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.

Infection-related mortality after HLA-identical and haploidentical hematopoietic cell transplantation using reduced-intensity conditioning in an outpatient setting.

BACKGROUND: Despite the improvements in supportive care for allogeneic-hematopoietic cell transplantation (allo-HCT) recipients, infectious complications and infection-related mortality (IRM) continue to be a major issue for transplantation centers. METHODS: We herein report the infectious complications and IRM of 107 and 89 patients that underwent haploidentical (haplo-HCT) or HLA-identical HCT at a tertiary referral center during 2013-2020. Patients in the haplo-HCT group received post-transplant cyclophosphamide (PT-Cy), and all received reduced-intensity conditioning regimens. RESULTS: More haplo-HCT recipients presented severe infections in the pre-engraftment period (22.4% vs. 6.7%, p = 0.003). Viral (14.9% vs. 4.5%, p = 0.016) and fungal (12.1% vs. 1.1%, p = 0.003) etiologies were more common in this period in this group. The 100-day and 2-year cumulative incidence of IRM was 15% and 21% for the haplo-HCT and 5.6% and 17% for the HLA-identical group; no significant differences were observed between the groups. Fungal pathogens mainly contributed to IRM (33.3%). Infections were the most common cause of mortality (40/81, 49.4%). There were significant differences in donor/recipient CMV serostatus between transplant groups (0.002). CONCLUSIONS: No differences in IRM were observed based on allo-HCT type, with more haplo-HCT patients suffering from severe infections in the pre-engraftment period. Studies to assess future prevention, diagnostic, and treatment strategies to reduce IRM are warranted.

Intermittent Soft-Tissue Tumor Enlargement in Episodic Angioedema With Eosinophilia Syndrome.

ABSTRACT: Episodic hypereosinophilia and angioedema syndrome, also known as Gleich syndrome, is a rare entity characterized by recurrent episodes of eosinophilia, angioedema, urticaria, fever and weight gain with spontaneous resolution. It is classified as an idiopathic hypereosinophilic syndrome. Unlike other hypereosinophilic syndromes, it has a low risk for internal organ damage. We report the case of a 42-year-old male with a 28-year history of recurrent erythematous wheals and plaques and persistent hypereosinophilia. Physical examination revealed a well-defined subcutaneous nodule on his right lower limb that increased in size with each episode of angioedema. Histopathology evidenced a lipoma with intense eosinophil infiltration within the mature adipose tissue, while the specimen of the wheal revealed scarce perivascular and interstitial eosinophilic inflammatory infiltrate. Diagnosis of episodic angioedema with eosinophilia syndrome was made based on clinical and laboratory findings.

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.

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.

Autologous ATG-free hematopoietic stem cell transplantation for refractory autoimmune rheumatic diseases: a Latin American cohort.

Autologous hematopoietic stem cell transplantation (HSCT) has been recognized as treatment alternative for patients with severe, refractory autoimmune rheumatic diseases (ARDs). Usually, anti-thymocyte globulin (ATG)-containing conditioning regimens are employed; however, ATG is unavailable in some developing nations. We report our 15-year clinical experience autografting patients with ARDs with an ATG-free conditioning regimen and a brief assessment of patient-reported outcomes post-HSCT. All patients had active disease and were resistant to multiple lines of treatment. Event-free survival (EFS) was assessed using the Kaplan-Meier method. Eight patients underwent autologous HSCT. Diagnoses included juvenile idiopathic arthritis (n = 3), systemic lupus erythematosus (n = 2), systemic sclerosis (n = 2), and rheumatoid arthritis (n = 1). Median time from diagnosis to HSCT was 3 years (0.75-19). Hematological recovery was documented in all recipients, and 4 patients (50%) completed the procedure in a completely ambulatory setting. Five (62.5%) patients achieved complete response and 3 (37.5%) partial response. The median EFS was 7 months (95% CI, 4.97-9.02), and the 1-year EFS rate was 21.9% (95% CI, 18.25-25.76). Transplant-related mortality was 0%, and 1 recipient died 8 years post-HSCT due to chronic kidney disease. Six (75%) patients presented steroid dosage reduction post-HSCT, and 2 (25%) perceived improvement in functionality despite having relapsed. HSCT is a viable treatment alternative for selected patients with severe therapy-resistant ARDs, as an improvement in disease management and quality of life was documented. The need remains to elucidate the characteristics of the optimal HSCT candidate, as well as the adequate conditioning regimen when ATG is not available. Key Points • Despite advances in the treatment of autoimmune rheumatic diseases, some patients remain refractory. In this context, autologous hematopoietic stem cell transplantation (HSCT) rises as a viable alternative. • Of 8 HSCT recipients with autoimmune rheumatic diseases, 5 (62.5%) patients achieved complete response and 3 (37.5%) partial response, with a 1-year event-free survival of 21.9%. • Transplant-related mortality was 0%, with 4 (50%) patients autografted in a completely outpatient setting. • Even when relapse presented, patients reported an improvement in functionality and quality of life; also, a better response to DMARDs and a reduction in steroid dependency post-HSCT were documented.

Moral Distress: Its Manifestations in Healthy Donors during Peripheral Blood Hematopoietic Stem Cell Harvesting.

Hematopoietic stem cell donors (HSCDs) may have ambivalent feelings about donation. These feelings are related to moral obligation to help a sick relative and/or fear about the donation procedure. This ambivalence can produce moral distress (MD) and anxiety, which are usually unnoticed by the treating physician. The aim of this study was to evaluate the incidence of MD and anxiety in a group of related HSCDs for allogeneic transplantation. In this prospective observational study, to assess MD and anxiety, we applied 3 self-answered questionnaires-a questionnaire developed to assess MD (MDQ), State Trait Anxiety Index (STAI), and Edmonton Symptom Assessment System (ESAS)-before, during, and after hematopoietic stem cell donation. A total of 60 consecutive related HSCDs with a mean age of 38.2 years were included. Thirty-six were male. Hematopoietic stem cell collections were done by apheresis, performed as an outpatient process in all cases. The incidence of MD during the donation process was 56%. The proportion of HSCDs with moderate to high state anxiety decreased significantly from before donation (63%) to after donation (30%). Higher scores for MD correlated with higher scores on the STAI questionnaire (r = 0.448; P < .005). Thirty-seven donors (62%) had at least 1 physical symptom even before the stem cell mobilization process started, mainly anxiety (33%), difficulty sleeping (33%), and fatigue (30%). The number of symptomatic donors increased during donation (100%) and decreased after the procedure (80%). We conclude that MD and anxiety symptoms experienced by HSCDs are very common and can be explained by mixed feelings about the donation process. Providing comprehensive psychological support before starting the donation process and guaranteeing respect for the donor's autonomy are needed to decrease the negative impact of the donation experience.

IMPACT OF HLA-DPB1 MATCHING ON CLINICAL OUTCOMES AFTER HAPLOIDENTICAL-RELATED HEMATOPOIETIC STEM CELL TRANSPLANTATION.

BACKGROUND: The impact of HLA-DPB1 compatibility and its role as a transplantation antigen in haploidentical-related hematopoietic stem cell transplant (haplo-R-HSCT) have not been established, and a negative effect on survival has been suggested. OBJECTIVE: The objective of the determine was to study the frequency and clinical effects of incompatibility at the HLA-DPB1 locus in the haplo-R-HSCT setting. METHODS: Clinical records and electronic files of 91 patients with a hematological disease who underwent haplo-HSCT from January 2009 to October 2017 in a university medical center were scrutinized. Overall survival (OS) was estimated by the Kaplan-Meier method; the cumulative incidence of transplant-related mortality (TRM) and relapse rates was determined. Acute graft-versus-host disease was assessed by binary logistic regression. Cox regression model with a 95% confidence interval was used to examine the association between the different variables and their effect on OS. RESULTS: Of the 91 donor-recipient pairs, 24 (26.37%) shared complete DPB1 identity, 60 (65.93%) had a mismatch at one allele, and 7 (7.70%) were mismatched at two alleles. Twenty-four different HLA-DPB1 alleles were found; the most frequent were DPB1*04:01 (34.1%) and DPB1*04:02 (27.5%). Two-year OS, the cumulative incidence of TRM and relapse was 51.3 ± 6.8%, 28 ± 6% and 60 ± 7.8% for all haplo-related transplants, respectively, with no statistical difference between HLA-DPB1 matched and partially matched patients. In Cox regression analysis, no risk factors associated with OS, TRM, or relapses were identified. CONCLUSION: HLA-DPB1 mismatching in the haplo-R-HSCT setting did not influence transplant outcomes and was clinically tolerable. A high degree of homozygosity was found.

Impact of hHLA-DPB1 matching on clinical outcomes after haploidentical-related hematopoietic stem cell transplantation

ABSTRACT Background: The impact of HLA-DPB1 compatibility and its role as a transplantation antigen in haploidentical-related hematopoietic stem cell transplant (haplo-R-HSCT) have not been established, and a negative effect on survival has been suggested. Objective: The objective of the determine was to study the frequency and clinical effects of incompatibility at the HLA-DPB1 locus in the haplo-R-HSCT setting. Methods: Clinical records and electronic files of 91 patients with a hematological disease who underwent haplo-HSCT from January 2009 to October 2017 in a university medical center were scrutinized. Overall survival (OS) was estimated by the Kaplan-Meier method; the cumulative incidence of transplant-related mortality (TRM) and relapse rates was determined. Acute graft-versus-host disease was assessed by binary logistic regression. Cox regression model with a 95% confidence interval was used to examine the association between the different variables and their effect on OS. Results: Of the 91 donor-recipient pairs, 24 (26.37%) shared complete DPB1 identity, 60 (65.93%) had a mismatch at one allele, and 7 (7.70%) were mismatched at two alleles. Twenty-four different HLA-DPB1 alleles were found; the most frequent were DPB1*04:01 (34.1%) and DPB1*04:02 (27.5%). Two-year OS, the cumulative incidence of TRM and relapse was 51.3 ± 6.8%, 28 ± 6% and 60 ± 7.8% for all haplo-related transplants, respectively, with no statistical difference between HLA-DPB1 matched and partially matched patients. In Cox regression analysis, no risk factors associated with OS, TRM, or relapses were identified. Conclusion: HLA-DPB1 mismatching in the haplo-R-HSCT setting did not influence transplant outcomes and was clinically tolerable. A high degree of homozygosity was found.

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.

Contributions of a regional approach to document hematologic disease in Mexico: a 10-year experience in an open population.

OBJECTIVES: To demonstrate the importance of regional efforts to register features and report frequency of hematology diseases in the context of incomplete national registries. METHODS: Frequencies and salient characteristics of hematologic diseases in Northeast Mexico were documented in a reference center at a tertiary care university hospital during the decade 2005-2015. Disease categories were grouped by age, sex and diagnosis. Age group distribution followed WHO guidelines in years as children (0-17), adults (18-64) and elders (+65). RESULTS: 2406 patients were included: 1239 (51.5%) were females and 1167 (48.5%) males; F:M ratio was 1.06:1; median age was 35 years (0-95). The frequency by age group included adults, 1370 cases (56.9%), children, 695 cases (28.9%), and elderly, 341 (14.2%). Most frequent diagnoses were acute lymphoblastic leukemia (ALL) 18.2% (n = 438), anemia 15.9% (n = 383), non-Hodgkin's lymphoma (NHL) 15.7% (n = 378), immune thrombocytopenic purpura (ITP) 9.8% (n = 235) and Hodgkin's lymphoma (HL) 6.5% (n = 156). Median age for the whole cohort was 35 years; for children, was 6 years, for adults 40 and for the elderly 73. Results for ALL, anemia and ITP were comparable to high-income countries; NHL, HL and chronic myeloid leukemia presented a decade earlier. DISCUSSION: Complete, opportune reliable information on the number of cases, age and sex distribution with the potential to influence strategies for timely diagnosis and treatment options for important hematologic diseases can be accrued by regional centers. CONCLUSION: Information on hematology diseases derived of regional registries in low-middle income countries is a reasonable alternative to complement and update national registries.

Real-world outcomes of treatment for acute lymphoblastic leukemia during adolescence in a financially restricted environment: Results at a single center in Latin America.

OBJECTIVE: There is a paucity of the studies of adolescents with acute lymphoblastic leukemia (ALL). This is more noticeable in low- and middle-income countries. The international 5-year event-free survival (EFS) and overall survival (OS) for this age group is around 80%, with pediatric-inspired protocols offering better results. METHODS: A retrospective analysis of adolescents aged 16-20 diagnosed with ALL during the period 2004-2015 treated with a high-risk pediatric protocol at an academic center from a middle-income country was performed. Five-year OS and EFS were estimated by the Kaplan-Meier analysis. Hazard ratios of relapse and death were estimated by the Cox regression model. RESULTS: Five-year EFS and OS for 57 adolescents were 23.3% and 48.9%, respectively. From the 41 patients who achieved complete remission, 24 (58.5%) relapsed. Bone marrow and central nervous system were the most frequent sites of relapse. Hazard ratio of treatment failure and death for patients with organomegaly at diagnosis was 2.026 and 2.970, respectively. Treatment-related toxicity developed in 31 (54.4%) patients and febrile neutropenia was the most frequent in 14 (24.6%) cases. Twelve patients (21.1%) had poor adherence to treatment. CONCLUSIONS: High relapse rate and low 5-year EFS compared with international standards, was documented. Use of intensified pediatric regimens, adherence to proven effective medications, improved supportive care, and prevention of abandonment are necessary to improve survival rates in these patients.

The treatment of CML at an environment with limited resources.

OBJECTIVES: This article reviews clinical experiences in the treatment of chronic myeloid leukemia (CML) in an environment of limited resources. METHODS: We reviewed recent publications on Pub med and abstracts from mayor congresses relevant to the disease. RESULTS: CML is a hematological neoplasm observed more frequently in adults, regardless of their socioeconomic status. Until recently, available treatments improved patients' quality of life but did not modify survival. It was not until interferon appeared that patients received a drug that reduced and even eliminated Philadelphia chromosome-positive (Ph+) cells. DISCUSSION: With the start of the new millennium, the International Randomized Study of Interferon-α plus cytarabine versus STI571 (IRIS) trial demonstrated a dramatic improvement in survival by comparing imatinib versus interferon alpha plus cytarabine. The Food and Drug Administration (FDA) approved imatinib as first-line treatment for newly diagnosed CML in 2001 due to its outstanding effectiveness. Years later, three second-generation (dasatinib, nilotinib, bosutinib) and one third-generation (ponatinib) tyrosine-kinase inhibitors (TKIs) were developed and approved. These highly effective treatment options, however, are not affordable for many low-income patients. Additionally, the use of drugs that effectively treat but do not cure the disease has resulted in an important economic impact for patients and health care systems worldwide, especially those in developing countries. Imatinib is the least expensive and a very effective TKI in many low-income countries. Early allogeneic stem cell transplantation must be considered in the management of selected patients before CML transformation.

Is There Still a Role for Low-Dose All-Transretinoic Acid in the Treatment of Acute Promyelocytic Leukemia in the Arsenic Trioxide Era?

BACKGROUND: Low-dose all-transretinoic acid (LD-ATRA) has shown similar peak plasma concentrations and a mean area under the concentration time curve in comparison with standard doses of ATRA. We evaluated the efficacy of LD-ATRA plus anthracycline-based chemotherapy in patients with newly diagnosed acute promyelocytic leukemia (APL). PATIENTS AND METHODS: Patients diagnosed with APL during the period of 2002 to 2014 were included. They received ATRA 25 mg/m(2) plus anthracycline (doxorubicin or mitoxantrone) as induction chemotherapy, followed by 3 consolidations with LD-ATRA and anthracycline and maintenance therapy with intermittent LD-ATRA and oral chemotherapy for 2 years. RESULTS: Twenty-two patients with a median age of 28 years (range, 18-55 years) were included; 17 (77%) were in the low-risk group. Complete remission occurred in 86%, and the early death rate was 9%. At a median follow-up of 32 months (range, 4-126 months) disease-free survival (DFS) was 75% and overall survival (OS) was 86%, with a relapse rate of 27% for the entire follow-up period. CONCLUSION: LD-ATRA plus anthracycline is safe and effective in achieving CR of APL. The early death rate is similar to that of treatment with standard doses, but it appears to be inferior in preventing relapses.

Cost structure and clinical outcome of a stem cell transplantation program in a developing country: the experience in northeast Mexico.

BACKGROUND AND OBJECTIVE: Hematopoietic stem cell transplantation (HSCT) in developing countries is cost-limited. Our primary goal was to determine the cost structure for the HSCT program model developed over the last decade at our public university hospital and to assess its clinical outcomes. MATERIALS AND METHODS: Adults and children receiving an allogeneic hematopoietic stem cell transplant from January 2010 to February 2011 at our hematology regional reference center were included. Laboratory tests, medical procedures, chemotherapy drugs, other drugs, and hospitalization costs were scrutinized to calculate the total cost for each patient and the median cost for the procedure. Data regarding clinical evolution were incorporated into the analysis. Physician fees are not charged at the institution and therefore were not included. RESULTS: Fifty patients were evaluated over a 1-year period. The total estimated cost for an allogeneic HSCT was $12,504. The two most expensive diseases to allograft were non-Hodgkin lymphoma ($11,760 ± $2,236) for the malignant group and thalassemia ($12,915 ± $5,170) for the nonmalignant group. Acute lymphoblastic leukemia ($11,053 ± 2,817) and acute myeloblastic leukemia ($10,251 ± $1,538) were the most frequent indications for HSCT, with 11 cases each. Median out-of-pocket expenses were $1,605, and 1-year follow-up costs amounted to $1,640, adding up to a total cost of $15,749 for the first year. The most expensive components were drugs and laboratory tests. CONCLUSION: Applying the cost structure described, HSCT is an affordable option for hematological patients living in a developing country.

Efficacy of mitoxantrone as frontline anthracycline during induction therapy in adults with newly diagnosed acute lymphoblastic leukemia: a single-center experience.

Remission induction regimens for acute lymphoblastic leukemia (ALL) in adults induce complete remission (CR) in 60-90% and cure in 20-40%. A cohort study of newly diagnosed patients with ALL treated with mitoxantrone versus doxorubicin was conducted from 2005 to 2013. The primary endpoint was the proportion of CR. Eighty-five patients were included. Fifty-three received induction with doxorubicin and 32 with mitoxantrone. Median follow-up in the cohort was 40.2 months (range 2-95). Twenty-nine patients (90.6%) achieved CR in the mitoxantrone arm compared with 37 (69.8%) in the doxorubicin group (p = 0.032). There was no difference in death or relapse rate (p = 0.095 and 0.075), hematological recovery (p = 0.654), incidence of adverse events (p = 0.6), in-hospital days during induction (p = 0.456) or overall survival (p = 0.105). Induction toxicities were comparable. Mitoxantrone can be safely and effectively used as a frontline anthracycline in adults newly diagnosed with ALL.