Is There a Virus-Versus-Leukemia Effect?

Mojtaba Akhtari, MD

The current dogma considers cytomegalovirus (CMV) seropositivity being associated with inferior outcomes post hematopoietic stem cell transplant (HSCT).[1] However, there has been a notion of virus-versus-leukemia effect since the 1980s; and recently, there have been some interesting reports[2-4] which may turn this into a hot topic.[5]

Lonnqvist et al evaluated relapse rate in 72 patients with hematological malignancies after bone marrow transplant (BMT) and showed reduced relapse in leukemia patients with CMV infection.[6] Jacobsen et al reported on reduced relapse risk in acute leukemia patients post HSCT when the donors and recipients were CMV seropositive.[7] Nachbaur et al also suggested donor CMV-seropositivity was associated with reduced relapse risk in acute leukemia patients after reduced intensity conditioning HSCT.[8] Another recent report by Behrendt et al showed a relationship between lower relapse risk after HSCT in pediatric acute leukemia patients with a positive pretransplant CMV of donors and/or recipients.[2]

Elmaagacli et al have also published very interesting data looking at the relationship between cytomegalovirus infection and risk of relapse following HSCT in patients with AML. First, they presented their data at the ASH 2009 Meeting where they showed cytotoxic effects of human CMV on Kasumi-1 AML cell lines in vitro. They also analyzed outcomes of 140 AML patients who underwent allogeneic HSCT and developed CMV reactivation.[3] They compared those patients’ outcomes with 60 CML patients who were treated with transplant and demonstrated that CMV reactivation in AML patients was associated with reduced relapse risk (11.6% versus 50.5%; P < .0001) and improved overall survival (73.6% vs 42.5%; P = .039).

Then, they examined the relationship between CMV reactivation and relapse risk in 266 AML patients after HSCT in a retrospective study and showed patients with early CMV reactivation, detected by pp65-antigenemia assay, had a decreased cumulative incidence of relapse at 10 years (9%) in comparison with patients without CMV reactivation (42%; P < .0001). [4] The Elmaagacli’s reports are challenging and can bring back the notion of “virus-versus-leukemia” effect for further greater discussions and scrutiny.

References:

1. Boeckh M, Nichols GW. The impact of cytomegalovirus serostatus of donor and recipient before hematopoietic stem cell transplantation in the era of antiviralprophylaxis and preemptive therapy. Blood. 2004; 103: 2003-2008.

2. Behrendt CE, Rosenthal J, Bolotin E, et al. Donor and recipient CMV serostatus and outcome of pediatric allogeneic HSCT for acute leukemia in the era of CMV-preemptive therapy. Biol Blood Marrow Transplant. 2009;15:54-60.

3. Elmaagacli AH, Lindermann M, Opalka B, et al.  Cytomegaloviurs reduces the relapse risl of acute leukemia after transplant: There is a virus-versus-leukemia effect. ASH 2009; Abstract 2261.

4. Elmaagacli AH, Steckel NK, Koldehoff M, et al. Early human cytomegalovirus replication after transplant is associated with a decreased relapse risk: Evidence for a putative virus-versus-leukemia effect. Blood. 2011 May 3. [Epub ahead of print]

5. Solano C, de la Camara R, Nieto J, Lopez J, Garcia-Noblejas A, et al. Active cytomegalovirus infection and the risk of leukemic relapse following allogeneic stem cell transplantation in patients with acute myeloid leukemia. Blood. 2011 June 3. [Epub ahead of print]

6. Lonnqvist B, Ringden O, Ljungman P, et al. Reduced risk of recurrent leukaemia in bone marrow transplant recipients after cytomegalovirus infection. Br J Haematol. 1986;63:671-679.

7. Jacobsen N, Badsberg JH, Lonnqvist B, et al. Graft-versus-leukaemia activity associated with CMV-seropositive donor, post-transplant CMV infection, young donor age and chronic graft-versus-host disease in bone marrow allograft recipients. The Nordic Bone Marrow Transplantation Group. Biol Blood Marrow Transplant. 1990;5:413-418.

8. Nachbaur D, Clausen J, Kircher B. Donor cytomegalovirus seropositivity and the risk of leukemic relapse after reduced-intensity transplants. Eur J Haematol. 2006;76:414-419.