» Articles » PMID: 32581286

Allogeneic Haematopoietic Stem Cell Transplantation Improves Outcome of Adults with Relapsed/refractory Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia Entering Remission Following CD19 Chimeric Antigen Receptor T Cells

Overview
Specialty General Surgery
Date 2020 Jun 26
PMID 32581286
Citations 11
Authors
Affiliations
Soon will be listed here.
Abstract

Relapsed/refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (r/r Ph+ ALL) has an extremely poor prognosis. Chimeric antigen receptor T-cell (CART) therapy has acquired unprecedented efficacy in B-cell malignancies, but its role in the long-term survival of r/r Ph+ ALL patients is unclear. We analyzed the effect of CART on 56 adults with r/r Ph+ ALL who accepted split doses of humanized CD19-targeted CART after lymphodepleting chemotherapy. 51/56 (91.1%) achieved complete remission (CR) or CR with inadequate count recovery (CRi), including 38 patients with negative minimal residual disease (MRD) tested by bone marrow BCR-ABL1 copies. Subsequently, 30/51 CR/CRi patients accepted consolidative allogeneic haematopoietic stem cell transplantation (alloHSCT). Their outcomes were compared with those of 21/51 contemporaneous patients without alloHSCT. The 2-year overall survival (OS) and leukemia-free survival (LFS) of CR/CRi patients with alloHSCT were significantly superior to those without alloHSCT (58.9%, CI 49.8-68.0% vs. 22.7%, CI 12.7-32.7%, p = 0.005; 53.2%, CI 43.6-62.8% vs. 18.8%, CI 9.2-28.4%, p = 0.000, respectively). Multivariate analysis revealed that alloHSCT and MRD-negative post-CART were the independent prognostic factors for OS and LFS. CART therapy is highly effective for r/r Ph+ ALL patients, and consolidative alloHSCT could prolong their OS and LFS.

Citing Articles

Safety and efficacy of CD22 and CD19 CAR-T bridging auto-HSCT as consolidation therapy for AYA and adult B-ALL.

Qiu Y, Wan C, Xu M, Zhou H, Liu M, Gong W Blood Cancer J. 2023; 13(1):66.

PMID: 37137904 PMC: 10156719. DOI: 10.1038/s41408-023-00837-3.


Comparable outcomes in patients with B-cell acute lymphoblastic leukemia receiving haploidentical hematopoietic stem cell transplantation: Pretransplant minimal residual disease-negative complete remission following chimeric antigen receptor T-cell....

Yang T, Meng Y, Kong D, Wei G, Zhang M, Wu W Front Immunol. 2022; 13:934442.

PMID: 36110859 PMC: 9468760. DOI: 10.3389/fimmu.2022.934442.


Combination strategies to optimize the efficacy of chimeric antigen receptor T cell therapy in haematological malignancies.

Xiao X, Wang Y, Zou Z, Yang Y, Wang X, Xin X Front Immunol. 2022; 13:954235.

PMID: 36091028 PMC: 9460961. DOI: 10.3389/fimmu.2022.954235.


Approved gene therapies in Australia: coming to a store near you.

Mallik S, Bailey C, Rasko J Intern Med J. 2022; 52(8):1313-1321.

PMID: 35973959 PMC: 9545855. DOI: 10.1111/imj.15880.


Efficacy and safety of CD19 CAR-T cell therapy for acute lymphoblastic leukemia patients relapsed after allogeneic hematopoietic stem cell transplantation.

Cao X, Li J, Lu P, Liu K Int J Hematol. 2022; 116(3):315-329.

PMID: 35737192 DOI: 10.1007/s12185-022-03398-6.


References
1.
Moorman A, Harrison C, Buck G, Richards S, Secker-Walker L, Martineau M . Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood. 2006; 109(8):3189-97. DOI: 10.1182/blood-2006-10-051912. View

2.
Fielding A, Rowe J, Buck G, Foroni L, Gerrard G, Litzow M . UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2013; 123(6):843-50. PMC: 3916877. DOI: 10.1182/blood-2013-09-529008. View

3.
Thomas D, Faderl S, Cortes J, OBrien S, Giles F, Kornblau S . Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood. 2003; 103(12):4396-407. DOI: 10.1182/blood-2003-08-2958. View

4.
Bassan R, Rossi G, Pogliani E, Di Bona E, Angelucci E, Cavattoni I . Chemotherapy-phased imatinib pulses improve long-term outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Northern Italy Leukemia Group protocol 09/00. J Clin Oncol. 2010; 28(22):3644-52. DOI: 10.1200/JCO.2010.28.1287. View

5.
Tanguy-Schmidt A, Rousselot P, Chalandon Y, Cayuela J, Hayette S, Vekemans M . Long-term follow-up of the imatinib GRAAPH-2003 study in newly diagnosed patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: a GRAALL study. Biol Blood Marrow Transplant. 2012; 19(1):150-5. DOI: 10.1016/j.bbmt.2012.08.021. View