|
|
 Previous Article | Table of Contents | Next Article 
Long-Term Immune Reconstitution and Outcome After HLA-Nonidentical
T-Cell-Depleted Bone Marrow Transplantation for Severe Combined
Immunodeficiency: A European Retrospective Study of 116 Patients
Elie Haddad,
Paul Landais,
Wilhelm Friedrich,
Bert Gerritsen,
M. Cavazzana-Calvo,
Gareth Morgan,
Yves Bertrand,
Anders Fasth,
Fulvio Porta,
Andrew Cant,
Theresa Espanol,
Susannah Müller,
Paul Veys,
Jaak Vossen, and
Alain Fischer
From the Unité d'Immunologie et d'Hématologie
Pédiatriques, Département de Pédiatrie, and the
Département de Statistiques Médicales, Hôpital
Necker-Enfants Malades, Paris, France; the
Universitätskinderklinik und Poliklinik, Ulm, Germany; the
Department of Pediatrics, University Hospital Leiden, Leiden, The
Netherlands; the Great Ormond Sreet Hospital for Children, NHS Trust,
London, UK; the Département d'Hématologie
Pédiatrique, Hôpital Debrousse, Lyon, France; the
Department of Pediatrics, Sahlgrenska University Hospital/East,
Göteborg, Sweden; the Department of Pediatrics, Spedali Civili,
Brescia, Italy; the Department of Pediatric Immunology, Newcastle
General Hospital Newcastle, UK; and the Hospital General, Immunologia,
Vall d'Hebron, Barcelona, Spain.
We have performed a retrospective analysis of the development of T-
and B-cell functions after HLA-nonidentical T-cell-depleted bone
marrow transplantation (BMT) performed in 193 patients with severe
combined immunodeficiency (SCID) at 18 European centers between
December 1982 and December 31, 1993. One hundred sixteen of 193 patients were alive with evidence of engraftment 6 months after BMT.
Development of T-cell function occurred earlier than B-cell function
and was achieved more frequently up to the time of last follow-up. The
median time to achieve normal T-cell function was 8.7 months, whereas
the median time to achieve normal B-cell function was 14.9 months.
Twenty-four patients died later than 6 months post-BMT, mainly due to
chronic graft-versus-host disease (cGVHD) and/or viral
infection. Absence of T-cell reconstitution 6 months after BMT, unlike
absence of B-cell reconstitution, was associated with a poor outcome.
Two additional factors were associated with a poor outcome: presence of
cGVHD 6 months after BMT and B SCID versus B+ SCID.
However, two of these three factors remained as significant prognostic
factors in a multivariate analysis: the absence of T-cell function and
the presence of cGVHD 6 months after BMT. Analysis of the factors
influencing the development of immune reconstitution showed that T- and
B-cell functions occurred earlier and more frequently in B+ SCID
versus B SCID patients. Acute GVHD was associated with a slower
development of T-cell function at 6 months, and cGVHD had a negative
influence on the development of T-cell function afterwards, but neither
acute nor chronic GVHD was found to influence the development of B-cell function. Once engraftment occurred, whether patients had or had not
received Busulfan in the conditioning regimen did not influence the
kinetics and quality of T-cell function development. In a multivariate
study, two factors were found to influence the T-cell function 6 months
after BMT: type of SCID and acute GVHD. The results of this
retrospective analysis should lead to new protocols adapted to SCID
disease, considering that disease-related as well as BMT-related
parameters influence the development of immune function and thereby
long-term outcome after HLA-nonidentical T-cell-depleted BMT.
Blood, Vol. 91 No. 10 (May 15), 1998:
pp. 3646-3653
© 1998 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:
|
|
|
|
 
B. Neven, S. Leroy, H. Decaluwe, F. Le Deist, C. Picard, D. Moshous, N. Mahlaoui, M. Debre, J.-L. Casanova, L. Dal Cortivo, et al.
Long-term outcome after hematopoietic stem cell transplantation of a single-center cohort of 90 patients with severe combined immunodeficiency
Blood,
April 23, 2009;
113(17):
4114 - 4124.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Chinen, J. Davis, S. S. De Ravin, B. N. Hay, A. P. Hsu, G. F. Linton, N. Naumann, E. Y. H. Nomicos, C. Silvin, J. Ulrick, et al.
Gene therapy improves immune function in preadolescents with X-linked severe combined immunodeficiency
Blood,
July 1, 2007;
110(1):
67 - 73.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Cavazzana-Calvo, F. Carlier, F. Le Deist, E. Morillon, P. Taupin, D. Gautier, I. Radford-Weiss, S. Caillat-Zucman, B. Neven, S. Blanche, et al.
Long-term T-cell reconstitution after hematopoietic stem-cell transplantation in primary T-cell-immunodeficient patients is associated with myeloid chimerism and possibly the primary disease phenotype
Blood,
May 15, 2007;
109(10):
4575 - 4581.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Hossain, J. D. Roback, B. P. Pollack, D. L. Jaye, A. Langston, and E. K. Waller
Chronic GvHD decreases antiviral immune responses in allogeneic BMT
Blood,
May 15, 2007;
109(10):
4548 - 4556.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Honig, M. H. Albert, A. Schulz, M. Sparber-Sauer, C. Schutz, B. Belohradsky, T. Gungor, M. T. Rojewski, H. Bode, U. Pannicke, et al.
Patients with adenosine deaminase deficiency surviving after hematopoietic stem cell transplantation are at high risk of CNS complications
Blood,
April 15, 2007;
109(8):
3595 - 3602.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. H. T. Paraiso, T. Ghansah, A. Costello, R. W. Engelman, and W. G. Kerr
Induced SHIP Deficiency Expands Myeloid Regulatory Cells and Abrogates Graft-versus-Host Disease
J. Immunol.,
March 1, 2007;
178(5):
2893 - 2900.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Mostoslavsky, A. J. Fabian, S. Rooney, F. W. Alt, and R. C. Mulligan
Complete correction of murine Artemis immunodeficiency by lentiviral vector-mediated gene transfer
PNAS,
October 31, 2006;
103(44):
16406 - 16411.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Amrolia, G. Muccioli-Casadei, H. Huls, S. Adams, A. Durett, A. Gee, E. Yvon, H. Weiss, M. Cobbold, H. B. Gaspar, et al.
Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation
Blood,
September 15, 2006;
108(6):
1797 - 1808.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Liu, C. A. J. Vosshenrich, C. Lagresle-Peyrou, M. Malassis-Seris, C. Hue, A. Fischer, J. P. Di Santo, and M. Cavazzana-Calvo
Competition within the early B-cell compartment conditions B-cell reconstitution after hematopoietic stem cell transplantation in nonirradiated recipients
Blood,
August 15, 2006;
108(4):
1123 - 1128.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Borghans, R. G. Bredius, M. D. Hazenberg, H. Roelofs, E. C. Jol-van der Zijde, J. Heidt, S. A. Otto, T. W. Kuijpers, W. E. Fibbe, J. M. Vossen, et al.
Early determinants of long-term T-cell reconstitution after hematopoietic stem cell transplantation for severe combined immunodeficiency
Blood,
July 15, 2006;
108(2):
763 - 769.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H. Goldschmidt, J. S. Kennedy, D. R. Kennedy, H. Yuan, D. E. Holt, M. L. Casal, A. M. Traas, E. A. Mauldin, P. F. Moore, P. S. Henthorn, et al.
Severe Papillomavirus Infection Progressing to Metastatic Squamous Cell Carcinoma in Bone Marrow-Transplanted X-Linked SCID Dogs.
J. Virol.,
July 1, 2006;
80(13):
6621 - 6628.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Neff, B. C. Beard, and H.-P. Kiem
Survival of the fittest: in vivo selection and stem cell gene therapy
Blood,
March 1, 2006;
107(5):
1751 - 1760.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Grunebaum, E. Mazzolari, F. Porta, D. Dallera, A. Atkinson, B. Reid, L. D. Notarangelo, and C. M. Roifman
Bone Marrow Transplantation for Severe Combined Immune Deficiency
JAMA,
February 1, 2006;
295(5):
508 - 518.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Rao, P. J. Amrolia, A. Jones, C. M. Cale, P. Naik, D. King, G. E. Davies, H. B. Gaspar, and P. A. Veys
Improved survival after unrelated donor bone marrow transplantation in children with primary immunodeficiency using a reduced-intensity conditioning regimen
Blood,
January 15, 2005;
105(2):
879 - 885.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Amrolia, G. Muccioli-Casadei, E. Yvon, H. Huls, U. Sili, E. D. Wieder, C. Bollard, J. Michalek, V. Ghetie, H. E. Heslop, et al.
Selective depletion of donor alloreactive T cells without loss of antiviral or antileukemic responses
Blood,
September 15, 2003;
102(6):
2292 - 2299.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Muul, L. M. Tuschong, S. L. Soenen, G. J. Jagadeesh, W. J. Ramsey, Z. Long, C. S. Carter, E. K. Garabedian, M. Alleyne, M. Brown, et al.
Persistence and expression of the adenosine deaminase gene for 12 years and immune reaction to gene transfer components: long-term results of the first clinical gene therapy trial
Blood,
April 1, 2003;
101(7):
2563 - 2569.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. J. Waldschmidt, A. Panoskaltsis-Mortari, R. T. McElmurry, L. T. Tygrett, P. A. Taylor, and B. R. Blazar
Abnormal T cell-dependent B-cell responses in SCID mice receiving allogeneic bone marrow in utero
Blood,
December 15, 2002;
100(13):
4557 - 4564.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Handgretinger, E. Koscielniak, D. Niethammer, M. Cavazzana-Calvo, S. Hacein-Bey-Abina, and A. Fischer
Gene Therapy for Severe Combined Immunodeficiency Disease
N. Engl. J. Med.,
August 22, 2002;
347(8):
613 - 614.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. G. Hawley and D. A. Sobieski
Of Mice and Men: The Tale of Two Therapies
Stem Cells,
July 1, 2002;
20(4):
275 - 278.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Tsai, H. L. Malech, M. R. Kirby, A. P. Hsu, N. E. Seidel, C. D. Porada, E. D. Zanjani, D. M. Bodine, and J. M. Puck
Retroviral transduction of IL2RG into CD34+ cells from X-linked severe combined immunodeficiency patients permits human T- and B-cell development in sheep chimeras
Blood,
June 17, 2002;
100(1):
72 - 79.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Hacein-Bey-Abina, F. Le Deist, F. Carlier, C. Bouneaud, C. Hue, J.-P. De Villartay, A. J. Thrasher, N. Wulffraat, R. Sorensen, S. Dupuis-Girod, et al.
Sustained Correction of X-Linked Severe Combined Immunodeficiency by ex Vivo Gene Therapy
N. Engl. J. Med.,
April 18, 2002;
346(16):
1185 - 1193.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Amrolia, H. B. Gaspar, A. Hassan, D. Webb, A. Jones, N. Sturt, G. Mieli-Vergani, A. Pagliuca, G. Mufti, N. Hadzic, et al.
Nonmyeloablative stem cell transplantation for congenital immunodeficiencies
Blood,
August 15, 2000;
96(4):
1239 - 1246.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. D. Greenberg and S. R. Riddell
Deficient Cellular Immunity--Finding and Fixing the Defects
Science,
July 23, 1999;
285(5427):
546 - 551.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
D. Montagna, E. Yvon, V. Calcaterra, P. Comoli, F. Locatelli, R. Maccario, A. Fisher, and M. Cavazzana-Calvo
Depletion of Alloreactive T Cells by a Specific Anti-Interleukin-2 Receptor p55 Chain Immunotoxin Does Not Impair In Vitro Antileukemia and Antiviral Activity
Blood,
May 15, 1999;
93(10):
3550 - 3557.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. H. Buckley, S. E. Schiff, R. I. Schiff, M. L. Markert, L. W. Williams, J. L. Roberts, L. A. Myers, and F. E. Ward
Hematopoietic Stem-Cell Transplantation for the Treatment of Severe Combined Immunodeficiency
N. Engl. J. Med.,
February 18, 1999;
340(7):
508 - 516.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Fischer
Thirty Years of Bone Marrow Transplantation for Severe Combined Immunodeficiency
N. Engl. J. Med.,
February 18, 1999;
340(7):
559 - 561.
[Full Text]
|
|
|
|
|
|
|
J. J. van Rood and M. Oudshoorn
The Quest for a Bone Marrow Donor -- Optimal or Maximal HLA Matching?
N. Engl. J. Med.,
October 22, 1998;
339(17):
1238 - 1239.
[Full Text]
|
|
|
|
|
