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LOW-DOSE PTCY PLUS HAPLO-INDENTICAL TRANSPLANTATION A FEASIBLE AND SAFE CONSOLIDATION STRATEGY FOR CAR T-CELL SALVAGED REFRACTORY/RELAPSED B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA------THREE CASE REPORT
Author(s): ,
Xm Fei
Affiliations:
Department of Hematlogoy,Affiliated Hospital of Jiangsu University,Zhenjiang,China
,
XIANQIU YU
Affiliations:
Department of Hematlogoy,Affiliated Hospital of Jiangsu University,Zhenjiang,China
,
LIXIA WANG
Affiliations:
Department of Hematlogoy,Affiliated Hospital of Jiangsu University,Zhenjiang,China
,
FANG LEI
Affiliations:
Department of Hematlogoy,Affiliated Hospital of Jiangsu University,Zhenjiang,China
WENPING LU
Affiliations:
Department of Hematlogoy,Affiliated Hospital of Jiangsu University,Zhenjiang,China
EHA Library. fei x. 06/09/21; 324468; PB1797
xm fei
xm fei
Contributions
Abstract

Abstract: PB1797

Type: Publication Only

Session title: Stem cell transplantation - Clinical

Background
Although chimeric antigen receptor (CAR) T-cell is highly-effective in remission induction for relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), a substantial proportion of responded patients will eventually relapse. Haplo-identical allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered one of subsequent consolidation options post CAR T-cell salvage, especially for those without marched related or unrelated donors. However, haplo-identical HSCT is usually associated with higher rate of graft-versus-host-disease (GVHD), so how to reduce the rates and degree of GVHD which maintain graft-versus-leukemia capacity, is an active field of exploration in this setting. Post-transplant cyclophosphomide (PTCY) was showed to be promising GVHD prophylaxis for allo-HSCT, and recently there were several reports showed low-dose PTCT could achieve similar outcome.

Aims
CAR T-cell has been approved for the salvage for refractory/relapsed (R/R) acute lymphoblastic leukemia, and a proportion of salvaged ALL patients can further consolidated by allo-HSCT. Here we reported three cases of CD19-targeted CAR T-cell salvaged R/R-ALL patients who intended for haplo-identical allo-HSCT.

Methods
There are three cases of R/R B-ALL in our institute, in whom two of them are Philadelphia chromosome-positive (ph-positive) B-ALL patients. All of them have already identified related haplo-identical donors prior to CAR-T salvage. Once patient achieved complete remission post CAR-T salvage, then proceeded to haplo-HSCT as soon as possible. Unmanipulated mobilized peripheral blood stem cell (MPBSC) from related haplo-identical donor was employed as a stem cell source, and GIAC protocol plus low-dose PTCY was employed for haplo-identical allo-HSCT. 

Results
All of three cases achieved CR post CAR T-cell salvage. During the preparation of HSCT, one case ph-positive ALL relapsed and did not proceed to allo-HSCT, and the other two cases successfully proceeded to haplo-identical allo-HSCT by GIAC protocol plus low-dose PTCY. Both patients had a rapid graft engraftment and achieved complete chimerism (CC) after MPBSC infusion, one case had grade II aGVHD which resolved rapidly with mono-steroid treatment. Both of them are leukemia-free and GVHD-free at the last follow-up.

Conclusion
Low-dose PTCY plus GIAC protocol with MPBSC is a feasible consolidation for CAR T-cell salvaged B-ALL patients, however, for patients with rapid relapse post CAR T-cell salvage, it is still an unmet clinical need. 

Keyword(s):

Abstract: PB1797

Type: Publication Only

Session title: Stem cell transplantation - Clinical

Background
Although chimeric antigen receptor (CAR) T-cell is highly-effective in remission induction for relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), a substantial proportion of responded patients will eventually relapse. Haplo-identical allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered one of subsequent consolidation options post CAR T-cell salvage, especially for those without marched related or unrelated donors. However, haplo-identical HSCT is usually associated with higher rate of graft-versus-host-disease (GVHD), so how to reduce the rates and degree of GVHD which maintain graft-versus-leukemia capacity, is an active field of exploration in this setting. Post-transplant cyclophosphomide (PTCY) was showed to be promising GVHD prophylaxis for allo-HSCT, and recently there were several reports showed low-dose PTCT could achieve similar outcome.

Aims
CAR T-cell has been approved for the salvage for refractory/relapsed (R/R) acute lymphoblastic leukemia, and a proportion of salvaged ALL patients can further consolidated by allo-HSCT. Here we reported three cases of CD19-targeted CAR T-cell salvaged R/R-ALL patients who intended for haplo-identical allo-HSCT.

Methods
There are three cases of R/R B-ALL in our institute, in whom two of them are Philadelphia chromosome-positive (ph-positive) B-ALL patients. All of them have already identified related haplo-identical donors prior to CAR-T salvage. Once patient achieved complete remission post CAR-T salvage, then proceeded to haplo-HSCT as soon as possible. Unmanipulated mobilized peripheral blood stem cell (MPBSC) from related haplo-identical donor was employed as a stem cell source, and GIAC protocol plus low-dose PTCY was employed for haplo-identical allo-HSCT. 

Results
All of three cases achieved CR post CAR T-cell salvage. During the preparation of HSCT, one case ph-positive ALL relapsed and did not proceed to allo-HSCT, and the other two cases successfully proceeded to haplo-identical allo-HSCT by GIAC protocol plus low-dose PTCY. Both patients had a rapid graft engraftment and achieved complete chimerism (CC) after MPBSC infusion, one case had grade II aGVHD which resolved rapidly with mono-steroid treatment. Both of them are leukemia-free and GVHD-free at the last follow-up.

Conclusion
Low-dose PTCY plus GIAC protocol with MPBSC is a feasible consolidation for CAR T-cell salvaged B-ALL patients, however, for patients with rapid relapse post CAR T-cell salvage, it is still an unmet clinical need. 

Keyword(s):

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