|
|
 Previous Article | Table of Contents | Next Article 
Allogeneic cell therapy with donor peripheral blood cells and recombinant
human interleukin-2 to treat leukemia relapse after allogeneic bone marrow
transplantation
S Slavin, E Naparstek, A Nagler, A Ackerstein, S Samuel, J Kapelushnik, C Brautbar and R Or
Department of Bone Marrow Transplantation, Hadassah University Hospital,
Jerusalem, Israel.
Allogeneic bone marrow transplantation (BMT) is the only effective
treatment for hematologic malignancies resistant to conventional
chemotherapy. Until recently, no cure existed for patients who relapsed
post-BMT. We present our long-term observations on remission induction,
after relapse post-BMT, by allogeneic cell therapy (allo-CT) and the
feasibility of remission induction in allo-CT-resistant patients by
activation of antileukemia effector cells with recombinant human
interleukin-2 (rhIL-2) in vitro and in vivo. The longest observation of
successful allo-CT (event-free survival, greater than 8 years) was made in
a patient with resistant pre-B lymphoblastic leukemia who received
infusions with graded increments of donor (female) peripheral blood
lymphocytes (PBL) as soon as bulky hematologic and extramedullary relapse
was noticed early post-BMT. The patient is currently without evidence of
residual host (male) cells as determined by polymerase chain reaction
(PCR). Of 17 patients with acute and chronic leukemia in relapse after BMT,
10 were reinduced into complete remission. Four patients with cytogenetic
relapse responded to allo-CT alone, while five of six patients with overt
hematologic relapse responded only after additional activation of donor
with rhIL-2. Allo-CT can, therefore, successfully reverse
chemoradiotherapy-resistant relapse of both acute and chronic leukemia.
Moreover, in patients resistant to donor lymphocyte infusion, remission can
be accomplished by additionally activating donor PBL in vitro and/or in
vivo with rhIL-2. Based on our observations, after BMT, allo-CT should be
considered the treatment of choice for patients with hematologic
malignancies resistant to conventional anticancer modalities. Allogeneic
activated cell therapy (allo ACT) should be considered for patients with
tumor cells resistant to allo-CT. Although allo-CT, followed if indicated
by allo-ACT, can be effective for patients with overt hematologic relapse,
reversal of persistent minimal residual disease or documented
molecular/cytogenetic relapse early after BMT may also be considered as a
possible indication for allo-CT.
Volume 87,
Issue 6,
pp. 2195-2204,
03/15/1996
Copyright © 1996 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
H.-J. Kolb
Graft-versus-leukemia effects of transplantation and donor lymphocytes
Blood,
December 1, 2008;
112(12):
4371 - 4383.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Mohty, M. Labopin, R. Tabrizzi, N. Theorin, A. A Fauser, A. Rambaldi, J. Maertens, S. Slavin, I. Majolino, A. Nagler, et al.
Reduced intensity conditioning allogeneic stem cell transplantation for adult patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation
Haematologica,
February 1, 2008;
93(2):
303 - 306.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Schmid, M. Labopin, A. Nagler, M. Bornhauser, J. Finke, A. Fassas, L. Volin, G. Gurman, J. Maertens, P. Bordigoni, 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.,
November 1, 2007;
25(31):
4938 - 4945.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Rezvani, A. S. M. Yong, B. N. Savani, S. Mielke, K. Keyvanfar, E. Gostick, D. A. Price, D. C. Douek, and A. J. Barrett
Graft-versus-leukemia effects associated with detectable Wilms tumor-1 specific T lymphocytes after allogeneic stem-cell transplantation for acute lymphoblastic leukemia
Blood,
September 15, 2007;
110(6):
1924 - 1932.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Introna, G. Borleri, E. Conti, M. Franceschetti, A. M. Barbui, R. Broady, E. Dander, G. Gaipa, G. D'Amico, E. Biagi, et al.
Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: a phase I study
Haematologica,
July 1, 2007;
92(7):
952 - 959.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Morecki, H. Lindhofer, E. Yacovlev, Y. Gelfand, and S. Slavin
Use of trifunctional bispecific antibodies to prevent graft versus host disease induced by allogeneic lymphocytes
Blood,
February 15, 2006;
107(4):
1564 - 1569.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. L. Porter, B. L. Levine, N. Bunin, E. A. Stadtmauer, S. M. Luger, S. Goldstein, A. Loren, J. Phillips, S. Nasta, A. Perl, et al.
A phase 1 trial of donor lymphocyte infusions expanded and activated ex vivo via CD3/CD28 costimulation
Blood,
February 15, 2006;
107(4):
1325 - 1331.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Yung, L. Weiss, A. Abdul-Hai, J. Kasir, S. Reich, and S. Slavin
Induction of Early Post-Transplant Graft-versus-Leukemia Effects Using Intentionally Mismatched Donor Lymphocytes and Elimination of Alloantigen-Primed Donor Lymphocytes for Prevention of Graft-versus-Host Disease
Cancer Res.,
November 1, 2005;
65(21):
9735 - 9740.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Imai, S. Iwamoto, and D. Campana
Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells
Blood,
July 1, 2005;
106(1):
376 - 383.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Bader, H. Kreyenberg, W. Hoelle, G. Dueckers, R. Handgretinger, P. Lang, B. Kremens, D. Dilloo, K.-W. Sykora, M. Schrappe, et al.
Increasing Mixed Chimerism Is an Important Prognostic Factor for Unfavorable Outcome in Children With Acute Lymphoblastic Leukemia After Allogeneic Stem-Cell Transplantation: Possible Role For Pre-Emptive Immunotherapy?
J. Clin. Oncol.,
May 1, 2004;
22(9):
1696 - 1705.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-J. Kolb, C. Schmid, A. J. Barrett, and D. J. Schendel
Graft-versus-leukemia reactions in allogeneic chimeras
Blood,
February 1, 2004;
103(3):
767 - 776.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Benesch and H. J. Deeg
Hematopoietic Cell Transplantation for Adult Patients With Myelodysplastic Syndromes and Myeloproliferative Disorders
Mayo Clin. Proc.,
August 1, 2003;
78(8):
981 - 990.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. D. Billiau, S. Fevery, O. Rutgeerts, W. Landuyt, and M. Waer
Transient expansion of Mac1+Ly6-G+Ly6-C+ early myeloid cells with suppressor activity in spleens of murine radiation marrow chimeras: possible implications for the graft-versus-host and graft-versus-leukemia reactivity of donor lymphocyte infusions
Blood,
July 15, 2003;
102(2):
740 - 748.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Marktel, Z. Magnani, F. Ciceri, S. Cazzaniga, S. R. Riddell, C. Traversari, C. Bordignon, and C. Bonini
Immunologic potential of donor lymphocytes expressing a suicide gene for early immune reconstitution after hematopoietic T-cell-depleted stem cell transplantation
Blood,
February 15, 2003;
101(4):
1290 - 1298.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Or, M. Y. Shapira, I. Resnick, A. Amar, A. Ackerstein, S. Samuel, M. Aker, E. Naparstek, A. Nagler, and S. Slavin
Nonmyeloablative allogeneic stem cell transplantation for the treatment of chronic myeloid leukemia in first chronic phase
Blood,
January 15, 2003;
101(2):
441 - 445.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Litvinova, S. Maury, O. Boyer, S. Bruel, L. Benard, G. Boisserie, D. Klatzmann, and J. L. Cohen
Graft-versus-leukemia effect after suicide-gene-mediated control of graft-versus-host disease
Blood,
August 28, 2002;
100(6):
2020 - 2025.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. D. Billiau, S. Fevery, O. Rutgeerts, W. Landuyt, and M. Waer
Crucial role of timing of donor lymphocyte infusion in generating dissociated graft-versus-host and graft-versus-leukemia responses in mice receiving allogeneic bone marrow transplants
Blood,
August 13, 2002;
100(5):
1894 - 1902.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. A. Tabbara, K. Zimmerman, C. Morgan, and Z. Nahleh
Allogeneic Hematopoietic Stem Cell Transplantation: Complications and Results
Arch Intern Med,
July 22, 2002;
162(14):
1558 - 1566.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Guimond, A. Balassy, M. Barrette, S. Brochu, C. Perreault, and D. C. Roy
P-glycoprotein targeting: a unique strategy to selectively eliminate immunoreactive T cells
Blood,
June 28, 2002;
100(2):
375 - 382.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Alizadeh, M. Bernard, B. Danic, C. Dauriac, B. Birebent, C. Lapart, T. Lamy, P.-Y. Le Prise, A. Beauplet, D. Bories, et al.
Quantitative assessment of hematopoietic chimerism after bone marrow transplantation by real-time quantitative polymerase chain reaction
Blood,
May 29, 2002;
99(12):
4618 - 4625.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Levine, T. Braun, S. L. Penza, P. Beatty, K. Cornetta, R. Martino, W. R. Drobyski, A. J. Barrett, D. L. Porter, S. Giralt, et al.
Prospective Trial of Chemotherapy and Donor Leukocyte Infusions for Relapse of Advanced Myeloid Malignancies After Allogeneic Stem-Cell Transplantation
J. Clin. Oncol.,
January 15, 2002;
20(2):
405 - 412.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Hoelzer, N. Gokbuget, O. Ottmann, C.-H. Pui, M. V. Relling, F. R. Appelbaum, J. J.M. van Dongen, and T. Szczepanski
Acute Lymphoblastic Leukemia
Hematology,
January 1, 2002;
2002(1):
162 - 192.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Bornhauser, C. Thiede, U. Platzbecker, A. Jenke, A. Helwig, R. Plettig, J. Freiberg-Richter, C. Rollig, G. Geissler, K. Lutterbeck, et al.
Dose-reduced Conditioning and Allogeneic Hematopoietic Stem Cell Transplantation from Unrelated Donors in 42 Patients
Clin. Cancer Res.,
August 1, 2001;
7(8):
2254 - 2262.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. D. Kottaridis, D. W. Milligan, R. Chopra, R. K. Chakraverty, S. Chakrabarti, S. Robinson, K. Peggs, S. Verfuerth, R. Pettengell, J. C. W. Marsh, et al.
In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation
Blood,
October 1, 2000;
96(7):
2419 - 2425.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Slavin
Cancer Immunotherapy with Alloreactive Lymphocytes
N. Engl. J. Med.,
September 14, 2000;
343(11):
802 - 803.
[Full Text]
|
|
|
|
|
|
|
H. M. Lokhorst, A. Schattenberg, J. J. Cornelissen, M. H. J. van Oers, W. Fibbe, I. Russell, N. W. C. J. v. d. Donk, and L. F. Verdonck
Donor Lymphocyte Infusions for Relapsed Multiple Myeloma After Allogeneic Stem-Cell Transplantation: Predictive Factors for Response and Long-Term Outcome
J. Clin. Oncol.,
August 16, 2000;
18(16):
3031 - 3037.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. Bishop, S. R. Tarantolo, Z. S. Pavletic, J. C. Lynch, M. E. Morris, D. Zacharias, J. O. Armitage, and A. Kessinger
Filgrastim as an Alternative to Donor Leukocyte Infusion for Relapse After Allogeneic Stem-Cell Transplantation
J. Clin. Oncol.,
June 11, 2000;
18(11):
2269 - 2272.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. L. Porter, R. H. Collins Jr, C. Hardy, N. A. Kernan, W. R. Drobyski, S. Giralt, M. E.D. Flowers, J. Casper, A. Leahey, P. Parker, et al.
Treatment of relapsed leukemia after unrelated donor marrow transplantation with unrelated donor leukocyte infusions
Blood,
February 15, 2000;
95(4):
1214 - 1221.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. C. Gorin, E. Estey, R. J. Jones, H. I. Levitsky, I. Borrello, and S. Slavin
New Developments in the Therapy of Acute Myelocytic Leukemia
Hematology,
January 1, 2000;
2000(1):
69 - 89.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Brenner, C. Rossig, U. Sili, J. W. Young, and E. Goulmy
Transfusion Medicine: New Clinical Applications of Cellular Immunotherapy
Hematology,
January 1, 2000;
2000(1):
356 - 375.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. D. Johnson, E. E. Becker, J. L. LaBelle, and R. L. Truitt
Role of Immunoregulatory Donor T Cells in Suppression of Graft-Versus-Host Disease Following Donor Leukocyte Infusion Therapy
J. Immunol.,
December 15, 1999;
163(12):
6479 - 6487.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Gao, T.-H. Yang, S. Tourdot, E. Sadovnikova, R. Hasserjian, and H. J. Stauss
Allo-Major Histocompatibility Complex-Restricted Cytotoxic T Lymphocytes Engraft in Bone Marrow Transplant Recipients Without Causing Graft-Versus-Host Disease
Blood,
November 1, 1999;
94(9):
2999 - 3006.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Bonnet, E. H. Warren, P. D. Greenberg, J. E. Dick, and S. R. Riddell
CD8+ minor histocompatibility antigen-specific cytotoxic T lymphocyte clones eliminate human acute myeloid leukemia stem cells
PNAS,
July 20, 1999;
96(15):
8639 - 8644.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. H. Sehn, E. P. Alyea, E. Weller, C. Canning, S. Lee, J. Ritz, J. H. Antin, and R. J. Soiffer
Comparative Outcomes of T-Cell–Depleted and Non–T-Cell–Depleted Allogeneic Bone Marrow Transplantation for Chronic Myelogenous Leukemia: Impact of Donor Lymphocyte Infusion
J. Clin. Oncol.,
February 1, 1999;
17(2):
561 - 561.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Mori, T. Nishimura, Y. Ikeda, T. Hotta, H. Yagita, and K. Ando
Involvement of Fas-Mediated Apoptosis in the Hematopoietic Progenitor Cells of Graft-Versus-Host Reaction-Associated Myelosuppression
Blood,
July 1, 1998;
92(1):
101 - 107.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. G. Lucas, R. L. Burton, S. E. Zimmerman, J. Wang, K. G. Cornetta, K. A. Robertson, C. H. Lee, and D. J. Emanuel
Semiquantitative Epstein-Barr Virus (EBV) Polymerase Chain Reaction for the Determination of Patients at Risk for EBV-Induced Lymphoproliferative Disease After Stem Cell Transplantation
Blood,
May 15, 1998;
91(10):
3654 - 3661.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. P. Alyea, R. J. Soiffer, C. Canning, D. Neuberg, R. Schlossman, C. Pickett, H. Collins, Y. Wang, K. C. Anderson, and J. Ritz
Toxicity and Efficacy of Defined Doses of CD4+ Donor Lymphocytes for Treatment of Relapse After Allogeneic Bone Marrow Transplant
Blood,
May 15, 1998;
91(10):
3671 - 3680.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Slavin, A. Nagler, E. Naparstek, Y. Kapelushnik, M. Aker, G. Cividalli, G. Varadi, M. Kirschbaum, A. Ackerstein, S. Samuel, et al.
Nonmyeloablative Stem Cell Transplantation and Cell Therapy as an Alternative to Conventional Bone Marrow Transplantation With Lethal Cytoreduction for the Treatment of Malignant and Nonmalignant Hematologic Diseases
Blood,
February 1, 1998;
91(3):
756 - 763.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.M. Lokhorst, A. Schattenberg, J.J. Cornelissen, L.L.M. Thomas, and L.F. Verdonck
Donor Leukocyte Infusions Are Effective in Relapsed Multiple Myeloma After Allogeneic Bone Marrow Transplantation
Blood,
November 15, 1997;
90(10):
4206 - 4211.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. S. Pavletic and J. O. Armitage
Bone Marrow Transplantation for Cancer--An Update
Oncologist,
June 1, 1996;
1(3):
159 - 168.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Asavaroengchai, Y. Kotera, and J. J. Mule
Tumor lysate-pulsed dendritic cells can elicit an effective antitumor immune response during early lymphoid recovery
PNAS,
January 22, 2002;
99(2):
931 - 936.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
