Increasing mixed haematopoietic chimaerism after BMT with total depletion of CD4(+) and partial depletion of CD8(+) lymphocytes is associated with a higher incidence of relapse
J. Serrano et al., Increasing mixed haematopoietic chimaerism after BMT with total depletion of CD4(+) and partial depletion of CD8(+) lymphocytes is associated with a higher incidence of relapse, BONE MAR TR, 23(5), 1999, pp. 475-482
Citations number
34
Categorie Soggetti
Hematology,"Medical Research Diagnosis & Treatment
In this study we analysed the incidence and clinical impact of the persiste
nce of host haemopoiesis (mixed chimaerism, MC) after allogeneic BMT in 35
consecutive patients with haematologic malignancies using a total CD4(+) ce
ll-depleted graft with an adjusted dose of CD8(+) cells (1 x 10(8)/kg). Chi
maerism was assessed by PCR amplification of VNTRs in 30 evaluable patients
: 19 non-CML and 11 CML cases which were also evaluated for the BCR-ABL tra
nscript by RT-PCR, All but one had complete engraftment with a donor profil
e early post-BMT, At the end of the study period, 12 of 30 patients display
ed MC (40%), The overall disease-free survival for MC patients was clearly
unfavourable when compared to those who exhibited a donor profile (24.7% vs
100%, P = 0.005). However, we found that only two of five patients with MC
in the non-CML group relapsed, whereas a clear correlation could be made b
etween MC and relapse in CML (seven showed MC, preceding cytogenetic or hae
matological relapse in six of them, which displayed a prior BCR-ABL mRNA po
sitivity). In addition, a quantitative-PCR approach enabled us to demonstra
te that increasing amounts of MC are invariably associated with subsequent
relapse, whereas a low stable level of host or complete donor haemopoiesis
is consistent with clinical complete remission. Although these results sugg
est that the clinical impact of MC may depend on the underlying disease, it
is compatible with the concept that the graft-versus-leukaemia effect agai
nst CML is mainly exerted by donor CD4(+) lymphocytes, Elimination of this
cellular subset may be responsible for the inability of the graft to preven
t a progressive increase in the tumor cell burden.