Dose-Escalated Donor Lymphocyte Infusions Post Allogeneic Transplantation in Non-Hodgkin’s Lymphoma.

The role of donor lymphocytes infusions (DLI) in the treatment of non-Hodgkin’s lymphoma (NHL) following allogeneic haemopoietic stem cell transplant (HCST) has not been clearly characterised. We report the results of 51 infusions of dose-escalating donor lymphocytes to 24 patients following myeloablative (n=3) or reduced intensity (n=21) transplantation as treatment for NHL. The diagnoses were low grade NHL (n=19), transformed low grade NHL and high grade NHL (n=5). Twenty patients were transplanted from an HLA-matched sibling, and 4 from an unrelated donor. The indications for DLI were progressive or relapsed disease (n=17), with or without mixed chimersim, and persistent mixed chimersim alone (n=7). Eight of the patients treated for disease progression or relapse had both clinical and radiological evidence of disease, a further 8 cases had radiological evidence of disease alone (CT scan in 3; CT-PET scan in 6) and one case of progressive disease was diagnosed following a bone marrow biopsy. Histological confirmation of relapse or disease progression was confirmed in 8 cases. Eighteen patients received an initial dose of 1x106/kg CD3 positive cells at a median of 265 days post transplant (range 181–728) and 6 received an initial dose of 1x107/kg cells at a median of 402 days post transplant (range 130–2674). Escalating doses of cells were administered at 3-month intervals (3 x 106/kg, 1 x 107/kg, 3 x 107/kg, 1 x 108/kg) in the absence of development of graft-versus-host disease (GvHD), if mixed chimerism persisted or if there was no evidence of disease response. Four of the patients treated for disease progression also received antitumoural chemotherapy shortly before DLI. Of the 16 evaluable patients treated for disease, 12 (75%) showed a significant response to DLI (9 patients with low grade NHL and 3 with transformed low grade NHL). A complete remission (CR) was observed in 10 patients and partial remission in 2 patients. Three of the patients achieving a CR following DLI subsequently relapsed; the median duration of the ongoing complete remissions is 574 days (range 122–1479). One patient died of sepsis before the response to DLI could be assessed. Conversion from mixed to multilineage full donor chimersim occurred in 18 of 18 (78%) evaluable patients. The major toxicity resulting from the use of DLI was GvHD. Following DLI, acute GvHD (grade II–IV) occurred in 5 out of 20 evaluable patients (24%) and chronic extensive GvHD in eight patients (38%); 1 patient died during treatment for grade IV acute gut GvHD. The incidence of GvHD did not correlate with the dose of DLI infused and 5 patients had graft-versus-lymphoma responses without GvHD. These data support the existence of a clinically significant graft versus tumour effect in non-Hodgkin’s lymphoma and indicate that this is an effective treatment for progressive disease post allogeneic HSCT.