Immune therapies for neuroblastoma

Cancer Biology and Therapy

Volumn 8, Issue 10, 2009, Pages 874-882

  Navid, Fariba ^a,b   Armstrong, Michael ^c   Barfield, Raymond C ^c  

^a ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

^b UNIVERSITY OF TENNESSEE COLLEGE OF MEDICINE   (United States)

^c DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Allogeneic hematopoietic stem cell transplant; Anti GD2 antibodies; Antibody therapy; Cellular therapy; Cytokine therapy; IL 12; Immune therapy; Neuroblastoma; Vaccine therapy

Indexed keywords

DENDRITIC CELL VACCINE; DNA VACCINE; DOPAMINE; ETOPOSIDE; GANGLIOSIDE ANTIBODY; GANGLIOSIDE GD2 ANTIBODY 14G2A; GANGLIOSIDE GD2 ANTIBODY 3F8; GANGLIOSIDE GD2 ANTIBODY CH14.18; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INTERLEUKIN 12; INTERLEUKIN 18; INTERLEUKIN 2; RECOMBINANT INTERLEUKIN 12; RETINOIC ACID; TUMOR VACCINE; UNCLASSIFIED DRUG;

ACTIVE IMMUNIZATION; ADIE SYNDROME; ADOPTIVE IMMUNOTHERAPY; ALLERGIC REACTION; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; ANGIONEUROTIC EDEMA; ANTIGEN RECOGNITION; ANTINEOPLASTIC ACTIVITY; B CELL LYMPHOMA; BRONCHOSPASM; CANCER IMMUNIZATION; CANCER RESEARCH; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL THERAPY; CELLULAR IMMUNITY; CHILD; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; CYTOKINE PRODUCTION; CYTOTOXICITY; DENDRITIC CELL; DIARRHEA; DRUG HYPERSENSITIVITY; DRUG TOLERABILITY; DYSPNEA; FATIGUE; FEVER; GRAFT VERSUS HOST REACTION; GRAFT VERSUS LEUKEMIA EFFECT; HEADACHE; HUMAN; HUMORAL IMMUNITY; HYPERBILIRUBINEMIA; HYPERTENSION; HYPONATREMIA; HYPOTENSION; HYPOXIA; IMMUNE RESPONSE; IMMUNOLOGICAL TOLERANCE; IMMUNOREGULATION; IMMUNOSCINTIGRAPHY; IMMUNOTHERAPY; INTRACRANIAL PRESSURE; KIDNEY CARCINOMA; LEUKAPHERESIS; LEUKOCYTE COUNT; LIVER DISEASE; LIVER TRANSAMINITIS; LOW DRUG DOSE; MAXIMUM TOLERATED DOSE; MELANOMA; MENINGITIS; MONOTHERAPY; MULTIMODALITY CANCER THERAPY; NEUROBLASTOMA; NEUTROPENIA; NONHUMAN; OSTEOSARCOMA; PAIN; PARESTHESIA; PASSIVE IMMUNIZATION; PERICARDIAL EFFUSION; PRURITUS; RASH; REVIEW; SIDE EFFECT; SOLID TUMOR; TACHYCARDIA; THROMBOCYTOPENIA; URTICARIA; VOMITING; WEAKNESS;

ANTIBODIES, MONOCLONAL; CANCER VACCINES; CHILD; CHILD, PRESCHOOL; CLINICAL TRIALS AS TOPIC; GANGLIOSIDES; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; IMMUNITY, CELLULAR; IMMUNOTHERAPY; INFANT; INTERLEUKIN-12; NEUROBLASTOMA; TRANSPLANTATION, HOMOLOGOUS; TREATMENT OUTCOME;

EID: 68049143298     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.4161/cbt.8.10.8358     Document Type: Review

References (85)

1. Brodeur GM, Maris JM. Neuoblastoma. In: Pizzo PA, Poplack DG, eds. Principles and Practice of Pediatric Oncology: Lippincott Williams & Wilkins 2006; 934.
2. Matthay KK, Villablanca JG, Seeger RC, Stram DO, Harris RE, Ramsay NK, et al. Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. N Engl J Med 1999; 341:1165-73.
3. Trinchieri G. Proinflammatory and immunoregulatory functions of interleukin-12. Int Rev Immunol 1998; 16:365-96.
4. Siapati KE, Barker S, Kinnon C, Michalski A, Anderson R, Brickell P, et al. Improved antitumour immunity in murine neuroblastoma using a combination of IL-2 and IL-12. Br J Cancer 2003; 88:1641-8.
5. Redlinger RE Jr, Shimizu T, Remy T, Alber S, Watkins SC, Barksdale EM Jr. Cellular mechanisms of interleukin-12-mediated neuroblastoma regression. J Pediatr Surg 2003; 38:199-204.
6. Szabo SJ, Sullivan BM, Peng SL, Glimcher LH. Molecular mechanisms regulating Th1 immune responses. Annu Rev Immunol 2003; 21:713-58.
7. York IA, Rock KL. Antigen processing and presentation by the class I major histocompatibility complex. Annu Rev Immunol 1996; 14:369-96.
8. Khan T, Hixon JA, Stauffer JK, Lincoln E, Back TC, Brenner J, et al. Therapeutic modulation of Akt activity and antitumor efficacy of interleukin-12 against orthotopic murine neuroblastoma. J Natl Cancer Inst 2006; 98:190-202.
9. Iinuma H, Okinaga K, Fukushima R, Inaba T, Iwasaki K, Okinaga A, et al. Superior protective and therapeutic effects of IL-12 and IL-18 gene-transduced dendritic neuroblastoma fusion cells on liver metastasis of murine neuroblastoma. J Immunol 2006; 176:3461-9.
10. Atkins MB, Robertson MJ, Gordon M, Lotze MT, DeCoste M, DuBois JS, et al. Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies. Clin Cancer Res 1997; 3:409-17.
11. Bajetta E, Del Vecchio M, Mortarini R, Nadeau R, Rakhit A, Rimassa L, et al. Pilot study of subcutaneous recombinant human interleukin 12 in metastatic melanoma. Clin Cancer Res 1998; 4:75-85.
12. Gollob JA, Mier JW, Veenstra K, McDermott DF, Clancy D, Clancy M, et al. Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: ability to maintain IFNgamma induction is associated with clinical response. Clin Cancer Res 2000; 6:1678-92.
13. Motzer RJ, Rakhit A, Schwartz LH, Olencki T, Malone TM, Sandstrom K, et al. Phase I trial of subcutaneous recombinant human interleukin-12 in patients with advanced renal cell carcinoma. Clin Cancer Res 1998; 4:1183-91.
14. Motzer RJ, Rakhit A, Thompson JA, Nemunaitis J, Murphy BA, Ellerhorst J, et al. Randomized multicenter phase II trial of subcutaneous recombinant human interleukin-12 versus interferon-alpha 2a for patients with advanced renal cell carcinoma. J Interferon Cytokine Res 2001; 21:257-63.
15. Hsu FJ, Benike C, Fagnoni F, Liles TM, Czerwinski D, Taidi B, et al. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med 1996; 2:52-8.
16. Bugis SP, Lotzova E, Savage HE, Hester JP, Racz T, Sacks PG, et al. Inhibition of lymphokine-activated killer cell generation by blocking factors in sera of patients with head and neck cancer. Cancer Immunol Immunother 1990; 31:176-81.
17. Lahn M, Kunzmann R, Kohler G, Ikle DN, Hentrich I, Jesuiter H, et al. Comparison of cytogenetics, cytokine secretion and oncogene expression in primary cultures of renal carcinoma cells. Oncology 1997; 54:429-37.
18. Shurin GV, Shurin MR, Bykovskaia S, Shogan J, Lotze MT, Barksdale EM Jr. Neuroblastoma-derived gangliosides inhibit dendritic cell generation and function. Cancer Res 2001; 61:363-9.
19. Sietsma H, Nijhof W, Dontje B, Vellenga E, Kamps WA, Kok JW. Inhibition of hemopoiesis in vitro by neuroblastoma-derived gangliosides. Cancer Res 1998; 58:4840-4.
20. Redlinger RE Jr, Mailliard RB, Barksdale EM Jr. Neuroblastoma and dendritic cell function. Semin Pediatr Surg 2004; 13:61-71.
21. + T cells. J Immunol 1995; 154:5071-9.
22. Nastala CL, Edington HD, McKinney TG, Tahara H, Nalesnik MA, Brunda MJ, et al. Recombinant IL-12 administration induces tumor regression in association with IFNgamma production. J Immunol 1994; 153:1697-706.
23. Huebener N, Fest S, Strandsby A, Michalsky E, Preissner R, Zeng Y, et al. A rationally designed tyrosine hydroxylase DNA vaccine induces specific antineuroblastoma immunity. Mol Cancer Ther 2008; 7:2241-51.
24. Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol 2004; 5:987-95.
25. Fest S, Huebener N, Weixler S, Bleeke M, Zeng Y, Strandsby A, et al. Characterization of GD2 peptide mimotope DNA vaccines effective against spontaneous neuroblastoma metastases. Cancer Res 2006; 66:10567-75.
26. Mond JJ, Vos Q, Lees A, Snapper CM. T cell independent antigens. Curr Opin Immunol 1995; 7:349-54.
27. Croce M, Meazza R, Orengo AM, Fabbi M, Borghi M, Ribatti D, et al. Immunotherapy of neuroblastoma by an Interleukin-21-secreting cell vaccine involves survivin as antigen. Cancer Immunol Immunother 2008; 57:1625-34.
28. Kasaian MT, Whitters MJ, Carter LL, Lowe LD, Jussif JM, Deng B, et al. IL-21 limits NK cell responses and promotes antigen-specific T cell activation: a mediator of the transition from innate to adaptive immunity. Immunity 2002; 16:559-69.
29. + T cells. J Immunol 2002; 169:5838-43.
30. Di Carlo E, Comes A, Orengo AM, Rosso O, Meazza R, Musiani P, et al. IL-21 induces tumor rejection by specific CTL and IFNgamma-dependent CXC chemokines in syngeneic mice. J Immunol 2004; 172:1540-7.
31. Geiger JD, Hutchinson RJ, Hohenkirk LF, McKenna EA, Yanik GA, Levine JE, et al. Vaccination of pediatric solid tumor patients with tumor lysate-pulsed dendritic cells can expand specific T cells and mediate tumor regression. Cancer Res 2001; 61:8513-9.
32. Caruso DA, Orme LM, Amor GM, Neale AM, Radcliff FJ, Downie P, et al. Results of a Phase I study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children with Stage 4 neuroblastoma. Cancer 2005; 103:1280-91.
33. Bowman L, Grossmann M, Rill D, Brown M, Zhong WY, Alexander B, et al. IL-2 adenovector-transduced autologous tumor cells induce antitumor immune responses in patients with neuroblastoma. Blood 1998; 92:1941-9.
34. Weiner GJ. Monoclonal antibody mechanisms of action in cancer. Immunol Res 2007; 39:271-8.
35. Zafir-Lavie I, Michaeli Y, Reiter Y. Novel antibodies as anticancer agents. Oncogene 2007; 26:3714-33.
36. Wu ZL, Schwartz E, Seeger R, Ladisch S. Expression of GD2 ganglioside by untreated primary human neuroblastomas. Cancer Res 1986; 46:440-3.
37. Cheresh DA, Pierschbacher MD, Herzig MA, Mujoo K. Disialogangliosides GD2 and GD3 are involved in the attachment of human melanoma and neuroblastoma cells to extracellular matrix proteins. J Cell Biol 1986; 102:688-96.
38. Mujoo K, Cheresh DA, Yang HM, Reisfeld RA. Disialoganglioside GD2 on human neuroblastoma cells: target antigen for monoclonal antibody-mediated cytolysis and suppression of tumor growth. Cancer Res 1987; 47:1098-104.
39. Schulz G, Cheresh DA, Varki NM, Yu A, Staffileno LK, Reisfeld RA. Detection of ganglioside GD2 in tumor tissues and sera of neuroblastoma patients. Cancer Res 1984; 44:5914-20.
40. Svennerholm L, Bostrom K, Fredman P, Jungbjer B, Lekman A, Mansson JE, et al. Gangliosides and allied glycosphingolipids in human peripheral nerve and spinal cord. Biochim Biophys Acta 1994; 1214:115-23.
41. Cheung NK, Saarinen UM, Neely JE, Landmeier B, Donovan D, Coccia PF. Monoclonal antibodies to a glycolipid antigen on human neuroblastoma cells. Cancer Res 1985; 45:2642-9.
42. Munn DH, Cheung NK. Interleukin-2 enhancement of monoclonal antibody-mediated cellular cytotoxicity against human melanoma. Cancer Res 1987; 47:6600-5.
43. Kushner BH, Cheung NK. GM-CSF enhances 3F8 monoclonal antibody-dependent cellular cytotoxicity against human melanoma and neuroblastoma. Blood 1989; 73:1936-41.
44. Munn DH, Garnick MB, Cheung NK. Effects of parenteral recombinant human macrophage colony-stimulating factor on monocyte number, phenotype and antitumor cytotoxicity in nonhuman primates. Blood 1990; 75:2042-8.
45. Cheung NK, Lazarus H, Miraldi FD, Abramowsky CR, Kallick S, Saarinen UM, et al. Ganglioside GD2 specific monoclonal antibody 3F8: a phase I study in patients with neuroblastoma and malignant melanoma. J Clin Oncol 1987; 5:1430-40.
46. Cheung NK, Kushner BH, Yeh SD, Larson SM. 3F8 monoclonal antibody treatment of patients with stage 4 neuroblastoma: a phase II study. Int J Oncol 1998; 12:1299-306.
47. Cheung NK, Kushner BH, Cheung IY, Kramer K, Canete A, Gerald W, et al. Anti-G(D2) antibody treatment of minimal residual stage 4 neuroblastoma diagnosed at more than 1 year of age. J Clin Oncol 1998; 16:3053-60.
48. Brodeur GM, Pritchard J, Berthold F, Carlsen NL, Castel V, Castelberry RP, et al. Revisions of the international criteria for neuroblastoma diagnosis, staging and response to treatment. J Clin Oncol 1993; 11:1466-77.
49. Kushner BH, Kramer K, Cheung NK. Phase II trial of the anti-G(D2) monoclonal antibody 3F8 and granulocyte-macrophage colony-stimulating factor for neuroblastoma. J Clin Oncol 2001; 19:4189-94.
50. Cheung NK, Sowers R, Vickers AJ, Cheung IY, Kushner BH, Gorlick R. FCGR2A polymorphism is correlated with clinical outcome after immunotherapy of neuroblastoma with anti-GD2 antibody and granulocyte macrophage colony-stimulating factor. J Clin Oncol 2006; 24:2885-90.
51. Kramer K, Humm JL, Souweidane MM, Zanzonico PB, Dunkel IJ, Gerald WL, et al. Phase I study of targeted radioimmunotherapy for leptomeningeal cancers using intra-Ommaya 131-I-3F8. J Clin Oncol 2007; 25:5465-70.
52. Saleh MN, Khazaeli MB, Wheeler RH, Dropcho E, Liu T, Urist M, et al. Phase I trial of the murine monoclonal anti-GD2 antibody 14G2a in metastatic melanoma. Cancer Res 1992; 52:4342-7.
53. Murray JL, Cunningham JE, Brewer H, Mujoo K, Zukiwski AA, Podoloff DA, et al. Phase I trial of murine monoclonal antibody 14G2a administered by prolonged intravenous infusion in patients with neuroectodermal tumors. J Clin Oncol 1994; 12:184-93.
54. Shiloni E, Eisenthal A, Sachs D, Rosenberg SA. Antibody-dependent cellular cytotoxicity mediated by murine lymphocytes activated in recombinant interleukin 2. J Immunol 1987; 138:1992-8.
55. Frost JD, Hank JA, Reaman GH, Frierdich S, Seeger RC, Gan J, et al. A phase I/IB trial of murine monoclonal anti-GD2 antibody 14.G2a plus interleukin-2 in children with refractory neuroblastoma: a report of the Children's Cancer Group. Cancer 1997; 80:317-33.
56. Gillies SD, Lo KM, Wesolowski J. High-level expression of chimeric antibodies using adapted cDNA variable region cassettes. J Immunol Methods 1989; 125:191-202.
57. Mueller BM, Romerdahl CA, Gillies SD, Reisfeld RA. Enhancement of antibody-dependent cytotoxicity with a chimeric anti-GD2 antibody. J Immunol 1990; 144:1382-6.
58. Saleh MN, Khazaeli MB, Wheeler RH, Allen L, Tilden AB, Grizzle W, et al. Phase I trial of the chimeric anti-GD2 monoclonal antibody ch14.18 in patients with malignant melanoma. Hum Antibodies Hybridomas 1992; 3:19-24.
59. Handgretinger R, Anderson K, Lang P, Dopfer R, Klingebiel T, Schrappe M, et al. A phase I study of human/mouse chimeric antiganglioside GD2 antibody ch14.18 in patients with neuroblastoma. Eur J Cancer 1995; 31:261-7.
60. Yu AL, Uttenreuther-Fischer MM, Huang CS, Tsui CC, Gillies SD, Reisfeld RA, et al. Phase I trial of a human-mouse chimeric anti-disialoganglioside monoclonal antibody ch14.18 in patients with refractory neuroblastoma and osteosarcoma. J Clin Oncol 1998; 16:2169-80.
61. Simon T, Hero B, Faldum A, Handgretinger R, Schrappe M, Niethammer D, et al. Consolidation treatment with chimeric anti-GD2-antibody ch14.18 in children older than 1 year with metastatic neuroblastoma. J Clin Oncol 2004; 22:3549-57.
62. Albertini MR, Hank JA, Schiller JH, Khorsand M, Borchert AA, Gan J, et al. Phase IB trial of chimeric antidisialoganglioside antibody plus interleukin 2 for melanoma patients. Clin Cancer Res 1997; 3:1277-88.
63. Ozkaynak MF, Sondel PM, Krailo MD, Gan J, Javorsky B, Reisfeld RA, et al. Phase I study of chimeric human/murine anti-ganglioside G(D2) monoclonal antibody (ch14.18) with granulocyte-macrophage colony-stimulating factor in children with neuroblastoma immediately after hematopoietic stem-cell transplantation: a Children's Cancer Group Study. J Clin Oncol 2000; 18:4077-85.
64. Gillies SD, Reilly EB, Lo KM, Reisfeld RA. Antibody-targeted interleukin 2 stimulates T-cell killing of autologous tumor cells. Proc Natl Acad Sci USA 1992; 89:1428-32.
65. Hank JA, Surfus JE, Gan J, Jaeger P, Gillies SD, Reisfeld RA, et al. Activation of human effector cells by a tumor reactive recombinant anti-ganglioside GD2 interleukin-2 fusion protein (ch14.18-IL2). Clin Cancer Res 1996; 2:1951-9.
66. Lode HN, Xiang R, Dreier T, Varki NM, Gillies SD, Reisfeld RA. Natural killer cell-mediated eradication of neuroblastoma metastases to bone marrow by targeted interleukin-2 therapy. Blood 1998; 91:1706-15.
67. King DM, Albertini MR, Schalch H, Hank JA, Gan J, Surfus J, et al. Phase I clinical trial of the immunocytokine EMD 273063 in melanoma patients. J Clin Oncol 2004; 22:4463-73.
68. Osenga KL, Hank JA, Albertini MR, Gan J, Sternberg AG, Eickhoff J, et al. A phase I clinical trial of the hu14.18-IL2 (EMD 273063) as a treatment for children with refractory or recurrent neuroblastoma and melanoma: a study of the Children's Oncology Group. Clin Cancer Res 2006; 12:1750-9.
69. Shusterman S, London WB, Gillies SD, Hank JA, Voss S, Seeger RC, et al. Anti-neuroblastoma activity of hu14.18-IL2 against minimal residual disease in a Children's Oncology Group (COG) phase II study. Proc Am Soc Clin Oncol 2008; 26:132.
70. Brignole C, Pastorino F, Marimpietri D, Pagnan G, Pistorio A, Allen TM, et al. Immune cell-mediated antitumor activities of GD2-targeted liposomal c-myb antisense oligonucleotides containing CpG motifs. J Natl Cancer Inst 2004; 96:1171-80.
71. Zeng Y, Huebener N, Fest S, Weixler S, Schroeder U, Gaedicke G, et al. Fractalkine (CX3CL1)- and interleukin-2-enriched neuroblastoma microenvironment induces eradication of metastases mediated by T cells and natural killer cells. Cancer Res 2007; 67:2331-8.
72. Otto M, Barfield RC, Martin WJ, Iyengar R, Leung W, Leimig T, et al. Combination immunotherapy with clinical-scale enriched human gammadelta T cells, hu14.18 antibody, and the immunocytokine Fc-IL7 in disseminated neuroblastoma. Clin Cancer Res 2005; 11:8486-91.
73. Begent RH, Verhaar MJ, Chester KA, Casey JL, Green AJ, Napier MP, et al. Clinical evidence of efficient tumor targeting based on single-chain Fv antibody selected from a combinatorial library. Nat Med 1996; 2:979-84.
74. Cheung NK, Modak S, Lin Y, Guo H, Zanzonico P, Chung J, et al. Single-chain Fv-streptavidin substantially improved therapeutic index in multistep targeting directed at disialoganglioside GD2. J Nucl Med 2004; 45:867-77.
75. Occhino M, Raffaghello L, Burrone O, Gambini C, Pistoia V, Corrias MV, et al. Generation and characterization of dimeric small immunoproteins specific for neuroblastoma associated antigen GD2. Int J Mol Med 2004; 14:383-8.
76. Thommesen JE, Michaelsen TE, Loset GA, Sandlie I, Brekke OH. Lysine 322 in the human IgG3 C(H)2 domain is crucial for antibody dependent complement activation. Mol Immunol 2000; 37:995-1004.
77. Imai M, Landen C, Ohta R, Cheung NK, Tomlinson S. Complement-mediated mechanisms in anti-GD2 monoclonal antibody therapy of murine metastatic cancer. Cancer Res 2005; 65:10562-8.
78. Shinkawa T, Nakamura K, Yamane N, Shoji-Hosaka E, Kanda Y, Sakurada M, et al. The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity. J Biol Chem 2003; 278:3466-73.
79. Kilmartin JV, Wright B, Milstein C. Rat monoclonal antitubulin antibodies derived by using a new nonsecreting rat cell line. J Cell Biol 1982; 93:576-82.
80. Ladenstein R, Lasset C, Hartmann O, Klingebiel T, Bouffet E, Gadner H, et al. Comparison of auto versus allografting as consolidation of primary treatments in advanced neuroblastoma over one year of age at diagnosis: report from the European Group for Bone Marrow Transplantation. Bone Marrow Transpl 1994; 14:37-46.
81. Matthay KK, Seeger RC, Reynolds CP, Stram DO, O'Leary MC, Harris RE, et al. Allogeneic versus autologous purged bone marrow transplantation for neuroblastoma: a report from the Childrens Cancer Group. J Clin Oncol 1994; 12:2382-9.
82. Kanold J, Paillard C, Tchirkov A, Merlin E, Marabelle A, Lutz P, et al. Allogeneic or haploidentical HSCT for refractory or relapsed solid tumors in children: toward a neuroblastoma model. Bone Marrow Transpl 2008; 42:25-30.
83. Inoue M, Nakano T, Yoneda A, Nishikawa M, Nakayama M, Yumura-Yagi K, et al. Graft-versus-tumor effect in a patient with advanced neuroblastoma who received HLA haplo-identical bone marrow transplantation. Bone Marrow Transpl 2003; 32:103-6.
84. Lang P, Pfeiffer M, Muller I, Schumm M, Ebinger M, Koscielniak E, et al. Haploidentical stem cell transplantation in patients with pediatric solid tumors: preliminary results of a pilot study and analysis of graft versus tumor effects. Klin Padiatr 2006; 218:321-6.
85. Yoshida H, Kusuki S, Hashii Y, Ohta H, Morio T, Ozono K. Ex vivo-expanded donor CD4(+) lymphocyte infusion against relapsing neuroblastoma: a transient graft-versus-tumor effect. Pediatr Blood Cancer 2009.