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Prophylactic use of low-dose interleukin-2 and the clinical outcomes of hematopoietic stem cell transplantation: A randomized study.

ABSTRACT: Leukemia relapse and chronic graft-versus-host disease (cGVHD) are still major obstacles of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The numbers and activity of natural killer (NK) and T-regulatory cells can be increased post-transplantation by exposure to interleukin-2 (IL-2). We tested whether administering low-dose IL-2 would decrease leukemia relapse while reducing cGVHD after allotransplantation. This controlled, open-label randomized trial included 90 recipients of allotransplants. Subjects were randomized in a 1:1 ratio to either receive or not receive low-dose IL-2 during the early post-transplantation period. Patients in the IL-2 arm received a subcutaneous injection of low-dose IL-2 (1×106 U/d) on day 60 after allo-HSCT. IL-2 was administered daily for 14 d followed by a 14-d hiatus. The primary endpoint was the cumulative incidence of leukemia relapse (CIR). Three-year CIRs for the IL-2 arm and control arm were 23% (range 16-30%) and 11% (range 6-15%; p = 0.20), respectively. Minimal residual disease-positive (MRD+) tests were more common in the IL-2 arm compared to the control arm (36% [range 29-44%] vs. 15% [range 10-20%], p = 0.03). The cumulative incidence of moderate-to-severe chronic GVHD (cGVHD) was lower in the IL-2 arm compared to the control arm (33% [range 26-39%] vs. 57% [range 49-64%), p = 0.02). Therefore, the 3-y GVHD-free and GVHD progression-free survival (GPFS) rates were significantly higher in the IL-2 arm compared to the control arm (47% [range 39-55%] vs. 31% [range 25-38%], p = 0.048). Blood Tregs, NK cells, and NK-cell cytotoxicity were increased in subjects in the IL-2 arm between 3 mo and 6 mo post-transplantation. Administration of low-dose IL-2 during the immediate post-transplantation period was associated with a higher GPFS but did not decrease the CIR.

SUBMITTER: Zhao XY

PROVIDER: S-EPMC5215224 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Prophylactic use of low-dose interleukin-2 and the clinical outcomes of hematopoietic stem cell transplantation: A randomized study.

Zhao Xiang-Yu XY Zhao Xiao-Su XS Wang Yu-Tong YT Chen Yu-Hong YH Xu Lan-Ping LP Zhang Xiao-Hui XH Han Wei W Chen Huan H Wang Yu Y Yan Chen-Hua CH Wang Feng-Rong FR Wang Jing-Zhi JZ Liu Kai-Yan KY Chang Ying-Jun YJ Huang Xiao-Jun XJ

Oncoimmunology 20161028 12

Leukemia relapse and chronic graft-versus-host disease (cGVHD) are still major obstacles of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The numbers and activity of natural killer (NK) and T-regulatory cells can be increased post-transplantation by exposure to interleukin-2 (IL-2). We tested whether administering low-dose IL-2 would decrease leukemia relapse while reducing cGVHD after allotransplantation. This controlled, open-label randomized trial included 90 recipients of a ...[more]

PMID: 28123892

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Project description:BackgroundA low-degree tumor necrosis after neoadjuvant chemotherapy is a poor prognostic factor for osteosarcoma (OSA). However, the role of high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation in OSA remains controversial. We analyzed the treatment outcomes and prognostic factors of nonmetastatic OSA and compared the HDC and conventional chemotherapy (CC) outcomes of patients with <90% necrosis after neoadjuvant chemotherapy.MethodsWe retrospectively evaluated patients with OSA treated at the Seoul National University Children's Hospital from 2000 to 2020. Totally, 113 patients with non-metastatic OSA at diagnosis were included. The majority were treated with cisplatin, doxorubicin, and methotrexate as neoadjuvant chemotherapy. This was continued when the postoperative necrosis rate was >90% (good response [GR]), whereas most cases with <90% (poor response [PR]) were changed to chemotherapy. The HDC regimen was composed of melphalan, etoposide, and carboplatin.ResultsThe median age at diagnosis was 12.6 years (range, 5.0-20.3), and 61.9% of patients were men. The 5-year event-free survival (EFS) and overall survival (OS) rates were 75.8% and 91.5%, respectively. Among these, 59 and 44 patients were included in the GR and PR groups, respectively. The GR group had a better 5-year EFS rate than the PR group (82.4% vs. 67.3%, p=0.071). Age at diagnosis, sex, tumor site, type of neoadjuvant chemotherapy, and degree of tumor necrosis were not different between the PR-HDC (n=24) and PR-CC (n=20) groups. The 5-year EFS and OS rates in the PR-HDC (n=24) and PR-CC (n=20) groups were 78.6% and 53.6% (p=0.065) and 100% and 76.9% (p=0.024), respectively. In the Cox regression analysis, the PR-CC group (hazard ratio, 4.95; p=0.004) and age ≥12 years (hazard ratio, 2.68; p=0.024) were significant risk factors for 5-year EFS.ConclusionsHDC showed favorable outcomes in patients with non-metastatic OSA and <90% necrosis after neoadjuvant chemotherapy.

Project description:Importance:Autologous hematopoietic stem cell transplantation (AHSCT) may be effective in aggressive forms of multiple sclerosis (MS) that fail to respond to standard therapies. Objective:To evaluate the long-term outcomes in patients who underwent AHSCT for the treatment of MS in a large multicenter cohort. Design, Setting, and Participants:Data were obtained in a multicenter, observational, retrospective cohort study. Eligibility criteria were receipt of AHSCT for the treatment of MS between January 1995 and December 2006 and the availability of a prespecified minimum data set comprising the disease subtype at baseline; the Expanded Disability Status Scale (EDSS) score at baseline; information on the administered conditioning regimen and graft manipulation; and at least 1 follow-up visit or report after transplant. The last patient visit was on July 1, 2012. To avoid bias, all eligible patients were included in the analysis regardless of their duration of follow-up. Data analysis was conducted from September 1, 2014 to April 27, 2015. Exposures:Demographic, disease-related, and treatment-related exposures were considered variables of interest, including age, disease subtype, baseline EDSS score, number of previous disease-modifying treatments, and intensity of the conditioning regimen. Main Outcomes and Measures:The primary outcomes were MS progression-free survival and overall survival. The probabilities of progression-free survival and overall survival were calculated using Kaplan-Meier survival curves and multivariable Cox proportional hazards regression analysis models. Results:Valid data were obtained from 25 centers in 13 countries for 281 evaluable patients, with median follow-up of 6.6 years (range, 0.2-16 years). Seventy-eight percent (218 of 281) of patients had progressive forms of MS. The median EDSS score before mobilization of peripheral blood stem cells was 6.5 (range, 1.5-9). Eight deaths (2.8%; 95% CI, 1.0%-4.9%) were reported within 100 days of transplant and were considered transplant-related mortality. The 5-year probability of progression-free survival as assessed by the EDSS score was 46% (95% CI, 42%-54%), and overall survival was 93% (95% CI, 89%-96%) at 5 years. Factors associated with neurological progression after transplant were older age (hazard ratio [HR], 1.03; 95% CI, 1.00-1.05), progressive vs relapsing form of MS (HR, 2.33; 95% CI, 1.27-4.28), and more than 2 previous disease-modifying therapies (HR, 1.65; 95% CI, 1.10-2.47). Higher baseline EDSS score was associated with worse overall survival (HR, 2.03; 95% CI, 1.40-2.95). Conclusions and Relevance:In this observational study of patients with MS treated with AHSCT, almost half of them remained free from neurological progression for 5 years after transplant. Younger age, relapsing form of MS, fewer prior immunotherapies, and lower baseline EDSS score were factors associated with better outcomes. The results support the rationale for further randomized clinical trials of AHSCT for the treatment of MS.

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Prophylactic use of low-dose interleukin-2 and the clinical outcomes of hematopoietic stem cell transplantation: A randomized study.

Publications

Prophylactic use of low-dose interleukin-2 and the clinical outcomes of hematopoietic stem cell transplantation: A randomized study.

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