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T-cell depletion of an HLA-haploidentical (haplo) graft is often used to reduce the risk of graft-versus-host disease (GVHD), but the lack of donor T cells in the infused product may lead to graft failure, slow T-cell reconstitution, infections, and relapse. More selective T-cell depletion targeting CD45RA can effectively deplete naive T cells but preserve large numbers of memory T cells leading to robust engraftment of diverse T-cell populations and reduction of viremia in the early posttransplant period. Herein, we report the outcome of 143 pediatric and young adult hematologic malignancy patients receiving a first allogeneic hematopoietic cell transplantation (HCT) on six consecutive ex vivo T-cell depleted haploHCT protocols over the past 15 years at a single institution—including the first 50 patients on an active CD45RA-depleted haploHCT study in which patients also received NK-cells and pharmacological GvHD prophylaxis post transplant. Our data demonstrated an increase in the 3-year overall survival and event-free survival in nonchemorefractory recipients receiving CD45RA-depleted grafts (78.9% and 77.7%, respectively) compared with historic T-cell depleted haploHCT cohorts (46.7% and 42.7%, respectively, p= 0.004, and 0.003). This improvement was primarily due to a reduction in transplant related mortality without significant increase in the rates of GVHD.

Recurrent/refractory hematologic malignancies have a poor prognosis, and there is a need for novel treatment regimens that can be tolerated by this heavily pretreated patient group. Clofarabine has antileukemic activity with an acceptable toxicity profile. In a phase I clinical trial (NCT00824135), we substituted clofarabine for fludarabine in a well-established reduced-intensity conditioning regimen for a T cell–depleted, mismatched-related (haploidentical) donor transplant backbone and explored the maximum tolerated dose of clofarabine in this combination in 15 patients undergoing hematopoietic cell transplantation for recurrent/refractory or secondary leukemia. Clofarabine was well tolerated at a dose of 50 mg/m2/d for 5 days in this regimen, with minimal treatment-related mortality in a heavily pretreated group of high-risk patients. All patients exhibited quick hematopoietic recovery, with median times to neutrophil and platelet engraftment being 11 and 16 days, respectively. Transient elevation of transaminases was the most common toxicity—observed in 13 patients (86.7%), with 6 (40%) grade III or above. Three patients (20%) developed hepatic veno-occlusive disease. Eleven patients (73.3%) died, with the most common cause of death being disease relapse (in 9 patients [60%]), followed by treatment-related mortality (in 2 patients [13.3%]). Four (26.6%) of the patients are long-term survivors.

Adenoviremia adversely affects prognosis in the post-hematopoietic stem cell transplant setting.

The data on human rhinovirus, coronavirus, bocavirus, metapneumovirus, Chlamydophila pneumoniae, Mycoplasma pneumoniaeand Bordetella pertussisinfections in children with cancer is limited.

Triplett: Miltenyi Biotec: Other: Travel Support, to present previously published work at EBMT symposium.

Background: Haploidentical hematopoietic cell transplantation (haploHCT) is an attractive option for patients, who have no suitable matched-related or -unrelated donor. While the increased alloreactivity of haploidentical grafts enhances graft-vs-leukemia effects, it also increases the risk of acute graft-vs-host disease (aGVHD). Therefore, extensive in vivoor ex vivoT-cell depletion is required to reduce the incidence of severe aGVHD. However, global T-cell depletion is associated with delayed immune recovery, serious viral infections, and relapse. To overcome this limitation, selective TCRɑß and CD45RA T-cell depletion was developed. Both aim to remove alloreactive T-cell subsets, and initial clinical experience has demonstrated the feasibility and safety of each individual approach. We reasoned that combining both approaches might further increase immune reconstitution and bolster graft-vs-leukemia effects. We therefore designed an early phase clinical study, NCT02790515, to evaluate the safety and efficacy of infusing two haploidentical allografts, one TCRɑß T-cell depleted and one CD45RA T-cell depleted, in pediatric patients with very-high risk hematological malignancies, who had recurrent disease after a previous allogeneic HCT.