No abstract

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 < .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; P < .0001) and 0.02 (95% CI, < 0.01 to 0.05; P = .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.

Key Points• Patients with thalassemia major or sickle cell disease had excellent outcomes after both CBT and BMT from an HLA-identical sibling.• Related cord blood transplantation is a suitable transplant option for patients with hemoglobinopathies.We analyzed the outcomes of 485 patients with thalassemia major (TM) or sickle cell disease (SCD) receiving HLA-identical sibling cord blood transplantation (CBT, n 5 96) or bone marrow transplantation (BMT, n 5 389). Compared with patients given BMT, CBT recipients were significantly younger (median age 6 vs 8 years, P 5 .02), and were treated more recently (median year 2001 vs 1999, P < .01). A higher proportion of patients with TM belonging to classes II-III of the Pesaro classification received BMT (44%) compared with CBT (39%, P < .01). In comparison with patients receiving BMT (n 5 259, TM; n 5 130, SCD), those given CBT (n 5 66, TM; n 5 30, SCD) had slower neutrophil recovery, less acute graft-versus-host disease (GVHD) and none had extensive chronic GVHD. With a median follow-up of 70 months, the 6-year overall survival was 95% and 97% after BMT and CBT, respectively (P 5 .92). The 6-year disease-free survival (DFS) was 86% and 80% in TM patients after BMT and CBT, respectively, whereas DFS in SCD patients was 92% and 90%, respectively. The cell dose infused did not influence outcome of patients given CBT. In multivariate analysis, DFS did not differ between CBT and BMT recipients. Patients with TM or SCD have excellent outcomes after both HLA-identical sibling CBT and BMT. (Blood. 2013;122(6):1072-1078

Key Points UCBT is a suitable option for children with JMML, being able to cure a relevant proportion of patients. Because disease recurrence remains the major cause of treatment failure after UCBT, strategies aimed at reducing relapse are desirable.

No abstract

Burnout is a major problem in pediatric oncology staff. Mindfulness practices can be taught in the workplace and may be a useful component of a multidimensional strategy to reduce burnout in this population.

BACKGROUND Stomatitis is a common consequence of chemotherapy and a condition for which there is little effective treatment. Although the management of patients with other chemotherapy‐related toxicities has improved in recent years, the incidence of stomatitis is increasing because of more intensive treatment and is often a dose limiting factor in chemotherapy. The authors assessed the efficacy of a homeopathic remedy, TRAUMEEL S®, in the management of chemotherapy‐induced stomatitis in children undergoing bone marrow transplantation. METHODS A randomized, placebo‐controlled, double‐blind clinical trial was conducted in 32 patients ages 3–25 years who had undergone allogeneic (16 patients) or autologous (16 patients) stem cell transplantation. Of the 30 evaluable patients, 15 were assigned placebo, and 15 were assigned TRAUMEEL S both as a mouth rinse, administered five times daily from 2 days after transplantation for a minimum of 14 days, or until at least 2 days after all signs of stomatitis were absent. Stomatitis scores were evaluated according to the World Health Organization grading system for mucositis. RESULTS A total of five patients (33%) in the TRAUMEEL S treatment group did not develop stomatitis compared with only one patient (7%) in the placebo group. Stomatitis worsened in only 7 patients (47%) in the TRAUMEEL S treatment group compared with 14 patients (93%) in the placebo group. The mean area under the curve stomatitis scores were 10.4 in the TRAUMEEL S treatment group and 24.3 in the placebo group. This difference was statistically significant (P < 0.01). CONCLUSIONS This study indicates that TRAUMEEL S may reduce significantly the severity and duration of chemotherapy‐induced stomatitis in children undergoing bone marrow transplantation. Cancer 2001;92:684–90. © 2001 American Cancer Society.

Endocrine dysfunction and parameters of metabolic syndrome were assessed in 91 patients aged 4.3-32.5 years who underwent allogeneic or autologous BMT in childhood. Final short stature, found in five of the 35 patients who attained final height, was associated with the underlying disease (specifically, Fanconi anemia) (P ¼ 0.0013), previous cranial irradiation (P ¼ 0.0007), type of conditioning irradiation (Po0.05) and allogeneic BMT (P ¼ 0.05). Growth hormone deficiency (n ¼ 10) was associated with previous cranial irradiation (Po0.005) and conditioning total body irradiation (Po0.001). Twelve patients had primary hypothyroidism, one had hyperthyroidism and one papillary thyroid carcinoma. Hypothyroidism was associated with neck/mediastinal (Po0.005) and conditioning irradiation (Po0.05). Primary gonadal failure was found in 24 of the mature patients (62.5% females). Hypogonadism was associated with the underlying disease (especially hematological malignancies) (Po0.05), pretransplant treatment (Po0.05), irradiation conditioning (Po0.001), older age (Po0.005) and advanced pubertal stage at BMT (Po0.05). Obesity (body mass index 42 s.d.) was found in 4.4% and type II diabetes and impaired glucose tolerance in 3.3% each. Dyslipidemia was found in 27.9% of the 43 patients tested. These findings emphasize the need for long-term follow-up of endocrine and metabolic parameters in young patients after BMT in order to offer proper treatment and improve quality of life.