Disease relapse occurs in 50% or more of patients who are autografted for relapsed or refractory lymphoma (NHL) or Hodgkin's disease (HD). The administration of non-cross-resistant therapies during the post-transplant phase could possibly control residual disease and delay or prevent its progression. To test this approach, 55 patients with relapsed/refractory or high-risk NHL or relapsed/refractory HD were enrolled in the following protocol: stem cell mobilization: cyclophosphamide (4.5 g/m2) + etoposide (2.0 g/m2) followed by GM-CSF or G-CSF; high-dose therapy: gemcitabine (1.0 g/m2) on day −5, BCNU (300 mg/m2) + gemcitabine (1.0 g/m2) on day −2, melphalan (140 mg/m2) on day −1, blood stem cell infusion on day 0; post-transplant immunotherapy (B cell NHL): rituxan (375 mg/m2) weekly for 4 weeks + GM-CSF (250 μg thrice weekly) (weeks 4–8); post-transplant involved-field radiotherapy (HD): 30–40 Gy to pre-transplant areas of disease (weeks 4–8); post-transplant consolidation chemotherapy (all patients): dexamethasone (40 mg daily)/cyclophosphamide (300 mg/m2/day)/etoposide (30 mg/m2/day)/cisplatin (15 mg/m2/day) by continuous intravenous infusion for 4 days + gemcitabine (1.0 g/m2, day 3) (months 3 + 9) alternating with dexamethasone/paclitaxel (135 mg/m2)/cisplatin (75 mg/m2) (months 6 + 12). Of the 33 patients with B cell lymphoma, 14 had primary refractory disease (42%), 12 had relapsed disease (36%) and seven had high-risk disease in first CR (21%). For the entire group, the 2-year Kaplan–Meier event-free survival (EFS) and overall survival (OS) were 30% and 35%, respectively, while six of 33 patients (18%) died before day 100 from transplant-related complications. The rituxan/GM-CSF phase was well-tolerated by the 26 patients who were treated and led to radiographic responses in seven patients; an eighth patient with a blastic variant of mantle-cell lymphoma had clearance of marrow involvement after rituxan/GM-CSF. Of the 22 patients with relapsed/refractory HD (21 patients) or high-risk T cell lymphoblastic lymphoma (one patient), the 2-year Kaplan–Meier EFS and OS were 70% and 85%, respectively, while two of 22 patients (9%) died before day 100 from transplant-related complications. Eight patients received involved field radiation and seven had radiographic responses within the treatment fields. A total of 72 courses of post-transplant consolidation chemotherapy were administered to 26 of the 55 total patients. Transient grade 3–4 myelosuppression was common and one patient died from neutropenic sepsis, but no patients required an infusion of backup stem cells. After adjustment for known prognostic factors, the EFS for the cohort of HD patients was significantly better than the EFS for an historical cohort of HD patients autografted after BEAC (BCNU/etoposide/cytarabine/cyclophosphamide) without consolidation chemotherapy (P = 0.015). In conclusion, post-transplant consolidation therapy is feasible and well-tolerated for patients autografted for aggressive NHL and HD and may be associated with improved progression-free survival particularly for patients with HD. Bone Marrow Transplantation (2002) 29, 303–312. doi:10.1038/sj.bmt.1703363

In a retrospective study, we examined the association between cytomegalovirus (CMV) infection and non-neutropenic fever immediately following autologous peripheral blood stem cell transplantation for a variety of haematological malignancies and solid tumours. Sixty non-neutropenic febrile episodes (41 in CMV-seropositive and 19 in CMV-seronegative patients) were evaluated. CMV reactivation, documented by CMV antigenaemia, was detected in 16 out of 41 (39%) seropositive patients compared with 0 out of 19 seronegative patients. In 12 of these 16 patients, CMV infection was considered the sole cause of fever. Thirteen patients had maximum antigenaemia levels > 5 cells/slide. Specific antiviral treatment led to the resolution of the fever in all, but two, patients, who developed fatal CMV pneumonia. Patients with multiple myeloma and lymphoma, possibly owing to a combination of disease-related characteristics and prior immunosuppressive treatment, had high rates of CMV reactivation and may require more frequent diagnostic evaluation and prompt therapeutic intervention.

Immunosuppressive therapy, routinely given after allogeneic transplantation to modulate graft-versus-host disease (GVHD) may have an adverse effect on the graft-versus-tumour (GVT) effect. Twelve patients with high-risk haematological malignancies were given cyclophosphamide, total body irradiation and antithymocyte globulin followed by peripheral blood stem cell grafts from HLA-identical siblings without prophylactic immunosuppression. At the earliest clinical evidence of GVHD, patients were treated with high-dose solumedrol and tacrolimus. Prompt haematological recovery [absolute neutrophil count (ANC) > 1.0 x 109/l] was observed (median time 9 d). All patients developed grade III-IV GVHD (median onset 9 d), involving the skin (11), intestine (five) and liver (three). Of nine evaluable patients, seven developed chronic GVHD [extensive (six), limited (one)]. Six patients died 1-6.5 months after transplantation. Three patients died from treatment-related complications, two from acute GVHD and one from relapsing disease. The remaining six patients are alive 5-26 months after transplantation, five in complete remission and one myeloma patient in very good partial remission. In conclusion, omission of post-transplantation GVHD prophylaxis is feasible, does not lead to graft failure or a high incidence of uncontrollable GVHD and appears to be associated with encouraging clinical responses in a group of patients with high-risk disease features.