Haploidentical hematopoietic stem cell transplantation for relapsed/refractory or metastatic pediatric solid tumors

Abstract

Background: Relapsed/refractory or metastatic pediatric solid tumor carries dismal prognosis with current salvage regimens, necessitating novel treatment approaches. Haploidentical HSCT (haploHSCT) can potentially exert graft-versus-tumor effect but data on its efficacy on solid tumor is scarce. Method: Review of outcome of patients <18 years with relapsed/refractory or metastatic solid tumors who underwent haploHSCT in a University-affiliated Pediatric Unit between 2001 and 2016. Results: 7 patients underwent haploHSCT. Four were male with median age at HSCT of 6.7y (range, 3.5-11.9y). Indications were relapsed/refractory neuroblastoma in 6 and metastatic alveolar rhabdomyosarcoma in 1. Disease status at haploHSCT was CR in 3, PR in 3 and PD in 1. KIR-mismatched parent was preferred as the donor. All patients received peripheral blood stem cell grafts after ex-vivo T cell depletion (CD3/CD19 depletion, 1; TCR-αβ/CD19 depletion, 4; CD3/CD45RA depletion, 2). Conditioning regimens of fludarabine/thiotepa/melphalan/ATG and fludarabine/thiotepa/cyclophosphamide/ATG were used in 5 and 2 cases, respectively. MMF and/or cyclosporine A were used as GvHD prophylaxis depending of efficiency of ex-vivo depletion. Neutrophil engrafted on median D+10 (range, D+9 to +10), while platelet engrafted (>20 x 109/L) on median D+8 (range, D+7 to D+10). 6 achieved 100% donor-chimerism post-HSCT while 1 developed acute rejection and died of culture-proven septicaemia before disease evaluation; 5 were rendered CR and 1 died from PD after haploHSCT. Among the 5 patients with CR, 2 received anti-GD2 immunotherapy for neuroblastoma; 3 remained in remission at 3m, 1.4y and 3.9y (given donor lymphocyte infusion) from HSCT, respectively whereas the other 2 relapsed. No GvHD was observed. All patients suffered from mucositis and neutropenic fever. Viral reactivation occurred in 5 cases including 2 with adenovirus infection. Conclusion: Early experience with haploHSCT indicated a potentially useful salvage strategy for selected cases of relapsed/refractory or metastatic pediatric solid tumors.