DR. BOLLARD: Thank you, Dr. Lowe. I really thank you all for speaking in a very detailed way about the importance of obtaining tumor tissue to perform these critical biologic studies, because I do feel that's an important issue to overcome for the future care of our pediatric patients with NHL. I would like to discuss late effects in our survivors. As Dr. Gross said, survival rates for patients with B-cell lymphomas are generally outstanding. Dr. Gross, do you feel that late effects are not something the NHL group has to worry about now that we have obviated the need for radiation, or not? And what are your feelings about trying to minimize these late effects even further?
DR. GROSS: The good news is that over time, we have been able to come up with regimens that are highly effective but have reduced the agents we know have the highest risk of late effects—radiation being the primary one, but also anthracyclines we have been able to reduce in the vast majority of the patients, and to keep alkylating agents in the vast majority of the patients to a level that most patients do not have infertility. The long-term side effects are becoming pretty minimal, but the question is, how low do they have to be to be acceptable? The goal would be cure without any long-term effects. As I said before, certainly we have paid the price in short-term effects. Our regimens are inpatient, and they can have quite severe short-term side effects such as mucositis. We've made great advances but I think there's still room to go.
DR. CAIRO: I agree, of course, with my colleague Dr. Gross. Again, when we look at large series of chronic health care conditions, certainly children with treated NHL still comes up as one showing over 40% to 50% of patients having one or two serious chronic health care conditions. We know the data are a little antiquated, because they include patients who were treated with different regimens in the 1970s and all of the 1980s. However, I think our goal continues to be to identify the most effective treatment regimen, but with the least toxic long-term complications for our patients. That struggle is very difficult because of the very high success rate we have today, and to identify without hurting that high success rate less toxic therapies will require a collaborative, multidisciplinary, international effort to reach that goal.
DR. BOLLARD: Thank you very much Drs. Cairo and Gross. Dr. Lowe, did you have any closing remarks on the late effects issues for the T-cell mediated diseases in particular?
DR. LOWE: I would absolutely agree with Dr. Gross and Dr. Cairo that this is an important issue. I think we in pediatrics do a good job at following our patients for long-term side effects and creating guidelines for screening for these long-term side effects. That said, I think as we start to talk about better and better therapy and even more and more targeted therapy, what we don't know about some of these targeted therapies is their 15 and 20 year long-term side effects. We obviously hope that there aren't any, and that's why we are moving toward these drugs, but again, surveillance of those long-term side effects will be extremely important, especially when you're talking about medications for young children.
DR. BOLLARD: I'd like to thank you all very much for participating in this expert roundtable discussion today. I think the overarching points are that prognoses at the current time for newly diagnosed pediatric patients with NHL range from 70% to over 90% even for patients with disseminated disease. The challenges that we need to overcome are how we can optimize our up front treatment to prevent relapse in all, because I think we've all reiterated the fact that the outcomes for those few patients who do relapse remains extremely poor. I think there is still controversy about how to manage patients with relapsed disease, and how to temper our therapies against long-term side effects of our surviving patients. Finally, I think with the advent of novel targeted agents, it is incredibly important for the optimal management of our current and future patients that we are able to access tumor tissues and perform the critical biologic studies that are required to develop an effective precision medicine approach for pediatric patients with NHL. I would like to again thank Dr. Cairo, Dr. Gross, and Dr. Lowe for their excellent answers to my, at times, difficult and challenging questions and I would like to thank the organizers of this expert roundtable discussion. I hope that in the next decade that we will see even greater advances for the patient population that we treat. Thank you very much.
References
1. Rosolen RA, Perkins SL, Pinkerton CR, et al. Revised International Pediatric Non-Hodgkin Lymphoma Staging System. J Clin Oncol. 2015;33(18):2112–2118.
2. Sandlund JT, Guillerman RP, Perkins SL, et al. International Pediatric Non-Hodgkin Lymphoma Response Criteria. J Clin Oncol. 2015;33(18)2106-2111.