Publications by authors named "Raquel Staciuk"

9 Publications

  • Page 1 of 1

Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multinational, Randomized, Noninferiority Phase III Study.

J Clin Oncol 2021 Feb 17;39(4):295-307. Epub 2020 Dec 17.

Goethe University, University Hospital Frankfurt, Department for Children and Adolescents, Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, Frankfurt am Main, Germany.

Purpose: Total body irradiation (TBI) before allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with acute lymphoblastic leukemia (ALL) is efficacious, but long-term side effects are concerning. We investigated whether preparative combination chemotherapy could replace TBI in such patients.

Patients And Methods: FORUM is a randomized, controlled, open-label, international, multicenter, phase III, noninferiority study. Patients ≤ 18 years at diagnosis, 4-21 years at HSCT, in complete remission pre-HSCT, and with an HLA-compatible related or unrelated donor were randomly assigned to myeloablative conditioning with fractionated 12 Gy TBI and etoposide versus fludarabine, thiotepa, and either busulfan or treosulfan. The noninferiority margin was 8%. With 1,000 patients randomly assigned in 5 years, 2-year minimum follow-up, and one-sided alpha of 5%, 80% power was calculated. A futility stopping rule would halt random assignment if chemoconditioning was significantly inferior to TBI (EudraCT: 2012-003032-22; NCT01949129).

Results: Between April 2013 and December 2018, 543 patients were screened, 417 were randomly assigned, 212 received TBI, and 201 received chemoconditioning. The stopping rule was applied on March 31, 2019. The median follow-up was 2.1 years. In the intention-to-treat population, 2-year overall survival (OS) was significantly higher following TBI (0.91; 95% CI, 0.86 to 0.95; < .0001) versus chemoconditioning (0.75; 95% CI, 0.67 to 0.81). Two-year cumulative incidence of relapse and treatment-related mortality were 0.12 (95% CI, 0.08 to 0.17; < .0001) and 0.02 (95% CI, < 0.01 to 0.05; = .0269) following TBI and 0.33 (95% CI, 0.25 to 0.40) and 0.09 (95% CI, 0.05 to 0.14) following chemoconditioning, respectively.

Conclusion: Improved OS and lower relapse risk were observed following TBI plus etoposide compared with chemoconditioning. We therefore recommend TBI plus etoposide for patients > 4 years old with high-risk ALL undergoing allogeneic HSCT.
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February 2021

Status of the transition/transfer process for adolescents with chronic diseases at a national pediatric referral hospital in Argentina.

Arch Argent Pediatr 2017 Dec;115(6):562-569

Servicio de Crecimiento y Desarrollo, Hospital Nacional de Pediatría "Prof. Dr. Juan P. Garrahan".

Introduction: The shift of adolescents from a pediatric to an adult health care facility is a complex process. The objective of this study was to assess the transition/transfer process for adolescents with chronic diseases at Hospital Garrahan.

Methods: Observational, cross-sectional, qualitative-quantitative study. Retrospective statistical data were obtained in relation to outpatient visits of patients aged 16-26; surveys and/or interviews were done with health care providers, adolescents, and family members from different follow-up programs.

Results: The prevalence of care provided to individuals older than 16 years was 7.2%. Surveys were administered to 54 attending health care providers, 150 patients (16-26.7 years old) and 141 family members. In addition, 45 health care providers with management functions were interviewed. Health care providers: 39% had received training on transition. All identified barriers and facilitators among the different participants and facilities. They recognized the importance of encouraging autonomy among their patients, but only 30% of them interviewed their patients alone, and 56.6% delivered medical reports. Strategies: the median age of transfer was 18 years (13-20); 62% had a protocol; 84% had an informal agreement with another facility; joint or parallel care: 49%; only 20% implemented a transition plan. Patients and family members: 4.7% of adolescents attended visits alone, and health care providers had asked 45% about their autonomy and preparation to take care of their health. Adolescents and their parents had feelings (mostly negative) regarding the process and identified facilitation strategies, such as receiving a summary, knowing the new facility, and having trained health care providers.

Conclusions: The transition process for adolescents with chronic diseases is still deficient and approaching it involves health care teams and the families. A lack of formal inter-institutional agreements was identified, although there were more informal agreements among health care providers; besides, the need to encourage chronically-ill patients' autonomy was also determined. In relation to facilitation strategies, patients and parents mainly recognized the need to have a medical summary, health care guidelines, and trust in the new provider.
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December 2017

Therapeutic monitoring of pediatric transplant patients with conversion to generic tacrolimus.

Farm Hosp 2017 Mar 1;41(2):150-168. Epub 2017 Mar 1.

Clinical Pharmacokinetics Department, J.P. Garrahan Children's Hospital, Buenos Aires. National Scientific and Technological Research Council (CONICET)..

Objective: Therapeutic monitoring during interchange of tacrolimus commercial formulations is essential to ensure similar exposure in transplant patients. However, there are limited data in the pediatric transplant population. This study aims to evaluate exposure, safety and efficacy in maintenance pediatric transplant patients under generic tacrolimus substitution.

Method: Pediatric patients who underwent interchange of tacrolimus formulations were detected by the Service of Pharmacy and included in this study. Tacrolimus trough levels (C0), laboratory parameters and clinical characteristics were recorded before and after the switch. Statistical analysis was performed using Wilcoxon matched pair t-test.

Results: In total, 10 patients with kidney, liver, heart and hematopoietic stem cell transplantation received the innovator and switched to the generic product. The median (range) of the C0 normalized by the dose before and after switch was 74.8 [(ng/ml)/(mg/kg)] (13.8-518.4) and 65.1 [(ng/ml)/(mg/kg)] (13.5-723.5), respectively (p>0.05). Tacrolimus dose was 0.070(mg/kg) (0.024-0.461) and 0.069(mg/kg) (0.017- 0.571) for the innovator and generic formulation, respectively, with no difference when comparing both values (p>0.05). Laboratory parameters did not change after conversion (p>0.05). Adverse events, acute rejection, death and graft loss were not observed.

Conclusion: In our study population, no significant differences in terms of laboratory parameters, drug exposure and dose were observed. We emphasize the need of close monitoring to ensure a safe interchange, especially in vulnerable populations such as the pediatric.
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March 2017

Validation of the Argentine Spanish version of Transition Readiness Assessment Questionnaire for adolescents with chronic conditions.

Arch Argent Pediatr 2017 02;115(1):18-27

Hospital Nacional de Pediatría Garrahan, Buenos Aires, Argentina.

Introduction: The transition of adolescents with chronic conditions to adult follow-up care is an increasingly complex process. Patients need to acquire knowledge and skills that ensure continuity of their care. The goal of this study was to validate the Argentinian Spanish version of the Transition Readiness Assessment Questionnaire (TRAQ) 5.0 tool in adolescents and young adults with chronic conditions.

Population And Methods: Descriptive, crosssectional, quantitative study. Patients with chronic conditions aged 14 years or older treated at Hospital Garrahan were included. The TRAQ is made up of 20 items divided into 5 subscales (Managing Medication, Appointment Keeping, Tracking Health Issues, Talking with Providers, Managing Daily Activities), and is designed to be self-administered. Patients completed the TRAQ, as well as an opinion survey about its use and a self-perceived autonomy scale; their physicians answered a scale about patients' health impairment due to the condition. Sociodemographic, clinical and TRAQ-related variables were recorded.

Results: A total of 191 patients participated. The majority of patients (96.3%) understood the TRAQ 5.0 questionnaire and completed it correctly, in self-administered modality, in a short time (median: 5 minutes), with little or no help (81%). Patients who live in poverty or have a lower education level than the one expected for their age needed more help. Internal consistency (Cronbach's alpha) for the overall score was 0.81. Construct validity was demonstrated by testing different hypotheses (all p < 0.05): discrimination by age ≥ 16 years (3.01 vs. 3.34), sex (women: 3.38 > men: 3.12) and having plans for the future (without plans: 3.01 < with plans: 3.34); correlation with self-perception scale (r= 0.49).

Conclusion: The TRAQ 5.0 tool is available for use in Argentinian adolescents with chronic conditions.
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February 2017

Validation of the Hematopoietic Cell Transplantation-Specific Comorbidity Index in a retrospective cohort of children and adolescents who received an allogeneic transplantation in Argentina.

Arch Argent Pediatr 2016 Aug 30;114(4):337-42. Epub 2016 Jun 30.

Servicio de Trasplante de Médula Ósea, Hospital Garrahan, Ciudad Autónoma de Buenos Aires, Argentina.

Introduction: Hematopoietic cell transplantationis a therapy with a risk of transplant-related mortality (TRM), which may vary depending on prior comorbidities. The Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) is an instrument developed to measure this risk. There are very few reports on its use in pediatrics. The objective of this study was to validate the HCT-CI in a pediatric cohort of allogeneic hematopoietic-cell transplantation recipients in Argentina.

Population And Methods: Retrospective cohort made up of 140 transplant patients a, Hospital J. P. Garrahan between 2008 and 2012. Medical records were reviewed to identify patient history and course. The HCT-CI was estimated for each patient, who was classified as having a low (score: 0), intermediate (score: 1-2) or high (score: >3) risk. Survival was estimated for each group using the Kaplan-Meier method and compared with the log-rank test. For malignancies, relapse was considered an event consistent with TRM. A p value 〈 0.05 was considered significant.

Results: The median score in the HCT-CI was 1 (r: 0-6). A score of 0 was observed in 45.7% of patients, 1-2 in 40.7%, and >3 in 13.6%. The most common comorbidities included obesity, infection, pulmonary and liver involvement. TRM was 14.1% among patients with a score of 0; 43.7% with a score of 1-2, and 52.6% with a score >3. Differences were observed among the survival curves of the three groups (p = 0.01).

Conclusions: The HCT-CI demonstrated to be an effective tool to predict the risk of TRM in our setting.

Key Words: comorbidity, hematopoietic stem cell transplantation, non-relapse mortality, pediatrics.
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August 2016

Allogeneic hematopoietic stem cell transplantation in pediatric myelodysplastic syndromes: a multicenter experience from Argentina.

Pediatr Blood Cancer 2015 Jan 27;62(1):153-7. Epub 2014 Sep 27.

Hospital Privado Centro Médico de Córdoba, Córdoba, Argentina; Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Córdoba, Argentina.

Background: Allogeneic hematopoietic stem cell transplantation (AHSCT) represents the only curative treatment for the majority of pediatric patients with Myelodysplastic Syndrome (MDS). We aimed to evaluate overall survival (OS), disease-free survival (DFS), non-relapse mortality (NRM) and relapse incidence in children who underwent AHSCT for MDS in six institutions from Argentina.

Procedure: A retrospective analysis of 54 AHSCT was carried out in 52 patients (mean age: 9 years; range: 2-19; 35 males).

Results: MDS subtypes were refractory cytopenia of childhood (RCC) (n: 26, 50%), refractory anemia with excess blasts (RAEB) (n: 9, 18%), RAEB in transformation (RAEB-T) (n: 8, 15%) and juvenile myelomonocytic leukemia (JMML) (n: 9, 17%). At time of transplant, seven (13%) patients transformed to acute myeloid leukemia (AML) and two patients with RCC to RAEB. Donors were related in 32 cases (59%) and the stem cells source was: bone marrow (63%), peripheral blood (26%), and umbilical cord blood (11%). Five-year DFS and OS were 50% and 55% respectively; and for patients with JMML, 57% and 67% respectively. Cumulative incidence of NRM and relapse were 27% and 21% respectively. In the multivariate analysis, umbilical cord blood (HR 4.07; P = 0.025) and age ≥ 9 years at transplantation (HR 3.28; P = 0.017) were associated with lower OS; age and graft-versus-host disease (GVHD) had a higher NRM.

Conclusions: In our series, more than half of the patients achieved long term OS with AHSCT. Less toxic conditioning regimens or more intensive GVHD prophylaxis could lead to better results in some children.
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January 2015

[Erythrocyte indexes in hereditary spherocytosis].

Medicina (B Aires) 2007 ;67(6 Pt 2):698-700

Servicio de Hematología-Oncología, Hospital de Pediatría Juan P. Garrahan, Buenos Aires, Argentina.

Hereditary spherocytosis is a group of heterogenous disorders characterized by variability in its clinical manifestations, membrane protein defects and inheritance. We analysed the sensitivity and specificity of mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width (RDW) in the diagnostic screening of hereditary spherocytosis. Ninety-four patients were compared to equal number of healthy, age-matched children. All indexes were derived from measurements obtained by aperture impedance (Coulter Counter Model JT). In patients with hereditary spherocytosis, MCHC (35.67+/-1.33 g/dl) and RDW (20.60+/-4.5%) were significantly higher than in normal control subjects (MCHC 33.48+/-0.68 g/dl, p: 0.000; RDW 13.22+/-0.9%, p: 0.000). By using a cutoff for the MCHC of 34.5 g/dl and for the RDW of 14.5%, both indexes showed a sensitivity of 81% and a specificity of 98.9%. The combination of the two test is an excellent predictor for the diagnosis of hereditary spherocytosis.
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January 2009

Hb Alesha [beta67(E11)Val-->Met, GTG-->ATG] in an Argentinean girl.

Hemoglobin 2007 ;31(3):379-82

Servicio de Hematología-Oncología, Hospital de Pediatría "Prof. Dr. Juan. P. Garrahan", Buenos Aires, Argentina.

Hb Alesha is caused by a GTG-->ATG mutation at codon 67 of the beta-globin gene, resulting in abnormal beta-globin chains in which the normal beta67(E11) valine is changed to methionine. This hemoglobin (Hb) is also known as Hb Bristol, the first unstable Hb described, since in a fraction of the variant the methionine is modified into an aspartic acid by a posttranslational modification. This replacement disrupts the apolar bonds between the valine and the heme group, producing an unstable Hb and severe hemolysis. We have identified this rare hemoglobinopathy in an Argentinean girl with severe hemolytic anemia, splenomegaly and frequent requirement for red blood cell transfusions.
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October 2007

Hb Southampton [beta106(G8)Leu-->Pro, CTG-->CCG] in an Argentinean boy.

Hemoglobin 2006 ;30(3):401-3

Servicio de Hematología-Oncología, Hospital de Pediatría, Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.

Hb Southampton (also known as Hb Casper) is characterized by the substitution of a leucine residue for a proline at codon beta106 (CTG-->CCG). This mutation breaks the G helix and severely distorts the tertiary structure of the molecule, producing an unstable hemoglobin (Hb) and severe hemolysis. We identified this hemoglobinopathy in a young patient with severe hemolytic anemia and hepatosplenomegaly.
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August 2006