Clinical trial NCT02044185: Clinical Implications of HMGB1 in Patients Treated With Chemotherapy or Hematopoietic Stem Cell Transplantation
Official title: Observational Study for Clinical Implications of HMGB1 (High-mobility Group Protein B1) in Patients Treated With Chemotherapy or Hematopoietic Stem Cell Transplantation
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Graft-versus-host Disease
Keywords: HMGB1 Protein
Graft versus Host Disease
Immunosuppressive Agents
oral mucositis
Lead sponsor: Seoul St. Mary's Hospital
Sponsor class: OTHER
First posted: 2014-01-23
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 1. patients with bone marrow transplantation of patients with acute leukemia, lymphoma in patients group
2. normal populations in Health Promotion Center in control group

Brief summary: Acute Graft-versus-host disease(aGVDH) after allogeneic hematopoietic stem cell transplantation is one of the meaningful issues in aspect of patient's recovery and survival. in recent years, the understanding of the pathology of GVHD is much important to prevent or treat aGVHD. additionally, (oral) mucositis is one of the problems in patients with high dose chemotherapy, and mucositis by high-dose chemotherapy is related to HMGB-1 as proinflamtory cytokines. HMGB1 is a nuclear protein acts as a transcription factor, but, if it was released to the outside of cells by damaged cell or necrotic tissues, it works as cytokines for promoter of inflammation and cancers. at this point, there are no reported articles about correlation of HMGB1 and aGVHD in human. recently, we have seen excessive secretion of serum HMGB1 in mouse model, then base on this results, we will check correlation of HMGB1 and aGVHD/ oral mucositis in human.

Detailed description: 1. materials 1) inclusion criteria

   1. over 18-year-old
   2. patients with myeloablative conditioning regimen
   3. autologous transplant
   4. patients with confirmation of acute GVHD as over grade II
   5. patients with salvage chemotherapy

      2) exclusion criteria

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   1. old age ( over 60-year-old)
   2. patients with reduced intensity stem cell transplantation
2. method 1) check the serum level of HMGB1, TNF-a, IL-1b, IL-6, Th1, Th2, Th17, FoxP3 on 7-day before transplant day(D-7), transplant day(D0), 7-day after transplant(D+7), D+14, D+21. 2) check the immunohistochemistry level of tissue in diagnosed aGVHD ( performed sigmoidoscopy and random biopsy of gut is routine process in our center) 3) check the oral mucositis grades (using WHO grading system, NCI -CTC ver.3 scoring system)
3. analysis 1) student t-test , chi-square test 2) survival analysis

Eligibility criteria: 1. Inclusion Criteria:

   1. over 18-year-old
   2. patients with myeloablative conditioning regimen
   3. autologous transplant
   4. patients with confirmation of acute GVHD as over grade II
   5. patients with salvage chemotherapy
2. Exclusion Criteria:

   1. very old age ( over 75-year-old)
   2. patients with reduced intensity stem cell transplantation

Primary outcomes:
measure: comparison of serum HMGB1 level before and after diagnosed acute GVHD
timeFrame: 6 months
Secondary outcomes:
measure: serum level of immunosuppressive drugs in patients with acute GVHD
timeFrame: 3 months
Other outcomes:
measure: tissue IHC stain level of biopsy samples of diagnosed acute GVHD
timeFrame: if patients diagnosed with acute GVHD will be performed random biopy of colon or stomach.
measure: oral mucositis
timeFrame: 1 month
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul St.Mary's hospital
Study officials:
affiliation: The Catholic University of Korea
name: seok-goo CHO, M.D,Ph.D
role: STUDY_CHAIR
References:
citation: Brennan TV, Lin L, Huang X, Cardona DM, Li Z, Dredge K, Chao NJ, Yang Y. Heparan sulfate, an endogenous TLR4 agonist, promotes acute GVHD after allogeneic stem cell transplantation. Blood. 2012 Oct 4;120(14):2899-908. doi: 10.1182/blood-2011-07-368720. Epub 2012 Jul 3.
citation: Kornblit B, Masmas T, Petersen SL, Madsen HO, Heilmann C, Schejbel L, Sengelov H, Muller K, Garred P, Vindelov L. Association of HMGB1 polymorphisms with outcome after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2010 Feb;16(2):239-52. doi: 10.1016/j.bbmt.2009.10.002. Epub 2009 Oct 9.
citation: Jube S, Rivera ZS, Bianchi ME, Powers A, Wang E, Pagano I, Pass HI, Gaudino G, Carbone M, Yang H. Cancer cell secretion of the DAMP protein HMGB1 supports progression in malignant mesothelioma. Cancer Res. 2012 Jul 1;72(13):3290-301. doi: 10.1158/0008-5472.CAN-11-3481. Epub 2012 May 2.
citation: Kang R, Zhang Q, Zeh HJ 3rd, Lotze MT, Tang D. HMGB1 in cancer: good, bad, or both? Clin Cancer Res. 2013 Aug 1;19(15):4046-57. doi: 10.1158/1078-0432.CCR-13-0495. Epub 2013 May 30.