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Posted by on Feb 6, 2022 in Leukemia | 0 comments

In a nutshell

The study aimed to investigate if allogeneic hematopoietic stem cell transplant (alloHSCT) was a suitable treatment strategy for patients with relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL) after chimeric antigen receptor (CAR) T-cell therapy.  

This study concluded that this was a suitable treatment strategy as it was safe and effective for these patients.  

Some background

CAR-T cell therapy is a type of immunotherapy that uses specially altered T cells (part of the immune system) to fight cancer. In patients with r/r B-cell ALL (B-ALL), treatment with CAR-T cell therapy can help obtain an early response. However, relapse can still occur after CAR-T treatment in some patients. However, there is no current recommendation on what would be the optimal treatment after CAR-T cell therapy. 

An allo-HSCT involves transplanting healthy blood-forming cells from donors. It is not known if an allo-HSCT is a good treatment option in patients with B-ALL after a CAR-T cell therapy. 

Methods & findings

This study involved 28 patients with r/r B-ALL who had previously received humanized CD19-targeted CAR-T cell therapy (hCART19). 10 patients then received an allo-HSCT (group 1). 7 patients received a second hCART19 infusion (group 2). 11 patients did not receive an HSCT or a second hCART19 infusion (group 3). The average follow-up was 1240 days (about 3.4 years). 

Overall, 92.6% of the patients achieved complete remission (CR) after hCART19. 74.7% achieved minimal residual disease (MRD) negativity. MRD is the small amount of cancer cells that can remain in the blood or bone marrow. Positive MRD is a common cause of relapse. There was no significant difference between the 3 groups regarding the rate of CR. 

The most common side effect of hCART18 was cytokine release syndrome (CRS) that happened in 27 of the 28 patients. CRS is an inflammatory syndrome characterized by fever and multiple organ dysfunction. One patient died from very severe CRS. 25% of patients experienced severe CRS. No patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS) of grade 3 or greater.  

1 year after the second therapy, 70% of group 1, 57.1% of group 1, and 36.4% of group 3 were alive. 1 year after the second therapy, 80% of group 1, 28.6% of group 2, and 33.3% of group 3 were alive without leukemia. 

After 3 years, 58.3% of patients in group 1 were alive compared to 0% in groups 2 and 3. 

The bottom line

This study concluded that allo-HSCT after CAR-T therapy can achieve long-term effectiveness, with manageable side effects in patients with r/r B-ALL. 

The fine print

This study had a very small number of participants and was based on medical records. Further larger studies are needed to validate these results. 

Published By :

Frontiers in immunology

Date :

Nov 16, 2021

Original Title :

Humanized Anti-CD19 CAR-T Cell Therapy and Sequential Allogeneic Hematopoietic Stem Cell Transplantation Achieved Long-Term Survival in Refractory and Relapsed B Lymphocytic Leukemia: A Retrospective Study of CAR-T Cell Therapy.

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