes and preventing lingual papillae atrophy. HCT patients received PBM (n = 42) on the tongue dorsum using an InGaAIP laser (660 nm, 100 mW, 1.1 W/cm2, 8.8 J/cm2). During the HCT conditioning (T0), severe neutropenia (T1), and after neutrophil engraftment (T2), taste acuity for sweet, bitter, sour, and salty solutions, and clinical appearance of lingual papillae were compared with those of a placebo group (n = 43). PBM significantly reduced hypogeusia, ageusia, and parageusia at T1 and T2, and also successfully prevented papillae atrophy during all the analyzed HCT periods. In conclusion, PBM enhanced taste acuity during HCT. The decrease in papillae atrophy indicated a potential regenerative effect of this therapy on tongue mucosa.

Transición a la medicina del adulto en sobrevivientes de un trasplante alogénico de células progenitoras hematopoyéticas / Transition to adult medicine in survivors of allogeneic hematopoietic stem cell transplantation

Los sobrevivientes de un trasplante alogénico de células progenitoras hematopoyéticas (TACPH) pediátrico presentan alto riesgo de padecer problemas de salud. Debido a esta vulnerabilidad, la continuidad del cuidado impacta en su pronóstico y la transición a la medicina del adulto (TMA) es un proceso clave. Objetivo: Evaluar el proceso actual de TMA de los receptores de TACPH en nuestro hospital. Métodos: Diseño: observacional retrospectivo y prospectivo. Población: todos los pacientes (p) que realizaron su TMA desde enero/2022 a marzo/2023. Instrumentos: entrevista personal; material escrito; resumen de historia clínica; escalas TRAQ 5.0 (transición), PedsQL 4.0 (CVRS) y Lansky (funcionalidad); elección de estrategias de seguimiento según complejidad y requerimientos; contacto con profesionales de adultos; entrevista telefónica luego de 6 meses posTMA; red conformada. Resultados: 36p completaron la TAM (33 presencial, 3 virtual). Edad m19 años (m6 años de seguimiento), 70% del interior del país, 58% TACPH por enfermedad maligna, 64% TACPH familiar. A la TMA: antecedente EICHc 50%, segunda enfermedad maligna 2%, compromiso órganos 75% (m2/p, r0-8, mayormente endocrinológicas, oculares y neurológicas), 94% Lansky ≥80 (r50-100), PedsQL m82 (27% ≤75), TRAQ m3.4 (r1.7- 4.8). Derivación: todos los p cubrían sus necesidades (30% en centros de alta complejidad o expertos en THA) pero 3p debieron readecuar las estrategias, 5p presentaban complicaciones en actividad o necesidad de pronta resolución. Contacto posterior: 30/33p continuaban seguimiento, 3p pudieron retomarlo, 9p nuevas complicaciones/tratamientos. Red: 20 profesionales/instituciones. Conclusiones: Se refuerza la necesidad y utilidad de un proceso de TMA tanto formal como personalizado según necesidades individuales de los pacientes con TACPH (AU)

Pediatric allogeneic hematopoietic stem cell transplant (HSCT) survivors are at high risk for health problems. Because of this vulnerability, continuity of care impacts their prognosis and transition to adult medicine (TAM) is a key process. Objective: To evaluate the current process of TAM of HSCT recipients in our hospital. Methods: A retrospective and prospective observational study was conducted. The population included all patients (p) who underwent TAM from January 2022 to March 2023. Instruments used included personal interviews, written materials, medical history summaries, the TRAQ 5.0 (transition), PedsQL 4.0 (HRQoL), and Lansky (functionality) scales. Follow-up strategies were chosen according to complexity and requirements, with contact established with adult professionals and a telephone interview conducted six months post-TAM in an established network network. Results: 36p completed TAM (33 face-to-face, 3 online). Mean age was 19 years (with a mean of 6 years of follow-up); 70% were from the provinces of the country, 58% underwent HSCT due to malignant disease, 64% had familial HSCT. At TAM: 50% had a history of GVHD, 2% had a second malignant disease, and 75% had organ involvement (mean of 2 per patient, ranging from 0 to 8, mostly endocrinological, ocular, and neurological), 94% had Lansky ≥80 (range, 50-100), mean PedsQL was 82 (27% ≤75), mean TRAQ was 3.4 (range, 1.7-4.8). Referral needs were met for all patients (30% in tertiary-level centers or with experts in allogeneic HSCT), although 3 patients had to readjust strategies, and 5 had complications requiring prompt resolution. In subsequent contact, 30 out of 33 patients continued follow-up, 3 resumed it, and 9 experienced new complications or treatments. The network included 20 healthcare providers/institutions. Conclusions: This study reinforces the need for and usefulness of a formal and personalized TAM process according to the individual needs of patients with HSCT (AU)

Increasing access to transplantation through telemedicine and patient navigation.

BACKGROUND: Hematopoietic cell transplantation (HCT) is a promising treatment for hematological diseases, yet access barriers like cost and limited transplant centers persist. Telemedicine-based patient navigation (PN) has emerged as a solution. This study presents a cost-free PN telemedicine clinic (TC) in collaboration with the National Marrow Donor Program. AIM: to assess its feasibility and impac on HCT access determined by the cumulative incidence of transplantation. METHODS: In this single-center cohort study, patients of all ages and diagnoses referred for HCT participated. Two transplant physician-navigators established patient relationships via video calls, collecting medical history, offering HCT education and recommending pretransplant tests. The analysis involved descriptive statistics and intent-to-transplant survival assessment. RESULTS: One hundred and three patients were included of whom n = 78 were referred for allogeneic HCT (alloHCT), with a median age of 28 years. The median time from initial contact to the first consult was 5 days. The cumulative incidence of transplantation was 50% at 6 months and 61% at 12 months, with varying outcomes based on HCT type. Notably, 49 patients were not transplanted, primarily due to refractory disease, progression or relapse (57.1%). Autologous HCT candidates and physician referrals were correlated with higher transplant success compared to alloHCT candidates and patients who were not referred by a physician. CONCLUSION: Our pretransplant TC was feasible, facilitating access to HCT. Disease relapse posed a significant barrier. Enhancing timely physician referrals should be a focus for future efforts.

Evaluation of blood cell count using an automatic hematology analyzer to optimize collection of peripheral blood progenitor cells by leukapheresis.

BACKGROUND: Autologous stem cell transplantation is a treatment modality for several diseases. Prediction of successful mobilization may be useful to optimize hematopoietic stem cell collection. STUDY DESIGN AND METHODS: This was a retrospective study with data from transplantation candidates between September 2015 and December 2021 being analyzed. The medical record of each patient was reviewed to mine mobilization information. The laboratory data analyzed were CD34+ cell enumeration and pre-collection peripheral blood cell count. The primary outcome, good mobilization, was defined as a CD34+ cell count ≥20/µL. RESULTS: This study included 807 patients. Increased patient weight, low mean corpuscular volume, high nucleated red blood cells, peripheral blood mononuclear cell and immature granulocyte counts were significantly associated with good mobilization. In addition, patients diagnosed with multiple myeloma were two times more likely to be good mobilizers than patients with lymphoma. The model was applied to a validation set to identify patients who underwent apheresis (CD34+ cell count ≥10 µL), resulting in a sensitivity of 69 %, a specificity of 95 %, positive predictive value of 98 %, and a negative predictive value of 50 %. CONCLUSION: Success in mobilization was greater in patients who underwent the first mobilization cycle and who had a diagnosis of multiple myeloma. Furthermore, higher body weight, and nucleated red blood cells, immature granulocytes and mononuclear cell counts, as well as low mean corpuscular volumes, were associated with successful mobilization.

Microcosting analysis of haematopoietic stem cell transplantation and chemotherapy with intermediate doses of cytarabine in the treatment of acute myeloid leukaemia.

BACKGROUND: Acute myeloid leukaemia (AML) is considered a costly disease. Depending on the risk stratification, the patient may receive consolidation with cycles of intermediate doses of cytarabine, auto-HSCT or allo-HSCT according to availability in each service and the availability of a compatible donor. Literature data indicate that safety and effectiveness do not differ between consolidation therapy with intermediate-dose cytarabine or auto-HSCT, and so the cost can help physicians and health managers in their choice. METHOD: The cost of the second consolidation was compared in 18 to 60-year-old patients with de novo AML who were included in the International Consortium of Acute Myeloid Leukaemia (ICAML) protocol. Patients treated with auto-HSCT or intermediate doses of cytarabine (IDAC) were analysed during four years using the microcosting methodology. RESULTS: The mean costs for auto-HSCT and IDAC were BRL$ 34,900.95 (range: 23,611.36-41,229.59) and 15,231.64 (range: 6,546.36-23,253.53), respectively. The mean duration of in-hospital stay was 88.4 (93-133) and 94 (50-153) days, respectively. The mean cost of the four cycles of treatment was BRL$ 114.212,78 for auto-HSCT and BRL$ 121.980,93 for the chemotherapy group. Regardless of the type of treatment, the input that had the greatest economic impact was hospital admission, mainly due to infections. CONCLUSION: Auto-HSCT had a lower average cost per patient and hospitalization rate than chemotherapy.

Therapeutic Choices in Patients with Ph-Positive Chronic Myelogenous Leukemia In Mexico in the Era of Tyrosine Kinase Inhibitors: Stem Cell Transplantation or Tyrosine Kinase Inhibitors? Fifteen Years Later.

Background: Chronic myelogenous leukemia is a neoplastic proliferation of the granulocytic series. In Mexico, chronic myelogenous leukemia accounts for approximately 10% of all leukemias. Tyrosine-kinase inhibitors are considered front-line therapy in high-income countries, whereas allogeneic hematopoietic stem cell transplantation is a recognized therapeutic approach, mainly in low- and middle-income countries. Objective: To analyze the overall survival of persons with chronic myelogenous leukemia who have received tyrosine-kinase inhibitors or allogeneic hematopoietic stem cell transplantation in a medical center, since 1994, and briefly discuss the current indications of these treatments in the tyrosine-kinase inhibitors era. Methods: We retrospectively analyzed all patients with a diagnosis of chronic myelogenous leukemia treated in a medical center between 1994 and 2023; subsets of individuals who received an allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors therapy as first-line treatment were analyzed. Results: 60 persons with chronic myelogenous leukemia were treated with allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors: 35 received an allogeneic hematopoietic stem cell transplantation, whereas 25 were given tyrosine-kinase inhibitors. All patients who underwent an allogeneic hematopoietic stem cell transplantation engrafted successfully, and the procedure was completed on an outpatient basis in most cases (29/35). The median survival in allogeneic hematopoietic stem cell transplantation was 78.3 months (CI 95%: 0-205.6) and in persons given tyrosine-kinase inhibitors the median was not reached. Conclusion: Tyrosine-kinase inhibitors were significantly superior to allogeneic hematopoietic stem cell transplantation in prolonging the overall survival of persons with chronic myelogenous leukemia in our single institution experience.

ST2 and Reg3α: Can they predict aGvHD, steroid refractoriness and transplant-related mortality in pediatric patients after HSCT?

BACKGROUND/AIM: There are several complications of hematopoietic stem cell transplantation. Without any doubt, most important of these is aGvHD that increases transplant-related mortality. The aim of this study is to investigate whether ST-2 and Reg3α levels measured at an early stage in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation can be individual biomarkers identifying future GvHD and predicting treatment response. MATERIALS AND METHODS: From January 2019 to January 2021, 27 patients undergoing hematopoietic stem cell transplantation for primary immunodeficiency or hematopoietic diseases formed the study group. During their follow-up, the patients were classified into two groups as those developing and those not developing aGvHD. Nineteen healthy volunteers from a similar age group who needed their blood samples drawn for other reasons and who did not have any history of chronic disease, infection or medication use formed the control group. Blood samples of patients scheduled to have allogeneic HSCT were obtained before the administration of the preparative regimen, on Day +7 post-transplant and on the day of diagnosis if they developed aGvHD. Serum samples were stored at -20ºC until the day of processing. ST2 and Reg3α levels were measured using the ELISA method. RESULTS: For patients who developed aGvHD (n = 13), ST2 levels obtained before the transplantation, on Day +7 post-transplant and on the day of aGvHD diagnosis (in patients developing GvHD) were significantly higher compared to the healthy Control Group (p-value <0.05). As regards to the samples obtained on the same days, ST2 levels did not differ significantly among patients who developed and those who did not develop GvHD (n = 14; p-value >0.05). ST2 levels of samples obtained on the days that acute skin and gastrointestinal tract GvHD developed did not differ significantly between these two groups (p-value >0.05). Reg3α levels of the pre-transplant samples, on Day +7 after the transplantation and on the day of aGvHD diagnosis did not show any difference between any of the groups (p-value >0.05). As only two patients died after transplantation, thus correlation of ST2 and Reg3α levels with transplant-related mortality could not be proven. CONCLUSION: The results of this study suggest that ST2 and Reg3α levels are neither diagnostic nor prognostic or predictive biomarkers of aGvHD, steroid resistance or transplant-related mortality in pediatric patients. This study can be regarded as a pilot study because of the small patient population; more research involving a larger patient population is required.

COVID-19 surveillance in a bone marrow transplantation unit: experience from a Brazilian tertiary-care teaching hospital.

PURPOSE: In this work, we aimed to describe the strategy of the weekly SARS-CoV-2 RT-PCR surveillance program that was implemented in our bone marrow transplantation (BMT) unit. METHODS: Our unit performed SARS-CoV-2 RT-PCR before admission and then weekly during hospitalization even if the patient was asymptomatic. From May 2021 to May 2022, we collected data from all patients that were admitted in the BMT unit to perform transplantation. The total of SARS-CoV-2 RT-PCR performed and the positive rate were described. RESULTS: During the study period, 65 patients were admitted for HSCT. A total of 414 SARS-CoV-2 RT-PCR were performed. Two cases were detected (positivity rate, 0.48%). After the positive test, both patients were isolated outside the BMT unit. CONCLUSION: We postulate that diagnosing these patients and isolating them outside the transplantation unit may have prevented secondary symptomatic cases.

Severe acute respiratory syndrome coronavirus 2 infection in hematopoietic stem cell transplant recipients in Mexico City.

BACKGROUND: Hematopoietic stem cell transplant (HSCT) recipients are among patients with highest risk of adverse coronavirus disease 2019 (COVID-19) outcomes. OBJECTIVE: We compared clinical outcomes in post-HSCT patients with COVID-19 before and during the Omicron period. STUDY DESIGN: This was a retrospective study including patients post-HSCT with severe acute respiratory syndrome coronavirus 2 infection from April 2020 to March 2023 at Instituto Nacional de Cancerología, Mexico City. We describe their clinical characteristics and report the variables associated with severe clinical disease, hospitalization, and death. RESULTS: Fifty-three patients were included; 31 (58.5%) from the pre-Omicron period and 22 (41.5%) from the Omicron period. Median age was 42-years old (interquartile range 26-53), and 31 patients (59%) were men. Only four patients (16%) had received a vaccine prior to COVID-19 diagnosis in the pre-Omicron period versus 20 (91%) in the Omicron period (p < 0.001). COVID-19 severe cases were more common before Omicron: seven patients (23%) versus two patients (9%). Only one patient (3%) received an antiviral in the pre-Omicron period compared to 11 patients (50%) during the Omicron period (p < 0.01). COVID-19-associated mortality was almost double in the pre-Omicron period (16% vs. 9%, p = 0.6). CONCLUSIONS: This study reports patients with a high proportion of severe outcomes during the first 2 years of the pandemic. Outcomes improved during Omicron with better access to vaccines and antivirals and no in-hospital cases. Variables associated with worse outcomes were similar to other reports. Strengthening infection control measures in the hospital and better access to preventive strategies and therapeutic options are mandatory in these high-risk patients.

Therapeutic Choices in Patients with Ph-Positive Chronic Myelogenous Leukemia In Mexico in the Era of Tyrosine Kinase Inhibitors: Stem Cell Transplantation or Tyrosine Kinase Inhibitors? Fifteen Years Later

ABSTRACT Background: Chronic myelogenous leukemia is a neoplastic proliferation of the granulocytic series. In Mexico, chronic myelogenous leukemia accounts for approximately 10% of all leukemias. Tyrosine-kinase inhibitors are considered front-line therapy in high-income countries, whereas allogeneic hematopoietic stem cell transplantation is a recognized therapeutic approach, mainly in low- and middle-income countries. Objective: To analyze the overall survival of persons with chronic myelogenous leukemia who have received tyrosine-kinase inhibitors or allogeneic hematopoietic stem cell transplantation in a medical center, since 1994, and briefly discuss the current indications of these treatments in the tyrosine-kinase inhibitors era. Methods: We retrospectively analyzed all patients with a diagnosis of chronic myelogenous leukemia treated in a medical center between 1994 and 2023; subsets of individuals who received an allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors therapy as first-line treatment were analyzed. Results: 60 persons with chronic myelogenous leukemia were treated with allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors: 35 received an allogeneic hematopoietic stem cell transplantation, whereas 25 were given tyrosine-kinase inhibitors. All patients who underwent an allogeneic hematopoietic stem cell transplantation engrafted successfully, and the procedure was completed on an outpatient basis in most cases (29/35). The median survival in allogeneic hematopoietic stem cell transplantation was 78.3 months (CI 95%: 0-205.6) and in persons given tyrosine-kinase inhibitors the median was not reached. Conclusion: Tyrosine-kinase inhibitors were significantly superior to allogeneic hematopoietic stem cell transplantation in prolonging the overall survival of persons with chronic myelogenous leukemia in our single institution experience. (Rev Invest Clin. 2024;76(2):91-6)

Intracranial non-germinomatous germ cell tumors in children and adolescents: how can the experience from an uppermiddle-income country contribute to the worldwide effort to improve outcomes?

Background: Non-germinomatous germ cell tumors (NGGCT) accounts for one third of intracranial GCT. While the germinoma group have an excellent overall survival, the standard of practice for children with NGGCT is still under evaluation. Aims: Describe the results of the of the Brazilian consortium protocol. Methods: Since 2013, 15 patients with a diagnosis of NGGCT by histopathology and/or serum/cerebrospinal fluid (CSF) tumor markers, ßHCG >200mlU/ml and/or positive alpha-fetoprotein were treated with neoadjuvant chemotherapy with carboplatin, cyclophosphamide and etoposide followed by ventricular radiotherapy (RTV) of 18Gy with boost (32Gy) to the primary site. Metastatic patients underwent craniospinal irradiation (CSI) and "slow responders" to the four initial cycles of CT, to autologous stem cell transplantation (ASCT) followed by CSI. Results: Mean age, 13.1 years. Thirteen males. Primary sites: pineal (n=12), suprasellar (n=2) and bifocal (n=1). Four patients were metastatic at diagnosis. Eight patients had CSF and/or serum alpha-fetoprotein levels > 1,000ng/ml. Tumor responses after chemotherapy demonstrated complete in six cases and partial in seven, with "second-look" surgery being performed in five cases, and two patients presenting viable lesions being referred to ASCT. The main toxicity observed was hematological grades 3/4. Two patients with metastatic disease, one with Down Syndrome and AFP > 1,000ng/ml and the other with choriocarcinoma and pulmonary metastases, developed progressive disease resulting in death, as well as two other patients without evidence of disease, due to endocrinological disorders. Event-free and overall survival at 2 and 5 years were 80% and 72.7%, respectively, with a mean follow-up of 48 months (range, 7-107). Conclusions: Despite the small number of patients, in our series, treatment with six cycles of chemotherapy and RTV with focal boost for localized disease (n=11) and ACST for identified slow responders (n=2) seem to be effective strategies contributing to the overall effort to improve outcomes of this group of patients.

Sarcopenia in children and adolescents submitted to hematopoietic stem cell transplantation.

BACKGROUND: Sarcopenia, characterized by decreased muscle mass, strength, and function, is associated with adverse outcomes. The prevalence of sarcopenia and the effect of the inflammatory response on muscle strength loss in children undergoing hematopoietic stem cell transplantation (HSCT) are unknown. This study aimed to estimate the prevalence of sarcopenia on admission and its associated clinical factors in children and adolescents undergoing HSCT and to determine the extent to which the systemic inflammatory response during hospitalization affects muscle strength. METHOD: This was a prospective study of patients aged 6-18 years old undergoing HSCT. The outcome variables were the prevalence of sarcopenia on admission (loss of strength and skeletal muscle mass) and the loss of handgrip strength during hospitalization. Potential explanatory variables included age, sarcopenia, nutritional status and systemic inflammation as measured by serum C-reactive protein, albumin and ferritin concentrations. RESULTS: Eighty patients with a mean age of 11.5 (± 3.5) years were included. The main diagnoses were acute lymphocytic leukemia, acute myeloid leukemia and aplastic anemia. Eleven percent of patients had sarcopenia upon admission. Female sex, sarcopenia on admission (ß coefficient: 0.70; 95% CI: -1.30 to -0.12; p-value = 0.018) and serum C-reactive protein concentration (ß coefficient: -0.10; 95% CI: -0.16 to -0.04; p-value = 0.001) were associated with handgrip strength loss from admission to 14 days after HSCT. CONCLUSION: Sarcopenia on admission and the degree of systemic inflammatory response are associated with decreased handgrip strength during hospitalization in pediatric patients undergoing HSCT. Further studies using the same criteria for diagnosing sarcopenia are required to enhance our understanding of these relationships.