Comparison of the safety and efficacy of prophylactic donor lymphocyte infusion after haploidentical versus matched-sibling PBSCT in very high-risk acute myeloid leukemia
Donor lymphocyte infusion (DLI) might be used prophylactically to reduce relapse after allogeneic hematopoietic stem cell transplantation for very high-risk leukemia/lymphoma without effective targeted therapy. To compare the safety and efficacy of prophylactic DLI for prevention of relapse after allogeneic peripheral blood stem cell transplantation from haploidentical donors (HID-SCT) and matched-sibling donors (MSD-SCT) in patients with very high-risk acute myeloid leukemia (AML), we performed a retrospective analysis in a cohort of 21 HID-SCT and 13 MSD-SCT recipients, displaying similar baseline characteristics except for donor’s gender distribution. Grade 2–4 acute graft-versus-host disease (GVHD) at 100-day post-DLI was higher in HID-SCT group than that in MSD-SCT group (59.5% vs. 30.8%, p = 0.05). The grade 3–4 acute GVHD (17.5% vs. 7.7%), 1-year chronic GVHD (36.6% vs. 33.2%), and severe chronic GVHD (15.3% vs. 27.3%) were not statistically significant different between groups. One-year non-relapse mortality was higher in HID-SCT group than that in MSD-SCT group with marginal significance (27.9% vs. 0.0%, p = 0.061). One-year relapse rate was not statistically significant different between HID-SCT group and MSD-SCT group (21.6% vs. 36.5%, p = 0.543). For HID-SCT recipients, 1-year relapse rate was lower in patients receiving prophylactic DLI than that in a control cohort of eight patients with same very high-risk features but not receiving prophylactic DLI (62.5% vs. 28.3%, p = 0.037). No statistically significant difference was observed in 1-year overall survival (OS, 55.1% vs. 83.9%, p = 0.325) and relapse-free survival (RFS, 50.1% vs. 74.0%, p = 0.419) rates between HID-SCT group and MSD-SCT group. In multivariate analyses, non-remission status prior to transplant, poor-risk gene mutations, and donor’s age ≥ 48 years predicted a higher risk of relapse after DLI. Non-remission status prior to transplant predicted inferior OS and RFS. Patient’s age ≥ 40 years also predicted an inferior OS. In conclusion, prophylactic DLI was very safe and efficient for reducing relapse in patients with very high-risk AML receiving MSD-SCT. In the recipients of HID-SCT, the application of prophylactic DLI could reduce the risk of relapse, although with a higher incidence of DLI-associated acute GVHD than those of MSD-SCT.
KeywordsDonor lymphocyte infusion Allogeneic peripheral blood stem cell transplantation Graft-versus-host disease Relapse Acute myeloid leukemia
This work was partially supported by grants from the National Natural Science Foundation of China (81770203 to D-H L, 81670135 and 81870109 to X-N G), the Natural Science Foundation of Beijing (7162174 to J L), and the National Clinical Specialist Focus on Military Construction Projects.
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Conflict of interest
The authors declare that they have no conflict of interests.
- 2.Duval M, Klein JP, He W, Cahn JY, Cairo M, Camitta BM, Kamble R, Copelan E, de Lima M, Gupta V, Keating A, Lazarus HM, Litzow MR, Marks DI, Maziarz RT, Rizzieri DA, Schiller G, Schultz KR, Tallman MS, Weisdorf D (2010) Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol 28(23):3730–3738CrossRefPubMedPubMedCentralGoogle Scholar
- 3.Middeke JM, Herold S, Rücker-Braun E, Berdel WE, Stelljes M, Kaufmann M, Schäfer-Eckart K, Baldus CD, Stuhlmann R, Ho AD, Einsele H, Rösler W, Serve H, Hänel M, Sohlbach K, Klesse C, Mohr B, Heidenreich F, Stölzel F, Röllig C, Platzbecker U, Ehninger G, Bornhäuser M, Thiede C, Schetelig J, Study Alliance Leukaemia (SAL) (2016) TP53 mutation in patients with high-risk acute myeloid leukaemia treated with allogeneic haematopoietic stem cell transplantation. Br J Haematol 172(6):914–922CrossRefPubMedGoogle Scholar
- 4.Metzeler KH, Maharry K, Radmacher MD, Mrózek K, Margeson D, Becker H, Curfman J, Holland KB, Schwind S, Whitman SP, Wu YZ, Blum W, Powell BL, Carter TH, Wetzler M, Moore JO, Kolitz JE, Baer MR, Carroll AJ, Larson RA, Caligiuri MA, Marcucci G, Bloomfield CD (2011) TET2 mutations improve the new European LeukemiaNet risk classification of acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol 29(10):1373–1381CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Ahn JS, Kim HJ, Kim YK, Lee SS, Jung SH, Yang DH, Lee JJ, Kim NY, Choi SH, Jung CW, Jang JH, Kim HJ, Moon JH, Sohn SK, Won JH, Kim SH, Kim DD (2016) DNMT3A R882 mutation with FLT3-ITD positivity is an extremely poor prognostic factor in patients with normal-karyotype acute myeloid leukemia after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 22(1):61–70CrossRefPubMedGoogle Scholar
- 6.Schlenk RF, Kayser S, Bullinger L, Kobbe G, Casper J, Ringhoffer M, Held G, Brossart P, Lübbert M, Salih HR, Kindler T, Horst HA, Wulf G, Nachbaur D, Götze K, Lamparter A, Paschka P, Gaidzik VI, Teleanu V, Späth D, Benner A, Krauter J, Ganser A, Döhner H, Döhner K, German-Austrian AML Study Group (2014) Differential impact of allelic ratio and insertion site in FLT3-ITD-positive AML with respect to allogeneic transplantation. Blood 124(23):3441–3449CrossRefPubMedGoogle Scholar
- 9.Wang Y, Liu DH, Fan ZP, Sun J, Wu XJ, Ma X, Xu LP, Liu KY, Liu QF, Wu DP, Huang XJ (2012) Prevention of relapse using DLI can increase survival following HLA-identical transplantation in patients with advanced-stage acute leukemia: a multi-center study. Clin Transpl 26(4):635–643CrossRefGoogle Scholar
- 10.Wang Y, Liu DH, Xu LP, Liu KY, Chen H, Zhang XH, Chen YH, Han W, Wang FR, Wang JZ, Yan CH, Huang XJ (2012) Prevention of relapse using granulocyte CSF-primed PBPCs following HLA-mismatched/haploidentical, T-cell-replete hematopoietic SCT in patients with advanced-stage acute leukemia: a retrospective risk-factor analysis. Bone Marrow Transplant 47(8):1099–1104CrossRefPubMedGoogle Scholar
- 11.Gao XN, Lin J, Wang SH, Huang WR, Li F, Li HH, Chen J, Wang LJ, Gao CJ, Yu L, Liu DH (2018) Donor lymphocyte infusion for prevention of relapse after unmanipulated haploidentical PBSCT for very high-risk hematologic malignancies. Ann Hematol 98:185–193. https://doi.org/10.1007/s00277-018-3482-7 CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Li HH, Li F, Gao CJ, Huang WR, Bo J, Dou LP, Wang LL, Jing Y, Wang L, Li WJ, Yu L, Liu DH (2017) Similar incidence of severe acute GVHD and less severe chronic GVHD in PBSCT from unmanipulated, haploidentical donors compared with that from matched sibling donors for patients with haematological malignancies. Br J Haematol 176(1):92–100CrossRefPubMedGoogle Scholar
- 13.Rowlings PA, Przepiorka D, Klein JP, Gale RP, Passweg JR, Henslee-Downey PJ, Cahn JY, Calderwood S, Gratwohl A, Socié G, Abecasis MM, Sobocinski KA, Zhang MJ, Horowitz MM (1997) IBMTR severity index for grading acute graft-versus-host disease: retrospective comparison with Glucksberg grade. Br J Haematol 97(4):855–864CrossRefPubMedGoogle Scholar
- 16.Yan CH, Liu DH, Xu LP, Liu KY, Zhao T, Wang Y, Chen H, Chen YH, Han W, Huang XJ (2012) Modified donor lymphocyte infusion-associated acute graft-versus-host disease after haploidentical T cell-replete hematopoietic stem cell transplantation: incidence and risk factors. Clin Transpl 26(6):868–876CrossRefGoogle Scholar
- 17.Yan CH, Xu LP, Liu DH, Chen H, Wang Y, Wang JZ, Wang FR, Han W, Liu KY, Huang XJ (2015) Low-dose methotrexate may preserve a stronger antileukemic effect than that of cyclosporine after modified donor lymphocyte infusion in unmanipulated haploidentical SCT. Clin Transpl 29(7):594–605CrossRefGoogle Scholar
- 18.Yan CH, Liu QF, Wu DP, Zhang X, Xu LP, Zhang XH, Wang Y, Huang H, Bai H, Huang F, Ma X, Huang XJ (2017) Prophylactic donor lymphocyte infusion (DLI) followed by minimal residual disease and graft-versus-host disease-guided multiple DLIs could improve outcomes after allogeneic hematopoietic stem cell transplantation in patients with refractory/relapsed acute leukemia. Biol Blood Marrow Transplant 23(8):1311–1319CrossRefPubMedGoogle Scholar