Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington.
Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington; VA Puget Sound Health Care System, Seattle, Washington.
Biol Blood Marrow Transplant. 2018 Feb;24(2):308-313. doi: 10.1016/j.bbmt.2017.10.016. Epub 2017 Oct 12.
In a multicenter, prospective, phase II study we evaluated the safety and efficacy of pentostatin followed by donor lymphocyte infusion (DLI) in patients with low donor Tcell chimerism after allogeneic hematopoietic cell transplantation (HCT). Thirty-six patients with low donor blood CD3 chimerism were enrolled in this study. Thirty-five patients received a total of 41 DLIs after a dose of pentostatin, and 1 patient received pentostatin only. Median donor CD3 chimerism prompting the initiation of pentostatin and DLI was 28% (range, 5% to 47%). Responses (defined by increases in donor CD3 chimerism ≥10% maintained to day 56 post-DLI) were seen in 16 patients (44.4%) with a median rise in CD3 donor chimerism to 64% (range, 48% to 100%). There was a trend for better responses among 21 patients who received first treatment within 100 days after transplant (57% response rate) compared with15 patients who received first treatment more than 100 days after HCT (27% response rate, P = .07). Fourteen patients (39%) developed grades II to IV acute graft-versus-host disease (GVHD) at a median of 10 days (range, 0 to 83) after DLI. Ten patients (28%) developed extensive chronic GVHD. Seventeen patients (47%) developed new grade 4 cytopenias after DLI. There was no difference in relapse between nonresponders and responders. Twenty-eight patients (78%) died, most (n = 21) because of relapse. Five of 16 responders (31%) are alive, all disease-free, at a median of 60 months (range, 21 to 132) after DLI. Six of 20 nonresponders (30%) are alive at a median of 47 months (range, 16 to 100) after DLI, 3 in complete remission. Pentostatin and DLI had acceptable toxicity and appeared to increase low donor CD3 chimerism after HCT but had no impact on mortality.
在一项多中心、前瞻性、二期研究中，我们评估了喷司他丁联合供者淋巴细胞输注（DLI）在异基因造血细胞移植（HCT）后供者 T 细胞嵌合率低的患者中的安全性和疗效。本研究纳入了 36 例供者血 CD3 嵌合率低的患者。35 例患者在接受喷司他丁治疗后共接受了 41 次 DLI，1 例患者仅接受了喷司他丁治疗。启动喷司他丁和 DLI 的中位供者 CD3 嵌合率为 28%（范围，5%47%）。16 例患者（44.4%）出现了应答（定义为 DLI 后第 56 天供者 CD3 嵌合率增加≥10%且持续），其中 CD3 供者嵌合率中位数升高至 64%（范围，48%100%）。在 21 例于移植后 100 天内首次治疗的患者中，应答率（57%）高于 15 例于 HCT 后 100 天以上首次治疗的患者（27%，P=0.07），这种情况有一定的趋势。14 例患者（39%）在 DLI 后 10 天（范围，083）中位时间发生 24 级急性移植物抗宿主病（GVHD）。10 例患者（28%）发生广泛的慢性 GVHD。17 例患者（47%）在 DLI 后出现新的 4 级血细胞减少症。无应答者和应答者的复发率无差异。28 例患者（78%）死亡，其中大多数（n=21）因复发。16 例应答者中有 5 例（31%）存活且无疾病，中位时间为 DLI 后 60 个月（范围，21132）。20 例无应答者中有 6 例（30%）存活，中位时间为 DLI 后 47 个月（范围，16100），其中 3 例处于完全缓解。喷司他丁和 DLI 的毒性可接受，且似乎可增加 HCT 后低供者 CD3 嵌合率，但对死亡率无影响。
