Abstract P169: Dipeptidyl Peptidase-4 Regulates Hematopoietic Stem Cell Activation in Response to Chronic Stress

Background: Dipeptidyl peptidase-4 (DPP4) inhibition exhibits multiple pleotrophic effects. Hematopoietic stem cell (HSC) activation has been implicated in the pathogenesis of stress-related metabolic disorder and cardiovascular disease. Given that interaction between β3-adrenergic receptor (Adrβ3) signaling and the immune system may link stress and the initiation and progression of disorders, we investigated whether DPP4 regulates immune over-reactions in a chronic stress mouse model, focusing on HSC activation. Methods and Results: Male 8-week-old mice fed a normal diet underwent chronic stress were randomly assigned to one of three groups and administered vehicle or a low or high dose of the DPP4 inhibitor anagliptin. Control mice were left undisturbed. The stress increased the blood and brain DPP4 activity, the levels of plasma adrenaline and noradrenaline, and the bone marrow (BM) niche cell adrenergic receptor (Adrβ3) expression, and it decreased the levels of plasma glucagon-like peptide (GLP-1) as well as brain GLP-1 receptor (GLP-1R) and BM Cxcl12 expressions. These changes were reversed by DPP4 inhibition. The stress activated the BM sca-1 high c-Kit high CD48 low CD150 high HSC proliferation, giving rise to high levels of blood leukocytes and monocytes. These DPP4 inhibition-related benefits were mimicked by DPP4 depletion and by GLP-1R activation. Adrβ3 inhibition mitigated BM Cxcl12 expressions and HSC activation. Conclusions: DPP4 activity appears to regulate chronic stress-induced BM HSC activation and inflammatory cell production via an Adrβ3-CXCLl12-dependent mechanism that is mediated by the GLP-1-GLP-1R axis, suggesting that the inhibition of DPP4 or the stimulation of GLP-1R may have applications in the treatment of inflammatory diseases.

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Dipeptidyl Peptidase‐4 Regulates Hematopoietic Stem Cell Activation in Response to Chronic Stress

Journal of the American Heart Association ◽

10.1161/jaha.117.006394 ◽

2017 ◽

Vol 6 (7) ◽

Cited By ~ 14

Author(s):

Enbo Zhu ◽

Lina Hu ◽

Hongxian Wu ◽

Limei Piao ◽

Guangxian Zhao ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell ◽

Chronic Stress ◽

Cell Activation ◽

Dipeptidyl Peptidase ◽

Hematopoietic Stem ◽

Dipeptidyl Peptidase 4

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High-dose chemotherapy and hematopoietic stem cell transplantation for breast cancer: Past or future?

Seminars in Oncology ◽

10.1053/sonc.2001.26148 ◽

2001 ◽

Vol 28 (4) ◽

pp. 377-388 ◽

Cited By ~ 1

Author(s):

Roy D. Baynes ◽

Roger D. Dansey ◽

Jared L. Klein ◽

Caroline Hamm ◽

Mark Campbell ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

High Dose Chemotherapy ◽

High Dose ◽

Hematopoietic Stem

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A Randomized Trial of Two 2-Dose Influenza Vaccination Strategies for Patients Following Autologous Hematopoietic Stem Cell Transplantation

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1711 ◽

2020 ◽

Author(s):

Benjamin W Teh ◽

Vivian K Y Leung ◽

Francesca L Mordant ◽

Sheena G Sullivan ◽

Trish Joyce ◽

...

Keyword(s):

Clinical Trials ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Influenza Vaccination ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Influenza B ◽

High Dose ◽

Hematopoietic Stem

Abstract Background Seroprotection and seroconversion rates are not well understood for 2-dose inactivated influenza vaccination (IIV) schedules in autologous hematopoietic stem cell transplantation (autoHCT) patients. Methods A randomized, single-blind, controlled trial of IIV in autoHCT patients in their first year post-transplant was conducted. Patients were randomized 1:1 to high-dose (HD) IIV followed by standard dose (SD) vaccine (HD-SD arm) or 2 SD vaccines (SD-SD arm) 4 weeks apart. Hemagglutination inhibition (HI) assay for IIV strains was performed at baseline, 1, 2, and 6 months post–first dose. Evaluable primary outcomes were seroprotection (HI titer ≥40) and seroconversion (4-fold titer increase) rates and secondary outcomes were geometric mean titers (GMTs), GMT ratios (GMRs), adverse events, influenza-like illness (ILI), and laboratory-confirmed influenza (LCI) rates and factors associated with seroconversion. Results Sixty-eight patients were enrolled (34/arm) with median age of 61.5 years, majority male (68%) with myeloma (68%). Median time from autoHCT to vaccination was 2.3 months. For HD-SD and SD-SD arms, percentages of patients achieving seroprotection were 75.8% and 79.4% for H1N1, 84.9% and 88.2% for H3N2 (all P > .05), and 78.8% and 97.1% for influenza-B/Yamagata (P = .03), respectively. Seroconversion rates, GMTs and GMRs, and number of ILI or LCIs were not significantly different between arms. Adverse event rates were similar. Receipt of concurrent cancer therapy was independently associated with higher odds of seroconversion (OR, 4.3; 95% CI, 1.2–14.9; P = .02). Conclusions High seroprotection and seroconversion rates against all influenza strains can be achieved with vaccination as early as 2 months post-autoHCT with either 2-dose vaccine schedules. Clinical Trials Registration Australian New Zealand Clinical Trials Registry: ACTRN12619000617167.

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SS-4 High dose chemotherapy with autologous hematopoietic stem cell transplantation for CNS lymphoma

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa143.005 ◽

2020 ◽

Vol 2 (Supplement_3) ◽

pp. ii2-ii2

Author(s):

Eisei Kondo

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Primary Cns Lymphoma ◽

High Dose Chemotherapy ◽

Cns Lymphoma ◽

High Dose ◽

Hematopoietic Stem

Abstract High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDT-ASCT) is listed as a consolidation therapy option for primary central nervous system (CNS) lymphoma in the guidelines of western countries. The advantages of HDT-ASCT for primary CNS lymphoma as consolidation are believed to be high rates of long-term remission and lower neurotoxicity, even though its eligibility is limited to younger fit patients. In the Japanese guideline, HDT-ASCT for primary CNS lymphoma is however not recommended in daily practice, mainly because thiotepa was unavailable since 2011. The Japanese registry data for hematopoietic transplantation have shown that primary CNS lymphoma patients were treated with various HDT regimens and thiotepa-containing HDT was associated with better progression free survival (P=.019), lower relapse (P=.042) and a trend toward a survival benefit (Kondo E et al, Biol Blood Marrow Transplant 2019). A pharmacokinetic study of thiotepa(DSP-1958) in HDT-ASCT for lymphoma was conducted in 2017, and thiotepa was approved for HDT-ASCT in lymphoma this March, meaning that optimal HDT regimen for CNS lymphoma is now available in Japan. The treatment strategy of CNS lymphoma needs further development to improve survival and reduce toxicity.

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Marrow irradiation with high-dose 153Samarium-EDTMP followed by chemotherapy and hematopoietic stem cell infusion for acute myelogenous leukemia

Leukemia & Lymphoma ◽

10.1080/10428190600580817 ◽

2006 ◽

Vol 47 (8) ◽

pp. 1583-1592 ◽

Cited By ~ 5

Author(s):

Vilmarie Rodriguez ◽

Peter M. Anderson ◽

Mark R. Litzow ◽

Linda Erlandson ◽

Barbara A. Trotz ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell ◽

Acute Myelogenous Leukemia ◽

Myelogenous Leukemia ◽

High Dose ◽

Hematopoietic Stem ◽

Acute Myelogenous

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High-Dose Chemotherapy with Autologous Hematopoietic Stem-Cell Rescue for Pediatric Brain Tumor Patients: A Single Institution Experience from UCLA

Journal of Transplantation ◽

10.1155/2011/740673 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 3

Author(s):

Eduard H. Panosyan ◽

Alan K. Ikeda ◽

Vivian Y. Chang ◽

Dan R. Laks ◽

Charles L. Reeb ◽

...

Keyword(s):

Stem Cell ◽

Brain Tumors ◽

Hematopoietic Stem Cell ◽

Germ Cell Tumors ◽

Pediatric Brain Tumors ◽

High Dose Chemotherapy ◽

High Dose ◽

Hematopoietic Stem ◽

Stem Cell Rescue ◽

Pediatric Brain

Background. Dose-dependent response makes certain pediatric brain tumors appropriate targets for high-dose chemotherapy with autologous hematopoietic stem-cell rescue (HDCT-AHSCR).Methods. The clinical outcomes and toxicities were analyzed retrospectively for 18 consecutive patients ≤19 y/o treated with HDCT-AHSCR at UCLA (1999–2009).Results. Patients' median age was 2.3 years. Fourteen had primary and 4 recurrent tumors: 12 neural/embryonal (7 medulloblastomas, 4 primitive neuroectodermal tumors, and a pineoblastoma), 3 glial/mixed, and 3 germ cell tumors. Eight patients had initial gross-total and seven subtotal resections. HDCT mostly consisted of carboplatin and/or thiotepa ± etoposide (n=16). Nine patients underwent a single AHSCR and nine ≥3 tandems. Three-year progression-free and overall survival probabilities were 60.5% ± 16 and 69.3% ± 11.5. Ten patients with pre-AHSCR complete remissions were alive/disease-free, whereas 5 of 8 with measurable disease were deceased (median followup: 2.3 yrs). Nine of 13 survivors avoided radiation. Single AHSCR regimens had greater toxicity than ≥3 AHSCR (P<.01).Conclusion. HDCT-AHSCR has a definitive, though limited role for selected pediatric brain tumors with poor prognosis and pretransplant complete/partial remissions.

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