Transplantation of HLA-mismatched CD34+ selected cells in patients with advanced malignancies: Severe immunodeficiency and related complications

A. Bacigalupo, N. Mordini, A. Pitto, G. Piaggio, M. Podesta, F. Benvenuto, M. T. Van Lint, M. Valbonesi, G. Lercari, P. Carlier, T. Lamparelli, F. Gualandi, D. Occhini, S. Bregante, O. Figari, M. Soracco, F. Vassallo, G. De Stefano

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Abstract

This trial was designed to test the use of CD34+ selected haemopoietic stem cells (HSC) in HLA-mismatched donor-recipient pairs, following intensive conditioning with thiotepa, antilymphocyte globulin (ALG), cyclophosphamide and single-dose total-body irradiation (sTBI). 10 patients aged 16-50 with advanced malignancies and a two- or three-antigen mismatched family donor entered this study. Donor marrow and G-CSF primed peripheral blood cells were processed separately on CD34 columns (Ceprate). The median number of infused CD34+ cells were 5.66x106/kg, with 0.55 X 106/kg CD3+ cells. Nine patients received cyclosporin for graft-versus-host disease (GvHD) prophylaxis. Median neutrophil counts on day 21 were 2 x 109/l with a median platelet count of 60 x 109/l, but CD4 counts remained extremely depressed throughout the study. Acute GvHD was scored as grade 0-I in two patients, as grade II in seven, and grade III in one. Eight patients died at a median interval of 72d from HSCT (range 20-144) due to cytomegalovirus (CMV) associated interstitial pneumonitis (IP) (n=5), renal failure (n=1), GvHD (n=1) and Aspergillus meningitis (n=1). Two patients are alive 365495 d post transplant, one in remission and one in relapse. This study suggests that large numbers of positively selected mismatched HSC can rapidly engraft after intensive conditioning regimen: however, profound post-transplant immunodeficiency leads to a high risk of lethal infectious complications.

Original languageEnglish
Pages (from-to)760-766
Number of pages7
JournalBritish Journal of Haematology
Volume98
Issue number3
Publication statusPublished - 1997

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Transplantation
Graft vs Host Disease
Tissue Donors
Neoplasms
Stem Cells
Thiotepa
Transplants
Antigens
Antilymphocyte Serum
Whole-Body Irradiation
Interstitial Lung Diseases
Granulocyte Colony-Stimulating Factor
Aspergillus
CD4 Lymphocyte Count
Cytomegalovirus
Platelet Count
Meningitis
Cyclophosphamide
Cyclosporine
Renal Insufficiency

Keywords

  • Bone marrow transplantation
  • CD34 selection
  • Immunodeficiency
  • Leukaemia
  • Stem cells

ASJC Scopus subject areas

  • Hematology

Cite this

Transplantation of HLA-mismatched CD34+ selected cells in patients with advanced malignancies : Severe immunodeficiency and related complications. / Bacigalupo, A.; Mordini, N.; Pitto, A.; Piaggio, G.; Podesta, M.; Benvenuto, F.; Van Lint, M. T.; Valbonesi, M.; Lercari, G.; Carlier, P.; Lamparelli, T.; Gualandi, F.; Occhini, D.; Bregante, S.; Figari, O.; Soracco, M.; Vassallo, F.; De Stefano, G.

In: British Journal of Haematology, Vol. 98, No. 3, 1997, p. 760-766.

Research output: Contribution to journalArticle

Bacigalupo, A, Mordini, N, Pitto, A, Piaggio, G, Podesta, M, Benvenuto, F, Van Lint, MT, Valbonesi, M, Lercari, G, Carlier, P, Lamparelli, T, Gualandi, F, Occhini, D, Bregante, S, Figari, O, Soracco, M, Vassallo, F & De Stefano, G 1997, 'Transplantation of HLA-mismatched CD34+ selected cells in patients with advanced malignancies: Severe immunodeficiency and related complications', British Journal of Haematology, vol. 98, no. 3, pp. 760-766.
Bacigalupo, A. ; Mordini, N. ; Pitto, A. ; Piaggio, G. ; Podesta, M. ; Benvenuto, F. ; Van Lint, M. T. ; Valbonesi, M. ; Lercari, G. ; Carlier, P. ; Lamparelli, T. ; Gualandi, F. ; Occhini, D. ; Bregante, S. ; Figari, O. ; Soracco, M. ; Vassallo, F. ; De Stefano, G. / Transplantation of HLA-mismatched CD34+ selected cells in patients with advanced malignancies : Severe immunodeficiency and related complications. In: British Journal of Haematology. 1997 ; Vol. 98, No. 3. pp. 760-766.
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AU - Podesta, M.

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AU - Carlier, P.

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AU - Gualandi, F.

AU - Occhini, D.

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AU - De Stefano, G.

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