An Observational Audit to Evaluate the Relation Between Transfusions and Iron Toxicity on Major Outcome Parameters in Patients With Adult Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukaemia (CMML) Treated With Myeloablative Conditioning (MAC) and Reduced Intensity Conditioning (RIC) Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) Without Prior Intensive Antileukemic Therapy by the Chronic Malignancies Working Party by the European Society for Blood and Marrow Transplantation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 222
- 试验地点
- 6
- 主要终点
- non-relapse mortality (treatment related mortality).
研究概览
简要总结
Stem cell transplantation and blood product transfusions are standard of care for Myelodysplastic Syndromes (MDS). Several studies have shown changes in serum ferritin and non-transferrin-bound iron (NTBI) in patients undergoing stem cell transplantation. A large proportion of MDS patients are at risk for organ damage from tissue siderosis, due to the development of iron overload.
Toxic effects of iron may play an important role in the complications associated with HSCT. Iron chelation therapy may reduce the acute and chronic treatment-related toxicity by removing excess of iron, iron radicals and reactive oxygen species (ROS).
There is little information about the efficacy and safety of iron chelation in MDS patients. This audit wants to evaluate the effect of iron toxicity on treatment-related mortality in untreated, adult MDS or CMML patients during and after treatment with myeloablative conditioning (MAC) and reduced intensity conditioning (RIC) allo-HSCT, by prospectively collecting data from 200 MDS or CMML patients from 2009 onwards.
详细描述
PRIMARY OBJECTIVE:
To evaluate in adult MDS or CMML patients the correlation between iron toxicity and treatment-related mortality in the context of the treatment of such toxicity with iron chelation during and after treatment with allo-HSCT
DETAILED DESCRIPTION:
Myelodysplastic syndromes (MDS) form a complex and heterogeneous group of bone marrow failure disorders. These are characterized by ineffective hematopoiesis leading to peripheral cytopenias and morphologic dysplasia. The incidence of MDS is about 5 per 100,000 persons a year in the general population. After 60 years of age the incidence increases tot 20-50 per 100,000 persons a year.
Care for MDS includes amelioration of hematological deficits with blood product transfusions, and stem cell transplantation after a standard myeloablative regimen. At the moment stem cell transplantation is the only known curative treatment for MDS patients . Allogeneic Stem cell transplantation can lead to considerable treatment-related morbidity and mortality among patients. Insight in factors contributing to treatment related mortality, could lead to a better treatment regimen in patients who are treated with allo-HSCT and subsequently lead to overall lower treatment related mortality.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with MDS or CMML, according to FAB-criteria (RA, RARS, RAEB, RAEBt, CMML) or according to WHO-criteria (RA, RARS, RAEB-1, RAEB-2, RCMD, RCMD-RS, with isolated del(5q), MDS OR CMML-U)
- •Patients with transformed MDS or CMML to AML at time of transplant
- •Patients received myeloablative or RIC allo-HSCT as primary treatment
- •Diagnosis at time of transplant
- •Informed Consent and of legal age at the time of obtaining informed consent (18+)
- •ECOG performance status 0-2
排除标准
- •Patients with previous intensive antileukemic therapy (intensive chemotherapy and/or HSCT); previous treatment with immunomodulatory drugs (thalidomide, or lenalidomide) or hypomethylating agents (Vidaza, decitabine) is allowed
- •Patients with juvenile chronic myelomonocytic leukemia (jMML)
- •Patients with secondary or therapy-related AML and MDS or CMML after treatment with immunosuppressive or cytotoxic treatment for a nonmyeloid malignancy
- •Patients who received auto-HSCT
- •Candidates for cord blood HSCT or syngeneic HSCT
- •Inadequate renal function (ECC <60 ml/min and/or creatinine >2.5 times upper limit of normal value)
- •Inadequate hepatic function (transaminases >2.5 times upper limit of normal value)
- •History of seizures
- •Pregnancy and women of child-bearing potential and not using adequate contraceptives
- •Uncontrolled hypertension
结局指标
主要结局
non-relapse mortality (treatment related mortality).
时间窗: 2 years after HSCT
次要结局
- relapse rate(2 years after HSCT)
- treatment-related toxic effects(2 years after HSCT)
- event-free survival(2 years after HSCT)
- overall survival(2 years after HSCT)