Donor CD7 Chimeric Antigen Receptor T Cell Bridging to Allogeneic Hematopoietic Stem Cell Transplantation for T Cell Hematologic Malignancy.

It is crucial to quickly bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematopoietic reconstitution. Here we report on the efficacy and safety of donor CD7 chimeric antigen receptor (CAR) T cell therapy (CAR-T) bridging to allo-HSCT in treating 12 patients with relapsed/refractory (r/r) T-ALL or T-cell lymphoblastic lymphoma (T-LBL). The median time from CAR-T infusion to allo-HSCT was 33.5 days (range, 30 to 55 days). With reduced-intensity conditioning, all patients except 1 successfully engrafted. With a mean follow-up of 301 days (range, 238 to 351 days), the remaining 11 patients were alive and disease-free at their last follow-up. Acute graft-versus-host disease (GVHD) was observed in 3 patients, and chronic GVHD developed in 3 patients, all with a limited pattern. Under the current protocol, infection was the main complication post-transplantation, and all infections were well controlled except in 1 patient, who died of multiple organ failure caused by an infection-induced inflammatory cytokine storm at days 14 post-transplantation. One patient relapsed (CD7+), and 3 patients became minimal residual disease (MRD) positive (CD7+ in 1, CD7- in 1, fusion gene positive only in 1). Subsequently, all 3 of these patients achieved an MRD-negative complete remission with either CD7 CAR-T reinfusion or immunosuppressive agent withdrawal. Our study shows for the first time that a novel strategy of donor CD7 CAR-T bridging to allo-HSCT can be highly effective and feasible in improving disease-free survival for patients with r/r T-ALL or T-LBL.

CAR-T therapy followed by allogeneic hematopoietic stem cell transplantation for refractory/relapsed acute B lymphocytic leukemia: Long-term follow-up results.

Background: Patients with refractory/relapsed (r/r) acute B lymphocytic leukemia (B-ALL) can achieve complete response (CR) after chimeric antigen receptor T-cell (CAR-T) therapy, but recurrence occurs in the short term. To reduce recurrence and improve survival, CAR-T therapy followed by transplantation is a feasible option. We analyzed the long-term follow-up outcomes and the risk factors for allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CR by CAR-T therapy in this study. Methods: A total of 144 patients who underwent allo-HSCT after CAR-T therapy in our hospital were enrolled in this study. Target gene analysis was performed in 137 r/r B-ALL patients receiving allo-HSCT after CR by CAR-T therapy. Among the 137 patients, 87 were evaluated for germline predisposition gene mutations, and 92 were evaluated for tumor somatic gene mutations using NGS. The clinical factors, germline predisposition gene and somatic gene mutations associated with the prognosis of patients receiving transplantation after CAR-T therapy were analyzed using univariate Cox regression. Factors related to disease-free survival (DFS) and overall survival (OS) were analyzed using multivariate Cox regression analysis. Results: In 137 r/r B-ALL patients, the 2-year cumulative incidence of recurrence (CIR), OS and DFS in patients receiving allo-HSCT after CAR-T therapy was 31.5%, 71.4%, and 60.5%, respectively. The 2-year OS and DFS in MRD-negative patients were 80.9% and 69.3%, respectively. Univariate Cox analysis showed that pretransplant MRD positivity, fungal infection, germline EP300 mutation and somatic TP53 mutation were associated with a poor prognosis after transplantation; a TBI-based regimen was a protective factor for survival and recurrence after transplantation. Multivariate Cox regression analysis showed that the TBI-based regimen was an independent protective factor for DFS, fungal infection and MRD positivity were independent risk factors for DFS, and tumor somatic TP53 mutation and germline EP300 mutation were independent risk factors for DFS and OS. Conclusion: Germline EP300 mutation and tumor somatic TP53 mutation are poor prognostic factors for posttransplant recurrence and survival in r/r B-ALL patients achieving CR after CAR-T therapy. The prognostic risk factors should be considered in adjusting treatment strategies to improve the efficacy of clinical diagnosis and treatment.

Graft-Versus-Host-Disease of the Central Nervous System and Lung in a Patient With Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report.

INTRODUCTION: The common etiology of central nervous system (CNS) complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) includes CNS infection, metabolic abnormalities, drug toxicity, cerebrovascular events, Epstein-Barr virus-associated posttransplant lymphoproliferative diseases, and hematologic CNS relapse of leukemia. Although graft-versus-host disease (GVHD) is a major complication of allo-HSCT, its CNS involvement is exceedingly rare. CASE PRESENTATION: In this report, we describe a patient who exhibited acute myeloid leukemia with t(8;21) (q22;q22) and who suddenly lost visual acuity ~1 year after receipt of allo-HSCT. Given the observation of negative cerebrospinal fluid findings, cyclosporine-related encephalopathy, intracranial hemorrhage, CNS infection, leukemia recurrence, and tumors were excluded. He was diagnosed with both CNS and pulmonary GVHD. After steroid treatment, the lesions gradually reduced in images acquired via cranial and pulmonary computed tomography. CONCLUSIONS: CNS-GVHD is a rare, serious complication of allo-HSCT that is difficult to diagnose. Biopsy and autopsy may identify the CNS as the target of GVHD in some patients. Treatment is mainly based on the use of immunosuppressive drugs, including high doses of steroids. Early diagnosis and treatment can improve disease outcome.