TRANSPLANTATION OF ENRICHED AND PURGED PERIPHERAL-BLOOD PROGENITOR CELLS FROM A SINGLE APHERESIS PRODUCT IN PATIENTS WITH NON-HODGKINS-LYMPHOMA
TRANSPLANTATION OF ENRICHED AND PURGED PERIPHERAL-BLOOD PROGENITOR CELLS FROM A SINGLE APHERESIS PRODUCT IN PATIENTS WITH NON-HODGKINS-LYMPHOMA
复制标题
DOI：
10.1182/blood.v85.11.3334.bloodjournal85113334
复制
发表时间：
1995-06-01
期刊：
影响因子：
20.3
通讯作者：
STROBER, S
中科院分区：
文献类型：
--
作者：
NEGRIN, RS;KUSNIERZGLAZ, CR;STROBER, S
大剂量化疗联合或不联合放疗后自体造血祖细胞移植是治疗高危或复发性非霍奇金淋巴瘤的有效方法。化疗和/或造血生长因子已用于动员外周血中的祖细胞用于移植。然而，已发现动员的血细胞产物经常被肿瘤细胞污染，并且尚未开发出从这些产物中清除肿瘤细胞的技术。此外，移植所需的造血祖细胞的最低数量尚未完全阐明。我们对21例患者进行了单次环磷酰胺（4 g/m2）输注，随后每日给予粒细胞集落刺激因子（G-CSF）。白色血细胞计数恢复后，进行单次3小时单采，然后将单采产物应用于不连续Percoll梯度。从该分离程序得到的低密度级分富集CD 34（+）祖细胞（总细胞产率，19.5%; CD 34（+）细胞回收率，81.2%）。这些富集的细胞产物用一组抗B细胞或抗T细胞单克隆抗体和补体处理，以去除残留的肿瘤细胞。患者接受清髓性治疗后，将富集和净化的细胞回输，血液学恢复迅速，中性粒细胞植入中位数为10天[中性粒细胞绝对计数（ANC）大于0.5 × 10（9）/L]和11天[ANC> 0.5 × 10（9）/L]。（ANC，大于1.0 x 10（9）/L），中位血小板输注独立性需要13天，多系移植的快速性与每公斤输注的CD 34（+）细胞数量相关。接受超过2 × 10（6）CD 34（+）细胞/kg的患者具有快速的血液学植入，而接受少于2 × 10（6）CD 34（+）细胞/kg的患者具有较慢的血小板恢复。18）染色体易位证明了在处理和净化后使用聚合酶链式反应（PCR）测定的肿瘤细胞的成功去除，21例患者中有4例在骨髓和外周血中有PCR可检测到的淋巴瘤细胞;然而，在所有4例患者中回输的富集和净化的血液制品中均不含可检测到的肿瘤细胞。使用这种方法，我们开发了一种优化的造血祖细胞产品，其保留了用动员的外周血观察到的快速植入，并且不含可检测到的肿瘤细胞。(C)1995年由美国血液学会，
High-dose chemotherapy with or without radiotherapy followed by autologous transplantation of hematopoietic progenitor cells is an effective treatment for patients with highrisk or relapsed non-Hodgkin's lymphoma. Chemotherapy and/or hematopoietic growth factors have been used to mobilize progenitor cells in the peripheral blood for transplantation. However, the mobilized blood cell products have been found to be frequently contaminated with tumor cells, and techniques have not been developed to purge tumor cells from these products. In addition, the minimum number of hematopoietic progenitor cells required for engraftment has not yet been fully elucidated. We treated 21 patients with a single infusion of cyclophosphamide (4 g/m(2)) followed by daily administration of granulocyte colony-stimulating factor (G-CSF). After recovery of the white blood cell count, a single 3-hour apheresis collection was performed, The apheresis product was then applied to a discontinuous Percoll gradient. The low-density fractions resulting from this separation procedure were enriched for CD34(+) progenitor cells (total cell yield, 19.5%; CD34(+) cell recovery, 81.2%), These enriched cellular products were treated with a panel of anti-B cell or anti-T cell monoclonal antibodies and complement in an effort to remove residual tumor cells. After treatment of the patient with myeloablative therapies, the enriched and purged cells were reinfused, Hematologic recovery was rapid, with median neutrophil engraftment in 10 days [absolute neutrophil count (ANC), greater than 0.5 x 10(9)/L] and 11 days (ANC, greater than 1.0 x 10(9)/L), Median platelet transfusion independence required 13 days, The rapidity of multilineage engraftment correlated with the number of CD34(+) cells per kilogram that were infused. Patients who received more than 2 x 10(6) CD34(+) cells per kilogram had rapid hematologic engraftment, whereas those patients transplanted with less than 2 x 10(6) CD34(+) cells per kilogram had slower platelet recovery, Modeling studies using a lymphoma cell line with a t(14;18) chromosomal translocation demonstrated the successful removal of tumor cells assayed using the polymerase chain reaction (PCR) after the processing and purging, Four of the 21 patients had PCR-detectable lymphoma cells in the bone marrow and peripheral blood; however, the enriched and purged blood products reinfused in all four did not contain detectable tumor cells. Using this approach, we developed an optimized hematopoietic progenitor cell product that retained the rapid engraftment observed with mobilized peripheral blood and contained no detectable tumor cells. (C) 1995 by The American Society of Hematology,