Phase I study of transfer of effector memory T cells (Tem) following allogeneic stem cell transplantation. Short title- Transfer of Tem (ToTem)

健康的骨髓产生血细胞，包括那些抵抗感染的免疫系统。所有这些血细胞都来源于干细胞。当癌症影响患者的骨髓时，它就不能再发挥正常的功能。为了恢复健康的血细胞生产和对抗癌症，一些患者从捐赠者的骨髓中获得健康的干细胞。虽然骨髓移植可以治愈许多患者，但它们可能有严重的副作用。这些严重的副作用之一，影响了大约一半的患者，是“移植物抗宿主病”（GVHD）。这是因为骨髓中含有供体免疫细胞（“移植物”），这些细胞将患者的健康细胞（“宿主”）视为外来细胞并攻击它们。它主要影响皮肤、肝脏和肠道组织，可能危及生命。有一些方法可以通过使用药物来预防GVHD，这些药物可以抑制患者体内的供体免疫细胞，从而阻止它们过度反应和攻击他们的身体。然而，使用这些免疫抑制药物有一个主要缺点，因为免疫系统变得更弱，也不能抵抗感染。这些感染有时非常严重，可能导致患者死亡。我们一直在研究新的方法，以防止供体的免疫系统在患者体内引起GVHD，而不会削弱它，使其无法抵抗感染。我们已经开发出一种新的，简单的方法，从同一个捐赠者的血液中提取额外的抗感染免疫细胞。当这些给患者使用时，它们可能有助于对抗感染，但不会反应过度并导致GVHD。如果成功，它可以在全国许多医院广泛使用。这是因为它使用的设备已经被大多数骨髓移植中心常规使用。因此，这项临床试验的目的是找出是否给患者这些额外的抗感染免疫细胞从捐赠者将减少他们得到感染的机会，而不引起GVHD。将询问接受骨髓移植的患者是否愿意同意参与研究。对于这些患者，我们将在移植后约一个月给予额外的供体免疫细胞。他们还将接受标准的GVHD预防治疗。不同剂量的供体免疫细胞将被给予个体患者，以确定哪种剂量最好。将密切监测所有患者的GVHD或感染体征。他们还将进行血液测试，以确定他们的免疫系统恢复得有多好和多快。如果试验显示可能对患者有益，我们将计划将研究扩展到更多患者。这将为需要骨髓移植的患者提供必要的证据。

Healthy bone marrow produces blood cells, including those of the immune system that fight infections. All these blood cells originate from stem cells. When cancer affects a patient's bone marrow, it can no longer carry out its normal function. In order to restore healthy blood cell production and to fight the cancer, some patients are given healthy stem cells from a donor's bone marrow. Although bone marrow transplants can cure many patients, they can have serious side effects. One of these serious side effects, that affects about half of patients, is 'graft versus host disease' (GVHD). This happens because the bone marrow contains donor immune cells (the 'graft') that see the patient's healthy cells (the 'host') as foreign and attacks them. It mainly affects the tissues of the skin, the liver and the gut and can be life threatening.There are ways of preventing GVHD by using drugs that dampen down (suppress) the donor's immune cells in the patient's body, therefore stopping them from overreacting and attacking their body. However, the use of these immune supressing drugs has a major drawback because the immune system becomes weaker and cannot fight infections as well. These infections are sometimes very severe and can lead to patients dying.We have been working on new ways to prevent the donor's immune system causing GVHD in the patient's body without weakening it so much that it cannot fight infections as well. We have developed a new, simple way to take additional infection-fighting immune cells from the same donor's blood. When these are given to patients, they may help fight infections but not overreact and cause GVHD. If this works, it could be widely used at many hospitals across the country. This is because it uses equipment that is already used routinely by most bone marrow transplant centres.Therefore, this clinical trial aims to find out if giving patients these additional infection-fighting immune cells from the donor will reduce their chance of getting an infection without causing GVHD. Patients undergoing a bone marrow transplant will be asked if they want to give their consent to be part of the study. For these patients, we will give additional donor immune cells about one month after the transplant. They will also receive the standard GVHD prevention treatment. Different doses of the donor immune cells will be given to individual patients to work out which dose is best. All patients will be closely monitored for signs of GVHD or infection. They will also have blood tests to determine how well and quickly their immune systems recover. If the trial shows a possible benefit to patients, we will plan to extend the study to a larger number of patients. This will provide the necessary proof whether the treatment works in patients needing a bone marrow transplant.