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.

Point of care thoracic ultrasound versus chest computed tomography in the approach of febrile neutropenia patients: A diagnostic accuracy cohort study.

Single-center prospective cohort diagnostic accuracy study. Our study aimed to evaluate the accuracy and reproducibility of Thoracic Ultrasound (TUS) in detecting pulmonary pathology in immunosuppressed patients. We conducted a single-center prospective study. Consecutive patients with febrile neutropenia who underwent CT (Computerized Tomography) underwent TUS evaluation within 24h of CT. Both studies were performed by an expert who was blinded to the clinical information and results of the alternative imaging modalities. 34 patients met the inclusion criteria. The median age was 39.9 years (±17 standard deviation). TUS as a diagnostic test had a sensitivity of 92.9% and specificity of 83.3%, negative predictive value of 71.4%, and positive predictive value of 96.3%. Substantial between-method agreement was demonstrated with a kappa of 0.71 (P = .001) between the TUS and chest CT findings. We obtained a kappa of 1 (P = .001) for the final diagnosis of Pleural Effusion (PE). We concluded that TUS is a promising screening test for immunocompromised individuals. The results showed good diagnostic performance of TUS compared to CT for the detection of pulmonary findings highly suggestive of pathology with high accuracy and reproducibility.

Lactate dehydrogenase as a hematopoietic stem cell mobilization biomarker in autologous transplantation

ABSTRACT Introduction: Pre-apheresis peripheral blood CD34+ cell count (PBCD34+) is the most important predictor of good cell mobilization before hematopoietic stem cell transplantation, albeit flow cytometry is not always immediately available. Identification of surrogate markers can be useful. The CD34+ cells proliferate after mobilization, resulting in elevated lactate dehydrogenase (LDH) activity and correlating with the PBCD34+ count. Objective: To determine the LDH cut-off value at which adequate CD34+ cell mobilization is achieved and its diagnostic yield. Materials and methods: A total of 103 patients who received an autologous stem cell transplantation (ASCT) between January 2015 and January 2020 were included. Demographic and laboratory characteristics were obtained, including complete blood count, pre-apheresis PBCD34+ and LDH levels. Receiver operating characteristic (ROC) curves were performed to identify the optimal serum LDH activity cut-off points for ≥ 2 and ≥ 4 × 106 cells/kg post-mobilization CD34+ count and their diagnostic yield. Results: A post-mobilization serum LDH cut-off value of 462 U/L yielded a sensitivity (Se) = 86.8% (positive predictive value [PPV] = 72.7%), a pre- and post-mobilization serum LDH difference cut-off value of 387 U/L, an Se = 45.7% (PPV = 97%) and an LDH ratio of 2.46, with an Se = 47.1% (PPV = 97%) for an optimal mobilization count (CD34+ ≥ 4 × 106). Conclusion: The LDH measurement represents a fast and affordable way to predict PBCD34+ mobilization in cases where flow cytometry is not immediately available. According to the LDH diagnostic yield, it could be used as a surrogate marker in transplant centers, supporting the CD34+ count, which remains the gold standard.

Low-dose rituximab in steroid-refractory chronic graft-versus-host disease.

BACKGROUND: Chronic graft-versus-host disease (cGvHD) is a major complication that puts patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) at risk of death or infection. Currently, there is no gold standard for the first-line treatment of patients who do not respond to steroids, and there are several therapeutic options being evaluated in clinical trials for this disease to be used even in the first-line treatment for GvHD. There is evidence of the benefit of rituximab, an anti-CD20 antibody, at a standard dose of 375 mg/m2 weekly in the treatment of steroid-refractory chronic graft-versus disease (SR-cGvHD). OBJECTIVE: To demonstrate the safety and efficacy of low-dose rituximab in a middle-income center in northeastern Mexico STUDY DESIGN: We report the experience of 26 patients with chronic graft-versus-graft disease who received low-dose rituximab (100 mg weekly for 4 weeks). We utilized the advances in the National Institutes of Health (NIH) criteria for diagnosis, scoring, trial design, and assessment of treatment response. RESULTS: We obtained a 5-year overall survival of 23.6%, including four patients with complete response. The 1-year event-free survival was 70% for patients with rituximab. During the treatment, there were 3 hospitalizations, and the causes were: immune thrombocytopenia, a parapneumonic effusion, and a cerebral vascular event. The median length of hospital stay was twelve days. CONCLUSION: A low dose of rituximab is an available and cost-effective option for patients with steroid-refractory cGvHD.

Comparison of CD4+/CD8+ Lymphocytic Subpopulations Pre- and Post-Antituberculosis Treatment in Patients with Diabetes and Tuberculosis.

Is there a CD4+ and CD8+ immunity alteration in patients with pulmonary tuberculosis (TB) and diabetes (DM) that does not recover after antituberculosis treatment? This prospective comparative study evaluated CD4+ and CD8+ lymphocytic subpopulations and antituberculosis antibodies in patients with diabetes and tuberculosis (TB-DM), before and after antituberculosis treatment. CD4+ T cell counts were lower in patients with TB-DM compared to those with only TB or only DM, and these levels remained low even after two months of anti-TB treatment. Regarding the CD8+ T cell analysis, we identified higher blood values in the DM-only group, which may be explained by the high prevalence of latent tuberculosis (LTBI) in patients with DM. IgM antituberculosis antibodies levels were elevated in patients with only TB at baseline, and 2 months post-anti-TB treatment, IgG did not express any relevant alterations. Our results suggest an alteration in CD4+ immunity in patients with TB-DM that did not normalize after antituberculosis treatment.

Acute Leukemia Relapse after Hematopoietic Stem Cell Transplantation: The Good, the Bad, and the Ugly of Isolated Extramedullary Relapse in a Latin American Population.

Hematopoietic stem cell transplantation (HSCT) is an effective therapy for acute leukemia (AL). Relapse represents the main cause of mortality. Isolated extramedullary relapse (iEMR) is atypical and has been related to better outcomes. Here we describe the clinical characteristics and outcomes of AL relapse after HSCT in our study population and analyze the impacts of different types of relapse on survival outcomes. This retrospective, multicenter study included 124 patients age ≥15 years with AL who underwent HSCT between 2004 and 2019. At diagnosis, 66.1% of the patients had lymphocytic AL, 19.7% presented with high-risk features, and 18.5% had extramedullary disease (EMD). At HSCT, 83.1% of the patients were in complete remission (CR), and 44.8% had negative measurable residual disease (MRD). The vast majority of donors were related (96%), including 48.4% HLA-matched and 47.6% haploidentical. Myeloablative conditioning was provided to 80.6% of patients. The median overall survival (OS) was 15 months (95% confidence interval [CI] 9.9 to 20.1 months). Factors associated with improved OS were adolescent and young adult (AYA) patient (P = .035), first or second CR (P = .026), and chronic graft-versus-host disease (GVHD) (P < .001). Acute GVHD grade III-IV (P = .009) was associated with increased mortality. The median relapse-free survival was 13 months (95% CI, 7.17 to 18.8 months); early disease status (P = .017) and chronic GVHD (P < .001) had protective roles. Sixty-eight patients (55%) relapsed after HSCT, with a median time to relapse of 6 months (95% CI, 3.6 to 8.4 months). iEMR was reported in 16 patients (23.5%). The most commonly involved extramedullary sites were the central nervous system and skin. Compared to patients with bone marrow relapse, all patients with iEMR had a diagnosis of acute lymphoid leukemia (P = .008), and 93.8% belonged to the AYA group; regarding pre-HSCT characteristics, iEMR patients had higher rates of negative MRD (P = .06) and a history of EMD (P = .009). Seventy-seven percent of relapsed patients received additional treatment with curative intent. The median OS after relapse (OSr) was 4 months (95% CI, 2.6 to 5.4 months). Factors related to increased OSr included lymphoid phenotype (P = .03), iEMR (P = .0042), late relapse (≥6 months) (P = .014), receipt of systemic therapy including second HSCT (P < .001), and response to therapy (P < .001). Rates of relapse and iEMR were higher than those previously reported in other studies. Advanced disease, reduced-intensity conditioning, and a diminished graft-versus-leukemia effect were factors influencing these findings. At relapse, presenting with iEMR after 6 months and receiving intensive therapy with adequate response were associated with better outcomes. Our results strongly suggest that a personalized approach to treating patients with HSCT is needed to counterbalance specific adverse factors and can positively impact clinical outcomes.

Orbital myeloid sarcoma treated with low-dose venetoclax and a potent cytochrome P450 inhibitor.

CASE REPORT: We report the first case of orbital myeloid sarcoma that was successfully treated with a standard venetoclax dose of 25%. A 38-year-old man with acute myeloid leukemia (AML) post-haplo-hematopoietic stem cell transplantation (HSCT) presented with a nine-month history of progressive right proptosis and a visual acuity deficit. The patient was treated with venetoclax (100 mg orally on days 1-28), cytarabine (40 mg subcutaneously, days 1-10), and itraconazole (100 mg twice daily orally on days 1-28). MANAGEMENT AND OUTCOME: The present case report shows that using cytochrome P450 (CYP) inhibitors is a helpful strategy to reduce the cost of expensive treatments. DISCUSSION: There are limited data on the use of CYP inhibitors as a strategy to reduce the costs of expensive drugs (i.e. venetoclax). This approach has some advantages over standard dose venetoclax (400 mg/day) such as significantly reduced costs (which is relevant for patients in low-income countries). In this case, we used itraconazole-a potent CYP3A4 inhibitor-which can theoretically reduce the dose to 100 mg/day without losing serum therapeutic concentrations.

Lactate dehydrogenase as a hematopoietic stem cell mobilization biomarker in autologous transplantation.

INTRODUCTION: Pre-apheresis peripheral blood CD34+ cell count (PBCD34+) is the most important predictor of good cell mobilization before hematopoietic stem cell transplantation, albeit flow cytometry is not always immediately available. Identification of surrogate markers can be useful. The CD34+ cells proliferate after mobilization, resulting in elevated lactate dehydrogenase (LDH) activity and correlating with the PBCD34+ count. OBJECTIVE: To determine the LDH cut-off value at which adequate CD34+ cell mobilization is achieved and its diagnostic yield. MATERIALS AND METHODS: A total of 103 patients who received an autologous stem cell transplantation (ASCT) between January 2015 and January 2020 were included. Demographic and laboratory characteristics were obtained, including complete blood count, pre-apheresis PBCD34+ and LDH levels. Receiver operating characteristic (ROC) curves were performed to identify the optimal serum LDH activity cut-off points for ≥ 2 and ≥ 4 × 106 cells/kg post-mobilization CD34+ count and their diagnostic yield. RESULTS: A post-mobilization serum LDH cut-off value of 462 U/L yielded a sensitivity (Se) = 86.8% (positive predictive value [PPV] = 72.7%), a pre- and post-mobilization serum LDH difference cut-off value of 387 U/L, an Se = 45.7% (PPV = 97%) and an LDH ratio of 2.46, with an Se = 47.1% (PPV = 97%) for an optimal mobilization count (CD34+ ≥ 4 × 106). CONCLUSION: The LDH measurement represents a fast and affordable way to predict PBCD34+ mobilization in cases where flow cytometry is not immediately available. According to the LDH diagnostic yield, it could be used as a surrogate marker in transplant centers, supporting the CD34+ count, which remains the gold standard.

Thoracic ultrasound alone or in combination with tracheal amylase as a tool predictor of ventilator-associated pneumonia in neurocritical patients.

In this study, we aim to evaluate whether thoracic ultrasound (TUS) and tracheal amylase (TA) alone or in combination can predict the development of ventilator-associated pneumonia (VAP) in neurocritical patients. Consecutive adult patients with neurocritical disease with normal chest radiographs who required intensive care unit admission and mechanical ventilation between March 2015 and July 2018 were included. TUS and Amylase levels were measured during the first 24 hours and repeated 48 hours after orotracheal intubation. Forty-three patients with a median age of 34 years (17-82) were included. TUS had a sensitivity of 100% and specificity of 96.3% as a predictor of VAP within the first 48 hours when nonpattern A was observed. TA levels > 200 UI/L in the first 48 hours had a sensitivity of 87.5%, and specificity of 63% as a predictor of VAP. Moreover, no benefit of TUS plus TA compared to TUS alone as a predictor of VAP was found. The identification of abnormal TUS patterns in the first 48 hours of orotracheal intubation is a significant predictor of VAP in neurocritical patients.

Treatment of Ph-Negative Acute Lymphoblastic Leukemia in Adolescents and Young Adults with an Affordable Outpatient Pediatric Regimen.

BACKGROUND: B-cell acute lymphoblastic leukemia is frequent in Hispanic adolescents and young adults. Outcomes of implementation of pediatric-inspired regimens in low-and middle-income countries are not well known. METHODS: In this study we treated 94 adolescents and young adults with a local BFM regimen designed to be affordable with the use of native L-asparaginase and mitoxantrone administered in an outpatient fashion, and the of BCR/ABL and measurable residual disease (MRD) determined by high sensitivity flow cytometry for risk stratification. RESULTS: Induction mortality was 11%; 25% of patients had to abandon treatment or be transferred to another health system. Two-year overall (OS) and event free survival (EFS) were 61.5% and 49.8%, MRD-negative patients had a 24-month OS of 85.6% vs. 69.6% (p = .024) and EFS of 76% vs. 45.5% (p = .004). Patients older than 40 years and those who abandoned treatment had worse EFS. Overall drug costs in our regimen were 52% lower than those of CALGB10403. CONCLUSION: The treatment of AYAs with ALL with an outpatient focus was implemented successfully at a reduced cost. Genetic risk assessment, treatment abandonment and lack of access to novel therapies remain major barriers for improving outcomes.

Diagnosis and treatment of acute lymphoblastic leukemia in Latin America.

OBJECTIVE: to discuss the status and challenges associated with the management of acute lymphoblastic leukemia (ALL) in Latin America. METHODS: This review summarizes various insights gained from information regarding diagnostic approaches and treatment strategies in adult patients with ALL in Latin American Countries. RESULTS: Information regarding ALL in Latin America is scarce; however, many efforts have been made to overcomes these barriers. Nevertheless, major obstacles to successful treatment in Latin America and LMIC remain poor adherence, abandonment of treatment, and lack of supportive therapy and new therapeutic agents. CONCLUSION: Further improvements in survival should be pursued by developing more Latin American registries, forming cooperative groups, developing educational models to facilitate earlier diagnosis and prevention of complications, better support therapy and management of infections, and adapting treatment strategies.

Alternatives for managing patients with newly diagnosed immune thrombocytopenia: a narrative review.

INTRODUCTION: Primary immune thrombocytopenia (ITP) is an acquired bleeding disorder. Conventionally, first-line ITP therapy aims to obtain a rapid response and stop or decrease the risk of bleeding by increasing the platelet count. At this point, the duration of the response, the tolerability, and the long-term safety of pharmacologic interventions are considered less of a priority. Combination treatments that simultaneously address multiple disease mechanisms are an attractive strategy to increase efficacy in acute ITP therapy. In this review, we discuss the treatment of newly diagnosed ITP patients, emphasizing the use of new combinations to benefit from their synergy. AREAS COVERED: This article summarizes conventional treatment, recent and novel combinations, and COVID-19 management recommendations of newly diagnosed ITP patients. EXPERT OPINION: The key areas for improvement consider the long-term effects of conventional first-line therapy, reducing relapse rates, and extending responses to achieve long-term remission. Although corticosteroids remain a first-line therapy, restricting their use to avoid toxicity and the increasing use of rituximab and TPO-RAs in the first three months after diagnosis open the landscape for future interventions in frontline therapy for ITP. First-line therapy intensification or synergistic drug combination offers a potential and realistic shift in future treatment guidelines.

Oseltamivir as rescue therapy for persistent, chronic, or refractory immune thrombocytopenia: a case series and review of the literature.

Immune thrombocytopenia (ITP) is an autoimmune disease that results from antibody-mediated platelet destruction and impaired platelet production. Novel therapies have emerged in the last decade, but 15-20% of patients will relapse or fail and require further therapy. We performed a prospective, single-arm intervention study on seven patients with chronic, persistent, or refractory ITP from the Hospital Universitario "Dr. José E González", in Monterrey, Mexico between 2015 and 2019. Eligible patients received oral oseltamivir 75 mg twice daily for 5 days and were followed up for six months. Most patients received a median of three distinct therapies (range 2-6). Four patients (57.1%) received combined therapy. The median time for any response was 55.5 days (range = 14-150). All patients responded at some point in time (ORR = 100%, six had a proportion of loss of response [PR], and one achieved [CR]). Six months after oseltamivir administration, three patients (42.9%) maintained a response, and one patient had a CR (14.3%). Oseltamivir was well tolerated with a good overall response rate and was useful for treating chronic ITP. We observed an initial increase in the number of platelets; however, this response was not maintained.

Outpatient allogeneic hematopoietic stem-cell transplantation: a review.

Hematopoietic stem-cell transplantation (HSCT) is usually performed in well-equipped units inside a hospital. The cost of this in-hospital transplant is usually very high; therefore, this procedure is more difficult to perform in low- and middle-income countries. Autologous outpatient HSCT is now a common procedure; however, outpatient allogeneic transplants are more complicated. Only a few centers in the world have incorporated outpatient HSCT. This transplant requires special adaptation, like a day hospital, careful selection of patients, oral medications, and the patient must live relatively close to the hospital. The results until now suggest that this outpatient transplant is factible and similar to inpatient HSCT. The objective was to review and describe the different methods and results following an outpatient allogeneic-HSCT strategy.

Venetoclax-based combinations for acute myeloid leukemia: optimizing their use in Latin-America.

Objectives: Venetoclax combinations are a new standard for patients with acute myeloid leukemia (AML). We aimed to evaluate the safety and efficacy of these combinations in a period of accelerated approval in Latin-America.Methods: This observational study evaluated adults with acute myeloid leukemia who received venetoclax-based therapy in 11 public or private centers in Mexico and Peru for both newly diagnosed or relapsed and refractory AML.Results: Fifty patients were included; 28 with newly diagnosed (ND) AML and 22 with relapsed/refractory (RR) disease. ND patients were older (64 vs. 40 years; p < 0.001) with a lower functional capacity (ECOG ≥2 64.3% vs 9%; p < 0.001). Venetoclax was frequently combined with azacytidine (60%) and prophylactic azoles (82%) with a median maximum dose of 200 mg (range, 100-600 mg). Hematologic toxicities were common. Complete response rates including patients with incomplete hematopoietic recovery were 78.6% in ND and 45.5% in RR patients, with a median overall survival of 9.6 (95% CI 3.7-15.5) and 8 months (95% CI 4.8-11.2).Discussion: Our study showed a preferred use of venetoclax plus azacytidine over cyatrabine. Patients in the first-line setting were similar to those in the landmark studies, while most patients with relapsed disease had received prior intensive therapies. Responses were favorable, with a median survival in agreement to other reports, albeit shorter than that observed in the randomized phase-3 trials.Conclusion: Venetoclax-based therapy in AML was effective despite dose reductions and prophylactic antifungals in two middle-income countries outside of a clinical trial setting.

Desensitization to Brentuximab Vedotin after anaphylaxis in refractory Hodgkin's lymphoma.

INTRODUCTION: Brentuximab vedotin (BV) is a monoclonal antibody that targets CD30 antigen. It is indicated for the treatment of CD30 + lymphomas and classical Hodgkin lymphoma (HL), including advanced (stage III-IV) untreated disease, relapsed/refractory disease, and consolidation after autologous hematopoietic stem cell transplantation. In clinical trials the incidence of a hypersensitivity reaction is 1.2%. CASES REPORT: We present 3 cases of patients with refractory HL and anaphylaxis to the administration of BV ( Table 1). Symptoms are analyzed using a grading system described by Brown (2004) and a desensitization protocol was performed with a total dose of 100 mg of BV in 4 solution bags with an initial concentration of 1:1000 of total dose for cases of severe anaphylaxis, and desensitization of 3 solution bags with baseline concentration of 1: 100 for cases of moderate anaphylaxis. MANAGEMENT & OUTCOME: Intradermal skin tests were positive. Before desensitization, premedication with methylprednisolone and chlorphenamine was administered, as well as fluid therapy with 0.9% physiological solution at 100 cc/hour at induction stage, 250 cc/hour at maintenance stage, and increased to 500 cc/hour in case of hypersensitivity reaction. DISCUSSION: Drug desensitization in 12 or 16 steps allows tolerable administration of brentuximab vedotin after moderate to severe anaphylaxis. The favorable response to treatment of these patients may indicate that desensitization is a viable strategy for patients with relapsed or refractory HL.