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Haploidentical transplantation has a superior graft-versus-leukemia effect than HLA-matched sibling transplantation for Ph- high-risk B-cell acute lymphoblastic leukemia
Fan, M., Wang, Y., Lin, R., Lin, T., Huang, F., Fan, Z., Xu, Y., Yang, T., Xu, N., Shi, P., et al
Chinese medical journal. 2021
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Abstract
BACKGROUND Compared with human leukocyte antigen (HLA)-matched sibling donor (MSD) transplantation, it remains unclear whether haploidentical donor (HID) transplantation has a superior graft-versus-leukemia (GVL) effect for Philadelphia-negative (Ph-) high-risk B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to compare the GVL effect between HID and MSD transplantation for Ph- high-risk B-ALL. METHODS This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Immunosuppressant withdrawal and prophylactic or pre-emptive donor lymphocyte infusion (DLI) were administered in patients without active graft-versus-host disease (GVHD) to prevent relapse. All patients with measurable residual disease (MRD) positivity post-transplantation (post-MRD+) or non-remission (NR) pre-transplantation received prophylactic/pre-emptive interventions. The primary endpoint was the incidence of post-MRD+. RESULTS A total of 335 patients with Ph- high-risk B-ALL were enrolled, including 145 and 190, respectively, in the HID and MSD groups. The 3-year cumulative incidence of post-MRD+ was 27.2% (95% confidence interval [CI]: 20.2%-34.7%) and 42.6% (35.5%-49.6%) in the HID and MSD groups (P = 0.003), respectively. A total of 156 patients received DLI, including 60 (41.4%) and 96 (50.5%), respectively, in the HID and MSD groups (P = 0.096). The 3-year cumulative incidence of relapse was 18.6% (95% CI: 12.7%-25.4%) and 25.9% (19.9%-32.3%; P = 0.116) in the two groups, respectively. The 3-year overall survival (OS) was 67.4% (95% CI: 59.1%-74.4%) and 61.6% (54.2%-68.1%; P = 0.382), leukemia-free survival (LFS) was 63.4% (95% CI: 55.0%-70.7%) and 58.2% (50.8%-64.9%; P = 0.429), and GVHD-free/relapse-free survival (GRFS) was 51.7% (95% CI: 43.3%-59.5%) and 37.8% (30.9%-44.6%; P = 0.041), respectively, in the HID and MSD groups. CONCLUSION HID transplantation has a lower incidence of post-MRD+ than MSD transplantation, suggesting that HID transplantation might have a superior GVL effect than MSD transplantation for Ph- high-risk B-ALL patients. TRIAL REGISTRATION ClinicalTrials.gov: NCT01883180, NCT02673008.
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Donor-derived CD19 CAR-T cell therapy of relapse of CD19-positive B-ALL post allotransplant
Zhang, C., Wang, X. Q., Zhang, R. L., Liu, F., Wang, Y., Yan, Z. L., Song, Y. P., Yang, T., Li, P., Wang, Z., et al
Leukemia. 2020
Abstract
Safety and efficacy of allogeneic anti-CD19 chimeric antigen receptor T cells (CAR-T cells) in persons with CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) relapsing after an allotransplant remain unclear. Forty-three subjects with B-ALL relapsing post allotransplant received CAR-T cells were analyzed. 34 (79%; 95% confidence interval [CI]: 66, 92%) achieved complete histological remission (CR). Cytokine release syndrome (CRS) occurred in 38 (88%; 78, 98%) and was ≥grade-3 in 7. Two subjects died from multiorgan failure and CRS. Nine subjects (21%; 8, 34%) developed ≤grade-2 immune effector cell-associated neurotoxicity syndrome (ICANS). Two subjects developed ≤grade-2 acute graft-versus-host disease (GvHD). 1-year event-free survival (EFS) and survival was 43% (25, 62%). In 32 subjects with a complete histological remission without a second transplant, 1-year cumulative incidence of relapse was 41% (25, 62%) and 1-year EFS and survival, 59% (37, 81%). Therapy of B-ALL subjects relapsing post transplant with donor-derived CAR-T cells is safe and effective but associated with a high rate of CRS. Outcomes seem comparable to those achieved with alternative therapies but data from a randomized trial are lacking.
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Single-center experience suggests donor lymphocyte infusion may promote long-term survival in children with high-risk acute lymphoblastic leukemia
Liberio, N., Robinson, H., Nugent, M., Simpson, P., Margolis, D. A., Malarkannan, S., Keever-Taylor, C., Thakar, M. S.
Pediatric blood & cancer. 2019;:e27950
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Abstract
BACKGROUND Donor lymphocyte infusion (DLI) is often used to treat leukemic relapse after hematopoietic cell transplantation (HCT). However, the relationship between outcomes and distinct DLI cellular composition has not been previously reported. Additionally, there are limited published data on efficacy in pediatrics. We evaluated whether DLI cellular content and development of graft-versus-host disease (GVHD) impacted disease and influenced overall survival (OS) in children receiving DLI for recurrent leukemia. METHODS We performed an Institutional Review Board-approved, retrospective study investigating all consecutive DLIs given to patients at the Children's Hospital of Wisconsin between 1980 and 2018. Analyses were conducted using Mann-Whitney, Fisher exact, and chi-square tests. RESULTS Thirty patients ≤20 years old with hematologic malignancies (myeloid [AML/MDS/CML/JMML], n = 23; lymphoid [ALL], n = 7) received DLI to treat post-transplant relapse. We found no significant difference in OS or development of GVHD based on CD3, CD4, CD8, CD56, or CD19 DLI cellular composition. With a median follow-up of 0.69 (range, 0.04-16.61) years, OS at five years was 32% +/- 9%. The lymphoid group had a five-year survival rate at 71% +/- 17% compared with the myeloid group at 22% +/- 9%, although not statistically significant (P = 0.11). The development of GVHD did not affect OS (P = 0.62). CONCLUSION Here, we report a single-center, long-term experience of pediatric DLIs. Surprisingly, many children with ALL were able to achieve durable remissions. Although cellular composition did not have a significant effect on GVHD or OS in our small study, engineering DLI products to maximize specific effector cell populations could be one strategy to improve efficacy.