scholarly journals CD19-CAR-T Therapy Followed By Allogeneic Hematopoietic Stem Cell Transplantation in Refractory/Relapsed and High Risk B-Cell Acute Lymphoblastic Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2660-2660 ◽  
Author(s):  
Yanli Zhao ◽  
Jianping Zhang ◽  
Deyan Liu ◽  
Min Xiong ◽  
Zhijie Wei ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Median Time ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Car T ◽  
Cell Acute Lymphoblastic Leukemia

Abstract Introduction: CD19-CAR-T cells induce high rates of initial response among patients with refractory/relapsed and MRD positive high risk B-cell acute lymphoblastic leukemia (B-ALL). Afterwards allogeneic hematopoietic stem cell transplantation (HSCT) can further reduce relapse rate. Our previous results had shown that CR obtained by CD19 CAR-T had comparable significance to CR by chemotherapy before Allogeneic HSCT in B-ALL. Patients and Methods: Between July 2015 and Mar 2018, consecutive 135 patients with refractory/relapsed or high risk B-ALL obtained CR with CD19-CART therapy followed by allogeneic HSCT were retrospective analyzed. Median follow-up of survivors was 13 months (range, 3-32 months). Results: The median age was 11 (2-49) years. The median disease course before transplant was 21(4-143) months. The median time from CART therapy to HSCT was 69 (35-312) days. Disease status was 108 cases relapsed diseases, 11 cases refractory, and 16 persistent/recurrent measurable residual diseases (MRD). MRD pre-conditioning measured by flow cytometry and QT-PCR was positive in 20(14.8%) subjects. Donor source was haploidentical donors in 107(79.3%), identical sibling in 7(5.1%), and unrelated in 21(15.6%). Most subjects (87.4%) received conventional myeloablative pretransplant conditioning with total body radiation (TBI), the rest with busulfan (Bu). Antithymocyte globulin was used in haploidentical and unrelated transplants. Cyclosporine, short-term methotrexate, and mycophenolate mofetil were employed for GVHD prophylaxis. There were no cases of graft-failure except one early death on Day 0 for septic shock. The median time to neutrophil engraftment was 14 days (10, 26 days), and median time to platelet engraftment 14 days (5, 70 days). The incidences of non-relapse mortality within 100 days were 4.4% (0.8, 7.9%) The incidence of grades II-IV acute graft-versus-host disease (GvHD) were 32.1% (24.3, 39.9%) and grades III-IV GvHD 10.5% (5.4, 15.6%). Chronic GvHD and extensive chronic GvHD were 69.7% (60.7, 78.7%) and17.6% (10.7, 24.5%). Cumulative incidence of relapses (CIRs) at 2-year was 11.1% (5.4, 16.8%). There were totally 14 subjects relapsed after HSCT, among which 8 were CD19 negative relapse, 5 CD19 positive and 1 partial CD19 positive. And among the 8 CD19 negative relapse after transplant, 4 subjects had CD19 negative MRD before conditioning. Leukemia-free survival (LFS) was 76.5% (64.2, 88.8%) and overall survival (OS) was 80.8% (72.6, 89.0%) at two years after transplant. In multivariate analysis subjects who were MRD- positive pre-transplant had a higher 2-year CIR (43.5% [18.4, 68.6%] vs. 5.9% [1.2, 10.6%]; p=0.000) and worse 2-year OS (61.5% [35.6, 87.4%] vs. 83.6% [75, 92.2%]; p=0.034). Conclusions: Our clinical results showed that CART therapy followed by allogeneic HSCT was a promising modality for refractory/relapsed B-ALL. CD19 negative relapse accounted for most relapse after allogeneic HSCT. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation, Especially Haploidentical, May Improve Long-term Survival for Children With High-risk T-cell Acute Lymphoblastic Leukemia in First Complete Remission

2021 ◽  
Author(s):  
Yongzhan Zhang ◽  
Lu Bai ◽  
Xiao-jun Huang ◽  
Ai-dong Lu ◽  
Yu Wang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Cell Acute Lymphoblastic Leukemia ◽  
First Complete Remission

Abstract Purpose The role of hematopoietic stem cell transplantation (HSCT) for children with high-risk (HR) T- cell acute lymphoblastic leukemia (T-ALL) in first complete remission (CR1) is still under critical discussion. This study explored the hierarchical criteria, prognostic factors of childhood T-ALL, and the role of HSCT, especially haplo-HSCT, for children with HR T-ALL in CR1. Methods Seventy-four pediatric T-ALL patients were included in this study and stratified into low-risk chemotherapy cohort (n=16), high-risk chemotherapy cohort (n=31) and high-risk transplant cohort (n=24). Results Patient prognosis in the high-risk chemotherapy cohort was significantly inferior to the low-risk chemotherapy cohort (5-year overall survival (OS): 51.2%±10% vs. 100%, P = 0.003; 5-year event-free survival (EFS): 48.4%±9.8% vs. 93.8%±6.1%, P = 0.01; 5-year cumulative incidence of relapse (CIR): 45.5%±0.8% vs. 6.3%±0.4%, P = 0.043). The 5-year OS, EFS, and CIR of the high-risk transplant cohort were 77.0%±8.3%, 77.0%±8.3%, and 11.9%±0.4%, respectively. When compared to the high-risk chemotherapy cohort, the P values were 0.084, 0.041, and 0.011, respectively. Minimal residual disease (MRD) re-emergence, initial white blood cell (WBC) count, and age≥10 years were independent risk factors for prognosis. ConclusionsHSCT, especially haplo-HSCT, might effectively improve the survival outcomes for HR childhood T-ALL in CR1.

Outcome of Hematopoietic Stem Cell Transplantation for Pediatric Acute Lymphoblastic Leukemia in Third Complete Remission (CR3): A Vital Role for Graft-Versus-Host-Disease/Graft-Versus-Leukemia Effect in Survival.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3667-3667
Author(s):  
Adam Gassas ◽  
Kashif Ishaqi ◽  
John Doyle
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Related Mortality

Abstract Children with acute lymphoblastic leukemia (ALL) who suffer 2 relapses could be salvaged by hematopoietic stem cell transplantation (HSCT) when a suitable stem cell source is available provided they respond to the pre HSCT chemotherapy and at least enter morphological remission. However, these patients are at very high risk for post HSCT relapse and also at a high risk for transplant related mortality (TRM). Our objective, herein, was to review the outcome of children (0–18years) with ALL who received allogeneic HSCT in third complete remission (CR3) at our institution. Between January 1994 – August 2005, twenty-two consecutive children in CR3 received HSCT in the Hospital for Sick Children, Toronto, Canada. Conditioning regimens included single dose of VP16 (60mg/kg infused over 4 hours) and fractionated total body irradiation (TBI; 1200cGy) in six fractions over 3 days (VP16/TBI) in 10 patients (1994–1998) and cyclophosphamide 50mg/kg infused over 1 hour daily for 4 days followed by the same dose of fractionated TBI (CY/TBI) in 12 patients (1999–2005). Graft-versus-host disease (GVHD) prophylaxis included cyclosporine A and a short course of methotrexate for the majority of patients, and all patients were in complete morphological remission prior to HSCT. Median age was 8.4 years (range 3–15.4). Donor source was as follows: matched sibling donor (MSD), 8; matched unrelated donor (MUD) 6; one antigen mismatch related donor (MMRD) 4; one antigen mismatched unrelated donor (MMUD) 3; and one patient received 1 antigen mismatched cord progenitor stem cells. White cell engraftment was successful in all patients at a median of 18 days (range 9–29). Ten patients died of TRM, seven relapsed, one died from other causes and four patients are long term survivors at a median follow up of 3.7 years (range 1–10.2). All patients who did not develop clinical acute or chronic GVHD relapsed and died. Event free survival was (EFS 19% ± 4%). Three out of the 4 survivors received MMUD and all 4 survivors had moderate to severe acute GVHD and three had chronic GVHD, limited in two and extensive in one. Conclusion: Children with ALL in CR3 receiving HSCT are extremely high risk for relapse and transplant related mortality. These children have already relapsed twice and demonstrated chemotherapy resistance and GVL/GVHD plays a key role in leukemia eradication. Although, TRM is high in such patients and GVHD could potentially increase TRM, there are no survivors without GVHD and exploring means of inducing GVHD by reduction of immunosuppressive medications or other means of immunotherapy should seriously be considered in these patients.

Superiority of Allogeneic Hematopoietic Stem-Cell Transplantation Compared With Chemotherapy Alone in High-Risk Childhood T-Cell Acute Lymphoblastic Leukemia: Results From ALL-BFM 90 and 95

2006 ◽  
Vol 24 (36) ◽  
pp. 5742-5749 ◽  
Author(s):  
André Schrauder ◽  
Alfred Reiter ◽  
Helmut Gadner ◽  
Dietrich Niethammer ◽  
Thomas Klingebiel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Median Time ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Free Survival

Purpose The role of hematopoietic stem-cell transplantation (SCT) in first complete remission (CR1) for children with very high–risk (VHR) acute lymphoblastic leukemia (ALL) is still under critical discussion. Patients and Methods In the ALL–Berlin-Frankfurt-Münster (BFM) 90 and ALL-BFM 95 trials, 387 patients were eligible for SCT if there was a matched sibling donor (MSD). T-cell ALL (T-ALL) patients with poor in vivo response to initial treatment represented the largest homogeneous subgroup within VHR patients. Results Of 191 high-risk (HR) T-ALL patients, 179 patients (94%) achieved CR1. Twenty-three patients received an MSD-SCT. Furthermore, in trial ALL-BFM 95, eight matched unrelated donors (MUDs) and five mismatched family donors (MMFDs) were used. The median time to SCT was 5 months (range, 2.4 to 10.8 months) from diagnosis. The 5-year disease-free survival (DFS) was 67% ± 8% for 36 patients who received an SCT in CR1 and 42% ± 5% for the 120 patients treated with chemotherapy alone having an event-free survival time of at least the median time to transplantation (Mantel-Byar, P = .01). Overall survival (OS) rate for the SCT group was 67% ± 8% at 5 years, whereas patients treated with chemotherapy alone had an OS rate of 47% ± 5% at 5 years (Mantel-Byar, P = .01). Outcome of patients who received MSD-SCT versus MUD-/MMFD-SCT was comparable (DFS, 65% ± 10% v 69% ± 13%, respectively). However, relapses only occurred after MSD-SCT (eight of 23 patients), whereas treatment-related mortality only occurred after MUD-/MMFD-SCT (four of 13 patients). Conclusion SCT in CR1 is superior to treatment with chemotherapy alone for childhood HR-T-ALL.

Sign in / Sign up

Export Citation Format

Share Document