To Lighten the Burden of Cure: Thyroid Disease in Long-Term Survivors After TBI Conditioning for Paediatric ALL

This consensus document is intended to serve 3 functions. First, it standardizes the criteria for diagnosis of chronic graft-versus-host disease (GVHD). Second, it proposes a new clinical scoring system (0-3) that describes the extent and severity of chronic GVHD for each organ or site at any given time, taking functional impact into account. Third, it proposes new guidelines for global assessment of chronic GVHD severity that are based on the number of organs or sites involved and the degree of involvement in affected organs (mild, moderate, or severe). Diagnosis of chronic GVHD requires the presence of at least 1 diagnostic clinical sign of chronic GVHD (e.g., poikiloderma or esophageal web) or the presence of at least 1 distinctive manifestation (e.g., keratoconjunctivitis sicca) confirmed by pertinent biopsy or other relevant tests (e.g., Schirmer test) in the same or another organ. Furthermore, other possible diagnoses for clinical symptoms must be excluded. No time limit is set for the diagnosis of chronic GVHD. The Working Group recognized 2 main categories of GVHD, each with 2 subcategories. The acute GVHD category is defined in the absence of diagnostic or distinctive features of chronic GVHD and includes (1) classic acute GVHD occurring within 100 days after transplantation and (2) persistent, recurrent, or late acute GVHD (features of acute GVHD occurring beyond 100 days, often during withdrawal of immune suppression). The broad category of chronic GVHD includes (1) classic chronic GVHD (without features or characteristics of acute GVHD) and (2) an overlap syndrome in which diagnostic or distinctive features of chronic GVHD and acute GVHD appear together. It is currently recommended that systemic therapy be considered for patients who meet criteria for chronic GVHD of moderate to severe global severity.

There is a high prevalence of thyroid nodules on ultrasonographic (US) examination. However, most of them are benign. US criteria may help to decide cost-effective management. Our objective was to develop a standardized US characterization and reporting data system of thyroid lesions for clinical management: the Thyroid Imaging Reporting and Data System (TIRADS). This was a prospective study using the TIRADS, which is based on the concepts of the Breast Imaging Reporting Data System of the American College of Radiology. A correlation of the US findings and fine needle aspiration biopsy (FNAB) results in 1959 lesions biopsied under US guidance and studied histologically during an 8-yr period was divided into three stages. In the first stage, 10 US patterns were defined. In the second stage, four TIRADS groups were defined according to risk. The percentages of malignancy defined in the Breast Imaging Reporting and Data System were followed: TIRADS 2 (0% malignancy), TIRADS 3 ( 80% malignancy). The TIRADS classification was evaluated at the third stage of the study in a sample of 1097 nodules (benign: 703; follicular lesions: 238; and carcinoma: 156). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 88, 49, 49, 88, and 94%, respectively. The ratio of benign to malignant or follicular FNAB results currently is 1.8. The TIRADS has allowed us to improve patient management and cost-effectiveness, avoiding unnecessary FNAB. In addition, we have established standard codes to be used both for radiologists and endocrinologists.

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; ClinicalTrials.gov: 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; P 4 years old with high-risk ALL undergoing allogeneic HSCT.