Bradstock K F, Hertzberg M S, Kerridge I H, Svennilson J, McGurgan M, Huang G, Antonenas V, Gottlieb D J
Blood and Marrow Transplant Service, Westmead Hospital, Sydney, New South Wales, Australia.
Intern Med J. 2006 Jun;36(6):355-61. doi: 10.1111/j.1445-5994.2006.01079.x.
A number of haematological malignancies can be cured by allogeneic stem cell transplantation but only approximately 30% of Australians have a suitable histocompatible related donor. Matched donors can be found on international registries of unrelated volunteers for a proportion of the remaining patients. For those patients in need of an allogeneic transplant, but for whom a suitable matched related or unrelated adult donor cannot be found, the use of banked unrelated umbilical cord blood has emerged as a potential option. However, there is uncertainty about the applicability of this technique for the majority of adult patients as a result of limitations in the number of cells in banked cord blood units and the degree of mismatching for histocompatibility antigens.
The aim of this study was to define the feasibility of allogeneic stem cell transplantation using single unrelated cord blood units in a cohort of adults with poor prognosis leukaemia or lymphoma.
Nine patients with haematological malignancies (five with acute myeloid leukaemia, one with acute lymphoblastic leukaemia, one with Hodgkin lymphoma and two with non-Hodgkin lymphomas) received transplants of cryopreserved cord blood after conditioning therapy with high-dose cyclophosphamide, total body irradiation and antithymocyte globulin. Cord units contained a median 2.6 x 10(7) nucleated cells/kg recipient bodyweight and were matched for four (seven cases) or five (two cases) major histocompatibility complex class 1 and 2 antigens. Patients were given post-transplant immunosuppression with cycosporin and methylprednisolone.
Neutrophil recovery to 0.5 x 10(9)/L was seen by median day 30 after transplant in all seven patients who survived more than 1 month post-transplant. Platelet recovery to 50 x 10(9)/L occurred by median day 81 in five evaluable patients. Acute graft versus host disease (GVHD) grades II-IV was seen in four of seven evaluable patients and limited chronic GVHD was seen in four of five. Infection was the most common complication. Four patients died before day 100 of infection (methicillin-resistant Staphylococcus aureus septicaemia, respiratory syncitial virus pneumonia), GVHD and multi-organ failure, and intracranial bleeding. Five patients survived 7-69 months post-transplant, without evidence of relapse of the underlying malignancy.
Unrelated cord blood transplantation is feasible in adults with high-risk malignancy, with infection relating to immunocompromise being the major limitation.
许多血液系统恶性肿瘤可通过异基因干细胞移植治愈，但只有约30%的澳大利亚人有合适的组织相容性相关供者。对于其余部分患者，可在国际无关志愿者登记处找到匹配的供者。对于那些需要异基因移植但无法找到合适的匹配相关或无关成年供者的患者，使用库存的无关脐带血已成为一种潜在选择。然而，由于库存脐带血单位中的细胞数量以及组织相容性抗原的错配程度存在限制，该技术对大多数成年患者的适用性尚不确定。
本研究的目的是确定在一组预后不良的白血病或淋巴瘤成年患者中使用单个无关脐带血单位进行异基因干细胞移植的可行性。
9例血液系统恶性肿瘤患者（5例急性髓系白血病、1例急性淋巴细胞白血病、1例霍奇金淋巴瘤和2例非霍奇金淋巴瘤）在接受大剂量环磷酰胺、全身照射和抗胸腺细胞球蛋白预处理后，接受了冷冻保存的脐带血移植。脐带血单位中核细胞的中位数为2.6×10⁷个/千克受者体重，并且与4个（7例）或5个（2例）主要组织相容性复合体1类和2类抗原相匹配。患者在移植后接受环孢素和甲泼尼龙的免疫抑制治疗。
在移植后存活超过1个月的所有7例患者中，中性粒细胞在移植后第30天中位数时恢复至0.5×10⁹/L。5例可评估患者的血小板在第81天中位数时恢复至50×10⁹/L。在7例可评估患者中有4例出现了II-IV级急性移植物抗宿主病（GVHD），在5例患者中有4例出现了局限性慢性GVHD。感染是最常见的并发症。4例患者在第100天前死于感染（耐甲氧西林金黄色葡萄球菌败血症、呼吸道合胞病毒肺炎）、GVHD和多器官功能衰竭以及颅内出血。5例患者在移植后存活了7至69个月，没有潜在恶性肿瘤复发的证据。
无关脐带血移植在高危恶性肿瘤成年患者中是可行的，免疫功能低下相关的感染是主要限制因素。
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