Graft-Versus-Lymphoma Effect in Hodgkin’s Disease: A Possible Role in Maintaining a Disease Control.

Introduction: non-myeloablative and highly immunosuppressive conditioning regimen instead of conventional bone marrow transplantation have been recently developed. The aim of this treatment is to establish a mixed chimerism and to allow the donor cell-mediated graft versus-tumor effect to occur. This is a well known effect in disease like CML and AML and much less investigated in Hodgkin Lymphoma.

Patients and methods: from September 2003 to November 2004, 5 pts affected by chemorefractory Hodgkin’s lymphoma, underwent a non-myeloablative conditioning regimen followed by allogeneic peripheral blood stem cell transplantation (PBSCT). Median age was 28 ys (range 26–33), 4 M and 1 F, all pts had failed previous conventional treatment including autologous PBSCT. Conditioning regimen were the following: Fludarabine 30 mg/mq, from day −4 to −2 followed by TBI 2Gy on day 0 in 2 pts; TBI 2Gy alone two month after an autologous PBSCT in 1pt; thiotepa 5mg/kg x2, Fludarabine 30mg/mq, Cyclofosfamide 30 mg/kg in 1pt or Rituximab 600 mg/mq on day −5; fludarabine 30 mg/mq + Cyclofosfamide 30 mg/kg from day −4 to day −3 in the other one. All patients received donor peripheral stem cell infusion on day 0. Prophylaxis of aGVHD was performed with Cyclosporine (6.25 mg/kg) po from day −3 to day +36 followed by a rapid tapering until day +56 and Mycophenolate Mofetil (15mg/kg) po from day 0 to +27.

Results: All pts experienced a complete engraftment, obtained a complete response after transplantation and 3/5 them experienced hepatic and/or cutaneous cGvHD. At a median follow-up of 13 months 2/3 pts, who received TBI and/or Fludarabine, are alive after 681 days, 612 days from transplantation and are in CR and SD respectively; both of them had cGvHD; the third one has died at +132 for cerebral hemorrhage. One of the remaining two patients has died at +200 in CR for septic shock after cGvHD, and the last one is still alive in +410 in PD, with no sign of cGvHD.

Conclusions: although limited, our data seem to suggest that even in pts affected by Hodgkin’s lymphoma with a chemoresitant disease, the development of cGvHD after a reduced conditioning allogeneic PBSCT, mostly immunosuppressive, seems to be associated with the presence of a graft-versus lymphoma effect able to mediate a good control of the disease.