Allogeneic Stem Cell Transplantation

A. Bosi, B. Bartolozzi, and S. Guidi

ABSTRACT
Allogeneic stem cell transplantation (HSCT) requires the harvest of an adequate number
of stem cells (SC) from a histocompatible donor and their infusion into a patient following
a conditioning regimen. During the past 35 years, the role of HSCT has changed from an
experimental procedure for terminally ill patients to a curative treatment. In 2003, 1170
procedures were registered in Italy (Italian Group for Blood and Marrow Transplanta-
tion). The main reported indications were as follows: leukemia, lymphoproliferative
diseases, myelodysplasia, and nonmalignant diseases such as thalassemia and severe
aplastic anemia. Important changes have been observed in the last 5 years: the shift from
bone marrow to peripheral blood as the SC source, the increasing number of alternative
donors such as unrelated, partially matched family donors and cord blood SC, and the new
extra-hematological indications including solid tumors. Moreover, the development of
nonmyeloablative conditionig regimens have allowed physicians to perform HSCT in
patients with advanced age or important comorbidities. In contrast, the availability of the
Tyrosine kinase inhibitor (STI-571) for treatment of patients affected by chronic myelog-
enous leukemia, which was formerly the main indication for HSCT, has produced a
dramatic decrease in the number of transplantations in this setting. HSCT performed in
the early phases of disease and in young patients offers more than a 50% cure rate. The
transplant-related mortality still represents the greatest obstacle, ranging from 20%–30%,
despite the less toxic conditioning regimens, high-resolution HLA typing, and better
supportive care. GvHD and infections remain the main causes of morbidity. As regards
relapses, they correlate with disease status at the time of transplantation. Promising results
have been recently obtained with haploidentical and with cord blood SC transplantation
also in adult patients.

data on all transplantation activity in Europe.4 According to

A LLOGENEIC hematopoietic stem cell transplanta-
tion (HSCT) is an increasingly used procedure. Its
role has changed from an emergency measure for dramatic
situations to a planned treatment for hematological and
nonhematological disease, both neoplastic and nonmalig-
nant. On the basis of the donor availability, the needs of the
patient and the disease, HSCT is performed from various
types of donors: syngeneic, allogeneic related and alloge-
neic unrelated donors, and fully or partially matched do-
nors.1–3 HSCT often represents the only way to cure
patients. It is an example of modern high-efficiency medical
technology that is associated with high mortality, morbidity,
and costs. For these reasons, HSCT is a procedure that has
to be performed only in selected patients. Decision-making
represents a challenge for treating physicians, patients, and
healthcare agencies. The activity survey of the European
Bone Marrow Transplant (EBMT) organization collects
EBMT criteria,4 the Italian Authority for Health has estab-
lished the indications for HSCT.5
HSCT is a developing procedure; in the last few years there
has been a change in the major indications and in the type of
conditioning regimens. An increase in the number of trans-
plantations has been observed with the introduction of non-
myeloablative conditioning. The activity survey of the Italian
Group for Blood and Marrow Transplantation (GITMO)
represents an important tool to provide a rapid description of
From the BMT Unit, Department of Hematology, University of
Florence, Florence, Italy.
This work was supported in part by the University of Florence.
Address reprint requests to Alberto Bosi, BMT Unit, Depart-
ment of Hematology, University of Florence, Viale Morgagui 85,
50139 Florence, Italy.

© 2005 by Elsevier Inc. All rights reserved. 0041-1345/05/$–see front matter

360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2005.06.087

Transplantation Proceedings, 37, 2667–2669 (2005) 2667

2668 BOSI, BARTOLOZZI, AND GUIDI

the status quo, assessment of trends, and determination of
factors influencing transplantation rates. This is important for
the physicians involved in patient management.
METHODS
GITMO Activity
The GITMO started its activity in 1987 with the aim to allow
physicians, researchers, and nurses involved in HSCT to share their
experiences, perform analyses of transplantation activity and results,
and promote cooperative studies. GITMO is linked to the Italian
Society of Hematology (SIE). The activity survey annually collects
numbers of HSCT from each participating institution, by indication,
donor type, and stem cell (SC) source. For GITMO members, it is
mandatory to register all transplant recipients per year according to
GITMO rules. On the basis of reported transplantation activity
(number of registered transplantations), Centers are accredited for
autologous, familial allogeneic and unrelated donor transplantation.
Transplant National Registries are as follows: Allogeneic Transplant
Registry located in Genoa (Hematology Department of S. Martino

Fig 1. GITMO data regarding allogeneic transplantations performed beetween 1990 and 2003. (a) Number of allogeneic transplan-
tations performed (N ⫽ 11,940); (b) type of transplant; (c) SC source; (d) age at transplantation; (e) transplantation indications 2003;
and (f) type of conditioning.
STEM CELL TRANSPLANTATION
Hospital, Genoa) and Autologous Registry in Rome (Hematology
Department, La Sapienza University, Rome).
Participating Teams
In 2003, 75 transplantation teams were accredited for autologous,
50 for allogeneic, and 47 for unrelated donor transplantations
(accreditation criteria: at least 10 transplantations per year for
autologous or allogeneic and 20 allogeneic transplantations for
unrelated in 2 consecutive years).
RESULTS
Numbers of HSCT by indication, donor type, and SC source
are made available to participating members every year.
One thousand one hundred seventy allogeneic transplanta-
tions were performed in 2003 (Fig 1a), including 56% from
HLA-identical siblings, 16% family nonidentical, 25% from
alternative donors, and 1% from twins (Fig 1b). The main
indications were acute followed by chronic myeloid leuke-
mia (CML) and thalassemia (Fig 1e). The SC source was
46% bone marrow and 50% peripheral blood (Fig. 1c). The
type of conditioning was 41% myeloablative and 30%
nonmyeloablative (Fig 1f) with an increased number of
transplantations performed in patients older than 60 years
of age (Fig 1d). HSCT outcomes were expressed in terms of
overall survival, disease-free survival, transplant-related
mortality, and relapse incidence. We report the results in
terms of overall survival of HLA identical sibling transplan-
tations performed between 1990 and 2003 regarding the
main indications: acute leukemias, CML, and thalassemia.
The overall survival rate of patients affected by acute
myeloid leukemia (AML) (1456 patients) was 68% (95%
confidence limit [CL]: 64 –71) for those in first complete
remission (CR); 56% (95% CL: 47– 64) for those in second
CR; and 25% (95% CL: 19 –29) for those with more than
second CR. The overall survival rate for patients affected by
acute lymphoblastic leukemia (950 patients) according to
the phase of disease at the time of transplantation was 57%
(95% CL: 50 – 62) for those in first CR; 47% (95% CL:
40 –53) for those in second CR, and 19% (95% CL: 14 –24
for those beyond second CR. Survival for CML (945
patients) was 63% (95% CL: 58 – 67) for subjects in the
chronic phase; 50% (95% CL: 41–57) for the accelerated
phase; and 28% (95% CL: 16 –39) for the blastic phase.
Overall survival rate for patients affected by thalassemia (n
⫽ 966) was 86% (95% CL: 79 – 89) for patients who
underwent transplantation between 1997 and 2003 and 80%
(95% CL: 76 – 83) for patients who underwent transplanta-
tion between 1990 and 1996.
2669
DISCUSSION
The data show a progressive increase during the last 10
years of HSCT activity and, in particular, in the allogeneic
unrelated donors.6,7 This phenomenon may probably be
due to the expansion of the unrelated donor registries.8 As
shown by EBMT data,4,6,8 in the last few years there has
been a change in trends in SC source and in the type of
conditioning. These changes, in particular the increase in
nonmyeloablative conditioning with the reduction in trans-
plant toxicity, have allowed physicians to perform trans-
plantations on older patients and with comorbidities. The
outcome for HSCT patients varies depending on the phase
of the disease at the time of transplantation; better results
are obtained when the transplant is treated in the earlier
phase of the disease.9
The GITMO activity represents an important tool be-
cause it reflects the transplantation status in Italy each year.
Providing assessment of trends and determination of factors
influencing transplantation rates allows it to be a central
base for many physicians and patients in decision-making. It
serves as a quality-control instrument for individual teams.
Moreover, it may be the starting point for the design of both
retrospective and prospective cooperative studies.
REFERENCES
1. Thomas DD: Bone marrow transplantation: a review. Semin
Hematol 36(suppl 7):95, 1999
2. Lennard AL, Jackson GH: Stem cell transplantation. BMJ
321:433, 2000
3. Baron F, Storb R, Little M: Hematopoietic cell transplanta-
tion: five decades of progress. Arch Med Res 34:528, 2003
4. Urbano-Ispizua A, Schmitz N, de Witte T, et al: For the
European Group for Blood and Marrow Transplantation: Alloge-
neic and autologous transplantation for haematological diseases,
solid tumours and immune disorders: definitions and current
practise in Europe. Bone Marrow Transplant 29:639, 2002
5. Gazzetta Ufficiale della Repubblica Italiana 227:34, 30/09/
2001
6. Gratwohl A, Schmid O, Baldomero HC: Accreditation Com-
mittee of the European Group for Blood and Marrow Transplan-
tation: Haematopoietic stem cell transplantation (HSCT) in Eu-
rope 2002. Changes in indication and impact of team density. A
report of the EBMT activity survey. Bone Marrow Transplant
34:855, 2004
7. Gratwohl A for the EBMT JACIE Accreditation Office:
Overview of transplant activity in Europe. Hematol J 5:29, 2004
8. Dini G, Cancedda R, Locatelli F, et al: Italian Bone Marrow
Transplant Group (GITMO): unrelated donor marrow transplan-
tation: an update of the experience of the Italian Bone Marrow
Group (GITMO). Haematologica 86:451, 2001
9. Bacigalupo A, Sormani MP, Lamparelli T, et al: Reducing
transplant-related mortality after allogeneic hematopoietic stem
cell transplantation. Haematologica 89:1238, 2004