Journal Article

Abstract 24: Granulocytes to Induce Donor-Derived T Cell Expansion after T Replete, Mismatched CB in Post-Transplant Relapsed and Refractory Paediatric Acute Leukaemia: Results of Grans Trial

Rauthan, Archana, Broderick, Valerie, Roberts, Wing, Senthil, Srividhya, Evans, Pamela, Patrick, katharine, Peppas, Ioannis, Moothedath, Abdul, Rao, Kanchan, Potluri, Sandeep, Calvert, Richard, Furness, Caroline, Wynn, Robert, Lawson, Sarah

2024

Overview

Abstract Introduction Refractory and post-transplant relapsed Acute Leukaemia remain difficult to cure. Third-party pooled granulocytes induce massive, transient, donor-derived T-cell expansion after Cord Blood (CB) transplant. These expanded T-cells are cytotoxic, memory CD8, in contrast to the infused graft T-cells which are predominantly naïve CD4, and appear a priori candidate anti-tumour T-cells. Objectives In our prospective clinical trial, GRANS study (NCT05425043), we have given granulocytes peri-transplant with T-replete, deliberately mismatched CB to enhance the graft-versus-leukaemia effect of the transplant, in those with either primary refractory or relapsed/ refractory paediatric acute leukaemia. Here we report outcomes of all patients treated with this approach, including trial and off-trial patients. Methods Case records were analysed and data collected about patients’ demographics, transplant and donor characteristics and the outcomes including engraftment, acute and chronic GVHD, relapse and transplant related mortality. All patients (n=25) were given 7 daily doses of granulocytes starting from D-1. Immune suppression was withdrawn early. Results The granulocytes are well tolerated, no grade 3 or 4 CRS was encountered. There is increased graft rejection (seen in 4 patients) compared to a cohort of T-replete cord blood transplants in children with haematologic malignancy. In those that reject, then there is always residual leukaemia present. 2 of these patients successfully engrafted after a second CBT. Low severe aGVHD. Only 12% (n=3) developed severe aGVHD, despite early withdrawal of immunosuppression. No cGVHD was seen. Treatment related mortality is low, and 2 patients died, one with severe VOD and one with disseminated, aciclovir-resistant HSV infection. In those that do not reject the graft, all but one patient became MRD negative. In some, there is later relapse (n=7).The OS and the EFS were 56% (n=14) and 48% (n=12) respectively. Discussion The rates of aGVHD are tolerable, there is no cGVHD and the TRM is remarkably low, despite the mismatched graft. There is a higher graft failure rate and in those that do not experience GF, the remission rates are high but some patients relapse. In our next protocol, we plan to use an expanded CB to reduce GF, and cord derived DLI after cessation of immune suppression to reduce late relapse. Figure 1: Relapse free survival of different sub groups stratified based on MRD and severe aGVHD

• Publisher: Oxford University Press
• Subject: CD4 antigen / CD8 antigen / Cord blood / Cytotoxicity / Graft rejection / Graft-versus-host reaction / Granulocytes / Immunological memory / Immunosuppression / Leukemia / Leukocytes (granulocytic) / Lymphocytes T / Malignancy / Memory cells / Mortality / Patients / Pediatrics / Remission / Supplement / Transplants & implants