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.

Lesson learned in pediatric haploidentical transplantation in a low-resource environment: delivering melphalan IV and using low dose radiation reduce graft failure.

Objectives: Primary graft failure (pGF) after hematopoietic stem-cell transplant is associated with considerable morbidity and mortality. The incidence in haplo-HSCT has been reported to be between 0% and 30%. In 2018, we identified a pGF incidence of 35% in our pediatric haplo-HSCT recipients with hematologic malignancies, which motivated us to enact changes to the conditioning regimen.Methods: We performed a single-center prospective, pre-post study of consecutive patients under 16 years with hematologic malignancies, from January 2015 to December 2022 who received a haplo-HSCT. Twenty-six pediatric patients received a haplo-HSCT before September 2018 (G1) and 36 patients after (G2). The main conditioning regimen for G1 was myeloablative with Flu/Cy/Bu, and for G2 the main regimen was reduced intensity Flu/Cy/Mel/TBI2.Results: Nine patients (35%) in G1 had primary graft failure, while in G2 there were no patients with pGF. The median follow-up for G1 was 15.9 months, and for G2 was 24.8 months, with an estimated overall survival at 12 months of 63% (95% CI 47-76) versus 85% (95% CI 73-93), and at 24 months of 47% (95% CI 31-64) versus 70% (95% CI 54-82) respectively (p = .007).Conclusion: After September 2018 conditioning regimen modifications were implemented with the objective of reducing primary failure, consisting mainly of switching from busulfan to melphalan as the alkylating agent of choice, and adding, when clinically possible TBI. Primary failure has been significantly reduced in our institution since then.

Real-world practice of acute leukemia intrathecal chemotherapy administration: A Mexican nationwide survey

ABSTRACT Introduction: Intrathecal chemotherapy is a mainstay component of acute lymphoblastic leukemia treatment. In Mexico, there is a considerable practice variability in aspects, such as the manner of preparation and the administration technique. Objective: Our objective was to describe the different techniques used for the application of ITC and review the existing recommendations in the literature. Method: A cross-sectional, nationwide survey study was conducted by an electronic questionnaire sent to hematologists and oncologists in Mexico. We collected demographic data, personal experience, intrathecal chemotherapy techniques, drug preparation and postprocedural conduct. Results: We received 173 responses. Twenty percent had an anesthesiologist administering sedation and pain management. The platelet count considered safe was 50 × 109/L in 48% of the participants. In 77% (n = 133) of the cases, the conventional needle with stylet used was, 49% did not receive any added diluent in the intrathecal chemotherapy and only 42% were recommended to rest in a horizontal position for more than 30 min. Conclusion: We identified a considerable variation in the administration of intrathecal chemotherapy across the hematologists in Mexico. We discuss the implications and opportunities in reducing the variation in our setting, highlighting the unmet need to establish guidelines that should be evaluated by the Mexican professional society to produce a position paper regarding practice standardization.

Mucopolysaccharidosis Type I in Mexico: Case-Based Review.

INTRODUCTION: Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease present in 1:100,000 newborns. Variants in the IDUA (alpha-L-iduronidase) gene decrease the enzyme activity for glycosaminoglycans metabolism. MPS I patients exhibit clinical manifestations that fall on the Hurler, Hurler-Scheie, and Scheie syndrome spectrum. CASE PRESENTATION: We present a male Mexican patient with respiratory exacerbations requiring recurrent hospitalizations. He showed macrocephaly, coarse facies, hepatomegaly, umbilical hernia, and dorsal kyphosis. The sequencing of the IDUA gene revealed the following genotype: c.46_57del12/c.1205G>A. He received combined therapy with hematopoietic stem cell transplantation and enzyme replacement. Mexican case reports were analyzed to estimate the prevalence of the associated genetic variants. CONCLUSION: Despite the challenges of managing this rare disease in Mexico, our patient benefited from the combined therapy. The discrete clinical manifestations and prompt evaluation by a geneticist were crucial in establishing a diagnosis, enabling an early intervention by a multidisciplinary team. The combination of ERT before and after HSCT provided health benefits to our patient.

Real-world practice of acute leukemia intrathecal chemotherapy administration: A Mexican nationwide survey.

INTRODUCTION: Intrathecal chemotherapy is a mainstay component of acute lymphoblastic leukemia treatment. In Mexico, there is a considerable practice variability in aspects, such as the manner of preparation and the administration technique. OBJECTIVE: Our objective was to describe the different techniques used for the application of ITC and review the existing recommendations in the literature. METHOD: A cross-sectional, nationwide survey study was conducted by an electronic questionnaire sent to hematologists and oncologists in Mexico. We collected demographic data, personal experience, intrathecal chemotherapy techniques, drug preparation and postprocedural conduct. RESULTS: We received 173 responses. Twenty percent had an anesthesiologist administering sedation and pain management. The platelet count considered safe was 50 × 109/L in 48% of the participants. In 77% (n = 133) of the cases, the conventional needle with stylet used was, 49% did not receive any added diluent in the intrathecal chemotherapy and only 42% were recommended to rest in a horizontal position for more than 30 min. CONCLUSION: We identified a considerable variation in the administration of intrathecal chemotherapy across the hematologists in Mexico. We discuss the implications and opportunities in reducing the variation in our setting, highlighting the unmet need to establish guidelines that should be evaluated by the Mexican professional society to produce a position paper regarding practice standardization.

Rituximab desensitization in pediatric acute lymphoblastic leukemia with severe anaphylaxis.

INTRODUCTION: Hypersensitivity reactions (HSRs) to rituximab occur during the first infusion in 29% to 40% of patients. Commonly, these hypersensitivity reactions are the result of a release of cytokines, although IgE mediated reactions have also been reported. CASE REPORT: A 7-year-old female patient with diagnosis of CD-20 positive acute lymphoblastic B-cell leukemia was included in a pilot study that consisted of two doses of rituximab treatment in the induction to remission phase by the pediatric hematology service; 30 minutes after the first administration of 300 mg of rituximab the patient started with generalized rash, nausea, vomiting, tachycardia, dyspnea, foreign body sensation in throat, oxygen desaturation until 89% and hypotension; therefore, the infusion of rituximab was suspended, and intramuscular epinephrine was administered as well as intravenous hydrocortisone and chlorphenamine and supplemental oxygen supply with adequate resolution of symptoms. MANAGEMENT & OUTCOME: Intradermal skin testing with rituximab at the concentration 1 mg/ml (dilution 1:10), was positive. Desensitization to rituximab was indicated by our service with 4 bags - 16 steps protocol with an initial concentration dose of 1/1,000 of the total dose. The patient was premedicated 1 hour prior with intravenous chlorphenamine, methylprednisolone and ondansetron. Intravenous prophylactic fluids with normal saline solution were administered during the infusion. The procedure was carried out with close monitoring of vital signs in a course of 6.67 hours, without presenting hypersensitivity reactions. DISCUSSION: HSR to rituximab may be induced by the activation of mast cells and basophils. Desensitization protocols are developed when there is no alternative drug for the underlying condition.

COVID-19 en el paciente pediátrico / COVID-19 in the pediatric patient

Resumen Este documento fue preparado (en junio de 2020) por y para los profesionales médicos (clínicos y proveedores de salud), y está disponible públicamente para propósitos de recomendaciones relacionada con pacientes pediátricos y enfermedad por coronavirus 2019 (COVID-19). Según datos disponibles hasta la fecha, los niños de todas las edades pueden contraer la COVID-19; sin embargo, tienen mejor pronóstico que los adultos, siendo pocos los casos graves reportados, y los casos leves se recuperan en 1-2 semanas después del inicio de la enfermedad. El objetivo de este documento es aportar peculiaridades que consideramos importantes para el diagnóstico y tratamiento. Debido a los cambios en la actual situación epidemiológica se pueden modificar algunos conceptos y acciones, por lo que la información aquí contenida debe ser adaptada a cada paciente, basada en el juicio clínico, necesidades del paciente y recursos disponibles.

Abstract This document was prepared (June 2020) by and for medical professionals (clinicians and health providers), and it is available as a guideline for pediatric patients with coronavirus disease 2019 (COVID-19). So far, according to available data although children of all ages can acquire COVID-19, they have better outcome than adults, with a little proportion of severe disease, and in mild cases they have a 1 to 2-week recovery after the beginning of the infection. The objective of this document is to provide particularities that we consider important for diagnosis and treatment. Owe to the changing epidemiological situation some concepts and actions can change, so this information must be adapted to each specific case, based on the clinical judgement according to patient requirements and available resources.

Outpatient low toxic regimen with bortezomib in relapsed/refractory acute lymphoblastic leukemia in pediatrics and AYA patients: Single-center Mexican experience.

Relapsed or refractory acute lymphoblastic leukemia represents a major challenge in low- and middle-income countries where new therapies are not easily accessible. Combinations of cost-effective drugs should be considered as a bridge for hematopoietic stem cell transplantation. We retrospectively analyzed pediatric and adolescent and young adult patients who received reinduction with a protocol based on l-asparaginase, doxorubicin, vincristine, dexamethasone, and bortezomib (BZ). Fifteen patients were included. Total complete response (CR) was achieved by nine of 15 patients (60%); five patients achieved CR with negative minimal residual disease, two achieved complete morphological response (CR), and two complete morphological response without platelet recovery. Eleven patients (73%) were not hospitalized and 10 (66%) did not require any blood component transfusions. There were no cases of serious toxicity or mortality. Nine patients (60%) underwent transplant. Five-year overall survival was 40%. This BZ-based protocol is effective and safe when administered as an outpatient regimen and feasible in a low resource setting.

Concordant acute myeloblastic leukemia in identical twins treated with allogeneic transplantation from a younger HLA-identical sibling following a single apheresis procedure.

A concordant leukemia is that which occurs in a pair of monozygotic twins; a similar genetic background suggests an in utero monoclonal origin. We present the case of a pair of monozygotic infants with concordant acute myeloid leukemia who underwent a peripheral blood hematopoietic stem-cell transplant (HSCT) from a single, younger human leukocyte antigen-identical sibling donor, using a fractioned graft collected during only one apheresis procedure. Twin A relapsed at +456 and received a second haploidentical HSCT from his father, twin B has been in complete remission since the first HSCT. Both children are in complete remission and with negative minimal residual disease at +900 (after second transplant) and +1488, respectively.

Cyclosporine A for the Prevention of Ocular Graft versus Host Disease in Allogeneic Hematopoietic Stem Cell Transplant Recipients Is Safe and Feasible.

PURPOSE: To evaluate the safety and efficacy of ocular cyclosporine in the prevention of the development of ocular graft versus host disease (oGVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT) in comparison with historic data. DESIGN: We developed a longitudinal, observational, prospective nonrandomized study. We evaluated the feasibility of prophylactic use of topical cyclosporine A (CsA) to prevent or decrease the incidence of oGVHD and compared this with historic data. METHODS: Patients undergoing AHSCT were treated with prophylactic topical CsA for 12 months after engraftment, followed by serial ophthalmic evaluations, including the Schirmer test. RESULTS: Twenty patients were included. No serious adverse effects were reported. Poor adherence was documented in 15% of patients. In spite of observing extra-ocular GVHD (acute and chronic GVHD incidence of 50 and 45%, respectively), only 1 in 20 patients developed oGVHD over the 20-month follow-up for the entire cohort. No statistically significant difference was observed in the incidence of oGVHD when compared to a historical cohort. CONCLUSIONS: Topical CsA as a prophylactic measure for oGVHD, administered over a period of 1 year after grafting, is safe and feasible and may decrease the incidence of ophthalmic manifestations of GVHD. These findings must be confirmed in a randomized trial.

Infarto esplénico masivo en un paciente pediátrico sin factores predisponentes / Massive splenic infarct in a pediatric patient without predisposing factors

El infarto esplénico es una entidad rara en la edad pediátrica que, cuando se encuentra, se asocia a otros factores predisponentes, como enfermedades oncológicas, hematológicas o infecciosas. Su presentación es asintomática o sintomática con dolor abdominal, fiebre y esplenomegalia. No existe consenso sobre cuál es la mejor opción de tratamiento, y se decide, en la mayoría de los casos, un manejo conservador o quirúrgico de acuerdo con las características individuales del paciente. Se presenta el caso de un paciente escolar que acude por un cuadro de dolor abdominal agudo y fiebre con diagnóstico de infarto esplénico masivo sin etiología aparente que fue manejado de manera conservadora, con evolución favorable. Es importante considerar este padecimiento como causa de dolor abdominal asociado a esplenomegalia y destacar la relevancia de esta presentación de caso, ya que se presenta sin relación con enfermedades subyacentes.

Splenic infarction is a rare entity in the paediatric age that, when found, is associated with other predisposing factors such as oncological, haematological or infectious diseases. It is whether asymptomatic or symptomatic with abdominal pain, fever and splenomegaly. There is no consensus on which is the best treatment option, in most cases deciding conservative or surgical management according to individual patient characteristics. We present the case of a patient with acute abdominal pain and fever with a diagnosis of massive splenic infarction without apparent aetiology that was managed conservatively with favourable evolution. It is important to consider this condition as a cause of abdominal pain associated with splenomegaly.

Efficacy of three filgrastim-intended copies for hematopoietic stem cell mobilization in healthy adult and pediatric donors in Mexico.

INTRODUCTION: The use of filgrastim biosimilars for healthy adult and pediatric donor mobilization in hematopoietic stem cell transplantation has been met with increased safety and efficacy concerns in contrast to generic small molecule drugs. In Mexico, several filgrastim-intended copies (FIC) have been available and marketed since 2001, while no clinical comparability studies to evaluate their use in this setting have been published and thus are not considered to be true biosimilars. In this study, we report our experience using three different FIC products currently available (Filatil, Dextrifyl, and Biofilgran). METHODS: We retrospectively evaluated 118 related donors of all ages who received any brand 5 µg/kg subcutaneously twice daily for 4 days and were harvested in a single apheresis system on day 5. RESULTS: Donors had a median age of 38 years (range, 1-69). A successful harvest defined as ≥2 × 106 CD34+ cells/kg of recipient weight was achieved in 95.8% of cases, with a median CD34+ cell dose of 9.4 × 106 /kg (range 1-42.8). A single apheresis session was performed in 89.8% of cases. No significant difference in cell yield between each brand was observed. All pediatric donors had a successful harvest with similar results to adult donors. No immediate severe adverse effects were documented in any case. CONCLUSIONS: In conclusion, three FICs available in Mexico were efficacious and without immediate severe adverse effects, resulting in significant cost savings. Evaluation of immunogenicity and establishment of a pharmacovigilance program with the use of FICs is warranted.

Treatment of classical Hodgkin's lymphoma in children and adolescents.

INTRODUCTION: The treatment of classical Hodgkin lymphoma (cHL) in children is a story of success. Nowadays, more than 90% of patients are cured and overall survival is nearly 100% at 5 years. Efforts have been made to avoid related effects of therapies; therefore, children are treated using different chemotherapy schemes in comparison with adults. AREAS COVERED: This review includes a view of the clinical classification and risk assessment in children suffering from HL. The chemotherapy more commonly employed is revisited. The use of PET/CT to evaluate the disease in order to guide therapy is analyzed. New options of chemotherapy and emerging immunotherapy are also included. EXPERT OPINION: In order to make the right treatment choice, a proper initial assessment of risk is mandatory. The choice of therapy in these kinds of patients must be done according to the experience of the team, and also, the cost and logistics related to the eligible scheme are very important. If possible, efforts must be made to include PET/CT in guiding therapy and avoiding overtreatment and long-term adverse effects in children. New options in immunotherapy are emerging and must be considered with caution in selected patients.

Relapse of childhood acute lymphoblastic leukemia and outcomes at a reference center in Latin America: organomegaly at diagnosis is a significant clinical predictor.

OBJECTIVE: Relapse is the major cause of treatment failure in acute lymphoblastic leukemia (ALL) of childhood; it is more frequent among high-risk patients from low-middle income than from high-income countries. The frequency, sites and outcome of relapsed ALL in children of northeast Mexico over a decade was documented. METHODS: A retrospective analysis of 246 children belonging to a low-income group <16 years with de novo ALL during 2004-2015 was performed. Five-year overall survival (OS) and event-free survival was estimated by Kaplan-Meier analysis. Data on time, site, response to therapy and final outcome of relapse were analyzed. Hazard ratios (HRs) of relapse and death were estimated by the Cox regression model. Very early relapse was defined as that occurring in <18 months, early relapse between 18 and 36 months, and late relapse >36 months from diagnosis, respectively. RESULTS: Eighty-seven (35.4%) children relapsed. Five-year OS was 82.6% in children without relapse vs. 42% for relapsed patients. Bone marrow (BM) was the most frequent site of relapse (51.72%). Isolated central nervous system (CNS) relapses occurred in 29.9%. Five-year OS was 11.2% for BM and 15.5% for early relapse. HR of relapse for organomegaly was 3.683, 2.247 for an initial white blood cell count >50 000 × 109/l and 1.169 for positive minimal residual disease status. CONCLUSION: A high rate of very early, CNS, and BM relapse with a considerably low 5-year OS requiring reassessment of therapy was documented. Organomegaly at diagnosis was a highly significant clinical predictor for relapse.