CD3/CD19 depletion and reduced intensity conditioning: A phase II study

Haematologica

Volumn 97, Issue 10, 2012, Pages 1523-1531

  Federmann, Birgit ^a   Bornhauser, Martin ^b   Meisner, Christoph ^c   Kordelas, Lambros ^d   Beelen, Dietrich W ^d   Stuhler, Gernot ^e   Stelljes, Matthias ^f   Schwerdtfeger, Rainer ^g   Christopeit, Maximilian ^h   Behre, Gerhard ^h,i   Faul, Christoph ^a   Vogel, Wichard ^a   Schumm, Michael ^c   Handgretinger, Rupert ^c   Kanz, Lothar ^a   Bethge, Wolfgang A ^a  

^a UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

^b DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

^c UNIVERSITY OF TÜBINGEN   (Germany)

^d UNIVERSITY HOSPITAL ESSEN   (Germany)

^e UNIVERSITY OF WÜRZBURG   (Germany)

^f UNIVERSITY OF MÜNSTER   (Germany)

^g DEUTSCHE KLINIK FÜR DIAGNOSTIK   (Germany)

^h MARTIN LUTHER UNIVERSITY HALLE WITTENBERG   (Germany)

ⁱ UNIVERSITY OF LEIPZIG   (Germany)

Author keywords

Aurora B kinase; Myelodysplastic syndromes; Survivin

Indexed keywords

CD19 ANTIGEN; CD3 ANTIGEN; CD34 ANTIGEN; CD56 ANTIGEN; FLUDARABINE; MELPHALAN; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; OKT 3; THIOTEPA; KILLER CELL IMMUNOGLOBULIN LIKE RECEPTOR;

ACUTE GRAFT VERSUS HOST DISEASE; ACUTE LYMPHOBLASTIC LEUKEMIA; ADULT; AGED; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; ARTICLE; CHRONIC GRAFT VERSUS HOST DISEASE; CHRONIC LYMPHATIC LEUKEMIA; CHRONIC MYELOID LEUKEMIA; DONOR LYMPHOCYTE INFUSION; DRUG DOSE REDUCTION; EVENT FREE SURVIVAL; FEMALE; FLOW CYTOMETRY; FOLLOW UP; HIGH RISK PATIENT; HLA TYPING; HUMAN; HUMAN CELL; LEUKEMIA REMISSION; MAJOR CLINICAL STUDY; MALE; MORTALITY; MULTICENTER STUDY; MYELODYSPLASTIC SYNDROME; MYELOID LEUKEMIA; MYELOMA; NEUROTOXICITY; NONHODGKIN LYMPHOMA; OVERALL SURVIVAL; PHASE 2 CLINICAL TRIAL; PROSPECTIVE STUDY; REDUCED INTENSITY CONDITIONING; RISK FACTOR; STEM CELL MOBILIZATION; TUMOR ENGRAFTMENT; ALLOTRANSPLANTATION; CHIMERA; DONOR; GENETICS; GRAFT SURVIVAL; GRAFT VERSUS HOST REACTION; HAPLOTYPE; HEMATOLOGIC DISEASE; HEMATOPOIETIC STEM CELL; HEMATOPOIETIC STEM CELL TRANSPLANTATION; IMMUNOLOGY; IMMUNOSUPPRESSIVE TREATMENT; LEUKEMIA; LYMPHOCYTE DEPLETION; MAJOR HISTOCOMPATIBILITY COMPLEX; METABOLISM; MIDDLE AGED; MULTIPLE MYELOMA; TREATMENT OUTCOME;

ADULT; AGED; ANTIGENS, CD19; ANTIGENS, CD3; ANTIGENS, CD34; CHIMERISM; FEMALE; GRAFT SURVIVAL; GRAFT VS HOST DISEASE; HAPLOTYPES; HEMATOLOGIC DISEASES; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HEMATOPOIETIC STEM CELLS; HUMANS; LEUKEMIA; LYMPHOCYTE DEPLETION; LYMPHOMA, NON-HODGKIN; MAJOR HISTOCOMPATIBILITY COMPLEX; MALE; MIDDLE AGED; MULTIPLE MYELOMA; MYELODYSPLASTIC SYNDROMES; RECEPTORS, KIR; RISK FACTORS; TISSUE DONORS; TRANSPLANTATION CONDITIONING; TRANSPLANTATION, HOMOLOGOUS; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84867254026     PISSN: 03906078     EISSN: 15928721     Source Type: Journal    
DOI: 10.3324/haematol.2011.059378     Document Type: Article

References (49)

1. Martin PJ. Overview of Marrow Transplantation Immunology. In: Blume KG, Forman SJ, Appelbaum FR, eds. Thomas' Hematopoietic cell transplantation. Malden, MA: Blackwell Science, Inc., 2004:16-30.
2. Anasetti C, Beatty PG, Storb R, Martin PJ, Mori M, Sanders JE, et al. Effect of HLA incompatibility on graft-versus-host disease, relapse, and survival after marrow transplantation for patients with leukemia or lymphoma. Hum Immunol. 1990;29(2):79-91.
3. Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F, et al. Treatment of high-risk acute leukemia with T-celldepleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med. 1998;339(17):1186-93.
4. Aversa F, Tabilio A, Terenzi A, Velardi A, Falzetti F, Giannoni C, et al. Successful engraftment of T-cell-depleted haploidentical three-loci incompatible transplants in leukemia patients by addition of recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells to bone marrow inoculum. Blood. 1994;84(11):3948-55.
5. Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S, et al. Full haplotypemismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol. 2005;23(15):3447-54.
6. Koh LP, Rizzieri DA, Chao NJ. Allogeneic hematopoietic stem cell transplant using mismatched/haploidentical donors. Biol Blood Marrow Transplant. 2007;13(11): 1249-67.
7. Bethge WA, Faul C, Bornhauser M, Stuhler G, Beelen DW, Lang P, et al. Haploidentical allogeneic hematopoietic cell transplantation in adults using CD3/CD19 depletion and reduced intensity conditioning: an update. Blood Cell Mol Dis. 2008;40(1):13-9.
8. Lang P, Bader P, Schumm M, Feuchtinger T, Einsele H, Fuhrer M, et al. Transplantation of a combination of CD133+ and CD34+ selected progenitor cells from alternative donors. Br J Haematol. 2004;124(1):72-9.
9. Barfield RC, Otto M, Houston J, Holladay M, Geiger T, Martin J, et al. A one-step large-scale method for T- and B-cell depletion of mobilized PBSC for allogeneic transplantation. Cytotherapy. 2004;6(1):1-6.
10. Hale G, Kimberly K, Lovins R, Woodard P, Leung W, Yusuf U, et al. CD3 Depleted Hematopoietic Peripheral Blood Stem Cell Grafts in Children with Refractory Hematologic Malignancies Undergoing Transplantation from Mismatched Related Donors. Blood. 2005;106(11), Abstract #5458.
11. Ruggeri L, Capanni M, Casucci M, Volpi I, Tosti A, Perruccio K, et al. Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation. Blood. 1999;94(1):333-9.
12. Bornhauser M, Thiede C, Brendel C, Geissler G, Oelschlagel U, Neubauer A, et al. Stable engraftment after megadose blood stem cell transplantation across the HLA barrier: the case for natural killer cells as graft-facilitating cells. Transplantation. 1999;68(1):87-8.
13. Fugier-Vivier IJ, Rezzoug F, Huang Y, Graul- Layman AJ, Schanie CL, Xu H, et al. Plasmacytoid precursor dendritic cells facilitate allogeneic hematopoietic stem cell engraftment. J Exp Med. 2005;201(3):373-83.
14. Grimes HL, Schanie CL, Huang Y, Cramer D, Rezzoug F, Fugier-Vivier I, et al. Graft facilitating cells are derived from hematopoietic stem cells and functionally require CD3, but are distinct from T lymphocytes. Exp Hematol. 2004;32(10):946-54.
15. Jacquet EG, Schanie CL, Fugier-Vivier I, Willer SS, Ildstad ST. Facilitating cells as a venue to establish mixed chimerism and tolerance. Pediatr Transplant. 2003;7(5): 348-57.
16. Tanaka J, Imamura M, Kasai M, Asaka M, Torok-Storb B. The role of accessory cells in allogeneic peripheral blood stem cell transplantation. Int J Hematol. 1999;69(2):70-4.
17. Bethge WA, Haegele M, Faul C, Lang P, Schumm M, Bornhauser M, et al. Haploidentical allogeneic hematopoietic cell transplantation in adults with reducedintensity conditioning and CD3/CD19 depletion: fast engraftment and low toxicity. Exp Hematol. 2006;34(12):1746-52.
18. Leuner S, Arland M, Kahl C, Jentsch-Ullrich K, Franke A, Hoffkes HG. Enumeration of CD34-positive hematopoietic progenitor cells by flow cytometry: comparison of a volumetric assay and the ISHAGE gating strategy. Bone Marrow Transplant. 1998;22(7):699-706.
19. Schumm M, Lang P, Taylor G, Kuci S, Klingebiel T, Buhring HJ, et al. Isolation of highly purified autologous and allogeneic peripheral CD34+ cells using the CliniMACS device. J Hematother. 1999;8(2):209-18.
20. Bader P, Beck J, Frey A, Schlegel PG, Hebarth H, Handgretinger R, et al. Serial and quantitative analysis of mixed hematopoietic chimerism by PCR in patients with acute leukemias allows the prediction of relapse after allogeneic BMT. Bone Marrow Transplant. 1998;21(5):487-95.
21. Schumm M, Feuchtinger T, Pfeiffer M, Hoelle W, Bethge W, Ebinger M, et al. Flow cytometry with anti HLA-antibodies: a simple but highly sensitive method for monitoring chimerism and minimal residual disease after HLA-mismatched stem cell transplantation. Bone Marrow Transplant. 2007;39(12):767-73.
22. Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579-86.
23. Sullivan KM. Graft-versus-host-disease. In: Blume KG, Forman SJ, Appelbaum FR, eds. Thomas' Hematopoietic Cell Transplantation. Blackwell Science Ltd., 2004:635-64.
24. Cheng SC, Fine JP, Wei LJ. Prediction of cumulative incidence function under the proportional hazards model. Biometrics. 1998;54(1):219-28.
25. Anderson JR, Cain KC, Gelber RD. Analysis of survival by tumor response. J Clin Oncol. 1983;1(11):710-9.
26. Gratwohl A, Stern M, Brand R, Apperley J, Baldomero H, de Witte T, et al. Risk score for outcome after allogeneic hematopoietic stem cell transplantation: a retrospective analysis. Cancer. 2009;115(20):4715-26.
27. Gratwohl A. The EBMT risk score. Bone Marrow Transplant. 2012;47(6):749-56.
28. Federmann B, Hagele M, Pfeiffer M, Wirths S, Schumm M, Faul C, et al. Immune reconstitution after haploidentical hematopoietic cell transplantation: impact of reduced intensity conditioning and CD3/CD19 depleted grafts. Leukemia. 2011;25(1):121-9.
29. Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295(5562):2097-100.
30. Ciurea SO, Saliba R, Rondon G, Pesoa S, Cano P, Fernandez-Vina M, et al. Reducedintensity conditioning using fludarabine, melphalan and thiotepa for adult patients undergoing haploidentical SCT. Bone Marrow Transplant. 2009;45(3):429-36.
31. Cesaro S, Gazzola MV, Marson P, Calore E, Caenazzo L, Destro R, et al. Successful engraftment and stable full donor chimerism after myeloablation with thiotepa, fludarabine, and melphalan and CD34-selected peripheral allogeneic stem cell transplantation in hemophagocytic lymphohistiocytosis. Am J Hematol. 2003; 72(2):143-6.
32. Majolino I, Davoli M, Carnevalli E, Locasciulli A, Di Bartolomeo P, Scime R, et al. Reduced intensity conditioning with thiotepa, fludarabine, and melphalan is effective in advanced multiple myeloma. Leuk Lymphoma. 2007;48(4):759-66.
33. Schwarer AP, Bollard G, Kapuscinski M, Muirhead J, Diviney M, Hart C, et al. Longterm follow-up of a pilot study using a chemotherapy-alone protocol for killer Iglike receptor-ligand-mismatched haploidentical haematopoietic SCT. Bone Marrow Transplant. 2011;46(10):1331-8.
34. Nguyen S, Dhedin N, Vernant JP, Kuentz M, Al Jijakli A, Rouas-Freiss N, et al. NKcell reconstitution after haploidentical hematopoietic stem-cell transplantations: immaturity of NK cells and inhibitory effect of NKG2A override GvL effect. Blood. 2005;105(10):4135-42.
35. Cook M, Briggs D, Craddock C, Mahendra P, Milligan D, Fegan C, et al. Donor KIR genotype has a major influence on the rate of cytomegalovirus reactivation following T-cell replete stem cell transplantation. Blood. 2005;107(3):1230-2.
36. Morrison BE, Park SJ, Mooney JM, Mehrad B. Chemokine-mediated recruitment of NK cells is a critical host defense mechanism in invasive aspergillosis. J Clin Invest. 2003;112(12):1862-70.
37. Ruggeri L, Mancusi A, Capanni M, Urbani E, Carotti A, Aloisi T, et al. Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value. Blood. 2007;110(1): 433-40.
38. Cooley S, McCullar V, Wangen R, Bergemann TL, Spellman S, Weisdorf DJ, et al. KIR reconstitution is altered by T cells in the graft and correlates with clinical outcomes after unrelated donor transplantation. Blood. 2005;106(13):4370-6.
39. Brunstein CG, Wagner JE, Weisdorf DJ, Cooley S, Noreen H, Barker JN, et al. Negative effect of KIR alloreactivity in recipients of umbilical cord blood transplant depends on transplantation conditioning intensity. Blood. 2009;113(22):5628-34.
40. Eyrich M, Lang P, Lal S, Bader P, Handgretinger R, Klingebiel T, et al. A prospective analysis of the pattern of immune reconstitution in a paediatric cohort following transplantation of positively selected human leucocyte antigendisparate haematopoietic stem cells from parental donors. Br J Haematol. 2001;114 (2):422-32.
41. Shaffer J, Villard J, Means TK, Alexander S, Dombkowski D, Dey BR, et al. Regulatory T-cell recovery in recipients of haploidentical nonmyeloablative hematopoietic cell transplantation with a humanized anti- CD2 mAb, MEDI-507, with or without fludarabine. Exp Hematol. 2007;35(7):1140-52.
42. Lang P, Schumm M, Greil J, Bader P, Klingebiel T, Muller I, et al. A comparison between three graft manipulation methods for haploidentical stem cell transplantation in pediatric patients: preliminary results of a pilot study. Klin Padiatr. 2005;217(6):334-8.
43. Ciceri F, Labopin M, Aversa F, Rowe JM, Bunjes D, Lewalle P, et al. A survey of fully haploidentical hematopoietic stem cell transplantation in adults with high-risk acute leukemia: a risk factor analysis of outcomes for patients in remission at transplantation. Blood. 2008;112(9):3574-81.
44. Huang XJ, Liu DH, Liu KY, Xu LP, Chen H, Han W, et al. Treatment of acute leukemia with unmanipulated HLAmismatched/ haploidentical blood and bone marrow transplantation. Biol Blood Marrow Transplant. 2009;15(2):257-65.
45. Luznik L, O'Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14 (6):641-50.
46. Ciceri F, Bonini C, Stanghellini MT, Bondanza A, Traversari C, Salomoni M, et al. Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial): a nonrandomised phase I-II study. Lancet Oncol. 2009;10(5):489-500.
47. Perruccio K, Topini F, Tosti A, Carotti A, Aloisi T, Aversa F, et al. Photodynamic purging of alloreactive T cells for adoptive immunotherapy after haploidentical stem cell transplantation. Blood Cells Mol Dis. 2008;40(1):76-83.
48. Di Ianni M, Falzetti F, Carotti A, Terenzi A, Castellino F, Bonifacio E, et al. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood. 2011;117(14):3921-8.
49. Chaleff S, Otto M, Barfield RC, Leimig T, Iyengar R, Martin J, et al. A large-scale method for the selective depletion of alphabeta T lymphocytes from PBSC for allogeneic transplantation. Cytotherapy. 2007; 9(8):746-54.