CONDITIONING REGIMEN FOR LANGERHANS HISTIOCYTOSIS

Langerhans cell histiocytosis (LCH) is a rare disease, with an estimated incidence of 0.5 per 100,000 children in the United States of America1. HCL occurs due to differentiation of myeloid precursors into CD1a+ / CD207+ cells and is characterized by constitutional activation of the MAPK2 signaling pathway, leading to a spectrum of organ involvement and dysfunction. Treatment of HCL is risk-adjusted: single lesions may respond to local treatment whereas multisystem disease requires systemic therapy. Although survival for patients without organ dysfunction is excellent3, mortality in those with compromised organs at risk (hematopoietic system, liver, and/or spleen) reaches 20%2,4. Despite the progress made in the treatment of HCL, disease reactivation rates remain above 30% and the best second-line treatment has not yet been established. Treatment failure is associated with increased morbidity and mortality, including an association with neurodegeneration2. As it is a rare disease and generally has a good prognosis, few scientific studies are evaluating the role of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of this disease. In 2015 Veys et al5 published retrospective results of 87 high-risk patients transplanted between 1990 and 2013. Myeloablative conditioning regimens (MAC) based on total body irradiation or busulfan6 were the most used until the 2000s, and reduced-intensity conditioning regimens (RIC) – predominantly a combination of Melphalan and Fludarabine – were most used between 2000 and 2013. Transplant-associated mortality rates in 3 years were similar between RIC and MAC conditioning regimens (21% versus 15%, respectively). Recurrence was higher in the RIC group compared to the MAC group (28% versus 8%, respectively), however, the 3-year overall survival (OS) was similar (77% versus 71%, respectively), since the patients who relapsed after RIC transplantation could be rescued with chemotherapy. More recently, Kudo et al7 published a retrospective study with 30 patients with refractory LCH who underwent HSCT between 1996 and 2014. Eleven patients received myeloablative conditioning regimen based on total body radiotherapy (RCT) with a dose equal to or greater than 8 Gy or busulfan, and 19 of reduced intensity based on Fludarabine and Melphalan, associated or not with low dose of RCT. There was no significant difference between the conditioning regimen modalities, with OS of 56.8% for the RIC group and 63.6% for the MAC group. Disease status was the main prognostic factor, with a 5-year OS of 100% for patients who arrived at HSCT with disease in remission or with partial remission, versus 54.5% for those who had active disease at the time of the procedure. Regarding the type of donor used and the source of stem cells, there is great variation, with greater frequency for unrelated and extensive use of bone marrow and umbilical cord, and apparently, there is no impact on survival rates.5, 6 There are few case reports and extremely restricted performance of autologous HSCT in HCL.

HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR PEDIATRIC LYMPHOMAS

Lymphomas are the third most common cancer of childhood in Brazil. Over the past few decades, the prognosis has significantly improved, however relapsed or refractory disease is still associated with an inferior outcome. Hematopoietic stem cell transplantation (HSCT) is the standard salvage treatment strategy for these patients. A review was made using the most relevant articles and discussion between the authors was done for guide the recomendations exposed here.

Acute and Chronic Graft-Versus-Host-Disease – A Focus on Pediatric Patients

Graft-versus-host disease (GVHD), either in its acute or chronic form, is the main contributory factor for morbidity and non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recent advancements in the classification of this disease, with better applicability and reproducibility of standardized criteria, coupled with improvements in the management of steroid-refractory or resistant cases, have led to promising results. In 2020, the Brazilian Group for Pediatric Bone Marrow Transplantation of the Brazilian Society for Blood and Marrow Transplantation and Cellular Therapy (SBTMO) convened a task force to provide updated, evidence-based guidance for the diagnosis, classification, staging, prophylaxis, and treatment of GVHD, with a focus on the pediatric population, the results of which are presented here.

Brazilian Consensus Guidelines for Hematopoietic Stem Cell Transplantation - Inborn errors of metabolismo

Hematopoietic stem cell transplantation (HSCT) has the potential to cure a significant proportion of patients with malignant and nonmalignant diseases. The main rationale for HSCT in inborn errors of metabolism (IEM) is based on correcting the decreases enzymes by the donor cells within and outside the intravascular compartment. In this article, Brazilian Group for Pediatric Bone Marrow Transplantation of the Brazilian Society of Bone Marrow Transplantation and Cellular Therapy (SBTMO) provides a review of HSCT indications in IEM.

Hematopoietic Stem Cell Transplantation for Pediatric Acute Myeloid Leukemia - SBTMO/SOPOBE 2020 Consensus Guidelines

Acute myeloid leukemia (AML) represents 15%–20% of acute leukemias in children, and the risk of treatment failure is based on genetic risk and response to therapy1-4. Although the initial remission rate exceeds 90%, more than 30-40% of children with AML die of refractory/relapsed disease or treatment-related toxicity5. The best therapeutic results are achieved by integrating intensive chemotherapy, optimal supportive care, and hematopoietic stem cell transplant (HSCT) adapted to each patient’s risk of relapse6–9. In 2020, the Brazilian Group for Pediatric Bone Marrow Transplantation of the Brazilian Society of Bone Marrow Transplantation and Cellular Therapy (SBTMO) and the Brazilian Society for Pediatric Oncology (SOBOPE) convened a task force to provide general guidance on HSCT for childhood AML to provide evidence-based guidance for the appropriate management of this disease.

Hematopoietic Stem Cell Transplantation for Pediatric Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) accounts for approximately 2 to 3% of all pediatric leukemias. Compared to adults, children tend to present with more aggressive features, such as higher leukocyte counts and massive splenomegaly, and are more likely to be diagnosed with advanced stage disease. Before the advent of tyrosine kinase inhibitors, a couple of decades ago, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was the mainstay of treatment for this disease. This, however, was associated with considerable treatment-related morbidity and mortality. Even so, despite its secondary and somewhat limited indication today, allo-HSCT remains an important alternative and the only curative treatment for CML. In 2020, the Brazilian Group for Pediatric Bone Marrow Transplantation of the Brazilian Society for Blood and Marrow Transplantation and Cellular Therapy (SBTMO) convened a task force to provide evidence-based guidance on the use of allo-HSCT for the appropriate management of childhood CML, the results of which are presented here.

Consensus on Indications for Hematopoietic Stem Cell Transplantation in Pediatrics. Update 2020: Germ Cell Tumors and Wilms tumors

The indications for hematopoietic stem cell transplantation in solid tumors in children do not change a lot since our first Brazilian consensus publication in 2009. In this article, we are going to review indications to hematopoietic stem cell transplantation in pediatric germ cell tumors and wilms tumor. For the consensus, a review was made using the most relevant articles, and a series of meetings was done to discuss the recommendations.

Long-Term Follow-Up of Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation

Hematopoietic stem cell transplantation (HSCT) offers the opportunity for cure to patients with malignant and non-malignant diseases. Given the myriad advances in the past few decades, coupled with the rising numbers of transplants worldwide, the number of long-term survivors, many of whom are free of the disease for which they were transplanted, is constantly increasing. Despite the improved prognosis observed overall, long-term outcome may be undermined by transplant-associated morbidity and mortality. Long-term survivors may present a variety of complications, comprising physical, psychological, social, and economic arenas, with a deep impact on quality of life. Therefore, drawing greater attention to and raising awareness of the potential long-term effects of HSCT is key to providing a tailored approach to pretransplant counseling and to devising appropriate recommendations for post-transplant screening, prevention, and timely treatment of secondary events. In 2020, the Brazilian Group for Pediatric Bone Marrow Transplantation of the Brazilian Society for Blood and Marrow Transplantation and Cellular Therapy (SBTMO) convened a task force to provide updated, evidence-based guidance for the long- term follow-up of pediatric patients undergoing HSCT, the results of which are presented here.

Antineoplastic agents used in pediatric hematopoietic bone marrow transplantation: a review about pharmacology and pharmaceutical issues.

This article proposes the characterization of the main chemotherapeutic agents used in hematopoietic stem cell transplantation in pediatric patients, carrying out a review of the main pharmacological and pharmacokinetic characteristics that are peculiar to children, as well as technical aspects for the handling, prescription, and administration of each one of these. It is extremely important that all professionals know how to recognize the characteristics of each drug and how its peculiarities impact the quality of patient's treatment, being able to predict and propose necessary interventions for potential problems of therapy, which can be identified and measured.

Hematopoietic stem cell transplantation for neuroblastoma

The indications for hematopoietic stem cell transplantation in solid tumors in children do not change a lot since our first Brazilian consensus publication in 2009. In this article, we are going to review indications to hematopoietic stem cell transplantation for neuroblastoma. For the consensus, a review was made using the most relevant articles, and a series of meetings was done to discuss the recommendations.