Cellular immunotherapy for refractory hematological malignancies
详细信息 查看全文
- 作者：John L Reagan (8)
Loren D Fast (8)
Howard Safran (8)
Martha Nevola (8)
Eric S Winer (8)
Jorge J Castillo (8)
James N Butera (8)
Matthew I Quesenberry (8)
Carolyn T Young (9)
Peter J Quesenberry (8) - 关键词：Acute myeloid leukemia ; Immunotherapy ; Hematological malignancies ; Non ; Hodgkin lymphoma ; Cellular therapy ; Cytokine release syndrome
- 刊名：Journal of Translational Medicine
- 出版年：2013
- 出版时间：December 2013
- 年：2013
- 卷：11
- 期：1
- 全文大小：233KB
- 参考文献：1. Howlader N, Noone AM, Krapcho M, Garshell J, Neyman N, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA: / SEER Cancer Statistics Review, 1975鈥?010. : ; 2013.
2. Koreth J, Schlenk R, Kopecky KJ, Honda S, Sierra J, Djulbegovic BJ, Wadleigh M, DeAngelo DJ, Stone RM, Sakamaki H, / et al.: Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials. / JAMA 2009,301(22):2349鈥?361. CrossRef
3. Schmid C, Labopin M, Nagler A, Niederwieser D, Castagna L, Tabrizi R, Stadler M, Kuball J, Cornelissen J, Vorlicek J, / et al.: Treatment, risk factors, and outcome of adults with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation. / Blood 2012,119(6):1599鈥?606. CrossRef
4. Fielding AK, Richards SM, Chopra R, Lazarus HM, Litzow MR, Buck G, Durrant IJ, Luger SM, Marks DI, Franklin IM, / et al.: Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. / Blood 2007,109(3):944鈥?50. CrossRef
5. Stock W, Johnson JL, Stone RM, Kolitz JE, Powell BL, Wetzler M, Westervelt P, Marcucci G, DeAngelo DJ, Vardiman JW, / et al.: Dose intensification of daunorubicin and cytarabine during treatment of adult acute lymphoblastic leukemia. / Cancer 2013,119(1):90鈥?8. CrossRef
6. Kantarjian H, Thomas D, O鈥橞rien S, Cortes J, Giles F, Jeha S, Bueso-Ramos CE, Pierce S, Shan J, Koller C, / et al.: Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. / Cancer 2004,101(12):2788鈥?801. CrossRef
7. Freytes CO, Zhang M-J, Carreras J, Burns LJ, Gale RP, Isola L, Perales M-A, Seftel M, Vose JM, Miller AM, / et al.: Outcome of Lower-Intensity Allogeneic Transplantation in Non-Hodgkin Lymphoma after Autologous Transplantation Failure. / Biol Blood Marrow Transplant 2012,18(8):1255鈥?264. CrossRef
8. Freytes CO, Loberiza FR, Rizzo JD, Bashey A, Bredeson CN, Cairo MS, Gale RP, Horowitz MM, Klumpp TR, Martino R, / et al.: Myeloablative allogeneic hematopoietic stem cell transplantation in patients who experience relapse after autologous stem cell transplantation for lymphoma: a report of the International Bone Marrow Transplant Registry. / Blood 2004,104(12):3797鈥?803. CrossRef
9. Gupta V, Richards S, Rowe J: Allogeneic, but not autologous, hematopoietic cell transplantation improves survival only among younger adults with acute lymphoblastic leukemia in first remission: an individual patient data meta-analysis. / Blood 2013,121(2):339鈥?50. CrossRef
10. Stewart F, Crittenden R, Lowry P, Pearson-White S, Quesenberry P: Long-term engraftment of normal and post-5-fluorouracil murine marrow into normal nonmyeloablated mice [see comments]. / Blood 1993,81(10):2566鈥?571.
11. Stewart FM, Zhong S, Wuu J, Hsieh C-c, Nilsson SK, Quesenberry PJ: Lymphohematopoietic Engraftment in Minimally Myeloablated Hosts. / Blood 1998,91(10):3681鈥?687.
12. Stewart FM, Zhong S, Lambert J-F, Colvin GA, Abedi M, Dooner MS, McAuliffe CI, Wang H, Hsieh C, Quesenberry PJ: Host marrow stem cell potential and engraftability at varying times after low-dose whole-body irradiation. / Blood 2001,98(4):1246鈥?251. CrossRef
13. Lambert J-F, Colvin GA, Zhong S, Wang H, D鈥橦ondt L, Abedi M, Frimberger AE, Stewart FM, Quesenberry PJ: H2-mismatched transplantation with repetitive cell infusions and CD40 ligand antibody infusions without myeloablation. / Br J Haematol 2002,119(1):155鈥?63. CrossRef
14. Ballen KK, Becker PS, Emmons RVB, Fitzgerald TJ, Hsieh CC, Liu Q, Heyes C, Clark Y, Levy W, Lambert JF, / et al.: Low-dose total body irradiation followed by allogeneic lymphocyte infusion may induce remission in patients with refractory hematologic malignancy. / Blood 2002,100(2):442鈥?50. CrossRef
15. Colvin GA, Berz D, Ramanathan M, Winer ES, Fast L, Elfenbein GJ, Quesenberry PJ: Nonengraftment haploidentical cellular immunotherapy for refractory malignancies: tumor responses without chimerism. / Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 2009,15(4):421鈥?31. CrossRef
16. Rubio M-T, Kim Y-M, Sachs T, Mapara M, Zhao G, Sykes M: Antitumor effect of donor marrow graft rejection induced by recipient leukocyte infusions in mixed chimeras prepared with nonmyeloablative conditioning: critical role for recipient-derived IFN-纬. / Blood 2003,102(6):2300鈥?307. CrossRef
17. Reagan JL, Fast LD, Winer ES, Safran H, Butera JN, Quesenberry PJ: Nonengraftment haploidentical cellular therapy for hematologic malignancies. / Adv Hematol 2012,2012(2):784213.
18. Porter DL, Grupp SA, Kalos M, Loren AW, Lledo L, Gilmore J, Milone MC, Chew A, Levine BL, June CH: Chimeric Antigen Receptor T Cells Directed Against CD19 Induce Durable Responses and Transient Cytokine Release Syndrome in Relapsed, Refractory CLL and ALL. / ASH Annual Meeting Abstracts 2012,120(21):717.
19. Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, Teachey DT, Chew A, Hauck B, Wright JF, / et al.: Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. / N Engl J Med 2013,368(16):1509鈥?518. CrossRef
20. Grupp SA, Porter DL, Teachey DT, Barrett DM, Chew A, Suppa E, Levine BL, Kalos M, June CH: CD19-Redirected Chimeric Antigen Receptor T (CART19) Cells Induce a Cytokine Release Syndrome (CRS) and Induction of Treatable Macrophage Activation Syndrome (MAS) That Can Be Managed by the IL-6 Antagonist Tocilizumab (toc). / ASH Annual Meeting Abstracts 2012,120(21):2604.
21. Guo M, Hu K-X, Yu C-L, Sun Q-Y, Qiao J-H, Wang D-H, Liu G-X, Sun W-J, Wei L, Sun X-D, / et al.: Infusion of HLA-mismatched peripheral blood stem cells improves the outcome of chemotherapy for acute myeloid leukemia in elderly patients. / Blood 2011,117(3):936鈥?41. CrossRef
22. Guo M, Hu K-X, Liu G-X, Yu C-L, Qiao J-H, Sun Q-Y, Qiao J-X, Dong Z, Sun W-J, Sun X-D, / et al.: HLA-Mismatched Stem-Cell Microtransplantation As Postremission Therapy for Acute Myeloid Leukemia: long-Term Follow-Up. / J Clin Oncol 2012,30(33):4084鈥?090. CrossRef
23. Byrd JC, Mr贸zek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC, Pettenati MJ, Patil SR, Rao KW, Watson MS, / et al.: Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461): presented in part at the 43rd annual meeting of the American Society of Hematology, Orlando, FL, December 10, 2001, and published in abstract form.59. / Blood 2002,100(13):4325鈥?336. CrossRef
24. Ai H, Hu K, Sun Q, Li X, Guo M, Yu C, Qiao J, Qiao J, Liu G, Dong Z, / et al.: Microtransplantation with Decitabine and Cytarabine Improves Patient Outcomes in Myelodysplastic Syndromes. / ASH Annual Meeting Abstracts 2012,120(21):1709.
25. Morris ES, MacDonald KPA, Hill GR: Stem cell mobilization with G-CSF analogs: a rational approach to separate GVHD and GVL? / Blood 2006,107(9):3430鈥?435. CrossRef
26. Cheson BD, Bennett JM, Kopecky KJ, B眉chner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, / et al.: Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. / J Clin Oncol 2003,21(24):4642鈥?649. CrossRef
27. Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, / et al.: Revised Response Criteria for Malignant Lymphoma. / J Clin Oncol 2007,25(5):579鈥?86. CrossRef
28. Reagan JL FL, Nevola M, Quesenberry PJ: Random unrelated donor peripheral blood mononuclear cells (PBMC) stimulate cytolytic host T cell activity against leukemia [abstract]. In / Proceedings of the 104th Annual Meeting of the American Association for Cancer Research: 2013; 2013 Apr 6鈥?0. AACR: Washington, DC: Philadelphia (PA); 2013. Abstract nr 1252
29. Venstrom JM, Pittari G, Gooley TA, Chewning JH, Spellman S, Haagenson M, Gallagher MM, Malkki M, Petersdorf E, Dupont B, / et al.: HLA-C-dependent prevention of leukemia relapse by donor activating KIR2DS1. / N Engl J Med 2012,367(9):805鈥?16. CrossRef
30. Drabbels JJ, van de Keur C, Kemps BM, Mulder A, Scherjon SA, Claas FH, Eikmans M: HLA-targeted flow cytometric sorting of blood cells allows separation of pure and viable microchimeric cell populations. / Blood 2011,118(19):e149鈥?55. CrossRef
31. Mulder A, Kardol MJ, Arn JS, Eijsink C, Franke ME, Schreuder GM, Haasnoot GW, Doxiadis II, Sachs DH, Smith DM, / et al.: Human monoclonal HLA antibodies reveal interspecies crossreactive swine MHC class I epitopes relevant for xenotransplantation. / Mol Immunol 2010,47(4):809鈥?15. CrossRef - 作者单位：John L Reagan (8)
Loren D Fast (8)
Howard Safran (8)
Martha Nevola (8)
Eric S Winer (8)
Jorge J Castillo (8)
James N Butera (8)
Matthew I Quesenberry (8)
Carolyn T Young (9)
Peter J Quesenberry (8)
8. Division of Hematology/Oncology, Rhode Island Hospital/The Miriam Hospital, The Warren Alpert Medical School of Brown University, Providence, USA
9. Department of Pathology, Rhode Island Blood Center, The Warren Alpert Medical School of Brown University, Providence, USA
文摘
Background Acute myeloid leukemia (AML) and other aggressive refractory hematological malignancies unresponsive to upfront therapy remain difficult conditions to treat. Often, the focus of therapy is centered on achieving complete remission of disease in order to proceed with a consolidative stem cell transplant. At issue with this paradigm is the multitude of patients who are unable to achieve complete remission with standard chemotherapeutic options. A major benefit of transplantation is the graft versus tumor effect that follows successful engraftment. However, with this graft versus tumor effect comes the risk of graft versus host disease. Therefore, alternative treatment options that utilize immunotherapy while minimizing toxicity are warranted. Herein, we propose a novel treatment protocol in which haploidentical peripheral blood stem cells are infused into patients with refractory hematological malignancies. The end goal of cellular therapy is not engraftment but instead is the purposeful rejection of donor cells so as to elicit a potent immune reaction that appears to break host tumor tolerance. Methods/design The trial is a FDA and institutional Rhode Island Hospital/The Miriam Hospital IRB approved Phase I/II study to determine the efficacy and safety of haploidentical peripheral blood cell infusions into patients with refractory hematological malignancies. The primary objective is the overall response rate while secondary objectives will assess the degree and duration of response as well as safety considerations. Patients with refractory acute leukemias and aggressive lymphomas over the age of 18 are eligible. Donors will be selected amongst family members. Full HLA typing of patients and donors will occur as will chimerism assessments. 1-2x108 CD3+ cells/kilogram will be infused on Day 0 without preconditioning. Patients will be monitored for their response to therapy, in particular for the development of a cytokine release syndrome (CRS) that has been previously described. Blood samples will be taken at the onset, during, and following the cessation of CRS so as to study effector cells, cytokine/chemokine release patterns, and extracellular vesicle populations. Initially, six patients will be enrolled on study to determine safety. Provided the treatment is deemed safe, a total of 25 patients will be enrolled to determine efficacy. Discussion Cellular Immunotherapy for Refractory Hematological Malignancies provides a novel treatment for patients with relapsed/refractory acute leukemia or aggressive lymphoma. We believe this therapy offers the immunological benefit of bone marrow transplantation without the deleterious effects of myeloablative conditioning regimens and minus the risk of GVHD. Laboratory correlative studies will be performed in conjunction with the clinical trial to determine the underlying mechanism of action. This provides a true bench to bedside approach that should serve to further enrich knowledge of host tumor tolerance and mechanisms by which this may be overcome. Trial registration NCT01685606.