Indice de comorbilidad específico para trasplante alogénico de células progenitoras hematopoyéticas: cohorte retrospectiva de niños y adolescentes con enfermedad maligna / Specific comorbidity index for allogeneic hematopoietic stem cell transplantation: a retrospective cohort of children and adolescents with malignancies

Introducción: Entre las variables que afectan el riesgo de mortalidad relacionada (MRT) al trasplante alogénico de células progenitoras hematopoyéticas (TACPH) se incluyen las comorbilidades previas. Los índices de comorbilidad (IC) buscan mejorar la predicción de eventos combinando factores de riesgo independientes. Objetivos: 1) evaluar el uso de la versión breve y adaptada para niños, adolescentes y adultos jóvenes con enfermedad maligna del índice de comorbilidad específico para trasplante alogénico de células progenitoras hematopoyéticas (smyHCT-CI ); 2) evaluar el uso de los biomarcadores ferritina y albúmina en un índice de comorbilidad ampliado (smyHCT-CIa). Población y métodos: Diseño: cohorte retrospectiva. Periodo 2017- 2022. A cada p se le asignó nuevos puntajes utilizando el smyHCT-CI y el smyHCT-CIa. Los p se clasificaron en grupos de riesgo (GR) bajo (puntaje 0), intermedio (1-2) y alto (>3) con cada índice. Se comparó el n° de p asignado a cada GR grupo de riesgo y la MRT en cada grupo al usar el HCT-CI, el smyHCTCI y el smyHCT-CIa. Resultados: n 75. Frecuencia de p por GR según cada indicador (IC95): HCT-CI bajo 36 (25-47), intermedio 57 (56-69), alto 7 (1-12); smyHCT-CI: bajo 48 (37-59), intermedio 33 (23-44), alto 19 (10-27); smyHCT-CIa: bajo 43 (31-54), intermedio 36 (25-47), alto 21 (12-31). MRT por GR según indicador (IC95): HCT-CI: bajo 6,8 (14-28), intermedio 20,9 (9-33), alto 17,9 (0-55); smyHCT-CIa bajo 12,5 (1-24), intermedio 18,5 (4-33), alto 31,2 (9-54). Conclusión: El smyHCT-CI permitió identificar mejor los pacientes con mayor comorbilidad y riesgo de MRT. La ferritina resultó un biomarcador útil en la estimación del riesgo de MRT (AU)

Introduction: Variables affecting allogeneic hematopoietic stem cell transplantation (HCT) related mortality risk (TMR) include prior comorbidities. Comorbidity indices (CI) aim to improve event prediction by combining independent risk factors. Objectives: 1) to evaluate the use of the brief and adapted version of the HCT-specific comorbidity index for children, adolescents and young adults with malignancies (ymHCT-CI); 2) to evaluate the use of the biomarkers ferritin and albumin in an expanded comorbidity index (expanded ymHCT-CI). Population and methods: Design: retrospective cohort. Period 2017- 2022. Each patient was assigned new scores using the ymHCTCI and expanded ymHCT-CI. The p were classified into low (score 0), intermediate (1-2) and high (>3) risk groups (RG) with each index. The number of patients assigned to each RG and the TMR in each group were compared using the HCTCI, the ymHCT-CI, and the expanded ymHCT-CI. Results: n 75. Frequency of patients per RG according to each indicator (95%CI): HCT-CI low 36 (25-47), intermediate 57 (56-69), high 7 (1-12); ymHCT-CI: low 48 (37-59), intermediate 33 (23-44), high 19 (10-27); expanded ymHCT-CI: low 43 (31-54), intermediate 36 (25-47), high 21 (12-31). TMR by RG according to indicator (95%CI): HCT-CI: low 6.8 (14-28), intermediate 20.9 (9-33), high 17.9 (0-55); expanded ymHCT-CI low 12.5 (1-24), intermediate 18.5 (4-33), high 31.2 (9-54). Conclusion: ymHCT-CI allowed better identification of patients with higher comorbidity and risk of TMR. Ferritin proved to be a useful biomarker to estimate TMR risk (AU)

Carbapenem-resistant Klebsiella pneumoniae colonization and infection is associated with lower overall survival in a cohort of haematopoietic stem-cell transplantation patients: mechanism of resistance and virulence by whole-genome sequencing.

Carbapenem-resistant Klebsiella pneumoniae (CRK) infections are a growing concern in immunocompromised patients. The aim of the present study was to evaluate the impact of CRK colonization and infection in overall mortality for haematopoietic stem-cell transplant (HSCT) patients. We also aimed to investigate resistance and virulence profiles of CRK isolates and assess their epidemiological and genetic relatedness. Patients in the HSCT unit were screened for colonization with CRK with weekly rectal swab or stool cultures and placed under contact precautions. We defined CRK colonization as positive culture from a swab or stool sample grown in MacConkey agar with meropenem at 1 µg ml-1. Demographic and clinical data were retrieved from the patients' charts and electronic records. According to resistance mechanisms and pulsed field gel electrophoresis profile, isolates were selected based on whole-genome sequencing (WGS) using MiSeq Illumina. Outcomes were defined as overall mortality (death up to D+100), and infection-related death (within 14 days of infection). We report a retrospective cohort of 569 haematopoietic stem-cell transplant patients with 105 (18.4 %) CRK colonizations and 30 (5.3 %) infections. blaKPC was the most frequent carbapenemase in our cohort with three isolates co-harbouring blaKPC and blaNDM. We found no difference in virulence profiles from the CRK isolates. There were also no significant differences in virulence profiles among colonization and infection isolates regarding genes encoding for type 1 and 3 fimbriae, siderophores, lipopolysaccharide and colibactin. In clonality analysis by PFGE and WGS, isolates were polyclonal and ST340 was the most prevalent. Overall survival at D+100 was 75.4 % in in CRK-colonized (P=0.02) and 35.7 % in infected patients and significantly lower than non-colonized patients (85.8 %; P<0.001). We found a higher overall mortality associated with colonization and infection; KPC was the main resistance mechanism for carbapenems. The polyclonal distribution of isolates and findings of CRK infection in patients not previously colonized suggest the need to reinforce antibiotic stewardship.

Niños con trasplante de progenitores hematopoyéticos admitidos en una unidad de cuidados intensivos: análisis de la sobrevida y los factores predictivos de mortalidad / Children admitted to a pediatric intensive care unit after hematopoietic stem cell transplantation: Analysis of survival and predictors of mortality

Introducción: El trasplante de células progenitoras hematopoyéticas (TPH) en niños es un procedimiento no exento de complicaciones graves. El ingreso de esta población a unidades de cuidados intensivos pediátricos (UCIP) se asocia con elevada mortalidad. Objetivos: Analizar la sobrevida y los factores predictivos de la mortalidad en niños que recibieron TPH e ingresaron a la UCIP y elaborar un modelo predictivo de mortalidad en esta población. Materiales y métodos: Revisión retrospectiva de niños y adolescentes que recibieron un TPH entre el 01/01/2005 y el 31/12/2019 e ingresaron a la UCIP de un hospital universitario de alta complejidad. Resultados: De un total de 264 niños que recibieron el trasplante, 114 ingresaron a la UCIP. La mortalidad general fue del 29 % (n = 34). El tipo de trasplante, enfermedad basal, evento de neutropenia febril, infección por citomegalovirus, insuficiencia respiratoria, enfermedad de injerto contra huésped (EICH), quimioterapia mieloablativa y desnutrición previa se asociaron con tasas de mortalidad más elevadas. En el análisis multivariado, la EICH (razón de posibilidades [OR, por su sigla en inglés]: 2,23; intervalo de confianza del 95 % [IC 95 %]: 1,92-2,98), la necesidad de ventilación mecánica invasiva (OR: 2,47; IC95 %: 1,39-5,73), el trasplante de donante alternativo (OR: 1,58; IC 95 %: 1,14-2,17) y la desnutrición previa (OR: 1,78; IC 95 %: 1,223-3,89) se asociaron con mayor mortalidad. Conclusión: En la población estudiada, dos de cada tres niños que recibieron TPH e ingresaron a la UCIP sobrevivieron. La EICH, ventilación mecánica, trasplante de donante alternativo y desnutrición previa fueron factores predictivos de mortalidad

Introduction: Hematopoietic stem cell transplantation (HSCT) in children is a procedure that is not exempt of severe complications. Admission to the pediatric intensive care unit (PICU) is associated with a high mortality rate. Objectives: To analyze survival and predictors of mortality among children who received a HSCT and were admitted to the PICU, and to develop a mortality prediction model in this population. Materials and methods: Retrospective review of children and adolescents who received a HSCT between January 1st, 2005 and December 31st, 2019 and were admitted to the PICU of a tertiary care teaching hospital. Results: Out of 264 children receiving the transplant 114 were admitted to the PICU. The overall mortality rate was 29 % (n = 34). The type of transplant, underlying disease, febrile neutropenia event, cytomegalovirus infection, respiratory failure, graft versus host disease (GVHD), myeloablative chemotherapy, and previous malnutrition were associated with higher mortality rates. In the multivariate analysis, GVHD (odds ratio [OR]: 2.23; 95 % confidence interval [CI]: 1.92-2.98), need for mechanical ventilation (OR: 2.47; 95 % CI: 1.39-5.73), alternative donor transplant (OR: 1.58; 95 % CI: 1.14-2.17), and previous malnutrition (OR: 1.78; 95 % CI: 1.22-3.89) were associated with a higher mortality rate. Conclusion: In the studied population, 2 out of 3 children who received a HSCT and were admitted to the PICU survived. GVHD, mechanical ventilation, alternative donor transplant, and previous malnutrition were predictors of mortality

Philadelphia-positive B-lymphoblastic leukemia in a middle-income country - A real-world multicenter cohort.

Outside of clinical trials, few studies have addressed the outcomes of Ph+ acute lymphoblastic leukemia (ALL) in adults, especially from developing world. In this study, we conducted a multicenter analysis on the outcomes of patients aged > 15 years with Ph+ ALL, aiming to get to know an overview of the Brazilian experience as well as to explore baseline factors associated with relapse and mortality in our setting. Over these 10 years, patients were treated with diverse protocols, all of them always combined with a frontline tyrosine-kinase inhibitor. A total of 123 Ph+ ALL patients was included. Imatinib was the first line TKI in 97 %. The complete response rate was 79 %. The early death rate was 15 %, being associated with increasing age at diagnosis (p = 0.06). The use of intensive versus attenuated induction regimen was not associated with higher induction mortality (p = 0.99). Overall, 29 % of patients aged ≤ 60 years underwent allogeneic transplantation, 87 % in first CR. 4-year overall survival (OS) and relapse-free survival were 25 % and 24 %, respectively. The incidence of relapse (death as a competitor) was 29 %, while the non-relapse mortality was 42 %. Only age was independently associated with OS, and lactate dehydrogenase level and central nervous disease at diagnosis were related to relapse in our cohort. This is the first historical cohort multicenter study on Ph+ ALL from Brazil. Reporting these outcomes is essential to encourage public policies to expand access to new drugs and transplantation in middle-income countries.

Comparable Outcomes of Matched Sibling Donor and Matched Unrelated Donor Stem Cell Transplantation in Children With Acute Leukemia in Argentina.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is an effective mode of consolidation therapy for children with high-risk acute leukemia. In high-income countries, match sibling donor (MSD) and match unrelated donor (MUD) HSCT have similar outcomes, but data are scarce in upper-middle-income countries. Our objective was to compare MSD and MUD HSCT outcomes for children with acute leukemia in Argentina. PATIENTS AND METHODS: This was a single-institution retrospective cohort study. We included children with acute leukemia who underwent HSCT with either MSD or MUD between 2014 and 2019. RESULTS: The study included 45 patients who received MSD (n=27) or MUD (n=18) for acute leukemia. Event-free survival was not significantly different between MSD (62.3±10.7%) versus MUD (54.2±15.0%; P=0.54) at 5 years. Similarly, there was no significant difference in 5-year overall survival between MSD (71.9±9.8%) versus MUD (65.1±13.5%; P=0.38). The cumulative incidence of treatment-related mortality (P=0.31), cumulative incidence of relapse (P=0.99), and proportion with acute-graft-versus-host disease (P=0.76) and chronic-graft-versus-host disease (P=0.68) were also not significantly different. CONCLUSIONS: In Argentina, we did not show significant differences in outcomes between MSD and MUD HSCT for children with high-risk leukemia. Future work should focus on strategies to reduce the relapse risk in children with high-risk leukemia in upper-middle-income countries.

Hematopoietic stem cell transplantation for systemic sclerosis: Brazilian experience.

BACKGROUND: In the past 20 years, hematopoietic stem cell transplantation (HSCT) has been investigated as treatment for systemic sclerosis (SSc). The goal of HSCT is to eradicate the autoreactive immune system, which is replaced by a new immune repertoire with long-lasting regulation and tolerance to autoantigens. Here, we describe the clinical outcomes of severe and refractory SSc patients that underwent HSCT at a single Brazilian center. PATIENTS AND METHODS: This is a longitudinal and retrospective study, including 70 adult SSc patients, with an established diagnosis of SSc, and who underwent autologous HSCT from 2009 to 2016. The procedure included harvesting and cryopreservation of autologous hematopoietic progenitor cells, followed by administration of an immunoablative regimen and subsequent infusion of the previously collected cells. Patients were evaluated immediately before transplantation, at 6 months and then yearly until at least 5-years of post-transplantation follow-up. At each evaluation time point, patients underwent clinical examination, including modified Rodnan's skin score (mRSS) assessment, echocardiography, high-resolution computed tomography of the lungs and pulmonary function. RESULTS: Median (range) age was 35.9 (19-59), with 57 (81.4%) female and median (range) non-Raynaud's disease duration of 2 (1-7) years. Before transplantation, 96% of the patients had diffuse skin involvement, 84.2%, interstitial lung disease and 67%, positive anti-topoisomerase I antibodies. Skin involvement significantly improved, with a decline in mRSS at all post-transplantation time points until at least 5-years of follow-up. When patients with pre-HSCT interstitial lung disease were analyzed, there was an improvement in pulmonary function (forced vital capacity and diffusing capacity of lung for carbon monoxide) over the 5-year follow-up. Overall survival was 81% and progression-free survival was 70.5% at 8-years after HSCT. Three patients died due to transplant-related toxicity, 9 patients died over follow-up due to disease reactivation and one patient died due to thrombotic thrombocytopenic purpura. CONCLUSIONS: Autologous hematopoietic progenitor cell transplantation improves skin and interstitial lung involvement. These results are in line with the international experience and support HSCT as a viable therapeutic alternative for patients with severe and progressive systemic sclerosis.

Mortality among pediatric hematopoietic stem cell transplantation patients: Report from a single center in southern Brazil.

INTRODUCTION: HSCT has grown in number in recent years. This treatment in children has its particularities and has been characterized in previous studies only on a limited basis. There are important causes of morbidity and mortality in this group of patients, including evolution of primary disease, graft failure, infectious diseases, and GVHD. The aim of this study was to report case series of TRM within 100 days after transplantation and associated factors. METHODS: Retrospective cohort. All children transplanted between January 1, 2010 and December 31, 2017 were included and those who underwent the first HSCT in another center were excluded. RESULTS: Data from 292 children were analyzed. TRM in 100 days was 5.8%, being significantly higher in patients with umbilical cord blood as the cell source. Infectious complications were frequent in this sample (bacterial infections in 27%, viral infections in 75.3%, and fungal infections in 12%) and both the presence of fungal disease and more than one infection during the follow-up (viral and bacterial, viral and fungal or bacterial and fungal) had statistically significant association with the outcome. CONCLUSIONS: The prognosis in allogeneic HSCT is influenced by the origin of the stem cells, the presence of acute GVHD and the occurrence of infectious diseases. Studies that evaluate pediatric individuals undergoing HSCT and analyze their mortality profile, can improve the management of these patients, possibly leading to a reduction in TRM.

Overcoming barriers for the establishment of a consolidated hematopoietic cell transplantation program in a developing country.

The first hematopoietic cell transplantation (HCT) in Mexico was performed at our institution; however, outcomes were suboptimal the following years, until 1998, when a consolidated HCT was established. The aim of this study was to describe the barriers and the implemented strategies to establish a successful HCT program at a referral center in Mexico and to analyze the outcomes. Barriers were detected based on the results from 1980 to 1997. For the analysis of outcomes, a retrospective study was performed including consecutive patients undergoing autologous, allogeneic, and haploidentical HCT. From November 1998 to December 2018, 363 HCTs were performed (autologous, 59%) in 323 patients. Overall non-relapse mortality (NRM) in autologous and allogeneic HCT was 2% and 14%, respectively. The 5-year overall survival was 71% and 57% for autologous and allogeneic HCT, respectively. The cost of the medications was one of the main limitations for the patients and was successfully overcome by the creation of the non-governmental organization "Unidos". NRM was diminished after reducing the BuCy2 regimen along with the use of bone marrow. Our results highlight that the implementation of unique strategies at our center, led HCT to represent a financially viable and feasible procedure with optimal results.

Infections after hematopoietic cell transplantation are not a burden for mortality at a limited-resource center in a developing country.

BACKGROUND: Hematopoietic cell transplantation (HCT) outcomes, including infectious complications, change between centers and countries. Thus, the aim of this study was to report the incidence of infections and isolated pathogens among recipients of HCT and the association with mortality at a tertiary referral center in Mexico. METHODS: Two hundred and eighty-two patients undergoing autologous or allogeneic HCT between January 2005 and December 2018 at the National Institute of Medical Sciences and Nutricion Salvador Zubiran were included. RESULTS: In autologous HCT (n = 176), within the preengraftment and the early postengraftment, 130 (74%) and 31 (18%) recipients presented infections, respectively. Within the preengraftment, the early postengraftment, and the late postengraftment, 81 (76%), 34 (33%), and 58 (60%) allogeneic HCT recipients presented infections, respectively. Non-relapse mortality (NRM) as a result of infections occurred in 1 (0.6%) and 5 (5%) autologous and allogeneic HCT recipients, respectively. CONCLUSIONS: Our results demonstrated that despite our limited resources, infections were not a significant burden for NRM among HCT recipients. More importantly, the isolation rates were higher than international studies, which could be explained by the existence of a specialized infectious diseases department and laboratory, which we consider key elements for the establishment of an HCT program worldwide.

Treatment of Childhood Acute Myeloid Leukemia in Uruguay: Results of 2 Consecutive Protocols Over 20 Years.

We evaluated the outcome of 71 children with de novo acute myeloid leukemia enrolled in 2 consecutive protocols in the main pediatric hospital in Uruguay. In the LAM97 protocol (n=34), patients received, as consolidation, autologous or allogeneic hematopoietic stem cell transplantation (HSCT), depending on the availability or not of a matched sibling donor. In the LAM08 protocol (n=37), patients were stratified into risk groups, autologous HSCT was abandoned, and allogeneic HSCT was limited to intermediate-risk patients with matched sibling donor and to all patients who fulfilled the high-risk criteria. Complete remission was achieved in 91% and 92% of patients in LAM97 and LAM08, respectively. Deaths in complete remission were 9.6% and 17.6%, respectively. The incidence of relapse was significantly higher in LAM97, 35.4%, versus 12.5% in LAM08. The 5-year event-free survival and overall survival were 50.0% and 55.9% in LAM97 and 59.9% and 64.8% in LAM08. The 5-year overall survival rates in each of the risk groups were 85.7% and 100% for low risk, 50.0% and 61.2% for intermediate risk, and 42.9% and 50.0% for high risk in LAM97 and LAM08 protocols, respectively. Survival has improved over the last 2 decades, and results are comparable to those published in Europe and North America.

Hepatitis B virus among hematopoietic stem cell transplant recipients: Antiviral impact in seroconversion, engraftment, and mortality in a Latin American center.

BACKGROUND: Hepatitis B virus (HBV) infection is a worldwide concern with a broad distribution. In immunosuppressed populations, such as solid organ and hematopoietic stem cell transplant (HSCT) recipients, it can reactivate leading to acute hepatic failure. Different risk factors are known for higher rates of reactivation, and entecavir, tenofovir, and lamivudine are often used for prophylaxis and treatment. However, data regarding the impact of antiviral drugs in neutrophil and platelet engraftment are still unknown and concern the management of viral hepatitis post-HSCT. METHODS: We performed a single-center, retrospective, observational study reviewing medical records of patients referred for hematopoietic stem cell transplant from 2010 to 2017, which were also HBV infected, aiming to describe outcomes related to antiviral treatment and also the impact on platelet and neutrophil recovery after transplant. A secondary goal consisted of analyzing the impact of HBV infection in early and late mortality post-HSCT. The study included patients with positive blood bank screening for hepatitis B infection (HBsAg, Anti-HBc or HBV-NAT), confirmed later on by a laboratory routine serology. RESULTS: A total of 1132 hematopoietic stem cell recipients were assessed between 2010 and 2017. Eighty-six patients were confirmed to have HBV infection, of which six were HBsAg-positive, 20 were isolated anti-HBc-positive, and 60 had resolved infection (anti-HBc-positive and anti-HBs-positive). With regard to prophylaxis, 19 patients underwent HSCT on HBV antiviral therapy or prophylaxis: two were HBeAg-positive, three were HBeAg-negative and HBV-DNA was only detectable in three of them. Moreover, one patient had an occult HBV infection. Regarding therapy, 9 patients were on entecavir, 6 patients on lamivudine, two on tenofovir, and two of them on a combination of tenofovir + lamivudine due to HIV co-infection. Reverse seroconversion was not identified in any patients receiving antiviral therapy or prophylaxis, but it was detected in one patient with occult hepatitis B and another with resolved infection. No severe side effects led to therapy discontinuation in the treated group, which also did not have any significant delay in neutrophil or platelet engraftment when compared to patients without antiviral therapy. In addition, the only factors associated with increased mortality were transplant onset after 50 years, allogeneic transplant and myeloablative conditioning regimens. Interestingly, the presence of HBsAg or detectable HBV-DNA was not related to worse outcomes, neither the use of rituximab. In multivariate analysis, the use of antiviral therapy, the occurrence of graft-versus-host disease or CMV reactivation also was not linked to increased mortality. CONCLUSIONS: To sum up, HBV serology, ALT, and HBV-DNA monitoring are essential to detect hepatic flares earlier, even in populations with chronic inactive hepatitis, due to the possibility of later seroconversion. HBV infection was not related to increased 2-year mortality post-transplant. Antiviral prophylaxis did not cause any important clinical or laboratory side effects that could demand discontinuation, and its use was not associated with later neutrophil and platelet engraftments.

Vacunación BCG e inmunodeficiencias primarias: ¿es momento de un cambio? / BCG vaccine administration schedule and primary immunodeficiencies: Is it time for a change?

Resumen: Los pacientes con Inmunodeficiencias primarias (IDP) tienen un riesgo elevado de complicaciones severas por la vacuna BCG, incluso mortalidad. Es necesario evaluar periódicamente el riesgo versus beneficio de la vacunación universal BCG en el periodo neonatal. Chile es un país con baja incidencia de tuberculosis (TB) pero cuya epidemiología ha cambiado recientemente con un aumento de los casos. Cambios en esquemas de vacunación BCG en países con incidencias mayores o similares de TB y con coberturas de vacunación menores han sido posibles sin aumento de los casos graves de TB que son los que previene la BCG. El cambio ha evitado complicaciones graves en pacientes con IDP. Creemos que un análisis crítico de la fecha de vacunación BCG debe realizarse hoy en Chile. Más aún dada la posibilidad técnica de realizar screening neonatal de IDP.

Abstract: Patients with Primary Immunodeficiencies (PID) are at a higher risk of developing severe morbidities and mortality due to the administration of BCG vaccine. Risk-to-benefit of universal BCG vaccina tion of newborns must be assessed periodically. Chile has a low incidence of tuberculosis (TB) but the local epidemiology has recently changed with an increase of TB cases. Changes in the BCG vaccine schedule have been made in countries with similar or higher TB incidences and lower BCG vaccine coverage, with no increase in the severe TB cases, which are prevented by BCG. These changes have prevented serious complications in PID patients. We propose a critical analysis of the BCG adminis tration date in Chile due to the technical possibility of performing neonatal PID screening.

Clinical outcomes in allogeneic haematopoietic stem cell transplantation: A comparison between young and elderly patients. Observational study.

OBJECTIVES: To analyse clinical outcomes comparing two age groups of patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT), and to identify risk factors associated with older patients' mortality. METHODS: In this retrospective study, the medical charts of all consecutive patients admitted in one hospital for allo-HSCT were reviewed. Overall survival (OS) and other outcomes were compared between patients aged up to 55 years (YG) and older than 55 (EG). RESULTS: From January 2007 to August 2014, 111 adult patients were admitted for allo-HSCT and were included 75 in the YG and 36 in the EG group. The OS rate at D+ 100 was 84% for YG individuals in contrast to 75% in the EG (p = 0.01), and 71% vs. 50% at one year after HSCT (p = 0.01) respectively. Therapy-related mortality (TRM) rates for the YG and EG were, respectively, 14% vs. 17% (p = 0.04) at D+ 100 and 17% vs. 32% (p = 0.04) at one year. Haploidentical donor type and active disease status significantly increased mortality risk in the EG (hazard ratio 2.42; p = 0.018; and 2.04; p = 0.033). CONCLUSION: YG and EG have similar TRM rates early after allo-HSCT, but the elderly had higher TRM during the critical period from 100 days to one year.

Chronic Cholangiopathy Associated with Primary Immune Deficiencies Can Be Resolved by Effective Hematopoietic Stem Cell Transplantation.

OBJECTIVES: To investigate effects and outcome of hematopoietic stem cell transplantation (HSCT) on sclerosing cholangitis, in pediatric patients with different primary immunodeficiencies (PIDs). STUDY DESIGN: From databases in 2 tertiary centers for immunodeficiencies and liver disease, we have identified children with PIDs and sclerosing cholangitis, who have paired clinical, radiologic, and histologic information before and after HSCT and studied their clinical progress and outcome. RESULTS: Seven of 13 children (53.8%) died at a median interval of 4 months (range, 3 months-5 years) after HSCT. However, 6 surviving children (46.2%) with different PIDs and less severe cholangiopathies showed an improvement in markers of liver injury within months of successful unrelated reduced intensity conditioning HSCT. The repeated native liver biopsy, performed in 4 patients at a median of 96 (range, 4-144) months post-HSCT, showed a considerable improvement. Biochemical markers of liver function in the survivors completely normalized after a median of 13 months (range, 2-48). All patients continue to have a mildly dilated extrahepatic biliary system on ultrasonography with no intrahepatic ductal changes on magnetic resonance cholangiography after a follow-up of median 18 years (range, 2-20). CONCLUSIONS: Effective HSCT has the potential to improve biochemical and histologic features of cholangiopathy in children with PIDs, presumably by clearance of chronic infection following establishment of immune competence. However, careful patient selection is critical as advanced liver injury is often associated with serious complications and mortality.

Autologous Transplantation, Consolidation, and Maintenance Therapy in Multiple Myeloma: Results of the BMT CTN 0702 Trial.

PURPOSE: Single-cycle melphalan 200 mg/m2 and autologous hematopoietic cell transplantation (AHCT) followed by lenalidomide (len) maintenance have improved progression-free survival (PFS) and overall survival (OS) for transplantation-eligible patients with multiple myeloma (MM). We designed a prospective, randomized, phase III study to test additional interventions to improve PFS by comparing AHCT, tandem AHCT (AHCT/AHCT), and AHCT and four subsequent cycles of len, bortezomib, and dexamethasone (RVD; AHCT + RVD), all followed by len until disease progression. PATIENTS AND METHODS: Patients with symptomatic MM within 12 months from starting therapy and without progression who were age 70 years or younger were randomly assigned to AHCT/AHCT + len (n = 247), AHCT + RVD + len (n = 254), or AHCT + len (n = 257). The primary end point was 38-month PFS. RESULTS: The study population had a median age of 56 years (range, 20 to 70 years); 24% of patients had high-risk MM, 73% had a triple-drug regimen as initial therapy, and 18% were in complete response at enrollment. The 38-month PFS rate was 58.5% (95% CI, 51.7% to 64.6%) for AHCT/AHCT + len, 57.8% (95% CI, 51.4% to 63.7%) for AHCT + RVD + len, and 53.9% (95% CI, 47.4% to 60%) for AHCT + len. For AHCT/AHCT + len, AHCT + RVD + len, and AHCT + len, the OS rates were 81.8% (95% CI, 76.2% to 86.2%), 85.4% (95% CI, 80.4% to 89.3%), and 83.7% (95% CI, 78.4% to 87.8%), respectively, and the complete response rates at 1 year were 50.5% (n = 192), 58.4% (n = 209), and 47.1% (n = 208), respectively. Toxicity profiles and development of second primary malignancies were similar across treatment arms. CONCLUSION: Second AHCT or RVD consolidation as post-AHCT interventions for the up-front treatment of transplantation-eligible patients with MM did not improve PFS or OS. Single AHCT and len should remain as the standard approach for this population.

Survival Outcomes of Younger Patients With Mantle Cell Lymphoma Treated in the Rituximab Era.

PURPOSE: Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit remains uncertain in the rituximab era. Herein we retrospectively assessed the impact of AHCT consolidation on survival in a large cohort of transplantation-eligible patients age 65 years or younger. PATIENTS AND METHODS: We retrospectively studied transplantation-eligible adults age 65 years or younger with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to assess for improved progression-free survival (PFS) with AHCT consolidation and secondarily to assess for improved overall survival (OS). Cox multivariable regression analysis and propensity score-weighted (PSW) analysis were performed. RESULTS: Data were collected from 25 medical centers for 1,254 patients; 1,029 met inclusion criteria. Median follow-up for the cohort was 76 months. Median PFS and OS were 62 and 139 months, respectively. On unadjusted analysis, AHCT was associated with improved PFS (75 v 44 months with v without AHCT, respectively; P < .01) and OS (147 v 115 months with v without AHCT, respectively; P < .05). On multivariable regression analysis, AHCT was associated with improved PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66; P < .01) and a trend toward improved OS (HR, 0.77; 95% CI, 0.59 to 1.01; P = .06). After PSW analysis, AHCT remained associated with improved PFS (HR, 0.70; 95% CI, 0.59 to 0.84; P < .05) but not improved OS (HR, 0.87; 95% CI, 0.69 to 1.1; P = .2). CONCLUSION: In this large cohort of younger, transplantation-eligible patients with MCL, AHCT consolidation after induction was associated with significantly improved PFS but not OS after PSW analysis. Within the limitations of a retrospective analysis, our findings suggest that in younger, fit patients, AHCT consolidation may improve PFS.

[BCG vaccine administration schedule and primary immunodeficiencies: Is it time for a change?] / Vacunación BCG e inmunodeficiencias primarias: ¿es momento de un cambio?

Patients with Primary Immunodeficiencies (PID) are at a higher risk of developing severe morbidities and mortality due to the administration of BCG vaccine. Risk-to-benefit of universal BCG vaccina tion of newborns must be assessed periodically. Chile has a low incidence of tuberculosis (TB) but the local epidemiology has recently changed with an increase of TB cases. Changes in the BCG vaccine schedule have been made in countries with similar or higher TB incidences and lower BCG vaccine coverage, with no increase in the severe TB cases, which are prevented by BCG. These changes have prevented serious complications in PID patients. We propose a critical analysis of the BCG adminis tration date in Chile due to the technical possibility of performing neonatal PID screening.

Bloodstream infection in hematopoietic stem cell transplantation outpatients: risk factors for hospitalization and death.

We described 235 bloodstream infection (BSI) episodes in 146 hematopoietic stem cell transplantation (HSCT) outpatients and evaluated risk factors for hospitalization and death. Records of outpatients presenting with positive blood cultures over a 5-year period (January 2005 to December 2008) were reviewed. Variables with p< 0.1 in bivariate analysis were used in a regression logistic model. A total of 266 agents were identified, being 175 (66.7%) gram-negative, 80 (30.3%) gram-positive bacteria and 9 (3.4%) fungi. The most common underlying disease was acute leukemia 40 (27.4%), followed by lymphoma non-Hodgkin 26 (18%) and 87 patients (59.6%) were submitted to allogeneic hematopoietic stem cell transplant (HSCT). BSI episodes were more frequent during the first 100 days after transplantation (183 or 77.8%), and ninety-one (38.7%) episodes of BSI occurred up to the first 30 days. Hospitalization occurred in 26% of the episodes and death in 10% of cases. Only autologous HSCT was protector for hospitalization. Although, central venous catheter (CVC) withdrawal and the Multinational Association of Supportive Care in Cancer (MASCC) score up to 21 points were protector factors for death in the bivariate analysis, only MASCC remained as protector.

Infecciones virales en receptores de trasplante alogénico de células progenitoras hematopoyéticas / Viral infections in allogeneic hematopoietic stem cell transplantation recipients

Introducción: El Trasplante alogénico de células progenitoras hematopoyéticas (TCPH) se asocia a una lenta recuperación de sistema inmune, lo que predispone a sus receptores a presentar múltiples complicaciones infecciosas. En este trabajo se analizan las infecciones virales de una cohorte retrospectiva. Material y métodos: se revisó la base de datos del servicio y se registraron las infecciones virales del periodo 2012-2016. Resultados: n 215. El 91% de los receptores y el 70% de los donantes eran CMV positivos antes del trasplante, el 47% de os receptores presentó reactivación de CMV y el 10% enfermedad, con una mortalidad directa del 3,1%. El 87% de los receptores y el 70% de los donantes tenían serología para EBV y el 13% tuvieron una reactivación con una carga viral > 20.000 copias/ml. El 11% de los pac tuvieron enfermedad por Herpes zoster, el 6% por Herpes 6 y el 5% por Herpes simple. Se detectó infección por adenovirus en el 25% de los pacientes, siendo el compromiso más frecuente el digestivo, seguido de la infección respiratoria baja. La mortalidad directa por adenovirus fue 5,1%. Se registraron 41 episodios de infección respiratoria aguda baja por virus respiratorios, con una mortalidad directa del 4%. El 18% de los pac tuvo cistitis hemorrágica por virus BK, con viremia asociada en el 41% de los casos. El 6% de los pacientes presentó falla hematológica asociada a Parvovirus, que un caso fue causa de la pérdida del injerto. Conclusión: las enfermedades virales son una complicación muy frecuente del TCPH y con gran peso en la mortalidad relacionada al trasplante. Los avances terapéuticos han sido menores que los alcanzados en los métodos diagnósticos (AU)

Introduction: Allogeneic hematopietic stem cell transplantation (HSCT) is associated with a slow recovery of the immune system leading to multiple infectious complications. In this study viral infections are evaluated in a retrospective cohort. Material and methods: The data base of the department was reviewed recording viral infections that occurred between 2012-2016. Results: n 215; 91% of the recipients and 70% of the donors were CMV prior to the transplant; 47% of the recipients had a CMV reactivation and 10% developed the disease with a related mortality of 3.1%. Overall, 87% of the recipients and 70% of the donor had a positive serology for EBV and 13% had a reactivation with a viral load of > 20,000 copies/ml. Of the patients, 11% had Herpes zoster, 6% Herpes 6, and 5% Herpes simplex. Adenovirus infection was detected in 25% of the patients, most commonly involving the digestive tract followed by lower respiratory tract infection. Adenovirusrelated mortality was 5.1%. Forty-one acute lower respiratory tract infections due to respiratory viruses were recorded leading to a mortality of 4%. Of all the patients, 18% had BK virus-related hemorrhagic cystitis with associated viremia in 41% of the cases. Six percent of the patients had parvovirusassociated hemotologic failure leading to graft loss in one case. Conclusion: Viral diseases are a very frequent complication in HSCT with a high transplant-related mortality. Advances in therapy have lagged behind advances in diagnostic methods (AU)

Impact of Oral and Gastrointestinal Mucositis on Body Weight Alterations during Hematopoietic Stem Cell Transplantation.

The aim of this study was to evaluate whether digestive tract mucositis is a predictive factor for body weight (BW) alterations during hematopoietic stem cell transplantation (HSCT). Data about characteristics of transplantation, initial nutritional conditions and gastrointestinal mucositis were collected from adult patients (n = 105) who underwent autologous and allogeneic HSCT. Oral mucositis (OM) was not a predictive factor for BW loss, but it was an independent factor for BW gain in autologous HSCT (ß = 0.329, P = 0.021). Busulfan-fludarabine conditioning regimen (ß = 1.531, P = 0.011) and gender (ß = 1.109, P = 0.038) were significant independent risk factors for BW loss in allogeneic HSCT. Overall survival (OS) was significantly affected by the duration of OM in autologous HSCT (HR = 1.243, P = 0.008). In allogeneic HSCT, BW loss (HR = 1.308, P = 0.049) and diarrhea (HR = 1.139, P = 0.012) interfered significantly with OS. In conclusion, OM was not a risk factor for BW loss, but it influenced BW gain and had a negative impact on OS in autologous HSCT patients. Intestinal mucositis explained partially the BW loss and had a negative impact on OS in allogeneic HSCT.