Journal of Hematology - Supplements - Haematologica

haematologica 2000; 85(supplement to n. 11):37-40
original paper
Haploidentical bone marrow transplantation in leukemia and genetic
diseases
M. ANDOLINA, N. MAXIMOVA, M. RABUSIN, D. VUJIC,° G. BUNJEVACKI,° C. VIDALI,* A. BEORCHIA*
IRCCS Burlo Garofolo, Trieste; *Unità Operativa di Radioterapia, Trieste, Italy;
Mother’s and Child’s Institute, Belgrade, Yugoslavia
ABSTRACT
From 1986 to June 2000, sixty children suffering
from acute and chronic leukemia (n = 42, 33 of
which in resistant relapse), genetic diseases (n = 11),
aplastic anemia (n = 2, one of which with platelet
refractoriness and bleeding), myelodysplasia (n = 5)
received an haploidentical bone marrow, mismatched
for 2-3 HLA loci. The donor’s marrow was
treated in vitro with vincristine and methylprednisolone
to obtain a functional T depletion (MLC and
CTL inhibition, functional blockade of Th1 and Th2).
The prevalence of infectious complications and
GVHD was similar to that recorded in matched unrelated
donor (MUD) transplants. In situations of high
risk of rejection (chronic leukemia, genetic diseases)
we infused immediately one half of the harvest and
then frozen aliquots from the second week. Of the 25
ALL and 8 AML in resistant relapse, 3 survived, disease-free
at 14, 8 and 1 years respectively. Of the
3 ALL, transplanted during remission, 1 is surviving
at 18 months. Of the 6 CML, 1 had fractionated
bone marrow and is surviving at 3 years, and 5 had
standard single dose infusion and died of progression
of their disease after rejection of the graft (4)
or blast crisis after complete engraftment (1). The 2
patients with aplastic anemia, those with myelodysplasia,
and 6 of the 10 with genetic disorders died
of transplant-related complications or disease progression.
4 patients with osteopetrosis (n=2), MLD
(n=1), Wiskott Aldrich dis. (n=1) survive at 8, 2, 5 and
1.5 years respectively. In patients transplanted with
fractionated marrow GVHD >2nd grade occurred in
15%. Only one patient rejected the graft. Compared
with MUD transplantation, mismatched BMT whenever
performed in patients in good conditions provides
similar outcome and widens the donor availability.
©2000, Ferrata Storti Foundation
Key words: haploidentical, mismatched bone marrow transplantation,
leukemia, genetic diseases
About 40 percent of patients fail to find a
perfectly matched donor among relatives
on in any of the donor registries. 1 Therefore,
more than one third of the patients who
could be theoretically cured by a bone marrow
Correspondence: Andolina Marino, MD, Transplant Department, IRCCS
Burlo Garofolo, 34100 Trieste, Italy. Phone: 0039-040-3785276 –Fax:
0039-040-3785494 – Email: andolina@burlo.trieste.it
transplantion fails to exploit this treatment. 1,2 It
has been shown that transplants using mismatched
bone marrow can be as effective as
those in which the donor and recipient are fully
matched. 7,8 Mismatched bone marrow transplant
increases the chances of finding a donor
and shortens the time for donor search. In fact,
the timing of the transplant is critical especially
in patients with ALL in CR2 and genetic diseases
for whom the BMT is a urgent procedure.
1,2,11
Haploidentical siblings and parents are suitable
donors, whenever healthy and of a proper
age and body size. Even if the first experiences
of 2-3 loci mismatched transplants were performed
more than 15 years ago, 3 this procedure
did not obtain a large approval from most
centres. However there is an increasing evidence
that a mismatched BMT is able to overcome the
most severe clinical situations. 4-6 Among strategies
of performing the 2-3 loci mismatch transplant
and not to perform the transplant when
an HLA identical donor is not available, we
adopted the former in 1986. Since then, we
have performed 60 transplants and the follow
up data are similar to those of MUD, with the
advantage that any patient is given opportunity
for treatment.
Selection of the patients
In the first series of patients we treated mainly
children with resistant relapse of acute
leukemia (25). These patients had not only
resistant blasts in their marrow and peripheral
blood, but in most cases suffered by several
untoward effects of chemotherapy (infections,
liver damage).
Later we began transplanting even chronic
leukemias (6), acute leukemias in remission
beyond the first (3), genetic diseases (13),
severe aplastic anemia (2) and myelodysplastic
syndromes(5). Since 1996, the patients who
had not previously undergone heavy treatment
with immunosuppressive drugs, and therefore
were particularly susceptible to rejecting the
marrow, received a conditioning regimen (protocol
#2) aimed at reducing this danger.
haematologica vol. 85(supplement to n. 11):November 2000