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

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 5.66 x 10(6)/ kg, with 0.55 x 10(6)/kg CD3+ cells. Nine patients received cyclosporin for graft-versus-host disease (GvHD) prophylaxis. Median neutrophil counts on day 21 were 2 x 10(9)/l with a median platelet count of 60 x 10(9)/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 72 d 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 365-495 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.