H e m a t o lo g y E d u c a t io n - European Hematology Association

effect. Surprisingly, none of the patients developed
GVHD and immune recovery was improved. 77 It is currently
unclear whether the in vitro T-cell depletion
method has a positive impact on immune recovery.
Federmann et al. reported faster immune reconstitution
in adult patients after non-myeloablative conditioning
followed by CD3/19 depleted haploidentical grafts, 35
and no lethal infections were seen in children after
reduced intensity conditioning and transplantation of
CD3/19-depleted PBSC. 78
The thymic damage induced by a myeloablative regimen
might also have an impact and immune reconstitution
was faster in pediatric patients after reduced intensity
conditioning and transplantation of CD3/19-depleted
PBSC compared with patients treated with a TBIbased
myeloablative regimen followed by CD3-depleted
PBSC 79 Thymic function as assessed by TREC prior
to allogeneic HSCT plays an important role for the subsequent
thymus-dependent T-cell production and
patients with low TREC copy numbers had a significantly
slower T-cell reconstitution. 80 Whether the rapidly
expanding non-alloreactive gδ+ T-lymphocytes after
transplantation of ab/CD19-depleted stem cells protect
London, United Kingdom, June 9-12, 2011
Figure 3. The HLA disparity in haploidentical transplantation facilitates the rapid and detailed flowcytometric analysis of
the lymphocyte populations post-transplant. In A, an example is shown 3 months after transplantation: Whereas all Blymphocytes
are donor derived, approx. 50% of the T-lymphocytes are recipient-derived. Most NK cells are donor-derived,
but there is a small recipient-derived CD56dim population. In B, the combination of flowcytometric chimerism analysis
and flowcytometric determination of minimal residual disease is shown 5 months after transplant: While all CD3+ T-cells
are donor-derived, there is a small population of recipient-derived HLA-A2-negative cells (a). Further analysis of this population
reveals a CD45dim phenotype (b) and most of the CD45dim cells stain positive for CD34 (c), which is identical to
the original phenotype of the patient’s blasts.
the patients from infections needs to be investigated in
further clinical studies.
Attempts to prevent relapse
Besides the optimal donor choice, the challenge in
haploidentical transplantation is the prevention of
GVHD without losing the GvL effect. Delayed donor
lymphocyte infusions, as often used in HLA-matched
transplantation, 81 carry the risk of GVHD in any haploidentical
HSCT and small T-cell inoculums can induce
severe GVHD in the absence of immunosuppression. 82
However, T-lymphocytes play an important role in
post-transplant immune surveillance for leukemic cells.
This is supported by the loss of mismatched HLA antigens
in leukemia after haploidentical HSCT. 83 In this
report, in 5 of 17 patients with leukemia relapse after
haploidentical HSCT and infusion of donor T-cells,
mutant variants of the original leukemic cells were
identified. In the mutant leukemic cells, the HLA haplotype
that differed from the donor’s haplotype had
been lost due to acquired uniparental disomy of chromosome
6p. Therefore, donor-derived T-cells could not
recognize the mutant leukemic cells, and this escape
Hematology Education: the education programme for the annual congress of the European Hematology Association | 2011; 5(1) | 69 |