Sequential myeloablative autologous stem cell transplantation and reduced intensity allogeneic hematopoietic cell transplantation is safe and feasible in children, adolescents and young adults with poor-risk refractory or recurrent Hodgkin and non-Hodgkin lymphoma

Abstract

The outcome of children, adolescents and young adults (CAYA) with poor-risk recurrent/refractory lymphoma is dismal (⩽30%). To overcome this poor prognosis, we designed an approach to maximize an allogeneic graft vs lymphoma effect in the setting of low disease burden. We conducted a multi-center prospective study of myeloablative conditioning (MAC) and autologous stem cell transplantation (AutoSCT), followed by a reduced intensity conditioning (RIC) and allogeneic hematopoietic cell transplantation (AlloHCT) in CAYA, with poor-risk refractory or recurrent lymphoma. Conditioning for MAC AutoSCT consisted of carmustine/etoposide/cyclophosphamide, RIC consisted of busulfan/fludarabine. Thirty patients, 16 Hodgkin lymphoma (HL) and 14 non-Hodgkin lymphoma (NHL), with a median age of 16 years and median follow-up of 5years, were enrolled. Twenty-three patients completed both MAC AutoSCT and RIC AlloHCT. Allogeneic donor sources included unrelated cord blood (n=9), unrelated donor (n=8) and matched siblings (n=6). The incidence of transplant-related mortality following RIC AlloHCT was only 12%. In patients with HL and NHL, 10 year EFS was 59.8% and 70% (P=0.613), respectively. In summary, this approach is safe, and long-term EFS with this approach is encouraging considering the poor-risk patient characteristics and the use of unrelated donors for RIC AlloHCT in the majority of cases.

Allogeneic hematopoietic stem cell transplantation in r/r Hodgkin lymphoma after treatment with checkpoint inhibitors: Feasibility and safety

“…Despite higher rate of grade 3-4 acute GVHD (28%; 95% CI, 20%-37%) in cohort 1 than cohort 2 (8%; 95% CI, 6%-10%), our results indicate similar chronic GVHD rates in investigational (26%; 95% CI, 19%-36%) and historical (29%; 95% CI, 26%-31%) arm. Additionally, the rate of NRM (15%; 95% CI, 9%-23%) in cohort 1 is similar to previously reported NRM rate (10%-29%) [9][10][11][12][13][14] in different historical studies without exposure to checkpoint inhibitors. This might be explained by recent improvements in prophylaxis and treatment of GVHD.…”

“…By the end, we had clean data from 6 publications with a total of 122 patients (age median range 18‐75 years) which fulfilled the inclusion criteria (Table ). In the comparator arm (cohort 2), we found 6 publications with 978 patients reporting on acute GVHD and/or NRM rates (Table ). Same selection criteria were applied for both cohorts.…”

Pediatric Hodgkin lymphoma- biomarkers, drugs, and clinical trials for translational science and medicine

“…The most common prognostic factors are chemosensitivity to initial salvage therapy [110], primary progressive disease [111, 112], time to relapse [113], and extranodal disease [114]. As with adult patients, pediatric patients also show poor prognosis, associated with time from diagnosis to first relapse of <1 year [115]. Likewise, primary progressive HL that remains refractory has a poor outcome with HDCT/ASCT in children.…”

“…Contemporary non-etoposide retrieval regimens in RR patients, such as the combination of ifosfamide with vinorelbine (IV) [118] or gemcitabine in combination with vinorelbine (GV) [119] resulted in overall response rates of 72-76% (Table 4). However, pediatric patients with early relapse or inadequate response rate are unlikely to achieve long-term remission with standard salvage therapy, and their survival remains very poor, ranging from 18-41% [109, 110, 115]. This low survival rate presents a therapeutic challenge for treating RR patients, and reinforces the need to test novel immune and non-immune strategies to combat HL.…”

Post-autologous transplant maintenance therapies in lymphoid malignancies: are we there yet?

“…A handful of studies have looked at auto-HCT followed by a tandem reduced-intensity allogeneic HCT in lymphoid malignancies. 9,10 However, no randomized data are available to support the use of this approach. Moreover, advanced age, comorbidities and matched-donor availability makes such a tandem HCT approach theoretically applicable to only a small fraction of lymphoma population.…”