Photochemotherapy and Graft-versus-leukemia in Acute-leukemia
Photochemotherapy of Acute Graft-versus-host Disease (aGVHD) of the Skin - is Graft-versus-leukemia Preserved in Patients Transplanted for Acute Leukemia?
Cure of leukemia after hematopoietic stem cell transplantation (HSCT) is sustained by the anti-leukemic effect of the grafted cells (graft-versus-leukemia (GVL)). However, it is not known whether the tumor-immunity is affected by photochemotherapy (psoralene photosensitization and ultraviolet light radiation) administered to attenuate graft-versus host disease (GVHD).
The present study aim to investigate what happens to the GVL after photochemotherapy of aGVHD in a predominantly retrospective setting with 10-years follow-up after HSCT
研究概览
详细说明
This is a 10-year follow-up of patients with Acute-myeloid-leukemia (AML) or acute-lymphatic-leukemia (ALL). AML is diagnosed by the French-American-British criteria (FAB-criteria) and ALL is separated into chief forms by immunohistological methods. All patients underwent myeloablative Hematopoietic Stem Cell Transplantation (HSCT) between 1985 and 2005 at the center for allogeneic stem cell transplantation (CAST) at Karolinska University Hospital. All patient receive GVHD-prophylaxis.
The risk for relapse after HSCT is graded into low-risk if the disease is in first complete remission before HSCT, all other disease states are classified as high-risk.
Eligible patients received photochemotherapy (Ultraviolet radiation type A on skin photosensitized by oral 8-methoxypsoralen) for acute graft-versus-host disease (GVHD within 100-days after HSCT). Photochemotherapy may be given as primary or later aGVHD therapy. Patients with aGVHD after booster doses of stem-cells or donor-lymphocyte-infusions are not included.
Additional treatment are registered where present. Methotrexate is not considered as an additional GVHD treatment as intravenous methotrexate a part of the governing GVHD prophylaxis and as the effects of methotrexate as a secondary aGVHD treatment is weak.
At the start, the end, at maximum and up until two weeks after end of PUVA-therapy the GVHD is diagnosed in accordance with Glucksberg and indexed by CIBMTR.
Relapse is diagnosed when leukemic cells is present extra medullary or with a bone marrow biopsy with ≥ 30% blasts. Early relapse is diagnosed when the medulla contain 5 - 30% blasts
The primary outcome is GVL i.e. abscence of relapse in malignant disease or minimal residual disease (MRD) i.e. threatening relapse in malignant disease demanding donor lymphocyte infusion (DLI).
Primary predictor: Time-to-treatment by photochemotherapy at day 0 - 7 vs. start at day 8 ≤ of aGVHD.
Continuous secondary predictor: Time-to-treatment by photochemotherapy as a continuous variable (days after start of aGVHD).
Binary secondary predictors: Risk (Low/High), Sibling donor-recipient (Yes/No), Mismatched related (Yes/No), Unrelated donor (Yes/No), (Male recipients of female grafts (Yes/No), T-cell depletion or Anti-Thymocyte Globulin (Yes/No).
Categorical secondary predictors: AGVHD organ disease stage and disease grade; Skin (+, ++, +++, ++++), Liver (+, ++, +++, ++++), Gastro-intestinal (+, ++, +++, ++++), Center for International Blood and Marrow Transplant Research CIBMTR index (A, B, C, D) respectively.
Statistical analysis:
Cox proportional Hazards ratio is used to conduct a univariate data analysis of all adequate variables in patient characteristics and disease towards the primary outcome. In the analysis, death, DLI or retransplantation due to graft-failure was treated as a competing event. The primary predictor (binary) and all binary or categorical covariates identified from the patient and disease characteristics are to be included in a multivariate forward regression analysis, controlled for with backward regression based on the log-likelihood method. P=0.05 is considered as significant and p=0.10 as a trend. StatSoft, Inc. (2013). STATISTICA (data analysis software system), version 12. www.statsoft.com. are used for statistical computation.
研究类型
注册 (实际的)
联系人和位置
学习地点
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Stockholm、瑞典、14186
- Department of Dermatology, Karolinska University Hospital Huddinge
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参与标准
资格标准
适合学习的年龄
- 孩子
- 成人
- 年长者
接受健康志愿者
有资格学习的性别
取样方法
研究人群
描述
Inclusion Criteria:
- Eligible patients received photochemotherapy (Ultraviolet radiation type A on skin photosensitized by oral 8-methoxypsoralen) for acute graft-versus-host disease (GVHD within 100-days after HSCT). Photochemotherapy may be given as primary or later aGVHD therapy.
Exclusion Criteria:
- Patients with aGVHD after booster doses of stem-cells or donor-lymphocyte-infusions are not included.
学习计划
研究是如何设计的?
设计细节
- 观测模型:队列
- 时间观点:追溯
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Graft-versus-leukemia (GVL)
大体时间:10-years after HSCT (2005 - 2015)
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i.e. abscence of relapse in malignant disease or minimal residual disease (MRD) i.e. threatening relapse in malignant disease demanding donor lymphocyte infusion (DLI).
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10-years after HSCT (2005 - 2015)
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Death
大体时间:10-years after HSCT (2005 - 2015)
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Competing event
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10-years after HSCT (2005 - 2015)
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Retransplantation
大体时间:10-years after HSCT (2005 - 2015)
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Competing event
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10-years after HSCT (2005 - 2015)
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Donor Lymphocyte Infusion (DLI)
大体时间:10-years after HSCT (2005 - 2015)
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Competing event
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10-years after HSCT (2005 - 2015)
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合作者和调查者
调查人员
- 首席研究员:Nicolas Feldreich, M.D.、Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institute
- 研究主任:Olle Ringden, Professor、Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institute
- 学习椅:Brigitta Omazic, PhD、Department of Oncology and Pathology,
出版物和有用的链接
一般刊物
- Thomas E, Storb R, Clift RA, Fefer A, Johnson FL, Neiman PE, Lerner KG, Glucksberg H, Buckner CD. Bone-marrow transplantation (first of two parts). N Engl J Med. 1975 Apr 17;292(16):832-43. doi: 10.1056/NEJM197504172921605. No abstract available.
- Ringden O, Witherspoon RP, Storb R, Ekelund E, Thomas ED. Increased in vitro B-cell IgG secretion during acute graft-versus-host disease and infection. Observations in 50 human marrow transplant recipients. Blood. 1980 Feb;55(2):179-86.
- Ringden O, Sundberg B, Lonnqvist B, Tollemar J, Gahrton G, Nilsson B. Allogeneic bone marrow transplantation for leukemia: factors of importance for long-term survival and relapse. Bone Marrow Transplant. 1988 Jul;3(4):281-90.
- Alyea EP, DeAngelo DJ, Moldrem J, Pagel JM, Przepiorka D, Sadelin M, Young JW, Giralt S, Bishop M, Riddell S. NCI First International Workshop on The Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Cell Transplantation: report from the committee on prevention of relapse following allogeneic cell transplantation for hematologic malignancies. Biol Blood Marrow Transplant. 2010 Aug;16(8):1037-69. doi: 10.1016/j.bbmt.2010.05.005. Epub 2010 May 24.
- Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ, Rimm AA, Ringden O, Rozman C, Speck B, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood. 1990 Feb 1;75(3):555-62.
- Ringden O, Labopin M, Solders M, Beelen D, Arnold R, Ehninger G, Milpied N, Niederwieser D, Hamladji RM, Kyrcz-Krzemien S, Ganser A, Socie G, Stelljes M, Volin L, Craddock C, Mohty M; Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation. Who is the best hematopoietic stem-cell donor for a male patient with acute leukemia? Transplantation. 2014 Sep 15;98(5):569-77. doi: 10.1097/TP.0000000000000102.
- Strauss GH, Bridges BA, Greaves M, Hall-Smith P, Price M, Vella-Briffa D. Inhibition of delayed hypersensitivity reaction in skin (DNCB test) by 8-methoxypsoralen photochemotherapy. Possible basis for pseudo-promoting action in skin carcinogenesis? Lancet. 1980 Sep 13;2(8194):556-9. doi: 10.1016/s0140-6736(80)91992-3.
- Wolf P, Nghiem DX, Walterscheid JP, Byrne S, Matsumura Y, Matsumura Y, Bucana C, Ananthaswamy HN, Ullrich SE. Platelet-activating factor is crucial in psoralen and ultraviolet A-induced immune suppression, inflammation, and apoptosis. Am J Pathol. 2006 Sep;169(3):795-805. doi: 10.2353/ajpath.2006.060079.
- Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, Lerner KG, Thomas ED. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974 Oct;18(4):295-304. doi: 10.1097/00007890-197410000-00001. No abstract available.
- Parrish JA, Fitzpatrick TB, Tanenbaum L, Pathak MA. Photochemotherapy of psoriasis with oral methoxsalen and longwave ultraviolet light. N Engl J Med. 1974 Dec 5;291(23):1207-11. doi: 10.1056/NEJM197412052912301. No abstract available.
- Ringden O, Karlsson H, Olsson R, Omazic B, Uhlin M. The allogeneic graft-versus-cancer effect. Br J Haematol. 2009 Dec;147(5):614-33. doi: 10.1111/j.1365-2141.2009.07886.x. Epub 2009 Sep 4.
- Hari P, Logan B, Drobyski WR. Temporal discordance between graft-versus-leukemia and graft-versus-host responses: a strategy for the separation of graft-versus-leukemia/graft-versus-host reactivity? Biol Blood Marrow Transplant. 2004 Nov;10(11):743-7. doi: 10.1016/j.bbmt.2004.07.006.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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