Superiority of reduced-intensity allogeneic transplantation over conventional treatment for relapse of Hodgkin's lymphoma following autologous stem cell transplantation

This study compares outcome of reduced-intensity conditioned transplant (RIT) with outcome of conventional non-transplant therapy in patients with Hodgkin's lymphoma relapsing following autograft. There were 72 patients in two groups who had relapsed, and received salvage therapy with chemotherapy+/-radiotherapy. One group (n=38) then underwent alemtuzumab-containing RIT. The second group-historical controls (n=34), relapsing before the advent of RIT-had no further high-dose therapy. This group was required to respond to salvage therapy and live for over 12 months post-relapse, demonstrating potential eligibility for RIT, had this been available. Overall survival (OS) from diagnosis was superior following RIT (48% at 10 years versus 15%; P=0.0014), as was survival from autograft (65% at 5 years versus 15%; P< or =0.0001). For the RIT group, OS at 5 years from allograft was 51%, and in chemoresponsive patients was 58%, with current progression-free survival of 42%. Responses were seen in 8 of 15 patients receiving donor lymphocyte infusions (DLI) for relapse/progression, with durable remission in five patients at median follow-up from DLI of 45 months (28-55). These data demonstrate the potential efficacy of RIT in heavily pre-treated patients whose outlook with conventional therapy is dismal, and provide evidence of a clinically relevant graft-versus-lymphoma effect.     

Germ cell damage and Leydig cell insufficiency in recipients of nonmyeloablative transplantation for haematological malignancies

Most bone marrow transplant recipients are infertile due to reversible or irreversible testicular failure. However, little is known about the gonadotoxic potential of the newly introduced nonmyeloablative transplants. We undertook a 24-month longitudinal study in a cohort of 32 recipients of nonmyeloablative transplantation to test whether the combined regimen of fludarabine, melphalan and CAMPATH-1H can induce damage to germ cell (GC) and Leydig cell (LC) compartments. Testicular function was assessed immediately prior to transplantation and at four time points post-transplant to compare hormonal levels before and after the procedure. Two other groups treated with BEAM- and TBI-related regimes were also included in the study group for comparative purposes. GC function was assessed by measuring basal serum follicle stimulating hormone (FSH). LC function was assessed by measuring basal luteinising hormone (LH) and testosterone (T) levels. LC reserve was assessed by measuring the T/LH ratio. As a group, patients who received a non myeloablative transplant sustained severe damage to the GC compartment, as evident from a substantial elevation in the FSH level post-transplant (12 IU/l vs 18.4 IU/l, P<0.001). Similar to the GC injury, patients as a group sustained significant damage to the LC compartment following the transplant (5.4 IU/l vs 9.6 IU/l, P<0.001). In general, patients had reduced LC reserve post-BMT, as evident from a diminished T/LH ratio (2.6 pretransplant vs 1.6 post-transplant P=0.05). Patients who received a nonmyeloablative transplant had a similar effect on the GC and LC compartments compared to those who had a BEAM autograft. On the other hand, patients who received a TBI-based transplant sustained more damage to their GC and LC compartments compared to those who received a nonmyeloblative transplant; however, this was not statistically significant (P=0.09). Our data suggest that this type of regimen is potentially gonadotoxic and consideration should be given to fertility counselling and testosterone replacement therapy post-transplant.     

Predictors of Adherence and Outcome in Internet-Based Cognitive Behavior Therapy Delivered in a Telephone Counseling Setting

This study investigated predictors of adherence and outcome in a sample of callers to a national crisis telephone counseling service who were randomized to receive a 6-week, online, self-administered psychoeducation and cognitive behavioral therapy (CBT) intervention. Age, sex, relationship status, employment status, level of education, baseline depression symptom severity, and motivation to undertake the intervention were examined as predictors of adherence to the intervention in participants assigned to receive the online intervention (n = 83). Predictors of depression outcome were assessed using mixed models repeated measures ANOVA, comparing the two web-CBT intervention groups to the tracking and control groups (n = 155). Lower baseline depression severity was significantly associated with greater adherence to the intervention. A significant interaction was found between measurement occasion and motivation to undertake the intervention. At 6 month follow-up, participants with low and moderate levels of motivation had lower depressive symptoms than those with high levels of motivation. At 12 month follow-up, those with moderate levels of motivation had lower depressive symptoms than those with high motivation. The findings suggest that lower pre-intervention depression symptoms may positively influence adherence to online treatment for depression, while low and moderate levels of motivation appear to be optimal for treatment outcome. The factors that relate to adherence and outcome need to be understood to prevent dropout and maximize treatment effectiveness in online interventions.