Effects of Priming with Recombinant Human Granulocyte Colony–Stimulating Factor on Conditioning Regimen for High-Risk Acute Myeloid Leukemia Patients Undergoing Human Leukocyte Antigen–Haploidentical Hematopoietic Stem Cell Transplantation: A Multicenter Randomized Controlled Study in Southwest China

Abstract

HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an effective and immediate treatment for high-risk acute myeloid leukemia (HR-AML) patients lacking matched donors. Relapse remains the leading cause of death for HR-AML patients after haplo-HSCT. Accordingly, the prevention of relapse remains a challenge in the treatment of HR-AML. In a multicenter randomized controlled trial in southwestern China, 178 HR-AML patients received haplo-HSCT with conditioning regimens involving recombinant human granulocyte colony-stimulating factor (rhG-CSF) or non-rhG-CSF. The cumulative incidences of relapse and graft-versus-host disease (GVHD), 2-year leukemia-free survival (LFS), and overall survival (OS) were evaluated. HR-AML patients who underwent the priming conditioning regimen with rhG-CSF had a lower relapse rate than those who were treated with non-rhG-CSF (38.2%; 95% confidence interval [CI], 28.1% to 48.3% versus 60.7%, 95% CI, 50.5% to 70.8%; P < .01). The cumulative incidences of acute GVHD, chronic GVHD, transplantation-related toxicity, and infectious complications appeared to be equivalent. In total, 53 patients in the rhG-CSF-priming group and 31 patients in the non-rhG-CSF-priming group were still alive at the median follow-up time of 42 months (range, 24 to 80 months). The 2-year probabilities of LFS and OS in the rhG-CSF-priming and non-rhG-CSF-priming groups were 55.1% (95% CI, 44.7% to 65.4%) versus 32.6% (95% CI, 22.8% to 42.3%) (P < .01) and 59.6% (95% CI, 49.4% to 69.7%) versus 34.8% (95% CI, 24.9% to 44.7%) (P < .01), respectively. Multivariate analyses indicated that the 2-year probability of LFS of patients who achieved complete remission (CR) before transplantation was better than that of patients who did not achieve CR. The 2-year probability of LFS of patients with no M4/M5/M6 subtype was better than that of patients with the M4/M5/M6 subtype in the G-CSF-priming group (67.4%; 95% CI, 53.8% to 80.9% versus 41.9%; 95% CI, 27.1% to 56.6%; P < .05). This study suggests that the rhG-CSF-priming conditioning regimen is an acceptable choice for HR-AML patients, especially for the patients with no M4/M5/M6 subtype who achieved CR before transplantation.

Effect of Granulocyte Colony–Stimulating Factor–Combined Conditioning in Cord Blood Transplantation for Myelodysplastic Syndrome and Secondary Acute Myeloid Leukemia: A Retrospective Study in Japan

“…Recently, an encouraging report from China showed that there was a lower relapse rate and better survival in patients treated with G-CSFecombined conditioning compared with those without G-CSF in haploidentical SCT for high-risk AML [36]. Although a decreased relapse rate was observed in our previous report of CBT for de novo AML [20], G-CSFecombined conditioning was not associated with a decreased risk of relapse in MDS and sAML in this study.…”

Long-term outcomes of granulocyte colony-stimulating factor-combined conditioning in allogeneic hematopoietic stem cell transplantation from HLA-identical family donors for myeloid malignancies

“…Recently, Gao, et al reported that there was a lower relapse rate and better survival in patients treated with G-CSF-combined conditioning compared to those without G-CSF in haploidentical HSCT for high-risk AML [24]. These data suggested that G-CSF-combined conditioning reduced the posttransplant relapse rate by enhancing the anti-leukemia effect without increasing the chemotherapy dose.…”

Update on Non-M3 Acute Myeloid Leukemia — Etiology, Classification, Risk Stratification, Emergencies, Complications, Disease in Special Circumstances and Current and Future Therapeutics

“…Haploidentical donors can safely extend transplantation options for AML patients without HLA matched siblings or unrelated donors [156,157]. HLA-haploidentical HSCT is an effective and immediate therapeutic modality for high-risk AML patients who lack matched donors [158]. The use of fractionated 800 cGy-TBI-based conditioning therapy and unmanipulated peripheral blood stem cell grafts seems feasible and can result in favorable outcomes for adult patients with AML in CR undergoing haploidentical HSCT [159].…”

“…The use of fractionated 800 cGy-TBI-based conditioning therapy and unmanipulated peripheral blood stem cell grafts seems feasible and can result in favorable outcomes for adult patients with AML in CR undergoing haploidentical HSCT [159]. However, relapse remains a leading cause of death in high-risk AML patients subjected to haploidentical HSCT [158]. Achievement of CR before transplantation and recombinant human G-CSF priming of conditioning therapy can improve the outcome of patients with high-risk AML receiving haploidentical allografts [158,160].…”

“…However, relapse remains a leading cause of death in high-risk AML patients subjected to haploidentical HSCT [158]. Achievement of CR before transplantation and recombinant human G-CSF priming of conditioning therapy can improve the outcome of patients with high-risk AML receiving haploidentical allografts [158,160].…”