Clofarabine-fludarabine-busulfan in HCT for pediatric leukemia: an effective, low toxicity, TBI-free conditioning regimen

We prospectively studied clofarabine-fludarabine-busulfan (CloFluBu)-conditioning in allogeneic hematopoietic cell therapy (HCT) for lymphoid and myeloid malignancies and hypothesized that CloFluBu provides a less toxic alternative to conventional conditioning regimens, with adequate antileukemic activity. All patients receiving their first HCT, from 2011-2019, were included and received CloFluBu. The primary endpoint was event-free survival (EFS). Secondary endpoints were overall survival (OS), graft-versus-host disease (GvHD)-relapse-free survival (GRFS), treatment-related mortality (TRM), cumulative incidence of relapse (CIR), acute and chronic GvHD (aGvHD and cGvHD), and veno-occlusive disease (VOD). Cox proportional hazard and Fine and Gray competing-risk models were used for data analysis. One hundred fifty-five children were included: 60 acute lymphoid leukemia (ALL), 69 acute myeloid leukemia (AML), and 26 other malignancies (mostly MDS-EB). The median age was 9.7 (0.5 to 18.6) years. Estimated 2-year EFS was 72.0% +/- 6.0 in ALL patients, and 62.4% +/- 6.0 in AML patients. TRM in the whole cohort was 11.0% +/- 2.6, incidence of aGvHD 3 to 4 at 6 months was 12.3% +/- 2.7, extensive cGvHD at 2 years was 6.4% +/- 2.1. Minimal residual disease-positivity prior to HCT was associated with higher CIR, both in ALL and AML. CloFluBu showed limited toxicity and encouraging EFS. CloFluBu is a potentially less toxic alternative to conventional conditioning regimens. Randomized prospective studies are needed.Transplantation and immunomodulatio

Immune Reconstitution after Allogeneic Hematopoietic stem Cell Transplantation in Children

An allogeneic hematopoietic stem cell transplantation is the only curative treatment option for children suffering from chemo-refractory leukemia or inborn errors such as metabolic diseases. During this therapy, the diseased bone marrow cells of the patient are replaced by stem cells from a healthy donor. After infusion of the donor stem cells, these cells find their way into the bone marrow of the patient, where they engraft and start differentiating into new immune cells. This essential process is called immune reconstitution. Since the first successful transplantation in 1968, the treatment of patients with this therapy has drastically improved over the last years. Despite of this, complications in this risky procedure are still common, causing 30-50% of patients to die after transplantation. This is why it is important to better understand what causes these complications, and how to better predict them. During my research, I found that children with a delayed immune reconstitution after their transplantation had much more complications and lower chance of survival. In particular a fast and adequate reconstitution of T-cells, the so-called soldiers of the immune system, is essential for lowering complications such as virus infections, graft-versus-host disease, and leukemia relapse. My research also describes different factors that affect the speed of T-cell reconstitution. These novel findings enable improvement of the treatment of patients who undergo a stem cell transplantation, which are expected to drastically enhance the survival chances of future transplantation recipients