Granulocyte colony-stimulating factor combined regimen in cord blood transplantation for acute myeloid leukemia: a nationwide retrospective analysis in Japan | Haematologica

摘要

Cord blood transplantation (CBT) from an unrelated donor has been increasingly used as an alternative transplant method for adult patients without human leukocyte antigen (HLA)-compatible related or unrelated donors.1–4 However, the main disadvantage of CBT is still the limited cell dose, especially in adults, and this might contribute to a higher incidence of graft failure and delayed hematopoietic recovery, leading to higher transplant-related mortality (TRM) or overall mortality after CBT.The purpose of a conditioning regimen prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematologic malignancies is disease eradication and immunosuppression to overcome graft rejection. Although the standard myeloablative conditioning regimen prior to allo-HSCT has been total body irradiation (TBI) or busulfan combined with cyclophosphamide (CY) for patients with adult acute myeloid leukemia (AML), the role of an intensified conditioning regimen has been analyzed extensively in order to reduce the rate of post-transplant relapse and improve survival.5–7 However, the majority of these studies analyzed patients receiving allo-HSCT using bone marrow (BM) or mobilized peripheral blood (PB) as a stem cell source. Therefore, an optimal myeloablative conditioning regimen prior to CBT for adult AML still has to be determined.Granulocyte colony-stimulating factor (G-CSF) stimulates proliferation, differentiation, and functional activation of neutrophils. In clinical use, G-CSF is most commonly used for reducing the duration of neutropenia after chemotherapy and HSCT, and for the mobilization of hematopoietic stem/progenitor cells from the BM into PB for HSCT. Furthermore, since administration of G-CSF increases the susceptibility to cytarabine arabinoside (Ara-C) through induction of cell cycle entry of dormant leukemia cells,8,9 the efficacy of concomitant use of G-CSF and chemotherapy has been analyzed.10,11 Several studies, as well as our own single institute studies, have demonstrated that G-CSF combined with myeloablative conditioning prior to allo-HSCT could be safely and effectively used for patients with myeloid malignancies in a single arm trial.9,12,13 However, there has been no comparative study of transplant outcomes for AML after allo-HSCT following a conditioning regimen with or without G-CSF. This retrospective study is the first to assess the effect of a G-CSF combination in a myeloablative conditioning regimen for CBT on the transplant outcome in adult AML patients in Japan. Patients and study methods are described in the Online Supplementary Appendix.Characteristics of patients and cord blood units are shown in Table 1. There was a significant difference in cumulative incidence of neutrophil recovery among the four groups in univariate analysis (P<0.001) (Figure 1A). In the multivariate analysis, the hazard risk of neutrophil engraftment was significantly higher in the TBI≥10Gy+Ara-C/G-CSF+CY group (P<0.001) and lower in the TBI≥10Gy+other group (P=0.03) and TBI<10Gy+other or non-TBI group (P<0.001) compared with the TBI≥10Gy+Ara-C+CY group (Table 2). Among patients achieving neutrophil engraftment, neutrophil recovery times were significantly shorter in the TBI≥10Gy+Ara-C/G-CSF+CY group compared with the TBI≥10Gy+Ara-C+CY group (P<0.001). There was a significant difference in cumulative incidence of platelet recovery among the four groups in univariate analysis (P<0.001) (Figure 1B). Multivariate analysis showed no significant difference between the TBI≥10Gy+Ara-C+CY group and TBI≥10Gy+Ara-C/G-CSF+CY group (P=0.14). However, the hazard risk of platelet engraftment was significantly lower in the TBI≥10Gy+other group (P<0.001) and TBI<10Gy+other or non-TBI group (P<0.001) compared with the TBI≥10Gy+Ara-C+CY group (Table 2). Among patients achieving platelet engraftment, there was no significant difference in platelet recovery times among the four groups (P=0.32).Download figureOpen in new tabDownload powe