A Pilot Trial Examining Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic Stem Cell Transplant Recipients Using Myeloablative Busulfan and Fludarabine

This study is examining a chemotherapy regimen and immune suppressive medications in the setting of an allogeneic stem cell transplant. A pilot clinical trial to characterize the incidence, prevalence and function of myeloid-derived suppressor cells (MDSCs) and immune checkpoint regulators (V-domain Ig Suppressor of T-cell Activation [VISTA], cytotoxic T-lymphocyte- associated protein 4 [CTLA-4], programmed death-ligand 1 [PD-L1]) during early immune recovery following an allogeneic stem cell transplant. The site will use a myeloablative regimen of fludarabine with busulfan, adopted from CALGB 100801, to define clinical endpoints, including engraftment, 100 day survival and one year survival (Objective #1). The site will characterize the incidence, prevalence and function of MDSCs and immune checkpoint regulators in patients' blood and bone marrow following transplantation (Objective #2). The site will correlate these laboratory results with clinical outcomes and the incidence of graft-versus-host disease (GVHD). As an exploratory aim, in those patients experiencing GVHD and requiring treatment, the site will define the MDSCs frequency and checkpoint regulator expression and correlate these results with the patient's response to GVHD therapy.

开始日期2016-09-06

申办/合作机构

Dartmouth-Hitchcock Medical Center

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项与 Rabbit Anti-Thymoglobulin(Dartmouth-Hitchcock Medical Center) 相关的文献（医药）

2024-10-01·Transplantation and Cellular Therapy

Superior survival after unrelated allogeneic stem cell transplantation with low-dose ATG compared to low-dose TBI in myeloablative fludarabine/busulfan-based regimen for MDS on behalf of the adult MDS Working Group of the JSTCT

Article

作者: Matsuoka, Ken-ichi ; Adachi, Koji ; Ichinohe, Tatsuo ; Kako, Shinichi ; Sakaida, Emiko ; Itonaga, Hidehiro ; Nakazawa, Hideyuki ; Atsuta, Yoshiko ; Fujiwara, Shini-Chiro ; Matsuoka, Ken-Ichi ; Ikeda, Takashi ; Miyazaki, Yasushi ; Kataoka, Keisuke ; Fujioka, Machiko ; Aotsuka, Nobuyuki ; Kawakita, Toshiro ; Fujiwara, Shini-chiro ; Ishiyama, Ken ; Kanda, Yoshinobu ; Nishida, Tetsuya

The fludarabine/intravenous busulfan 12.8 mg/kg (FB4) regimen is an effective conditioning regimen in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome (MDS); however, limited data is available on the prognostic impact of FB4 with low-dose anti-thymoglobulin (ATG ≤ 5 mg/kg) or low-dose total body irradiation (TBI ≤ 4 Gy). Therefore, we retrospectively evaluated the outcomes in 280 adults with de novo MDS who underwent their first transplantation from an unrelated donor between 2009 and 2018. Median age was 61 yr (range, 16 to 70 yr). In the FB4 alone (FB4), FB4 plus ATG (FB4-ATG), and FB4 plus TBI (FB4-TBI) groups, 3-yr overall survival (OS) rates were 39.9%, 64.8%, and 43.7%; 3-yr nonrelapse mortality (NRM) were 32.1%, 22.1%, and 27.1%; and 3-yr relapse incidences were 34.7%, 21.2%, and 28.9%, respectively. The multivariate analyses showed that FB4-ATG group significantly correlated with better OS (hazard Ratio [HR], 0.51; 95% confidence interval [CI], 0.27 to 0.95; P = .032) than FB4 group. FB4-ATG group tended to correlate with lower NRM (HR, 0.36; 95% CI, 0.13 to 1.06; P = .063) than FB4 group. In comparison with FB4-TBI group, FB4-ATG group showed better OS (HR 0.52, 95% CI 0.27 to 0.99, P = .049) and NRM (HR 0.034, 95% CI 0.11 to 0.92, P = .034). No significant differences were observed in OS and NRM between the FB4-TBI and FB4 groups. The present study demonstrated that the FB4 plus low-dose ATG regimen improved OS and NRM, but FB4 plus low-dose TBI regimen had no clear benefit over FB4 alone, in MDS patients who used unrelated donors.

2024-07-01·Annals of Hematology

Immune reconstitution after single-unit umbilical cord blood transplantation using anti-thymoglobulin and myeloablative conditioning in adults with hematological malignancies

Article

作者: Montoro, Juan ; Sempere, Amparo ; Bataller, Ana ; Santiago, Marta ; Chorão, Pedro ; Gómez, Inés ; Villalba, Marta ; Granados, Pablo ; Asensi, Pedro ; Sanz, Jaime ; Facal, Ana ; Sanz, Miguel A ; Guerreiro, Manuel ; Balaguer, Aitana ; Cordón, Lourdes ; Sanz, Guillermo F ; Solves, Pilar ; Martín-Herreros, Beatriz ; Lamas, Brais

This study aimed to investigate the kinetics of immune recovery following umbilical cord blood transplantation (UCBT) in adults who received a myeloablative conditioning (MAC) regimen and antithymocyte globulin (ATG). While the immune recovery kinetics has been extensively studied in pediatric UCBT recipients, limited data exist for adults. We conducted a comprehensive analysis of 221 consecutive adult patients who underwent UCBT with MAC and ATG at a single institution. Our objective was to evaluate the influence of patient, disease, and transplant factors, along with acute graft-versus-host disease (aGVHD), on immune reconstitution and overall survival. Our findings confirm a delayed recovery of T cells, while B and NK cell reconstitution exhibited rapid progress, with NK cell counts reaching normal levels within 3 months post-transplantation and B cells within 6 months. Within CD3⁺ T cells, CD8⁺ T cells also experienced a delayed recovery (12 months), but to a lesser extent compared to CD4⁺ T cells (18 months). Delayed immune recovery of T-cell subsets was associated with the development of aGVHD grade II-IV, older age, CMV negativity, and a female donor. Patients with lymphoproliferative diseases showed slower NK cell recovery. Our study demonstrates that adult patients undergoing MAC with ATG and receiving a single unit UCBT for hematologic malignancies experienced rapid reconstitution of NK and B cells. However, T cell recovery, particularly CD4⁺ T cells, was significantly delayed. To enhance T cell recovery, it may be crucial to consider UCB units with higher cellularity and optimize ATG doses in conditioning.

2024-06-01·eJHaem

Clinical outcomes of patients receiving three versus four doses of methotrexate with concomitant antithymocyte globulin in match unrelated donor allogeneic stem cell transplant: A single‐center experience

Article

作者: Farooq, Umar ; Lochner, Jonathan ; Magalhaes‐Silverman, Margarida ; Strouse, Christopher ; Miller, Benda ; Poonsombudlert, Kittika ; Yodsuwan, Ratdanai ; Shaikh, Hira ; Mott, Sarah

AbstractMethotrexate (MTX) doses on days +1, +3, +6, and +11 after match unrelated donor allogeneic stem cell transplant (MUD HSCT) is a common graft‐versus‐host disease (GVHD) prophylaxis regimen. However, the overlapping toxicity of MTX with conditioning chemotherapy sometimes warrants the omission of the fourth dose of MTX. Prior single‐institution studies showed conflicting results comparing the outcomes of patients who received three versus four doses of MTX, but to our knowledge, the effect of concomitant antithymocyte globulin (ATG) has not been reported. Charts of patients who underwent MUD HSCT between 2009 and 2023 were reviewed. Patients received rabbit ATG (Thymoglobulin), given at 0.5 mg/kg on day −3, 2 mg/kg on day −2, and 2.5 mg/kg on day −1. MTX is given at 15 mg/m2 on day +1 and 10 mg/m2 on days +3, +6, and +11. Severe mucositis was the most common indication for day +11 MTX omission (82%). We identified 292 patients (116 in 3 dose cohort and 176 in 4 dose cohort). Median follow‐up was 23 months (range 1–151). Patients in the 4 doses cohort were more frequently male (68% vs. 50%, p < 0.01), received a reduced intensity conditioning regimen (38.0% vs. 22%, p < 0.01), were older (median 58 vs. 54 years, p = 0.02), and received a transplant in the earlier era (median HSCT year 2014 vs. 2018, p < 0.01). A statistically significant difference was not evidenced between the cohorts for the following outcomes: acute GVHD (aGVHD) (HR 1.1, 95% CI 0.9–1.5), chronic GVHD (cGVHD) (HR 1.3, 95% CI 0.8–1.6), relapse‐free survival (RFS) (HR 1.0, 95% CI 0.6–1.5), non‐relapse mortality (NRM) (HR 1.4, 95% CI 0.9–2.2), and overall survival (OS) (HR 1.2, 95% CI 0.9–1.7). Both cohorts had similar median time to neutrophil engraftment at 14 days. When ATG is incorporated, omission of day +11 MTX does not significantly impact the rate of engraftment or cumulative incidence of aGVHD, cGVHD, RFS, NRM, and OS.

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适应症	最高研发状态	国家/地区	公司	日期
移植物抗宿主病	临床1期	美国	Dartmouth-Hitchcock Medical Center	2016-08-31
淋巴细胞白血病	临床1期	美国	Dartmouth-Hitchcock Medical Center	2016-08-31
多发性骨髓瘤	临床1期	美国	Dartmouth-Hitchcock Medical Center	2016-08-31
骨髓增生异常综合征	临床1期	美国	Dartmouth-Hitchcock Medical Center	2016-08-31
髓系白血病	临床1期	美国	Dartmouth-Hitchcock Medical Center	2016-08-31
原发性骨髓纤维化	临床1期	美国	Dartmouth-Hitchcock Medical Center	2016-08-31
巨球蛋白血症	临床1期	美国	Dartmouth-Hitchcock Medical Center	2016-08-31