Can GCSF-stimulated donor lymphocyte infusions improve outcomes for relapsed disease following allogeneic hematopoietic cell transplantation? A systematic review and meta-analysis

References

• van den Brink MR, Porter DL, Giralt S, et al. Relapse after allogeneic hematopoietic cell therapy. Biol Blood Marrow Transplant. 2010;16(1):S138–S145.
   PubMed Web of Science ®Google Scholar
• de Lima M, Porter DL, Battiwalla M, et al. Proceedings from the national cancer institute’s second international workshop on the biology, prevention, and treatment of relapse after hematopoietic stem cell transplantation: part III. Prevention and treatment of relapse after allogeneic transplantation. Biol Blood Marrow Transplant. 2014;20(1):4–13.
   PubMed Web of Science ®Google Scholar
• Dazzi F, Szydlo RM, Goldman JM. Donor lymphocyte infusions for relapse of chronic myeloid leukemia after allogeneic stem cell transplant: where we now stand. Exp Hematol. 1999;27(10):1477–1486.
   PubMed Web of Science ®Google Scholar
• Jin CH, Li Y, Xia J, et al. CXCR4 blockade improves leukemia eradication by allogeneic lymphocyte infusion. Am J Hematol. 2018;93(6):786–793.
   PubMed Web of Science ®Google Scholar
• Dazzi F, Goldman J. Donor lymphocyte infusions. Curr Opin Hematol. 1999;6(6):394–399.
   PubMedGoogle Scholar
• Arat M, Arslan O, Gürman G, et al. The impact of granulocyte colony stimulating factor at content of donor lymphocytes collected for cellular immunotherapy. Transfus Apher Sci. 2004;30(1):9–15.
   PubMed Web of Science ®Google Scholar
• Minculescu L, Sengelov H, Marquart HV, et al. Granulocyte colony-stimulating factor effectively mobilizes TCR γδ and NK cells providing an allograft potentially enhanced for the graft-versus-leukemia effect for allogeneic stem cell transplantation. Front Immunol. 2021;12:625165.
   PubMed Web of Science ®Google Scholar
• Pan L, Teshima T, Hill GR, et al. Granulocyte colony-stimulating factor-mobilized allogeneic stem cell transplantation maintains graft-versus-leukemia effects through a perforin-dependent pathway while preventing graft-versus-host disease. Blood. 1999;93(12):4071–4078.
   PubMed Web of Science ®Google Scholar
• Franzke A, Piao W, Lauber J, et al. G-CSF as immune regulator in T cells expressing the G-CSF receptor: implications for transplantation and autoimmune diseases. Blood. 2003;102(2):734–739.
   PubMed Web of Science ®Google Scholar
• Arpinati M, Green CL, Heimfeld S, et al. Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dendritic cells. Blood. 2000;95(8):2484–2490.
   PubMed Web of Science ®Google Scholar
• Roberts AW. G-CSF: a key regulator of neutrophil production, but that’s not all! Growth Factors. 2005;23(1):33–41.
   PubMed Web of Science ®Google Scholar
• Mielcarek M, Martin PJ, Torok-Storb B. Suppression of alloantigen-induced T-cell proliferation by CD14+ cells derived from granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells. Blood. 1997;89(5):1629–1634.
   PubMed Web of Science ®Google Scholar
• Root RK, Dale DC. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor: comparisons and potential for use in the treatment of infections in nonneutropenic patients. J Infect Dis. 1999;179(2):S342–S352.
   PubMedGoogle Scholar
• Lotfi N, Zhang GX, Esmaeil N, et al. Evaluation of the effect of GM-CSF blocking on the phenotype and function of human monocytes. Sci Rep. 2020;10(1):1567.
   PubMed Web of Science ®Google Scholar
• Mathias B, Szpila BE, Moore FA, et al. A review of GM-CSF therapy in sepsis. Medicine. 2015;94(50):e2044.
   PubMed Web of Science ®Google Scholar
• Ye Y, Yang L, Yuan X, et al. Optimization of donor lymphocyte infusion for AML relapse after Allo-HCT in the era of new drugs and cell engineering. Front Oncol. 2021;11:790299.
   PubMed Web of Science ®Google Scholar
• Yan CH, Liu QF, Wu DP, et al. 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. 2017;23(8):1311–1319.
   PubMed Web of Science ®Google Scholar
• Tan Y, Du K, Luo Y, et al. Superiority of preemptive donor lymphocyte infusion based on minimal residual disease in acute leukemia patients after allogeneic hematopoietic stem cell transplantation. Transfusion. 2014;54(6):1493–1500.
   PubMed Web of Science ®Google Scholar
• Nikiforow S, Alyea EP. Maximizing GVL in allogeneic transplantation: role of donor lymphocyte infusions. Hematology Am Soc Hematol Educ Program. 2014;2014(1):570–575.
   PubMedGoogle Scholar
• Orti G, Barba P, Fox L, et al. Donor lymphocyte infusions in AML and MDS: enhancing the graft-versus-leukemia effect. Exp Hematol. 2017;48:1–11.
   PubMed Web of Science ®Google Scholar
• Hossain NM, Klumpp T, Ulicny J, et al. Donor lymphocyte infusion in hematologic malignancies–good to be fresh? Clin Lymphoma Myeloma Leuk. 2016;16(2):111–115.
   PubMed Web of Science ®Google Scholar
• Hasskarl J, Zerweck A, Wäsch R, et al. Induction of graft versus malignancy effect after unrelated allogeneic PBSCT using donor lymphocyte infusions derived from frozen aliquots of the original graft. Bone Marrow Transplant. 2012;47(2):277–282.
   PubMed Web of Science ®Google Scholar
• Schleuning M. Adoptive allogeneic immunotherapy–history and future perspectives. Transfus Sci. 2000;23(2):133–150.
   PubMedGoogle Scholar
• Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.
   PubMed Web of Science ®Google Scholar
• Sampson M, McGowan J, Cogo E, et al. An evidence-based practice guideline for the peer review of electronic search strategies. J Clin Epidemiol. 2009;62(9):944–952.
   PubMed Web of Science ®Google Scholar
• DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–188.
   PubMedGoogle Scholar
• Higgins JPT, Thomas J, Chandler J, et al., editors. Cochrane handbook for systematic reviews of interventions version 6.2. Updated February 2021. London (UK): Cochrane; 2021.
   Google Scholar
• Sterne JA, Egger M. Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis. J Clin Epidemiol. 2001;54(10):1046–1055.
   PubMed Web of Science ®Google Scholar
• Ouzzani M, Hammady H, Fedorowicz Z, et al. Rayyan-a web and mobile app for systematic reviews. Syst Rev. 2016;5(1):210.
   PubMedGoogle Scholar
• Sterne JA, Hernán MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919.
   PubMed Web of Science ®Google Scholar
• Wells GA, Connell DO, Peterson J, et al. Newcastle-Ottawa quality assessment scale. Ottawa (Canada): Ottawa Hospital Research Institute; 2014. p. 2–4.
   Google Scholar
• Murad MH, Sultan S, Haffar S, et al. Methodological quality and synthesis of case series and case reports. BMJ Evid Based Med. 2018;23(2):60–63.
   PubMedGoogle Scholar
• Lamure S, Paul F, Gagez AL, et al. A retrospective comparison of DLI and gDLI for post-transplant treatment. J Clin Med. 2020;9(7):2204.
   PubMed Web of Science ®Google Scholar
• Schneidawind C, Jahnke S, Schober-Melms I, et al. G-CSF administration prior to donor lymphocyte apheresis promotes anti-leukaemic effects in allogeneic HCT patients. Br J Haematol. 2019;186(1):60–71.
   PubMed Web of Science ®Google Scholar
• Abbi K, Zhu J, Ehmann W, et al. G-CSF mobilized vs conventional donor lymphocytes for therapy of relapse or incomplete engraftment after allogeneic hematopoietic transplantation. Bone Marrow Transplant. 2013;48(3):357–362.
   PubMed Web of Science ®Google Scholar
• Flowers ME, Leisenring W, Beach K, et al. Granulocyte colony-stimulating factor given to donors before apheresis does not prevent aplasia in patients treated with donor leukocyte infusion for recurrent chronic myeloid leukemia after bone marrow transplantation. Biol Blood Marrow Transplant. 2000;6(3):321–326.
   PubMedGoogle Scholar
• Choi SJ, Lee JH, Lee JH, et al. Treatment of relapsed acute myeloid leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a high incidence of isolated extramedullary relapse. Leukemia. 2004;18(11):1789–1797.
   PubMed Web of Science ®Google Scholar
• Choi SJ, Lee JH, Lee JH, et al. Treatment of relapsed acute lymphoblastic leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a prospective study. Bone Marrow Transplant. 2005;36(2):163–169.
   PubMed Web of Science ®Google Scholar
• Grigg A, Kannan K, Schwarer AP, et al. Chemotherapy and granulocyte colony stimulating factor-mobilized blood cell infusion followed by interferon-alpha for relapsed malignancy after allogeneic bone marrow transplantation. Intern Med J. 2001;31(1):15–22.
   PubMed Web of Science ®Google Scholar
• Huang XJ, Liu DH, Liu KY, et al. Donor lymphocyte infusion for the treatment of leukemia relapse after HLA-mismatched/haploidentical T-cell-replete hematopoietic stem cell transplantation. Haematologica. 2007;92(3):414–417.
   PubMed Web of Science ®Google Scholar
• Huang XJ, Wang Y, Liu DH, et al. Administration of short-term immunosuppressive agents after DLI reduces the incidence of DLI-associated acute GVHD without influencing the GVL effect. Bone Marrow Transplant. 2009;44(5):309–316.
   PubMed Web of Science ®Google Scholar
• Lee JH, Lee KH, Kim S, et al. Combination chemotherapy of intermediate-dose cytarabine, idarubicin, plus etoposide and subsequent mobilized donor leukocyte infusion for relapsed acute leukemia after allogeneic bone marrow transplantation. Leuk Res. 2001;25(4):305–312.
   PubMed Web of Science ®Google Scholar
• Levine JE, Braun T, Penza SL, et al. Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation. J Clin Oncol. 2002;20(2):405–412.
   PubMed Web of Science ®Google Scholar
• Sun W, Mo XD, Zhang XH, et al. Chemotherapy plus DLI for relapse after haploidentical HSCT: the biological characteristics of relapse influences clinical outcomes of acute leukemia patients. Bone Marrow Transplant. 2019;54(8):1198–1207.
   PubMed Web of Science ®Google Scholar
• Mandanas RA, Saez RA, Selby GB, et al. G-CSF-mobilized donor leukocyte infusions as immunotherapy in acute leukemia relapsing after allogeneic marrow transplantation. J Hematother. 1998;7(5):449–456.
   PubMedGoogle Scholar
• Siegert W, Beyer J, Kingreen D, et al. Treatment of relapse after allogeneic bone marrow transplantation with unmanipulated G-CSF-mobilized peripheral blood stem cell preparation. Bone Marrow Transplant. 1998;22(6):579–583.
   PubMed Web of Science ®Google Scholar
• Gürman G. Donor leukocyte infusions for the treatment of leukemia relapse after allogeneic hematopoietic cell transplantation with myeloablative conditioning. Turk J Haematol. 2000;17(4):171–181.
   PubMedGoogle Scholar
• Kim JG, Sohn SK, Kim DH, et al. A pilot study of cytoreductive chemotherapy combined with infusion of additional peripheral blood stem cells reserved at time of harvest for transplantation in case of relapsed hematologic malignancies after allogeneic peripheral blood stem cell transplant. Bone Marrow Transplant. 2004;33(2):231–236.
   PubMed Web of Science ®Google Scholar
• Webster JA, Luznik L, Gojo I. Treatment of AML relapse after allo-HCT. Front Oncol. 2021;11:812207.
   PubMed Web of Science ®Google Scholar
• Poon LM, Hamdi A, Saliba R, et al. Outcomes of adults with acute lymphoblastic leukemia relapsing after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2013;19(7):1059–1064.
   PubMed Web of Science ®Google Scholar
• Toh HC, Sun L, Soe Y, et al. G-CSF induces a potentially tolerant gene and immunophenotype profile in T cells in vivo. Clin Immunol. 2009;132(1):83–92.
   PubMed Web of Science ®Google Scholar
• Xuan L, Wu X, Zhang Y, et al. Granulocyte colony-stimulating factor affects the distribution and clonality of TRGV and TRDV repertoire of T cells and graft-versus-host disease. J Transl Med. 2011;9:215.
   PubMed Web of Science ®Google Scholar
• Malashchenko VV, Meniailo ME, Shmarov VA, et al. Direct anti-inflammatory effects of granulocyte colony-stimulating factor (G-CSF) on activation and functional properties of human T cell subpopulations in vitro. Cell Immunol. 2018;325:23–32.
   PubMed Web of Science ®Google Scholar
• Boneberg EM, Hartung T. Molecular aspects of anti-inflammatory action of G-CSF. Inflamm Res. 2002;51(3):119–128.
   PubMed Web of Science ®Google Scholar
• Mavroudis D, Barrett J. The graft-versus-leukemia effect. Curr Opin Hematol. 1996;3(6):423–429.
   PubMedGoogle Scholar
• Jiang YZ, Barrett AJ, Goldman JM, et al. Association of natural killer cell immune recovery with a graft-versus-leukemia effect independent of graft-versus-host disease following allogeneic bone marrow transplantation. Ann Hematol. 1997;74(1):1–6.
   PubMed Web of Science ®Google Scholar
• Karantanou C, Godavarthy PS, Krause DS. Targeting the bone marrow microenvironment in acute leukemia. Leuk Lymphoma. 2018;59(11):2535–2545.
   PubMed Web of Science ®Google Scholar
• Chang X, Zang X, Xia CQ. New strategies of DLI in the management of relapse of hematological malignancies after allogeneic hematopoietic SCT. Bone Marrow Transplant. 2016;51(3):324–332.
   PubMed Web of Science ®Google Scholar
• Maganti H, Visram A, Shorr R, et al. Plerixafor in combination with chemotherapy and/or hematopoietic cell transplantation to treat acute leukemia: a systematic review and metanalysis of preclinical and clinical studies. Leuk Res. 2020;97:106442.
   PubMed Web of Science ®Google Scholar
• Isidori A, Cerchione C, Daver N, et al. Immunotherapy in acute myeloid leukemia: where we stand. Front Oncol. 2021;11:656218.
   PubMedGoogle Scholar
• Estey EH. Acute myeloid leukemia: 2021 update on risk-stratification and management. Am J Hematol. 2020;95(11):1368–1398.
   PubMed Web of Science ®Google Scholar
• Kantarjian HM, Kadia TM, DiNardo CD, et al. Acute myeloid leukemia: treatment and research outlook for 2021 and the MD Anderson approach. Cancer. 2021;127(8):1186–1207.
   PubMed Web of Science ®Google Scholar
• Dholaria B, Savani BN, Labopin M, et al. Clinical applications of donor lymphocyte infusion from an HLA-haploidentical donor: consensus recommendations from the acute leukemia working party of the EBMT. Haematologica. 2020;105(1):47–58.
   PubMed Web of Science ®Google Scholar
• Schmid C, Labopin M, Nagler A, et al. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT acute leukemia working party. J Clin Oncol. 2007;25(31):4938–4945.
   PubMed Web of Science ®Google Scholar
• Maffini E, Labopin M, Blaise D, et al. CD34+ cell dose effects on clinical outcomes after T-cell replete haploidentical allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia using peripheral blood stem cells. A study from the acute leukemia working party of the European Society for Blood and Marrow Transplantation (EBMT). Am J Hematol. 2020;95(8):892–899.
   PubMed Web of Science ®Google Scholar
• Remberger M, Grønvold B, Ali M, et al. The CD34+ cell dose matters in hematopoietic stem cell transplantation with peripheral blood stem cells from sibling donors. Clin Hematol Int. 2020;2(2):74–81.
   PubMedGoogle Scholar
• Basquiera AL, Abichaín P, Damonte JC, et al. CD34+ cell dose in allogeneic transplantation: weight considerations. Biol Blood Marrow Transplant. 2015;21(1):196.
   PubMed Web of Science ®Google Scholar
• Yokoyama Y, Maie K, Fukuda T, et al. A high CD34+ cell dose is associated with better disease-free survival in patients with low-risk diseases undergoing peripheral blood stem cell transplantation from HLA-matched related donors. Bone Marrow Transplant. 2020;55(9):1726–1735.
   PubMed Web of Science ®Google Scholar
• Ringdén O, Karlsson H, Olsson R, et al. The allogeneic graft-versus-cancer effect. Br J Haematol. 2009;147(5):614–633.
   PubMed Web of Science ®Google Scholar
• Baron F, Maris MB, Storer BE, et al. High doses of transplanted CD34+ cells are associated with rapid T-cell engraftment and lessened risk of graft rejection, but not more graft-versus-host disease after nonmyeloablative conditioning and unrelated hematopoietic cell transplantation. Leukemia. 2005;19(5):822–828.
   PubMed Web of Science ®Google Scholar
• Mavroudis D, Read E, Cottler-Fox M, et al. CD34+ cell dose predicts survival, posttransplant morbidity, and rate of hematologic recovery after allogeneic marrow transplants for hematologic malignancies. Blood. 1996;88(8):3223–3229.
   PubMed Web of Science ®Google Scholar
• Dercksen MW, Rodenhuis S, Dirkson MK, et al. Subsets of CD34+ cells and rapid hematopoietic recovery after peripheral-blood stem-cell transplantation. J Clin Oncol. 1995;13(8):1922–1932.
   PubMed Web of Science ®Google Scholar