Journal of Hematology - Supplements - Haematologica

haematologica 2000; 85(supplement to n. 11):41-46
original paper
Haploidentical peripheral blood and marrow stem cell transplantation
in nine cases of primary immunodeficiency
A. LANFRANCHI,* R. VERARDI,* K. TETTONI,° A. NEVA,* E. MAZZOLARI,° M. PENNACCHIO,° S. PASIC,° A.G. UGAZIO,°
A. ALBERTINI,* F. PORTA°
*Institute of Chemistry and °Dept. of Pediatrics, University of Brescia, Italy
ABSTRACT
Bone marrow transplantation (BMT) is the treatment
of choice in children affected by primary immunodeficiency
(PID). Because only 10-15% of affected
children have a familial HLA-identical donor alternative
therapeutic options are BMT from a matched
unrelated donor or an haploidentical BMT. In our
experience only 40% of these children find a donor
within the International Registry. Therefore, the
remaining 50% children affected by PID are candidates
for haploidentical BMT. Unfortunately, in PID
other than sever-combined immunodeficiency
(SCID), low engraftment rates have been reported
because of minimal residual immunity. In order to
enhance engraftment rate in haploidentical BMT in
PID we suggest a protocol with addition of donor
peripheral stem cells after mobilization with granulocyte
colony-stimulating factor (G-CSF) (16 µg/kg
for 5 days) and bone marrow cells. This procedure
increases the cell load, which allows intensification
of the conditioning regimen for induction of faster
engraftment. The separation of CD34 + cells from
leukapheresis products was achieved in the first 6
patients by the Isolex 300 system (Baxter) with a
CD34 + cell purity range of 80-95% and in another
three patients by the Clinimacs System (Miltenyi).
The peripheral blood stem cells were cryopreserved
until BMT, 15 days after G-CSF stimulation when the
bone marrow was harvested, processed and T-cell
depleted with Campath 1-M in the first 6 cases while
the Clinimacs System was used in the remaining cases
and no T-cell depletion was required. We included
9 patients in the study protocol: SCID (4), Omenn’s
syndrome (3), LAD (1) and CID (1). The mean value
of peripheral CD34 + cells infused was
13.42×10 6 /kg and the mean CD3 + cells number was
0.38510 5 /kg; the mean value of BM CD34 + cells
infused was 10.6210 6 /kg and the mean CD3 + cell
number was 2.3910 5 /kg.The mean number of
infused CFU was 8.110 5 /kg for PBSC and
3.5910 5 /kg for BM. The 9 patients achieved more
than 0.510 9 peripheral blood neutrophils/L at a
mean of 14.6 days (range: 6-22 days). One patient
affected by SCID showed complete chimerism, but
he died after BMT of systemic CMV infection; the
other 8 patients are alive and well and 4 of them
Correspondence: Dr. F. Porta, Dept. of Pediatrics, University of Brescia,
Italy.
show complete chimerism in all cell lines. Split
chimerism was documented in 2 SCID cases (CD3 +
lymphocytes were of donor origin, monocytes were
autologous and granulocytes were mainly autologous);
1 patient affected by Omenn’s syndrome
received 3 transplants (1 from the mother and 2
from the father, T-cells alone and bone marrow) and
achieved engraftment with complete chimerism
after the third transplant; the patient affected by
LAD also received 3 transplants (2 bone marrow
infusions and 1 PBSC infusion) achieving complete
chimerism after the third one. In conclusion, the
engraftment achieved in all treated patients, and the
acceptable conditioning-related toxicity suggest that
this approach could be successfully applied to children
affected by PID and candidates for haploidentical
BMT.
©2000, Ferrata Storti Foundation
Key words: bone marrow transplantation, primary immunodeficiency
, peripheral blood stem cells
Primary immunodeficiencies (PID) are a heterogeneous
group of congenital diseases
that affect cellular and/or humoral immunity,
resulting in abnormal susceptibility to infections.
1 The combined defects of the two immune
compartments (severe combined immunodeficiencies,
SCID; combined immunodeficiencies,
CID) lead to severe infections and are usually
fatal within the first year of life. Bone marrow
transplantation (BMT) is the only treatment
option for patients affected by SCID. 2 Only
about 10-15% of these children have a family
matched donor, so that an alternative donor is
required. Almost half of the patients who lack a
matched family donor can be successfully treated
with BMT from an HLA-matched unrelated
donor found within the International Bone Marrow
Donor Registry 3 The remaining patients require a
haploidentical BMT. The results of haploidentical
BMT are good (75% overall survival) only in
patients affected by SCID with B-cells (SCID T-
B + ). For other diseases such as SCID T-B-,
Omenn’s syndrome, Wiskott-Aldrich syndrome,
haematologica vol. 85(supplement to n. 11):November 2000