Phase I study of azacitidine following donor lymphocyte infusion for relapsed acute myeloid leukemia post allogeneic stem cell transplantation.
Phase I study of azacitidine following donor lymphocyte infusion for relapsed acute myeloid leukemia post allogeneic stem cell transplantation.
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DOI：
10.1016/j.leukres.2016.07.010
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发表时间：
2016-10
影响因子：
2.7
通讯作者：
Westervelt, Peter
中科院分区：
文献类型：
--
作者：
Ghobadi, Armin;Choi, Jaebok;Fiala, Mark A.;Fletcher, Theresa;Liu, Jingxia;Eissenberg, Linda G.;Abboud, Camille;Cashen, Amanda;Vij, Ravi;Schroeder, Mark A.;Pusic, Iskra;Stockerl-Goldstein, Keith;Jacoby, Meagan;Uy, Geoffrey;DiPersio, John;Westervelt, Peter
关键词：
Donor lymphocyte infusion (DLI) without prophylactic immunosuppression has been used for relapsed AML after allogeneic stem cell transplant (allo-SCT). However DLI is associated with an increased incidence of acute Graft vs. Host Disease (aGVHD). In mice, administration of azacitidine (AzaC) on days 4, 6, 8, and 10 post DLI increases regulatory T cell (Treg) numbers and prevents GVHD without hindering Graft vs. Leukemia (GVL). Based on these findings, we conducted a phase 1 study of AzaC post DLI for AML relapse post allo-SCT. AzaC was administered on days 4, 6, 8 and 10 post-DLI. Dose escalation was done using a 3+3 design with three AzaC dose levels: 30 mg/m2 (level -1), 45 mg/m2 (level 1) and 75 mg/m2 (level 2). Three patients were treated in the 45 mg/m2 dose level and 5 patients were treated in the 75 mg/m2 dose level; no DLTs or grade 3-5 treatment related toxicities were observed. After a median follow-up of 5.2 months, no patients developed grade III-IV aGVHD and no patients died of aGVHD. Six out of 8 patients in the treatment group responded to treatment including two cytogenetic complete remissions, one hematologic complete remission, and three complete remissions with incomplete count recovery. In conclusion, administration of AzaC early post DLI is well tolerated and can potentially prevent GVHD after DLI. Further studies are required to evaluate the effect of azacitidine early post DLI on GVHD and GVL.
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影响因子：
20.3
作者：
Goodyear, Oliver C.;Dennis, Mike;Craddock, Charles F.
通讯作者：
Craddock, Charles F.
影响因子：
20.3
作者：
Goodyear, Oliver;Agathanggelou, Angelo;Craddock, Charles
通讯作者：
Craddock, Charles
影响因子：
3.2
作者：
Bennett, CL;Brunkow, ME;Chance, PF
通讯作者：
Chance, PF
影响因子：
45.3
作者：
Schmid, Christoph;Labopin, Myriam;Rocha, Vanderson
通讯作者：
Rocha, Vanderson
影响因子：
9.8
作者：
Floess S;Freyer J;Siewert C;Baron U;Olek S;Polansky J;Schlawe K;Chang HD;Bopp T;Schmitt E;Klein-Hessling S;Serfling E;Hamann A;Huehn J
通讯作者：
Huehn J