The purpose of our study was to evaluate the outcomes of first HSCT in pediatric and young adult patients with relapsed Hodgkin’s Lymphoma (HL) who were transplanted at our institution. Most clinical studies evaluating outcomes of salvage therapy for HL have not specifically subdivided the three distinct clinical forms: a childhood form that presents at age <12years, a young adult form that occurs in patients 12–35 years and the older adult form seen in patients >50 years old.21
The historic outcomes for conventional salvage chemotherapy (CT) of HL for all age groups show overall progression free survival at 5 years of about 20% range.2
In this single center study we established that the outcomes of adolescent and young adult patients with HL support the proposition that relapsed patients benefit from either autologous or allogeneic stem cell transplantation.
Early prospective randomized controlled trials from cooperative groups such as the European Group for Blood and Marrow Transplantation (EBMT) and the German Hodgkin’s Study Group have demonstrated the superiority of autologous HSCT (ABMT) over chemotherapy for relapsed HL and have established the standard of care for the majority of adult patients with relapsed HL.9,15,22,23
Specifically, the prospective randomized trial from the EBMT showed a 3 year PFS of 41% for patients after ABMT compared to 12% for patients who received conventional chemotherapy alone 9
We determined whether these adult data would be reflected in our cohort of consecutively treated adolescents and young adults from a single center. Our data supports the excellent outcome of select patients with chemo-sensitive disease, with a 2 year PFS of 80% and 2 year OS of 89%. This is consistent with reported outcomes for adult patients with chemo-sensitive disease which demonstrate a 5yr PFS in the 40–70% range 5,7,18,24,25
. Additionally, in our series, we showed that patients with chemosensitive disease who relapsed > 1 year after therapy (n=7) had a 100% PFS after HSCT thus affirming that late relapse predicts excellent prognosis to salvage therapy. Studies in adult patients have also shown that the 2 year survival data for patients receiving HSCT transplant for chemosensitive relapsed HL is predictive, with low numbers of late failures after HSCT.19
However, to truly evaluate late effects such as secondary malignancies, longer follow-up is required. Although this study was not powered to perform a sub group analysis, we also observed improved outcomes among the patients with bulky disease and/or post HSCT PET positive disease who were consolidated with radiation after HSCT suggesting that these results should be evaluated in a larger study.
Whereas the clinical benefit of ABMT in chemo-sensitive patients is clear, it is less evident from the literature how to treat patients (especially adolescent/young adult patients) with chemoresistant disease. While multiple prognostic factors correlate with patient outcome after ABMT including disease stage, extra-nodal disease and anemia, the most consistent and compelling factor remains response to therapy which is either assessed by disease response to salvage therapy or by the number of chemotherapy regimens prior to transplantation. Our data supports the use of HSCT within the chemoresistant group since these patients had a 2 year PFS and OS of 32% and 53% respectively. Although this is a more modest clinical response compared to patients with chemosensitive disease, these results are an improvement from the dismal outcomes observed with CT alone 2
. This data therefore suggests that the benefits of the transplant procedure have been maintained even in these high risk patients 1,8,26–28
Importantly, the use of submyeloablative conditioning regimens and improved supportive therapies, allows both autologous as well as allogeneic HSCTs to be better tolerated with <20% regimen related mortality, an apparent improvement also noted by recent reports in adult patients 29
. While we acknowledge our small sample size and although this study was not powered to establish whether allogeneic transplant confers a significant advantage over autologous transplant in terms of PFS in high-risk pediatric/young adult patients, we observed a trend to better outcomes in chemoresistant patients who received an allogeneic HSCT compared to those who received an autologous HSCT. Since prognostic models have now been established it will therefore be important for future studies to establish whether allogeneic transplant is truly beneficial in these high risk adolescent and young adult patients with relapsed HL, as suggested by this study.
In conclusion, our retrospective analysis indicates that most adolescent and young adult patients with relapsed Hodgkin’s lymphoma can achieve excellent outcomes with high dose chemotherapy and autologous stem cell transplant. Physicians treating these patients can be especially optimistic for patients who have an initial cytoreductive response to upfront therapy and who are sensitive to salvage therapy. However, for pediatric and young adult patients who have refractory or chemoresistant disease the outlook especially with autologous HSCT is less satisfactory and novel therapeutic strategies need to be explored either in the context of autologous or allogeneic HSCT.