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

Bin Gu; Bing Yu Shi; Xiang Zhang; Shi Yuan Zhou; Jian Hong Chu; Xiao Jin Wu; Cheng Cheng Fu; Hui Ying Qiu; Yue Han; Su Ning Chen; Lei Yu; Xiao Ma; De Pei Wu

doi:10.1038/s41409-020-0982-6

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

Bin Gu, Bing Yu Shi, Xiang Zhang, Shi Yuan Zhou, Jian Hong Chu, Xiao Jin Wu, Cheng Cheng Fu, Hui Ying Qiu, Yue Han, Su Ning Chen, Lei Yu, Xiao Ma^*, De Pei Wu^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

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.

Original language	English
Pages (from-to)	91-100
Number of pages	10
Journal	Bone Marrow Transplantation
Volume	56
Issue number	1
DOIs	https://doi.org/10.1038/s41409-020-0982-6
Publication status	Published - Jan 2021
Externally published	Yes

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Gu, B., Shi, B. Y., Zhang, X., Zhou, S. Y., Chu, J. H., Wu, X. J., Fu, C. C., Qiu, H. Y., Han, Y., Chen, S. N., Yu, L., Ma, X., & Wu, D. P. (2021). 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. Bone Marrow Transplantation, 56(1), 91-100. https://doi.org/10.1038/s41409-020-0982-6

@article{f497a20fe4514e12bd47f83ca1267a0a,

title = "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",

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.",

author = "Bin Gu and Shi, {Bing Yu} and Xiang Zhang and Zhou, {Shi Yuan} and Chu, {Jian Hong} and Wu, {Xiao Jin} and Fu, {Cheng Cheng} and Qiu, {Hui Ying} and Yue Han and Chen, {Su Ning} and Lei Yu and Xiao Ma and Wu, {De Pei}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

month = jan,

doi = "10.1038/s41409-020-0982-6",

language = "English",

volume = "56",

pages = "91--100",

journal = "Bone Marrow Transplantation",

issn = "0268-3369",

publisher = "Springer Nature",

number = "1",

}

Gu, B, Shi, BY, Zhang, X, Zhou, SY, Chu, JH, Wu, XJ, Fu, CC, Qiu, HY, Han, Y, Chen, SN, Yu, L, Ma, X & Wu, DP 2021, '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', Bone Marrow Transplantation, vol. 56, no. 1, pp. 91-100. https://doi.org/10.1038/s41409-020-0982-6

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. / Gu, Bin; Shi, Bing Yu; Zhang, Xiang et al.
In: Bone Marrow Transplantation, Vol. 56, No. 1, 01.2021, p. 91-100.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - Gu, Bin

AU - Shi, Bing Yu

AU - Zhang, Xiang

AU - Zhou, Shi Yuan

AU - Chu, Jian Hong

AU - Wu, Xiao Jin

AU - Fu, Cheng Cheng

AU - Qiu, Hui Ying

AU - Han, Yue

AU - Chen, Su Ning

AU - Yu, Lei

AU - Ma, Xiao

AU - Wu, De Pei

PY - 2021/1

Y1 - 2021/1

N2 - 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.

AB - 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.

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DO - 10.1038/s41409-020-0982-6

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SN - 0268-3369

VL - 56

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JF - Bone Marrow Transplantation

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Gu B, Shi BY, Zhang X, Zhou SY, Chu JH, Wu XJ et al. 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. Bone Marrow Transplantation. 2021 Jan;56(1):91-100. doi: 10.1038/s41409-020-0982-6

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

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