HLA-matched and HLA-haploidentical allogeneic CD19-directed chimeric antigen receptor T-cell infusions are feasible in relapsed or refractory B-cell acute lymphoblastic leukemia before hematopoietic stem cell transplantation

The consensus from The Chinese Society of Hematology on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation: 2021 update

“…2. Acute lymphoblastic leukemia Ph + ALL in adults and adolescents (aged > 14 years old) Ph + ALL in CR1 Ph + ALL ≥ CR2 Relapsed or refractory Ph + ALL: allo-HSCT as salvage therapy and novel immunotherapies, especially CAR-T therapies, can be applied and then bridged to allo-HSCT [ 36 , 37 , 41 , 64 ] Ph + ALL in pediatric patients (aged ≤ 14 years old) Ph + ALL in CR1, especially in patients exhibiting a poor response to prednisone and positive MRD at any time between 4 and 12 weeks after therapy Ph + ALL ≥ CR2 Relapsed or refractory Ph + ALL: allo-HSCT as salvage therapy, and novel immunotherapies, especially CAR-T therapies, can be applied and then bridged to allo-HSCT Ph-ALL in adults and adolescents (aged > 14 years old) Ph-ALL in CR1: especially in patients with MRD + status or those showing poor-risk factors (aged ≥ 40 years old, high WBC count at diagnosis [100 × 10 9 /L for T lineage and ≥ 30 × 10 9 /L for B lineage], or poor-risk cytogenetics, including Ph + ALL) Ph-ALL ≥ CR2 Relapsed or refractory Ph-ALL: allo-HSCT as salvage therapy, and novel immunotherapies, especially CAR-T therapies, can be applied and then bridged to allo-HSCT Ph-ALL in pediatric patients (aged ≤ 14 years old) Ph-ALL in CR1: Patients who fail to achieve hematological CR or MRD >1% within 28-30 days Patients who achieve CR with MRD > 0.01% (B-ALL) or MRD>0.1% (T-ALL) post consolidation Patients with MLL/KMT2A+ ALL Ph-ALL ≥ CR2 Relapsed or refractory Ph-ALL: allo-HSCT as salvage therapy and novel immunotherapies, especially CAR-T therapies, can be applied and then bridged to allo-HSCT …”

“…Ph + ALL in adults and adolescents (aged > 14 years old) Ph + ALL in CR1 Ph + ALL ≥ CR2 Relapsed or refractory Ph + ALL: allo-HSCT as salvage therapy and novel immunotherapies, especially CAR-T therapies, can be applied and then bridged to allo-HSCT [ 36 , 37 , 41 , 64 ] …”

Optimizing the Clinical Impact of CAR-T Cell Therapy in B-Cell Acute Lymphoblastic Leukemia: Looking Back While Moving Forward

“…Recently, it has been shown that TPE (Figure 2A) in combination with glucocorticoid therapy can result in the gradual resolution of the CRS-related symptoms of CAR-T therapy recipients (105,106). These findings suggest that this strategy can be a feasible procedure, at least in patients with severe CRS (grade ≥ 3), even though TPE is not included in CRS management guidelines (105,106).…”

“…Recently, it has been shown that TPE (Figure 2A) in combination with glucocorticoid therapy can result in the gradual resolution of the CRS-related symptoms of CAR-T therapy recipients (105,106). These findings suggest that this strategy can be a feasible procedure, at least in patients with severe CRS (grade ≥ 3), even though TPE is not included in CRS management guidelines (105,106). In a case report, Xiao et al reported that in a 23-year-old male R/R B-ALL patient, after performing TPE along with the administration of dexamethasone, CRS (grade 3) was mitigated and controlled whereas treatment with antiallergic and antipyretic drugs, glucocorticoids, and tocilizumab was not effective against the progressing condition of the patient's CRS (105).…”

“…Using HLA-matched or HLA-haploidentical allogeneic CAR-Ts can lead to different clinical outcomes in B-ALL CAR-T therapy (106). Researchers have investigated the use of HLA-matched or HLA-haploidentical allogeneic CD19-redirected CAR-Ts (M-CAR-Ts and H-CAR-Ts, respectively) for the treatment of R/R B-ALL patients to evaluate which one can result in better clinical outcomes (106). Recently, Jin et al described the first-in-human application of M-CAR-Ts in R/R B-ALL patients before allogeneic hematopoietic stem cell transplantation (allo-HSCT) (106).…”