Unrelated donor α/β T-cell and B-cell-depleted HSCT for the treatment of pediatric acute leukemia

Unrelated donor (URD) hematopoietic stem cell transplant (HSCT) is associated with an increased risk of severe GVHD. TCRαβ/CD19 depletion may reduce this risk, while maintaining graft-versus-leukemia. Outcome data with TCRαβ/CD19 depletion generally describes haploidentical donors, with relatively few URDs. We hypothesized that TCRαβ/CD19-depletion would attenuate the risks of GVHD and relapse for URD HSCT. Sixty pediatric and young adult (YA) patients with hematologic malignancies who lacked a matched-related donor were enrolled at two large pediatric transplantation centers between 10/2014 and 09/2019. All patients with acute leukemia had minimal residual disease testing and DP typing was available for 77%. All patients received myeloablative TBI- or busulfan-based conditioning with no post-transplant immune suppression. Engraftment occurred in 98%. Four-year overall survival was 69% (95%CI 52-81%) and leukemia-free survival was 64% (95%CI 48-76%), with no difference between lymphoid and myeloid malignancies (p=0.6297 and p=0.5441, respectively). One patient (1.7%) experienced primary graft failure. Relapse occurred in 11 patients (3-year cumulative incidence 21%, 95%CI 11-34), and 8 patients (cumulative incidence 15%, 95%CI 6.7-26) experienced non-relapse mortality. Grade III-IV acute GVHD was seen in 8 patients (13%), and 14 patients (26%) developed chronic GVHD, of which 6 (11%) had extensive disease. Non-permissive DP mismatch was associated with higher likelihood of acute GVHD (OR 16.50, 95%CI 1.67-163.42, p=0.0166), but not with the development of chronic GVHD. URD TCRαβ/CD19-depleted peripheral HSCT is a safe and effective approach to transplantation for children/YAs with leukemia. This trial was registered at www.clinicaltrials.gov as #NCT02323867.

Clinical Outcomes of Unrelated Umbilical Cord Blood Graft vs. Haploidentical Donor Transplantation: Critical Issues for an Adequate Comparison

Unrelated umbilical cord blood (UCB) and haploidentical grafts have been used for allogeneic hematopoietic stem and progenitor cell (HSPC) transplantation in patients without a related or non-related human leukocyte antigen (HLA)-matched donor. The less stringent HLA-matching requirement in both sources raises an important possibility for patients in need of urgent transplantation to treat any hematological disease. Selection of the best alternative donor is a difficult task that will depend on donor criteria, center experience, patient disease conditions, and risk, among others. Most comparisons available in scientific publications between both graft sources are obtained from retrospective analysis in wide time windows and a heterogeneous number of patients, types of disease, disease stages, previous treatments, graft source, conditioning regimen, graft vs. host disease (GVHD) approach, and evaluable endpoints. There is also an evident impact of the economic traits since low-income countries must consider less expensive treatments to satisfy the needs of the patients in the most effective possible path. Therefore, haploidentical transplantation could be an appealing option, even though it has not been completely established if any chronic treatment derived from the procedure could become a higher cost. In Colombia, there is a huge experience in UCB transplantation especially in units of pediatric transplantation where benign indications are more common than in adults. Due to the availability of a public UCB bank and HLA high-resolution typing in Colombia, there is a wider inventory of cord blood donors. Unfortunately, we do not have an unrelated bone marrow donor registry, so UCB is an important source along with haploidentical transplantation to consider in decision-making. This minireview focuses on comparing the main issues associated with the use of both HSCP sources and provides tools for physicians who face the difficult decision between these alternative donor sources.

Current Practices on Diagnosis, Prevention and Treatment of Post-Transplant Lymphoproliferative Disorder in Pediatric Patients after Solid Organ Transplantation: Results of ERN TransplantChild Healthcare Working Group Survey

(1) Background: Post-transplant lymphoproliferative disease (PTLD) is a significant complication of solid organ transplantation (SOT). However, there is lack of consensus in PTLD management. Our aim was to establish a present benchmark for comparison between international centers and between various organ transplant systems and modalities; (2) Methods: A cross-sectional questionnaire of relevant PTLD practices in pediatric transplantation was sent to multidisciplinary teams from 17 European center members of ERN TransplantChild to evaluate the centers’ approach strategies for diagnosis and treatment and how current practices impact a cross-sectional series of PTLD cases; (3) Results: A total of 34 SOT programs from 13 European centers participated. The decision to start preemptive treatment and its guidance was based on both EBV viremia monitoring plus additional laboratory methods and clinical assessment (61%). Among treatment modalities the most common initial practice at diagnosis was to reduce the immunosuppression (61%). A total of 126 PTLD cases were reported during the period 2012–2016. According to their histopathological classification, monomorphic lesions were the most frequent (46%). Graft rejection after PTLD remission was 33%. Of the total cases diagnosed with PTLD, 88% survived; (4) Conclusions: There is still no consensus on prevention and treatment of PTLD, which implies the need to generate evidence. This might successively allow the development of clinical guidelines.