Allotransplantation in pediatric HL

Fifty-one patients received a reduced intensity transplantation (primarily a fludarabine-based regimen) while 40 patients received a myeloablative conditioning regimen. The probability of progression-free survival at 2 and 5 years was 40% plus or minus 6% and 30% plus or minus 6%, respectively. Overall survival at 2 and 5 years was 54% plus or minus 6% and 41% plus or minus 6%, respectively. Although the relapse rate for patients receiving myeloablative conditioning was similar to that for patients receiving a reduced-intensity conditioning for the first 9 months after transplantation, subsequent relapses were more frequent in the group receiving reduced-intensity conditioning.

Before one examines the overall and subgroup analyses presented by the authors, the potential problems associated with the analysis of “registry” data need to be considered. Because the clinical history for an individual patient is not presented, it is not clear why a particular treatment was given to an individual patient. In this registry dataset, approximately 55% of patients received an allogeneic transplantation as their first transplantation. Currently, no guidelines for treating relapsed Hodgkin lymphoma (HL) recommend allogeneic transplantation as the initial transplantation.²  It would be interesting to know why investigators chose allogeneic transplantation over the more standard autologous transplantation. It would have been helpful if the authors had presented separate outcome data for patients who received an initial allogeneic transplantation and those who received an allogeneic transplantation after a failed autologous transplantation. The fact that more than half of the patients reported had nonstandard treatment limits the usefulness of this data.

In this paper, the authors compare the results of patients receiving myeloablative to reduced-intensity conditioning. The authors conclude that reduced-intensity conditioning is associated with similar nonrelapse mortality and a higher relapse rate. But, before considering whether differences in outcome among subgroups are relevant, one must ensure comparability of the analyzed groups.

Salvage chemotherapy followed by autologous stem cell transplantation is the standard of care for pediatric HL patients who present with advanced-stage disease and fail front-line therapy. Patients who received reduced-intensity conditioning were more likely to have received 4 or more salvage regimens (P = .001) and were more likely to have undergone an unsuccessful previous autologous transplantation (P < .001), compared with patients receiving a myeloablative chemotherapy regimen. Even though chemotherapy sensitivity and disease status at transplantation were comparable, my impression is that the patients receiving reduced-intensity conditioning represent a group with a higher likelihood of dying from complications related to the transplantation and to relapse. Thus, I think the “evidence” that reduced-intensity conditioning is associated with a higher relapse rate compared with myeloablative conditioning is flawed and should not be given significant credence.

It is unlikely there will ever be a randomized study evaluating the role of either autologous or allogeneic transplantation for treating relapse or primary progression in pediatric patients with HL. There is a general consensus among pediatric oncologists that high-dose chemotherapy and autologous peripheral stem cell transplantation is effective treatment for patients with primary refractory HL and for patients with advanced-stage disease at presentation who experience a relapse. Currently there is no indication to use allogeneic transplantation as the first transplantation unless the patient's stem cells cannot be mobilized. The article by Claviez et al provides important information that patients who relapse following an autologous transplantation still have the potential for cure following allogeneic stem cell transplantation. In our center, such patients are generally offered a reduced-intensity conditioning regimen in an effort to reduce the nonrelapse mortality. It is clear from this article that reduced-intensity conditioning is being used more frequently. Between 1987 and 2001, 36% of patients received reduced-intensity conditioning compared with 75% between 2001 and 2005.

Only a registry study could provide sufficient data to begin to evaluate the role of allogeneic transplantation in the treatment of pediatric patients with HL. However, in evaluating conclusions drawn from registry data, reported subgroups must be analyzed carefully to ensure that they are comparable. This study clearly shows that allogeneic transplantation following a failed autologous transplantation is feasible and potentially curative for pediatric patients with relapsed HL. However, the comparison between myeloablative and reduced-intensity conditioning is limited in value because the 2 groups have significantly different earlier treatment. It is likely that reduced-intensity conditioning will continue to increase in frequency.