Reduced-toxicity myeloablative conditioning consisting of 8-Gy total body irradiation, cyclophosphamide and fludarabine for pediatric hematological malignancies

Abstract

Conventional myeloablative conditioning (MAC) regimens often cause severe regimen-related toxicity (RRT). Furthermore, many patients suffer from poor quality of life in accordance with the increase in long-term survivors. We therefore devised a reduced-toxicity myeloablative conditioning (RTMAC) regimen consisting of 8-Gy total body irradiation (TBI), fludarabine (FLU) and cyclophosphamide (CY) for pediatric hematological malignancies. A retrospective single-center analysis was performed on patients with leukemia or myelodysplastic syndrome (MDS), aged ≤20 years, who had received an 8-Gy TBI/FLU/CY RTMAC regimen followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Thirty-one patients underwent first allo-HSCT after an RTMAC regimen. The diagnoses were acute lymphoblastic leukemia (n = 11), acute myeloid leukemia (n = 13), MDS (n = 4), juvenile myelomonocytic leukemia (n = 1) and acute leukemias of ambiguous lineage (n = 2). While 3 patients showed early hematological relapse, the remaining 28 patients achieved engraftments. None of the patients developed grade 4 or 5 toxicities during the study period. The 5-year overall survival and relapse-free survival were 80% [95% confidence interval: CI, 61–91%] and 71% [95% CI, 52–84%], respectively. Our RTMAC regimen would be less toxic and offers a high probability of survival for children with hematological malignancies.

Reduced 8-Gray Compared to Standard 12-Gray Total Body Irradiation for Allogeneic Transplantation in First Remission Acute Lymphoblastic Leukemia: A Study of the Acute Leukemia Working Party of the EBMT

“… 16 Lowering the total TBI dose from 12- to 8-Gy to reduce short- and long-term irradiation toxicity has been attempted in pediatric patients with hematologic malignancies with good outcomes. 17 , 18 The comparison of 8-Gy TBI to the standard 12-Gy TBI has never been the subject of a prospective or retrospective study in adult ALL patients.…”

Ovarian function after allogeneic hematopoietic stem cell transplantation in children and young adults given 8‐Gy total body irradiation‐based reduced‐toxicity myeloablative conditioning

“…Some patients who were eligible per our criteria did not undergo our RTMAC conditioning owing to the patient's guardians’ request or enrollment into another study. Detailed clarification is included in our previous report . All patients underwent HSCT at Shinshu University Hospital, and all clinical data were collected from the clinical charts of Shinshu University Hospital.…”

“…After HSCT, patients with central nervous system disease underwent additional CSI (brain, 10‐Gy; spinal, 7‐Gy). Details regarding GvHD prophylaxis and supportive care before/after HSCT have been reported elsewhere …”

“…Therefore, we have previously developed (in 2003) a treatment protocol, which aimed at reducing RRT while maintaining antitumor effect(s). Specifically, this protocol uses a RTMAC regimen consisting of 8‐Gy TBI (2 Gy/d, days −7 to −4), FLU (30 mg/m 2 /d, days −8 to −4), and CY (60 mg/kg/d, days −3 and −2) for pediatric hematological malignancies, which showed low toxicity during the early post‐transplant period (until day 100) and a high probability of survival in the medium term after the transplant . Even though previous reports state that exposure to high‐dose CY, BU, or TBI is associated with gonadal failure, these studies have used conventional MAC (12‐Gy of TBI or 16 mg/kg of BU), and the impact of HSCT after 8‐Gy TBI‐based RTMAC on ovarian function is not clear.…”

“…Detailed clarification is included in our previous report. 15 All patients underwent HSCT at Shinshu University Hospital, and all clinical data were collected from the clinical charts of Shinshu University Hospital.…”