Transplantation of TCRalpha/beta/CD19 depleted stem cells from haploidentical donors: robust engraftment and rapid immune reconstitution in children with high-risk leukaemia

Ref ID: 18541

Author:

F. Locatelli (1), P. Lang (2), M.E. Bernardo (1), T. Feuchtinger
(2), S. Rutella (1), A. Bertaina (1), M. Schumm (2),
H.M. Teltschik (2), A.S. Schulz (3), A. Moretta (4), M. Caniglia
(1), F. Zinno (1), L. Moretta (4), R. Handgretinger (2)

Author address:

)IRCCS Bambino Gesu’ Children’s Hospital (Rome, IT);
(2)Children’s University Hospital (Tübingen, DE); (3)Children’s
University Hospital (Ulm, DE); (4)University of Genoa (Genoa, IT)

Full conference title:

Annual Meeting of the EBMT, 38th

Abstract:

In haploidentical HSCT, in vitro T-cell depletion of the graft is
an effective method to prevent GvHD. We investigated a new
T-cell depletion method (using the Clini-MACS system) which
removes alpha/beta T cells and B cells, while retaining gamma/
delta T-cells, NK and other cells in the graft. So far, 32 pts have
been treated in Tübingen and Rome. PBSC manipulation resulted in 4.5 (range 3.8-5) and 4.3 (3.7-5) log-depletion of alpha/
beta T cells in Tübingen and Rome, respectively. The median
number of CD34+ cells in the 2 centers was 12×10
6
/kg (5-38)
and 11×10
6
/kg (8-40), respectively. Pts were given 107×10
6
/kg
(35-192) and 83×10
6
/kg (34-242) CD56+ NK cells, respectively.
The median number of gamma/delta T cells was 11.3×10
6
/kg (5-
30) and 7.5×10
6
/kg (1.4-25), respectively. No further post-transplant GvHD prophylaxis was given. The 15 Tübingen pts had
advanced/refractory leukemias (8 ALL; 7 AML/MDS/JMML; 9
active disease, 6 in CR2-6). For these poor-prognosis pts, a RIC
regimen (L-PAM, Thiotepa, fl udarabine or clofarabine and OKT-3
or ATG) was used. All pts engrafted, the median time to PMN and
PLT recovery being 10 (8-12) and 11 days (6-28) respectively.
Three and 1 pts had grade II and III acute GvHD, respectively.
Three pts experienced chronic GvHD (1 extensive). Three pts
relapsed after HSCT and died; 1 pt died of multi-organ failure.
8 pts are in remission (median FU: 7 months, 5-15). The Rome
cohort comprised 17 pts with ALL (13), AML (3) and NHL (1). All
children but 1 had relapsed/refractory disease. In particular, 10
pts were transplanted in CR2 and 6 with more advanced disease.
Myeloablative conditioning included fractionated TBI, Thiotepa,
fl udarabine/L-PAM and ATG. All pts but 1 engrafted, the median
time to PMN and PLT recovery being 12 (10-18) and 13 (8-15)
days, respectively. Only 1 pt had grade I acute GvHD. No pt of
the 12 at risk experienced chronic GvHD. At a median FU of 7
months (1-13), 14 pts are alive and disease-free; 3 pts relapsed (1
died) and 1 had fatal lung aspergillosis. In both cohorts, gamma/
delta T cells started to expand faster than alpha/beta T cells in the
early post-HSCT period, whereas at day +100 alpha/beta T cells
were predominant. These data indicate that transplantation of
TCR alpha/beta/CD19 depleted cells from a haploidentical donor
results in sustained engraftment, rapid immune recovery and low
incidence of GvHD. The anti-leukemic effi cacy of this approach
needs to be evaluated with a longer follow-up.

Abstract Number: O132

Conference Year: 2012

Link to conference website: NULL

New link: NULL

Conference abstracts, posters & presentations

Showing 10 posts of 17325 posts found.

  • Title

    Author

    Year

    Number

    Poster