Reduced-Intensity Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Solid Tumors in Pediatric and Young Adult Patients

Abstract

High-risk, recurrent, or refractory solid tumors in pediatric, adolescent, and young adult (AYA) patients have an extremely poor prognosis despite current intensive treatment regimens. We piloted an allogeneic bone marrow transplant platform using reduced-intensity conditioning (RIC) and partially HLA-mismatched (haploidentical) related donors for this population of pediatric and AYA solid tumor patients. Sixteen patients received fludarabine, cyclophosphamide, melphalan, and low-dose total body irradiation RIC haploidentical BMT (haploBMT) followed by post-transplantation cyclophosphamide (PTCy), mycophenolate mofetil, and sirolimus. All assessable patients were full donor chimeras on day 30 with a median neutrophil recovery of 19 days and platelet recovery of 21 days. One patient (7%) exhibited secondary graft failure associated with concomitant infection. The median follow-up time was 15 months. Overall survival was 88%, 56%, and 21% at 6, 12, and 24 months, respectively. Median survival from transplant date was 14 months with a median progression-free survival 7 months. We observed limited graft-versus-host disease in 3 patients and nonrelapse mortality in 1 patient. We demonstrated that RIC haploBMT with PTCy is feasible and has acceptable toxicities in patients with incurable pediatric and AYA solid tumors; thus, this approach serves as a platform for post-transplant strategies to prevent relapse and optimize progression-free survival.

Características Clínicas e Complicações do Transplante Haploidêntico com Ciclofosfamida Pós-Transplante: Implicações para a Enfermagem

“…A hiper--hidratação durante e até pelo menos 24 horas após a administração da droga e a diurese forçada com diuréticos, se for necessária, são as principais medidas de prevenção da complicação. Nos estudos revisados, também foi frequente o uso do medicamento uroprotetor mesna [8][9][10][11]13,18,22,28,29 . Cabe à enfermagem administrá-lo rigorosamente, nos horários estabelecidos, antes e até 12 a 24 horas após a ciclofosfamida, conforme o protocolo institucional 32 .…”

Pediatric unmanipulated haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide and reduced intensity, TBI-free conditioning regimens in salvage transplantations

“…11 Llosa et al included melphalan in the chemotherapy backbone, although without elimination of low-dose TBI. 12 Similarly, Shima reported the combination of TBI with melphalan. 13 The usage of TBI as a part of haploSCT with a PTCY regimen is continued even in patients with Fanconi anemia 14,15 or in combination with busulfan.…”

Graft-versus-cancereffect and innovative approaches in the treatment of refractory solid tumors

“…Innovative allo-HSCT approaches such as haploidentical HSCT, which takes advantage of GvT effects in order to control disease, while minimizing the treatment related mortality or scale of GvHD, are being studied in many recent clinical trials [21][22][23][24]. The evidence of haploidentical HSCT in solid tumors are mainly limited to pediatric solid tumors such as neuroblastoma and sarcomas [21][22][23]. A pilot study by Lang et al evaluated the feasibility and toxicity of transplantation of haploidentical T and B-cell depleted grafts with high numbers of NK cells.…”

“…A limited GvHD was seen in 3 patients and non-relapse mortality in 1 patient. This approach may serve as a platform for posttransplant strategies to prevent relapse and optimize PFS [22].…”

“…GvT effect in a solid tumor after allo-HSCT has also been reported in a murine model in 1984 after the demonstration of graft-versus-leukemia (GvL) effect in a leukemic murine model following allo-HSCT from other strains of mice [19,20]. Phase I and II trials using allo-HSCT with RIC conducted by the European Society for Blood and Marrow Transplantation Solid Tumors Working Party (EMBT-STWP) have reported the presence of a GvT effect in patients with various refractorysolid tumors,including renal, ovarian and colon cancers,as well as soft tissue sarcomas [1].The growing data on haploidentical transplants also indicate GvT effect in some pediatric refractory solid tumors [21][22][23][24][25].…”