Hematopoietic stem cell transplantation in children with chronic granulomatous disease: the Spanish experience.

Introduction: Hematopoietic stem cell transplantation (HCT) can cure chronic granulomatous disease (CGD). However, transplant-associated morbidity or mortality may occur, and it is still controversial which patients benefit from this procedure. The aim of this retrospective study was to evaluate the outcome of pediatric patients who received HCT in one of the Spanish pediatric transplant units. Results: Thirty children with a median age of 6.9 years (range 0.6-12.7) were evaluated: 8 patients received a transplant from a sibling donor (MSD), 21 received a transplant from an unrelated donor (UD), and 1 received a haploidentical transplant. The majority of the patients received reduced-intensity conditioning regimens based on either busulfan plus fludarabine or treosulfan. Relevant post-HCT complications were as follows: i) graft failure (GF), with a global incidence of 28.26% (CI: 15.15-48.88), 11.1% in patients with MSD (1.64-56.70) and 37.08% in unrelated donors (19.33-63.17); and ii) chronic graft-versus-host disease (GVHD), with an incidence of 20.5% (8.9-43.2), 11.1% in patients with MSD (1.64-56.70) and 26.7% in unrelated donors (10.42-58.44). Post-HCT infections were usually manageable, but two episodes of pulmonary aspergillosis were diagnosed in the context of graft rejection. The 2-year OS was 77.3% (55.92-89.23). There were no statistically significant differences among donor types. Discussion: HCT in patients with CGD is a complex procedure with significant morbidity and mortality, especially in patients who receive grafts from unrelated donors. These factors need to be considered in the decision-making process and when discussing conditioning and GVHD prophylaxis.

Measurable residual disease study through three different methods can anticipate relapse and guide early interventions in childhood acute lymphoblastic leukemia.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most common cancer among children. Measurable residual disease (MRD, previously named minimal residual disease) study can guide therapy adjustments or preemptive interventions that might avoid hematological relapse. METHODS: Clinical decision making and patient outcome were evaluated in 80 real-life childhood ALL patients, according to the results observed in 544 bone marrow samples analyzed with three MRD methods: multiparametric flow cytometry (MFC), fluorescent in-situ hybridization (FISH) on B or T-purified lymphocytes and patient-specific nested reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Estimated 5 year overall survival and event-free survival were 94% and 84.1%, respectively. A total of 12 relapses in 7 patients were associated with positive MRD detection with at least one of the three methods: MFC (p < 0.00001), FISH (p < 0.00001) and RT-PCR (p = 0.013). MRD assessment allowed the anticipation of relapse and adapted early interventions with different approaches including chemotherapy intensification, blinatumomab, HSCT and targeted therapy to halt relapse in five patients, although two of them relapsed afterwards. CONCLUSION: MFC, FISH and RT-PCR are complementary methods for MRD monitoring in pediatric ALL. Although, our data clearly show that MDR positive detection is associated with relapse, continuation of standard treatment, intensification or other early interventions were able to halt relapse in patients with different risks and genetic background. More sensitive and specific methods are warranted to enhance this approach. However, whether early treatment of MRD can improve overall survival in patients with childhood ALL needs to be evaluated in adequately controlled clinical trials.

Measurable residual disease study through three different methods can anticipate relapse and guide pre-emptive therapy in childhood acute myeloid leukemia.

PURPOSE: Although outcomes of children with acute myeloid leukemia (AML) have improved over the last decades, around one-third of patients relapse. Measurable (or minimal) residual disease (MRD) monitoring may guide therapy adjustments or pre-emptive treatments before overt hematological relapse. METHODS: In this study, we review 297 bone marrow samples from 20 real-life pediatric AML patients using three MRD monitoring methods: multiparametric flow cytometry (MFC), fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR). RESULTS: Patients showed a 3-year overall survival of 73% and a 3-year event-free survival of 68%. Global relapse rate was of 25%. All relapses were preceded by the reappearance of MRD detection by: (1) MFC (p = 0.001), (2) PCR and/or FISH in patients with an identifiable chromosomal translocation (p = 0.03) and/or (3) one log increase of Wilms tumor gene 1 (WT1) expression in two consecutive samples (p = 0.02). The median times from MRD detection to relapse were 26, 111, and 140 days for MFC, specific PCR and FISH, and a one log increment of WT1, respectively. CONCLUSIONS: MFC, FISH and PCR are complementary methods that can anticipate relapse of childhood AML by weeks to several months. However, in our series, pre-emptive therapies were not able to prevent disease progression. Therefore, more sensitive MRD monitoring methods that further anticipate relapse and more effective pre-emptive therapies are needed.