Favorable Outcome of Post-Transplantation Cyclophosphamide Haploidentical Peripheral Blood Stem Cell Transplantation with Targeted Busulfan-Based Myeloablative Conditioning Using Intensive Pharmacokinetic Monitoring in Pediatric Patients

Abstract

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplantation cyclophosphamide (PTCy) was performed previously in adults using a nonmyeloablative conditioning regimen and bone marrow as a graft source. In an effort to reduce relapse rates, myeloablative conditioning regimens with higher intensities are now used. We used an intensive daily pharmacokinetic monitoring method for busulfan dosing in children for effective myeloablation and to reduce toxicity. Here, we report the retrospective results of 34 patients (median age 11.1 years) who underwent haplo-HSCT with PTCy using a targeted busulfan-based myeloablative conditioning regimen and peripheral blood as a stem cell source. The donor-type neutrophil engraftment rate was 97.1%, and the cumulative incidence rates of grade II to IV and grade III to IV acute and extensive chronic graft-versus-host disease were 38.2%, 5.9%, and 9.1%, respectively. The overall survival and event-free survival rates, and treatment-related mortality were 85.0%, 79.4%, and 2.9%, respectively. Based on the subgroup analysis of patients with malignancies (n = 23), the relapse incidence rate was 21.7%. Haplo-HSCT using PTCy with targeted busulfan-based myeloablative conditioning and peripheral blood as a stem cell source was a safe and promising therapeutic option for children.

Haploidentical transplantation in high‐risk pediatric leukemia: A retrospective comparative analysis on behalf of the Spanish working Group for bone marrow transplantation in children (GETMON) and the Spanish Grupo for hematopoietic transplantation (GETH)

“…Antithymocyte globulin (ATG) was avoided in most of the cases. Alternatives to ATG were 8 Gy total lymphoid irradiation (TLI) over 4 equal fractions, TBI 4 Gy on 2 fractions instead of TLI or a high dose of methylprednisolone, (25 mg/kg, over 5 days) . For those patients who required a second haploidentical transplant due to primary graft failure ATG was used.…”

“…Promising results have been shown in pediatric patients with malignant and nonmalignant disorders, with low rates of GvHD and improved immune reconstitution using an ex vivo αβ + TCD platform and B cell depletion; however, there are very limited haplo‐HSCT PT‐Cy data, with studies restricted by a low number of samples . This retrospective and multicenter study aimed to compare and analyze the feasibility and outcome of a Spanish cohort of 2 haplo‐HSCT platforms in children and adolescents with high‐risk hematological malignancies: PT‐Cy and ex vivo TCD grafts.…”

The Predicted Indirectly Recognizable HLA Epitopes (PIRCHE) Score for HLA Class I Graft-versus-Host Disparity Is Associated with Increased Acute Graft-versus-Host Disease in Haploidentical Transplantation with Post-Transplantation Cyclophosphamide

“…With the use of post-transplantation cyclophosphamide (PTCy) to selectively deplete or functionally impair alloreactive T cells [6À12], haplo-HCT in adults has been shown to have similar outcomes as MUD allo-HCT, MRD allo-HCT, and allo-HCT from other alternative donors [9,13À20]. In addition, haplo-HCT with PTCy appears to have favorable outcomes in the pediatric and young adult population [21,22].…”

Haploidentical Stem Cell Transplantation in Children with Benign Disorders: Improved Survival and Cost-Effective Care Over 15 Years from a Single Center in India

“…Hong et al [ 10 ] have reported in 2018 an overall survival of 85% in a mixed cohort of paediatric patients who underwent haplo SCT with PTCy using targeted busulphan based myeloablative conditioning with pharmacokinetic monitoring. Data has also been published from India by Rastogi et al [ 11 ] on children with PIDs undergoing haplo SCTs with PTCy with survival in 6 of the 8 children in their cohort.…”