Journal of Hematology - Supplements - Haematologica

56
In the group of 14 patients who needed a second
BMT the incidence of CMV infection was
35.7%.The infections occurred between 10 and
46 days post-transplantation (median, 31).
Discussion
In this study we evaluated the sensitivity and
specificity of the antigenemia assay and the polymerase
chain reaction for monitoring BMT
recipients; moreover incidence of CMV infections
was evaluated by antigenemia and analyzed
for clinical and personal variables such as
age, sex, underlying disease, donor compatibility
and GVHD.
In a subset of 60 samples PCR detected all 20
infected patients with a sensitivity of 100% and
a specificity of 100%, antigenemia failed to recognize
one case (sensitivity 95%). The discordant
PCR positive result preceded the onset of
antigenemia by a week indicating that PCR is
important in the diagnosis of the very early
phase of CMV infection 17 although it may be
too sensitive a marker in the clinical setting and
its introduction in routine diagnostic protocols
needs further evaluation.
The incidence of CMV in the group of patients
receiving allogeneic BMT was 46.7% similar to
that observed in similar studies. 18 The relevant
result of our work is that the incidence of CMV
infections is related to the severity of immunosuppression
induced by the conditioning regimen,
the treatment of marrow and GVHD prophylaxis.
There is, therefore, no surprise about
the lack of antigenemia among the patients submitted
to an autologous BMT, and the increase
of positive antigenemia when a donor different
from a HLA matched sibling was used.
Rather impressive was the discovery of the
higher incidence in matched unrelated donor
(MUD) BMT (85.7%) than in haploidentical
BMT (41.7%). From the theoretical point of view
a matched transplant should assure a better
immunologic reconstitution and a reduced risk
of viral infections. As a matter of fact in our clinical
experience there was no difference in GVHD
severity in MUD and haploidentical transplants.
We must consider that the so-called HLA match
is an illusion outside the family of the patient;
beyond the 6 HLA loci that result as being identical,
there are other genetic markers that are
unavoidably different between a patient and his
MUD donor. In order to reduce the severity of
GVHD these patients are submitted to a conditioning
regimen and GVHD prophylaxis that are
heavier than that used for a transplant from a
matched sibling donor. In most cases anti-thymocytic
globulin is given before the transplant.
Our patients submitted to a mismatched BMT
received a conditioning regimen not different from
the one received by MUD transplant recipients;
GVHD prophylaxis did not include metothrexate
together cyclosporin A, while MUD BMT protocols
usually provide a double drug prophylaxis.
The treatment of donor’s marrow in haploidentical
transplants was performed with a
technique that does not deplete T-lymphocytes:
we use a functional T-cell depletion achieved by
means of in vivo incubation with vincristine and
methylprednisolone. Such a cocktail interferes
with the activity of both Th1 and Th2 lymphocytes,
without inducing apoptosis. 19 The viability
of T-lymphocytes is assured and therefore the
risk of late viral infections is, as demonstrated in
our survey, not worse than that following a
MUD transplant.
References
1. HG Prentice, E Gluckman, RL Powles, et al. Long- term
survival in allogeneic bone marrow transplant recipients
following acyclovir prophylaxis for CMV infection.
Bone Marrow Transplant 1997; 19:129-33.
2. Griffiths PD Current management of cytomegalovirus
disease.J Med Virol 1993; 1:106-11.
3. D Couriel, J Canosa, H Engler, et al. Early reactivation
of cytomegalovirus and high risk of interstizial pneumonitis
following T-depleted BMT for adults with
hematological malignancies. Bone Marrow Transplant
1996; 18:347-53.
4. Y Takemoto, H Takatsuka, H Wada, et al. Evaluation
of CMV/human herpes virus-6 positivity in bronchoalveolar
lavage fluids as early detection of acute
GVHD following BMT: evidence of a significant relationship.
Bone Marrow Transplant 2000; 26:77-81.
5. AJ Huaringa, FJ Leyva, J Signes-Costa, et al. Bronchoalveolar
lavage in the diagnosis of pulmonary complications
of bone marrow transplant patients. Bone
Marrow Transplant 2000; 25:975-9.
6. D Gor, C Sabin, HG Prentice, et al. Longitudinal fluctuations
in cytomegalovirus load in bone marrow
transplant patients: relationship between peak virus
load, donor/recipient serostatus, acute GVHD and
CMV disease. Bone Marrow Transplant 1998; 21:
597-605.
7. HG Prentice, P Kho. Clinical strategies for the management
of Cytomegalovirus infection and disease in
allogeneic bone marrow transplant. Bone Marrow
Transplant 1998; 19:135-42.
8. G Gerna, M Zavattoni, E Percivalle, et al. Rising Levels
of Human Cytomegalovirus (HCMV) Antigenemia
during Initial Antiviral Treatment of Solid-Organ
Transplant Recipients with Primary HCMV Infection.
J Clin Microbiol 1998; 4:1113-6.
9. CM Machado, FL Dulley, LS Vilas Boas, et al. CMV
pneumonia in allogeneic BMT recipients undergoing
early treatment or pre-emptive ganciclovir therapy.
Bone Marrow Transplant 2000; 26:413-7.
10. P Ljungman. Immune reconstitution and viral infections
after stem cell transplantation. Bone Marrow
Transplant 1998; 21 (Suppl. 2): S72-4.
11. M Boeckh, S Riddel, T Cunninggham, et al. Increased
risk of late CMV infection and disease in allogeneic
marrow transplant recipients after ganciclovir prophylaxis
is due to a lack of CMV specific T-cell responses.
Blood, 1996; 88 (Suppl. 1):302a.
12. CR Li, PD Greenberg, Mj Gilbert, et al. Recovery of
haematologica vol. 85(supplement to n. 11):November 2000