Ferrá C, Rodríguez-Luaces M, Gallardo D, Encuentra M, Martín-Henao G A, Peris J, Ancín I, Sarrá J, Berlanga J J, García J, Grañena A
Hematology Department, Institut Català d'Oncologia, Duran i Reynals Hospital, Barcelona, Spain.
Bone Marrow Transplant. 2001 Nov;28(10):963-8. doi: 10.1038/sj.bmt.1703277.
T cell depletion of the graft increases graft failure and relapse rate in allogeneic PBSC transplantation. Delayed lymphocyte add-back after T cell-depleted transplants might prevent these complications. We present 22 consecutive allogeneic PBSC transplants from related histocompatible donors with positive selection of CD34+ cells. Recipients received prophylactic donor lymphocyte infusions (DLI) depending on their risk of relapse and of developing GVHD. Patients were considered at high risk of relapse with AML > first CR, ALL > second CR, and CML in accelerated or blastic phase. Patients were considered at high risk of developing GVHD if older than 35 years, or with a donor sensitized through previous pregnancy or blood transfusion. Patients at high risk of relapse and low risk of GVHD were scheduled to receive three DLI. Patients at low risk of relapse and high risk of GVHD did not receive DLI. The remaining patients were scheduled to receive two DLI. The DLI were administered on days +28 (2 x 10(5)/kg), +60 (2 x 10(5)/kg) and +90 (2 x 10(6)/kg) after transplant. G-CSF mobilized peripheral stem cells from healthy donors were positively selected by an immunomagnetic method. The mean CD34+ cells and CD3+ cells infused were 4.4 x 10(6)(range 1.9-10.6) and 0.085 x 10(5) (range 0.01-0.67). Cyclosporin A was given to prevent GVHD. All the patients engrafted. Twenty-two prophylactic DLI were performed in 12 patients: seven developed acute GVHD (one case grade III-IV) and none presented pancytopenia. At a mean follow-up of 585 days (range 89-1103), 14 patients were alive in CR, one patient was alive in relapse, four patients had died of relapse and three had died of transplant-related complication. Individually adjusted prophylactic DLI at the doses we used with an escalating schedule allowed an acceptable GVHD rate and a good engraftment of donor hematopoiesis.
移植物的T细胞清除会增加异基因外周血干细胞移植中的移植物失败率和复发率。T细胞清除后的移植中延迟回输淋巴细胞可能预防这些并发症。我们展示了22例连续的来自相关组织相容性供体的异基因外周血干细胞移植，对CD34+细胞进行阳性选择。根据复发风险和发生移植物抗宿主病（GVHD）的风险，接受者接受预防性供体淋巴细胞输注（DLI）。急性髓系白血病（AML）处于首次完全缓解（CR）后、急性淋巴细胞白血病（ALL）处于第二次CR后以及处于加速期或急变期的慢性髓系白血病（CML）患者被认为复发风险高。年龄超过35岁、或供体因既往妊娠或输血致敏的患者被认为发生GVHD风险高。复发风险高且GVHD风险低的患者计划接受三次DLI。复发风险低且GVHD风险高的患者不接受DLI。其余患者计划接受两次DLI。DLI在移植后第28天（2×10⁵/kg）、第60天（2×10⁵/kg）和第90天（2×10⁶/kg）给予。通过免疫磁珠法对健康供体经粒细胞集落刺激因子（G-CSF）动员的外周干细胞进行阳性选择。输注的平均CD34+细胞和CD3+细胞分别为4.4×10⁶（范围1.9 - 10.6）和0.085×10⁵（范围0.01 - 0.67）。给予环孢素A预防GVHD。所有患者均实现造血重建。12例患者进行了22次预防性DLI：7例发生急性GVHD（1例为III - IV级），无1例出现全血细胞减少。平均随访585天（范围89 - 1103天）时，14例患者处于CR存活，1例患者复发存活，4例患者死于复发，3例患者死于移植相关并发症。我们使用的剂量并采用递增方案进行个体化调整的预防性DLI可使GVHD发生率可接受，并使供体造血良好植入。
