Reduced Intensity Allogeneic Stem Cell Transplantation for Hodgkin’s Disease. Outcome Depends Primarily on Disease Status at the Time of Transplantation.

The use of reduced intensity conditioning regimens has extended the application of allogeneic stem cell transplantation to patients previously considered to old or medically unfit for high dose chemo-radiotherapy. However, the role of reduced intensity allogeneic transplantation (RIT) in the treatment of Hodgkin’s disease remains controversial due in part to the limited information available on the outcome of this procedure.We have therefore analysed a large cohort of patients with HD who have undergone RIT. A total of 311 patients from 127 centres were reported to the EBMT registry. Their median age at transplantation was 31.3 years (range 8–61) and 57% were male. They had undergone a median of 2 lines of prior therapy (range 1–6) and 45% of patients had undergone a prior high dose procedure. The median time from diagnosis to RIT was 3.2 years (range 0.25–24.5 years). At transplantation 158 patients had chemosensitive disease, 100 had chemoresistant disease and 53 had untested relapse. All patients underwent conditioning with reduced intensity regimens followed by bone marrow stem cell transplantation from matched family donors (221), matched unrelated donors (61) or mismatched donors (17). Peripheral blood stem cells were used in 263 patients, bone marrow in 46 and a combination in 2. In 294 cases assessable for engraftment sustained engraftment was seen in 93.6%. Chimerism studies performed in 115 patients revealed full donor chimerism in 85 and mixed chimerism in 30. Acute graft versus host disease (grade II–IV) was reported in 24% of patients and chronic graft versus host disease in 20%. With a median follow up of 1 year 59% of patients remain alive and the projected 2 year overall survival (OS) was 46%. In a univariate analysis only disease status at transplantation predicted for a worse OS (p<0.0001). The 100 day transplant related mortality (TRM) was 17% but this increased to 24% at 1 year and 27% at two years and was significantly worse for patients with chemoresistant disease at transplantation (p=0.02). Patient age and prior high dose therapy had no significant impact on TRM. At 1 and 2 years following transplantion 48% and 64% of patients had experienced relapse or progression of their disease. Only disease status at transplantation predicted for a higher risk of disease progression. Consequently the progression free survival (PFS) at 2 years was 26% and was significantly worse for patients with chemoresistant disease (p<0.0001). In univariate analysis patient age, prior high dose therapy and number of lines of prior therapy had no significant effect on PFS. Patients with HD may undergo RIT with acceptable toxicity irrespective of age and prior high dose therapy. However, the outcome depends upon the chemosensitivity of the disease at the time of transplantation and this factor should be a major consideration in the selection of patients for RIT.