Contributions
Abstract: EP1223
Type: E-Poster Presentation
Session title: Stem cell transplantation - Clinical
Background
The prognosis of refractory/relapsed T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LBL) was extremely poor. In our previous clinical study (unpublished data), more than 90% complete remission (CR) has been obtained with allogeneic CD7-CART therapy in refractory/relapsed T-ALL/T-LBL, but hematopoiesis reconstitution is crucial for long-term disease-free survival (DFS) in this setting.
Aims
A clinical trial was designed to examine the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) after allogeneic CD7-CART for refractory/relapsed T-ALL/T-LBL.
Methods
From October 2020 to January 2021, 7 patients with refractory/relapsed T-ALL/T-LBL (refractory in 1, relapsed in 6; with extramedullary disease (EMD) in 4) after allogeneic CD7-CART therapy followed by allo-HSCT from the same donor were enrolled. The median age was 12 (3-44) years old. The median blasts in bone marrow (BM) were 35 (15-90) % before CD7-CART. Before allo-HSCT, minimal residual disease (MRD) in BM and cerebrospinal fluid was negative in all cases, and EMDs were detectable in 3 patients but with much smaller sizes. Pancytopenia was seen in all cases before HSCT. The median time from CART cell infusion to allo-HSCT was 32 (29-36) days. The types of HSCT were haploidentical in 5 cases and identical sibling in 2 cases. Conditioning regimens were busulfan/fludarabine-based (6 cases) or TBI/fludarabine-based (1 case). ATG (rabbit anti-human T-lymphocyte immunoglobulin 10mg/kg in 4, rabbit anti-human Thymocyte globulin 6mg/kg in 1) was applied in haploidentical transplants. Cyclosporine, MMF and short-term MTX were employed for GVHD prophylaxis. Chimerism was analyzed by STR. MRD was detected by flow cytometry (FCM) and PCR, and EMD was evaluated by PET-CT. CART cells were monitored by FCM and PCR.
Results
Before HSCT, all patients were with mixed chimerism. The median percentage of chimerism in BM and peripheral blood were 58.05 (1.57-73.42) %, 92.34 (35.11-98) %, respectively. The median time of neutrophil engraftment was 19 (12-21) days. The median time of platelet engraftment was 21 (6-100) days. At one month post-transplant, all patients achieved MRD- CR without EMD, and full donor chimerism in CD3+ lymphocytes and BM was detected in all cases. Acute graft-versus-host disease (aGVHD) was mild with only grade I in 2 patients, and no chronic GVHD was noted. Bacterial infections occurred in some patients (perianal infection in 1, sepsis in 1, intestinal infections in 3). Four cases developed CMV viremia and 1 patient had CMV retinitis. Hemorrhagic cystitis occurred in 2 patients. One case had post-transplant lymphoproliferative disease and resolved with rituximab and chemotherapy. One patient died from multi-organ failure on days 14 after HSCT. With the median follow-up 61 (25-151) days, no recurrence was found, 6/7 cases have been survived free of diseases. The median time of CART cell detectable was 39 (28-60) days post-HSCT. The median CART cell percentage was 0.52 (0.17-3.62) %.
Conclusion
With our protocol, hematopoiesis reconstitution has been achieved in all patients. Allogeneic CD7-CART combined with allo-HSCT has shown powerful anti-T-ALL/T-LBL effects and good safety profile. The existence of CD7-CART early after transplant had no influence on engraftment and may contribute to prolonged anti-tumor effect. Infections are main complications in this setting, therefore, appropriate dosages of immunosuppressants and the timing bridge to allo-HSCT need to be further investigated. This trial is still ongoing.
Keyword(s): Allogeneic hematopoietic stem cell transplant, CAR-T, T cell acute lymphoblastic leukemia, T cell lymphoma
Abstract: EP1223
Type: E-Poster Presentation
Session title: Stem cell transplantation - Clinical
Background
The prognosis of refractory/relapsed T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LBL) was extremely poor. In our previous clinical study (unpublished data), more than 90% complete remission (CR) has been obtained with allogeneic CD7-CART therapy in refractory/relapsed T-ALL/T-LBL, but hematopoiesis reconstitution is crucial for long-term disease-free survival (DFS) in this setting.
Aims
A clinical trial was designed to examine the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) after allogeneic CD7-CART for refractory/relapsed T-ALL/T-LBL.
Methods
From October 2020 to January 2021, 7 patients with refractory/relapsed T-ALL/T-LBL (refractory in 1, relapsed in 6; with extramedullary disease (EMD) in 4) after allogeneic CD7-CART therapy followed by allo-HSCT from the same donor were enrolled. The median age was 12 (3-44) years old. The median blasts in bone marrow (BM) were 35 (15-90) % before CD7-CART. Before allo-HSCT, minimal residual disease (MRD) in BM and cerebrospinal fluid was negative in all cases, and EMDs were detectable in 3 patients but with much smaller sizes. Pancytopenia was seen in all cases before HSCT. The median time from CART cell infusion to allo-HSCT was 32 (29-36) days. The types of HSCT were haploidentical in 5 cases and identical sibling in 2 cases. Conditioning regimens were busulfan/fludarabine-based (6 cases) or TBI/fludarabine-based (1 case). ATG (rabbit anti-human T-lymphocyte immunoglobulin 10mg/kg in 4, rabbit anti-human Thymocyte globulin 6mg/kg in 1) was applied in haploidentical transplants. Cyclosporine, MMF and short-term MTX were employed for GVHD prophylaxis. Chimerism was analyzed by STR. MRD was detected by flow cytometry (FCM) and PCR, and EMD was evaluated by PET-CT. CART cells were monitored by FCM and PCR.
Results
Before HSCT, all patients were with mixed chimerism. The median percentage of chimerism in BM and peripheral blood were 58.05 (1.57-73.42) %, 92.34 (35.11-98) %, respectively. The median time of neutrophil engraftment was 19 (12-21) days. The median time of platelet engraftment was 21 (6-100) days. At one month post-transplant, all patients achieved MRD- CR without EMD, and full donor chimerism in CD3+ lymphocytes and BM was detected in all cases. Acute graft-versus-host disease (aGVHD) was mild with only grade I in 2 patients, and no chronic GVHD was noted. Bacterial infections occurred in some patients (perianal infection in 1, sepsis in 1, intestinal infections in 3). Four cases developed CMV viremia and 1 patient had CMV retinitis. Hemorrhagic cystitis occurred in 2 patients. One case had post-transplant lymphoproliferative disease and resolved with rituximab and chemotherapy. One patient died from multi-organ failure on days 14 after HSCT. With the median follow-up 61 (25-151) days, no recurrence was found, 6/7 cases have been survived free of diseases. The median time of CART cell detectable was 39 (28-60) days post-HSCT. The median CART cell percentage was 0.52 (0.17-3.62) %.
Conclusion
With our protocol, hematopoiesis reconstitution has been achieved in all patients. Allogeneic CD7-CART combined with allo-HSCT has shown powerful anti-T-ALL/T-LBL effects and good safety profile. The existence of CD7-CART early after transplant had no influence on engraftment and may contribute to prolonged anti-tumor effect. Infections are main complications in this setting, therefore, appropriate dosages of immunosuppressants and the timing bridge to allo-HSCT need to be further investigated. This trial is still ongoing.
Keyword(s): Allogeneic hematopoietic stem cell transplant, CAR-T, T cell acute lymphoblastic leukemia, T cell lymphoma