Allogeneic Hematopoietic Stem Cell Transplantation for Children and Adolescents with Acute Myeloid Leukemia in Brazil: A Multicentric Retrospective Study

Abstract

The survival rates of children with high-risk acute myeloid leukemia (AML) treated with hematopoietic stem cell transplant (HSCT) range from 60% to 70% in high-income countries. The corresponding rate for Brazilian children with AML who undergo HSCT is unknown. We conducted a retrospective analysis of 114 children with AML who underwent HSCT between 2008 and 2012 at institutions participating in the Brazilian Pediatric Bone Marrow Transplant Working Group. At transplant, 38% of the children were in first complete remission (CR1), 37% were in CR2, and 25% were in CR3+ or had persistent disease. The donors included 49 matched-related, 59 matched-unrelated, and six haploidentical donors. The most frequent source of cells was bone marrow (69%), followed by the umbilical cord (19%) and peripheral blood (12%). The 4-year overall survival was 47% (95% confidence interval [CI] 30%–57%), and the 4-year progression-free survival was 40% (95% CI 30%–49%). Relapse occurred in 49 patients, at a median of 122 days after HSCT. There were 65 deaths: 40 related to AML, 19 to infection, and six to graft versus host disease. In conclusion, our study suggests that HSCT outcomes for children with AML in CR1 or CR2 are acceptable and that this should be considered in the overall treatment planning for children with AML in Brazil. Therapeutic standardization through the adoption of multicentric protocols and appropriate supportive care treatment will have a significant impact on the results of HSCT for AML in Brazil and possibly in other countries with limited resources.

The use of micro-costing in an economic analysis of allogeneic HSCT in Brazil

“…Other studies from the same public institution where our patients came from also reported long hospitalization time and long time between diagnosis and HSCT (>12 months) for patients with low socioeconomic status (Paz et al, 2018;Pitombeira et al, 2013;Silla et al, 2009). Since the limitation in the number of hospital beds for performing HSCT in Brazil, patients with indications for transplantation and with a donor located remain on a waiting list until bed availability (Rodrigues et al, 2020). Besides the order of arrival, this list considers prioritization criteria such as age and disease type (Brazil, 2017).…”

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

“…11 In a study with Brazilian HSCT centers for children, adolescents, and young adults, OS and EFS in 4 years were 47% and 40%, respectively. 12 Brazilian outcomes of HSCT in children with AML appear to be inferior to those reported in the United States and Europe. A report by Bitan et al from the Center for International Blood and Marrow Transplant Research (CIBMTR) on 141 pediatric patients with AML who underwent the transplant in CR1 showed a 5-year PFS of 54% after myeloablative conditioning 13 .…”

“…The results of transplants using related, unrelated (matched or partially matched, with a greater than a 8/10 HLA-match) and haploidentical donors are very similar in AML, with no significant difference between type of donor, whether in overall survival, incidence of acute or chronic graft-versus-host disease (GVHD) 12,19 . In children, bone marrow is preferable in comparison to peripheral blood (PB) as stemcell source, given the higher extensive chronic GVHD and transplant-related mortality with the use of peripheral blood stem cells 20,21 .…”

Prevention and Management of Relapse of Acute Leukemia and Myelodysplastic Syndrome After Allogeneic Hematopoietic Cell Transplantation in Pediatric Patients

“…A higher relapse incidence (43%) was published by de Melo Rodrigues and cols. 8 when they analyzed 114 AML patients that received MSD (49), MUD (59) and haploidentical (6) HCT. The 4-year progression-free survival (PFS) for all cohort was 40%.…”

“…Advances in immunomodulatory interventions and maintenance approaches, with tyrosine kinase inhibitors (TKI) or hypomethylating agents (HMAs), have benefit selected patients. [8][9][10][11][12][13] Pulsipher et al reported 9 , in a multicenter prospective study, risk factors and timing of relapse after allogeneic transplantation in a pediatric population diagnosed with ALL. They concluded that there is a window between day +55 and day +100 to 200 when most high-risk patients have not relapsed yet and that this population could benefit from measures to avoid relapse at that time.…”