Allogeneic transplantation for children and adolescents with Hodgkin lymphoma

To the editor:

Our article on allogeneic hematopoietic stem cell transplantation in children and adolescents with recurrent and refractory Hodgkin lymphoma¹  was accompanied by an Inside Blood commentary written by Dr James Nachman. Although we agree that registry data need special attention in order not to draw unjustified conclusions, we disagree with other conclusions not supported by any data and reject his “impression” that “the evidence that reduced-intensity conditioning (RIC) is associated with a higher relapse rate compared with myeloablative conditioning is flawed and should not be given significant credence.”

In fact, several papers on allogeneic transplantation for Hodgkin lymphoma²  and other diseases^3,4  repeatedly demonstrated that RIC results in significantly increased relapse rates if compared with myeloablative conditioning (MAC). We maintain our conclusion that more vigorous (not necessarily fully myeloablative) conditioning is a viable option to reduce the high relapse rates seen in all patients receiving transplants for Hodgkin lymphoma. This may be particularly attractive in children and adolescents who tolerate aggressive chemotherapy as part of the conditioning regimen much better than older patients. The unique difference between children/adolescents and adult patients is that nonrelapse mortality (NRM) after MAC is high in adults, whereas this was not seen in children and adolescents.¹  To further substantiate this finding we reanalyzed NRM in our dataset but this time included all patients below the age of 21 years. Even in this still young population (n = 151) NRM after MAC was significantly higher than after RIC, whereas in our paper we reported that NRM curves were superimposable in 91 patients aged 18 years or younger who received RIC or MAC.

Another concern raised by Dr Nachman is based on the fact that approximately half of the patients reported by the European Group for Blood and Marrow Transplantation (EBMT) underwent allogeneic transplantation as their first transplantation. We do not have all the information available to describe fully the decision-making process in individual transplant centers. However, Dr Nachman and the reader should be aware that EBMT has been running the only prospective study on allogeneic transplantation for Hodgkin lymphoma (HD-R ALLO study; A.S., C. Canals, R. Arranz, D. Caballero, J. M. Ribera, M. Brune, J. Passweg, J. Besalduch, R. F. Duarte, A. Léon, M. J. Pascual, N.S., oral presentation submitted for 2009 ASH annual meeting), in which patients with refractory disease after first-line therapy or early first relapse could be included. Because of the discussions preceding this study and the poor results of autologous transplantation in chemorefractory patients, some clinicians obviously preferred an allogeneic over an autologous transplantation. To address the question of any potential bias introduced by analyzing patients who had not received an autologous transplant before allogeneic transplantation, we did a multivariate analysis and reported the results in our paper. Neither the number of previous lines of therapy nor a prior autologous transplantation influenced the relapse rates; one significant factor with a negative impact on relapse rate was RIC. Thus, we do not believe that our results are flawed by including patients who had not failed an autologous transplantation or by any other selection process. We do believe, however, that clinical decision-making should be guided by facts and not by “impressions” or “general consensus” as recommended by Dr Nachman. We agree with Sigmund Freud, who stated in Reflection on War and Death: “Illusions commend themselves to us because they save us pain and allow us to enjoy pleasure instead. We must therefore accept it without complaint when they sometimes collide with a bit of reality against which they are dashed to pieces.”⁵  Undoubtedly, RIC represents a major achievement in hematopoietic stem cell transplantation; however, we believe that a more sophisticated approach to conditioning, rather than “one size fits all,” is warranted.