JORGE SIERRA (BARCELONA)
HAPLOIDENTICAL HEMATOPOIETIC TRANSPLANTATION IN PATIENTS
WITH ACUTE LEUKAEMIA
Hematology Department. Hospital de la Santa Creu i Sant Pau. Autonomous University of Barcelona.
Spain.
The treatment for acute myeloid leukemia (AML) in fit patients consists of intensive intravenous
chemotherapy based on cytarabine (7 days) and anthracyclines (3 days). With this 3+7 regimen
complete remission (CR) is achieved in 60-80% of young (up to 65 years of age) and 30-60% of
elderly patients. Once in CR, consolidation treatment with intermediate or high dose of cytarabine is
needed to avoid early relapse (from one to four courses). Following, allogeneic hematopoietic
transplantation is indicated or not, depending on risk allocation of the patient and the disease, as
well as the availability of a suitable donor. Fit patients with intermediate and adverse risk AML do
benefit from allografts.1
In acute lymphoblastic leukemia (ALL) intensive chemotherapy is also the first choice. Initial
treatment includes more agents than in AML, with vincristine, prednisone, daunorubicin, L-asparaginase,
cyclophosphamide, and methotrexate being the backbones of the schemes. Additional
drugs are subsequently administered in different sequences. In essence, the treatment consists of
an induction phase and several consolidations followed by low-dose maintenance during 2-3 years.
Currently, protocols for relatively young adults base on intensive pediatric combinations. These
approaches may not be administered to the elderly because the high morbidity and mortality.
Allogeneic stem cell transplantation has indication in first complete remission in patients with initial
high-risk features, residual disease after chemotherapy, or both, as well as after a relapse.2.
In short, allogeneic stem cell transplantation is the best option for high-risk AL, but only 30% of
patients in need have a matched related donor 3. The probability to identify a closely HLA-matched
unrelated donor is 80% for Spanish and other Caucasian populations. This probability decreases if
the patients belong to ethnic minorities. Other options for patients who lack an HLA-compatible
adult donor are umbilical cord blood and haploidentical related donor transplantation. These two
alternatives have the advantage of the rapid availability of hematopoietic stem cells, although cord
blood has the limitation of the usually low dose of the graft for adult patients. In any case, if the
transplant has to be performed shortly and the patient lacks an HLA-identical sibling, these stem cell
sources have to be seriously considered, since unrelated donor search and cell procurement may
take several months.
Due to the historically dismal results after unmanipulated BMT from fully haploidentical donors 4
using myeloablative conditioning (MAC) and posttransplant graft versus host disease (GVHD)
prophylaxis, different strategies have been developed in this setting. Deep “ex vivo” T-cell depletion
of the graft was investigated to avoid lethal GVHD. In this regard, a pioneer haploidentical transplant
program was established by the Perugia group in the 1990s. After initial experiences, in 2005, the
Perugia group published their updated data on 104 patients with AML or ALL who received MAC and
megadose of CD34+ cells without posttransplant GVHD prophylaxis. Median cell dose infused was
13.8x106/kg CD34 cells. Ninety-one percent of patients achieved a fast engraftment and only 8 of the
100 evaluable patients developed acute GVHD grades 2-4. In 3 of the 8 patients there was a
progression to chronic GVHD. Non-relapse mortality (NRM) was 36% with infections as the main