Corradini Paolo, Tarella Corrado, Olivieri Attilio, Gianni Alessandro M, Voena Claudia, Zallio Francesco, Ladetto Marco, Falda Michele, Lucesole Moira, Dodero Anna, Ciceri Fabio, Benedetti Fabio, Rambaldi Alessandro, Sajeva Maria R, Tresoldi Moreno, Pileri Alessandro, Bordignon Claudio, Bregni Marco
Department of Hematology, Istituto Scientifico HS Raffaele, Milano, Italy.
Blood. 2002 Jan 1;99(1):75-82. doi: 10.1182/blood.v99.1.75.
A reduced-intensity conditioning regimen was investigated in 45 patients with hematologic malignancies who were considered poor candidates for conventional myeloablative regimens. Median patient age was 49 years. Twenty-six patients previously failed autologous transplantation, and 18 patients had a refractory disease at the time of transplantation. In order to decrease nonrelapse mortality, and enhance the graft-versus-tumor effect, a program was designed in which a reduced conditioning with thiotepa, fludarabine, and cyclophosphamide was associated with programmed reinfusions of donor lymphocytes for patients without graft-versus-host disease (GVHD), not achieving clinical and molecular remission after transplantation. GVHD prophylaxis consisted of cyclosporine A and methotrexate. Seventeen patients received marrow cells and 28 received mobilized hematopoietic cells. All patients engrafted. The probability of grades II-IV and III-IV acute GVHD were 47% and 13%, respectively. The probability of nonrelapse mortality, progression-free survival, and overall survival were 13%, 57%, and 53%, respectively. Thirteen patients in complete remission had a polymerase chain reaction marker for minimal disease monitoring; 10 achieved molecular remission after transplantation. Nine patients received donor lymphocytes: one patient with mantle cell lymphoma had a minimal response, one patient with refractory anemia with excess of blasts in transformation achieved complete remission, and 7 patients did not respond. At a median follow-up of 385 days (range, 24 to 820 days), 25 patients (55%) were alive in complete remission. Although longer follow-up is needed to evaluate the long-term outcome, the study shows that this regimen is associated with a durable engraftment, has a low nonrelapse mortality rate, and can induce clinical and molecular remissions.
对45例血液系统恶性肿瘤患者进行了低强度预处理方案的研究，这些患者被认为不适宜采用传统的清髓性方案。患者中位年龄为49岁。26例患者既往自体移植失败，18例患者在移植时患有难治性疾病。为了降低非复发死亡率并增强移植物抗肿瘤效应，设计了一个方案，即对无移植物抗宿主病（GVHD）且移植后未达到临床和分子缓解的患者，采用噻替派、氟达拉滨和环磷酰胺进行低强度预处理，并计划性回输供体淋巴细胞。GVHD预防采用环孢素A和甲氨蝶呤。17例患者接受了骨髓细胞，28例患者接受了动员的造血细胞。所有患者均实现造血重建。Ⅱ-Ⅳ级和Ⅲ-Ⅳ级急性GVHD的发生率分别为47%和13%。非复发死亡率、无进展生存率和总生存率分别为13%、57%和53%。13例完全缓解的患者有用于微小疾病监测的聚合酶链反应标志物；10例患者移植后实现分子缓解。9例患者接受了供体淋巴细胞：1例套细胞淋巴瘤患者有微小反应，1例难治性贫血伴原始细胞过多转化患者实现完全缓解，7例患者无反应。中位随访385天（范围24至820天）时，25例患者（55%）存活且处于完全缓解状态。尽管需要更长时间的随访来评估长期结果，但该研究表明，该方案与持久的造血重建相关，非复发死亡率低，且可诱导临床和分子缓解。
