CD34+-enriched peripheral blood progenitor cells from unrelated donors for allografting of adult patients:: high risk of graft failure, infection and relapse despite donor lymphocyte add-back

被引:23
作者
Bornhäuser, M [1 ]
Platzbecker, U [1 ]
Theuser, C [1 ]
Hölig, K [1 ]
Ehninger, G [1 ]
机构
[1] Univ Klinikum Carl Gustav Carus, Med Klin & Poliklin 1, Dresden, Germany
关键词
unrelated donor; PBPC; CD34(+) selection; T-cell add-back; infection;
D O I
10.1046/j.1365-2141.2002.03731.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Fifty-one adults with haematological malignancies were transplanted with CD34(+) -selected peripheral blood progenitor cells (PBPC) from unrelated donors. The conditioning protocol contained total body irradiation (n = 17) or combinations of busulphan and other alkylating agents (n = 34). Antithymocyte globulin was infused in all patients. The median number of CD3(+) T cells infused with the graft after purification with the Isolex 300(R) system in the first cohort of 18 patients was 2.1 x 10(5) /kg. Prophylactic donor lymphocyte infusion (DLI) containing 1 x 10(5) CD3(+) T cells was performed on d 21 in the following 33 patients who had received PBPC purified by the CliniMACS(R) system. Early graft failure occurred in 8/51 patients (16%). After a median follow-up of 31 months (range 8-60), the probability of disease-free survival (DFS) was 36% for the whole group. Reasons for death were opportunistic infections (n = 15), graft-versus-host disease (GvHD, n = 7) and relapse (n = 4). Pre-transplant factors with significant impact on DFS were cytomegalovirus status and risk category of underlying disease. The occurrence of graft failure or GvHD was associated with poor outcome. Recipients of CD34(+) -selected PBPC from unrelated donors are at high risk of infectious complications, relapse and graft failure which cannot be prevented by early reinfusion of unmodified donor lymphocytes.
引用
收藏
页码:1095 / 1103
页数:9
相关论文
共 45 条
[1]   Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype [J].
Aversa, F ;
Tabilio, A ;
Velardi, A ;
Cunningham, I ;
Terenzi, A ;
Falzetti, F ;
Ruggeri, L ;
Barbabietola, G ;
Aristei, C ;
Latini, P ;
Reisner, Y ;
Martelli, MF .
NEW ENGLAND JOURNAL OF MEDICINE, 1998, 339 (17) :1186-1193
[2]  
Bensinger W I, 1990, J Clin Apher, V5, P74
[3]   Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. [J].
Bensinger, WI ;
Martin, PJ ;
Storer, B ;
Clift, R ;
Forman, SJ ;
Negrin, R ;
Kashyap, A ;
Flowers, MED ;
Lilleby, K ;
Chauncey, TR ;
Storb, R ;
Appelbaum, FR ;
Rowley, S ;
Heimfeld, S ;
Blume, K .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (03) :175-181
[4]  
Bensinger WI, 1996, BLOOD, V88, P4132
[5]   HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia [J].
Bonini, C ;
Ferrari, G ;
Verzeletti, S ;
Servida, P ;
Zappone, E ;
Ruggieri, L ;
Ponzoni, M ;
Rossini, S ;
Mavilio, F ;
Traversari, C ;
Bordignon, C .
SCIENCE, 1997, 276 (5319) :1719-1724
[6]   Rhenium 188-labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome:: results of a phase I-II study [J].
Bunjes, D ;
Buchmann, I ;
Duncker, C ;
Seitz, U ;
Kotzerke, J ;
Wiesneth, M ;
Dohr, D ;
Stefanic, M ;
Buck, A ;
Harsdorf, SV ;
Glatting, G ;
Grimminger, W ;
Karakas, T ;
Munzert, G ;
Döhner, H ;
Bergmann, L ;
Reske, SN .
BLOOD, 2001, 98 (03) :565-572
[7]   Changes in thymic function with age and during the treatment of HIV infection [J].
Douek, DC ;
McFarland, RD ;
Keiser, PH ;
Gage, EA ;
Massey, JM ;
Haynes, BF ;
Polis, MA ;
Haase, AT ;
Feinberg, MB ;
Sullivan, JL ;
Jamieson, BD ;
Zack, JA ;
Picker, LJ ;
Koup, RA .
NATURE, 1998, 396 (6712) :690-695
[8]   T-cell depletion plus salvage immunotherapy with donor leukocyte infusions as a strategy to treat chronic-phase chronic myelogenous leukemia patients undergoing HLA-identical sibling marrow transplantation [J].
Drobyski, WR ;
Hessner, MJ ;
Klein, JP ;
Kabler-Babbitt, C ;
Vesole, DH ;
Keever-Taylor, CA .
BLOOD, 1999, 94 (02) :434-441
[9]   A prospective analysis of the pattern of immune reconstitution in a paediatric cohort following transplantation of positively selected human leucocyte antigen-disparate haematopoietic stem cells from parental donors [J].
Eyrich, M ;
Lang, P ;
Lal, S ;
Bader, P ;
Handgretinger, R ;
Klingebiel, T ;
Niethammer, D ;
Schlegel, PG .
BRITISH JOURNAL OF HAEMATOLOGY, 2001, 114 (02) :422-432
[10]   Cytotoxic T-lymphocyte (CTL) responses against acute or chronic myeloid leukemia [J].
Falkenburg, JHF ;
Smit, WM ;
Willemze, R .
IMMUNOLOGICAL REVIEWS, 1997, 157 :223-230