Journal of Hematology - Supplements - Haematologica

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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
57 HLA-restricted cytomegalovirus (CMV)-specific T-cell responses after allogeneic bone marrow transplant: correlation with CMV disease and effect of ganciclovir prophylaxis. Blood, 1994; 83:1971-9. 13. CR de Medeiros, VA Moreira, R Pasquini. Cytomegalovirus as a cause of very late interstitial pneumonia after bone marrow transplantation. Bone Marrow Transplant 2000; 26:443-4. 14. H Sakuma, M Hosoya, H Kanno, et al. Risk of cytomegalovirus infection after peripheral blood stem cell transplantation. Bone Marrow Transplant 1997; 19:49-53. 15. Alejo Erice. Resistance of human cytomegalovirus to antiviral drugs. Clin Microbiol Rev 1999; 2:286-97. 16. GJ Demmler, GJ Buffone, CM Schimbor, et al. Detection of cytomegalovirus in urine from newborns by using polymerase chain reaction DNA amplification. J Infect Dis 1988; 158:1177-84. 17. AM Vlieger, GJ Boland, NM Jiwa, et al. Cytomegalovirus antigenemia assay or PCR can be used to monitor ganciclovir treatment in bone marrow transplant recipients. Bone Marrow Transplant 1992; 9:247-53. 18. H Einsele, G Ehninger, H Hebart, et al. Polymerase chain reaction monitoring reduces the incidence of cytomegalovirus disease and the duration and side effects of antiviral therapy after bone marrow transplantation. Blood 1995; 86:2815-20. 19. A Lanfranchi, M Andolina, K Tettoni, et al. Functional depletion of cells by vincristine and methylprednisolone as an in vitro model for the prevention of graft versus host disease. Haematologica 1992; 77:11- 5. haematologica vol. 85(supplement to n. 11):November 2000
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