Prospective PTCTC trial of myeloablative haplo-BMT with posttransplant cyclophosphamide for pediatric acute leukemias.

Promising results have been reported for adult patients with high-risk hematologic malignancies undergoing haploidentical bone marrow transplant (haploBMT) with posttransplant cyclophosphamide (PTCy). To our knowledge, we report results from the first multicenter trial for pediatric and young adult patients with high-risk acute leukemias and myelodysplastic syndrome (MDS) in the Pediatric Transplantation and Cellular Therapy Consortium. Nine centers performed transplants in 32 patients having acute leukemias or MDS, with myeloablative conditioning (MAC), haploBMT with PTCy, mycophenolate mofetil, and tacrolimus. The median patient age was 12 years. Diagnoses included AML (15), ALL (11), mixed-lineage leukemia (1), and MDS (5). Transplant-related mortality (TRM) at 180 days was 0%. The cumulative incidence (CuI) of grade 2 acute graft-versus-host disease (aGVHD) on day 100 was 13%. No patients developed grades 3-4 aGVHD. The CuI of moderate-to-severe chronic GVHD (cGVHD) at 1 year was 4%. Donor engraftment occurred in 27 patients (84%). Primary graft failures included 3 patients who received suboptimal bone marrow grafts; all successfully engrafted after second transplants. The CuI of relapse at 1 year was 32%, with more relapse among patients MRD positive pre-BMT vs MRD negative. Overall survival rates at 1 and 2 years were 77% and 73%, and event-free survival rate at 1 and 2 years were 68% and 64%. There was no TRM or severe aGVHD, low cGVHD, and favorable relapse and survival rates. This successful pilot trial has led to a phase 3 trial comparing MAC haploBMT vs HLA-matched unrelated donor BMT in the Children's Oncology Group. This trial was registered at www.clinicaltrials.gov as #NCT02120157.

Immunotherapy approaches for rare pediatric solid tumors: advances and future directions.

PURPOSE OF REVIEW: Immunotherapy for pediatric tumors is rapidly evolving. From major successes in pediatric hematologic malignancies, immunotherapy utility increased in the pediatric solid tumor landscape. Numerous pediatric solid tumors are defined as rare with limitations in diagnosis and treatment. This review will describe four major immunotherapies used in pediatrics and discuss results seen in rare pediatric tumors. We will also briefly review the challenges of immunotherapy in solid tumors and opportunities to drive this therapy forward. RECENT FINDINGS: Despite rare success employing immunotherapy for pediatric solid tumors, recently there have been several successes in pediatric rare solid tumors. After describing the evolving landscape of rare pediatric tumors, we will demonstrate the successes or disappointments of immunotherapy. We will describe the mechanism of four immunotherapies used in the pediatrics, followed by the published results. Finally, we will discuss the challenges and opportunities for immunotherapies in pediatric rare tumors. SUMMARY: Pediatric rare tumors are lacking in treatment options. Despite numerous disappointments utilizing immunotherapies in the more common pediatric solid tumors, there have been several successes within the pediatric rare tumor landscape. Much work is still needed to enhance our understanding and knowledge on utilizing these immunotherapies for pediatric rare solid tumors.