Myeloid Growth Factors骨髓生长因子
NCCN Guidelines Version 2.2016
Mobilization and Post Hematopoietic Cell Transplant
MGFs are commonly administered in the transplant setting, either for mobilization of hematopoietic progenitor cells or as supportive care after transplantation.
Mobilization with Growth Factors in the Autologous Setting
Mobilization of PBPCs by G-CSF has largely replaced bone marrow collection for autologous transplantation due to ease of collection, avoidance of general anesthesia, and more rapid recovery of blood counts. Most data are focused on filgrastim, although studies suggest that single-dose pegfilgrastim has similar efficacy.
While apheresis usually commences on the fourth or fifth day of G-CSF initiation when it is used as a single agent, recent studies have shown that the addition of the CXCR4 inhibitor plerixafor to chemo-mobilization accelerated the increase in PBPC count. This may be used as a rescue strategy when PBPC yield is poor, or when the CD34+ cell count does not reach the target level. Plerixafor is indicated for patients who were heavily pre-treated or had prior treatment with greater than 10 cycles of cytotoxic chemotherapy, or those who have had failed prior collection attempts that failed or who exhibit risk factors for being poor mobilizes due to more than 6 cycles of lenalidomide or fludarabine, or radiation to the pelvis. One retrospective analysis demonstrated that pegfilgrastim resulted in a better PBPC yield than filgrastim, requiring less use of rescue plerixafor, but there have not been any randomized trials that address the effect of plerixafor when used in combination with pegfilgrastim.
While filgrastim-sndz has been accepted as an equivalent treatment option to filgrastim for patients with FN, there is discussion among medical professions regarding equivalency in hematopoietic cell mobilization or in patients with chronic neutropenia. There are data to support the use of filgrastim-sndz in the autologous hematopoietic cell transplant setting. However, the panel acknowledges the limitations of these studies regarding long-term outcomes and the potential impact of the different manufacturing processes. Therefore, while it is reasonable to substitute with filgrastim-sndz, clinicians should be alert to any complications presented in the literature or in their patients. Accurate and timely disclosure of any variation in expected outcome with the biosimilar compared to the originator filgrastim will be of paramount importance.
The NCCN Panel recommends administration of filgrastim, filgrastim-sndz, or tbo-filgrastim as a single agent or as part of a chemo-mobilization regimen, starting on the day after completion of chemotherapy (category 2A). Several regimens are effective in chemo-mobilization of hematopoietic progenitors, including cyclophosphamide, ICE, DHAP, VTD-PACE, and others. Studies using GM-CSF as a single mobilization agent or in sequential combination with G-CSF reported good yields of PBPC in normal donors. Although both MGFs have been used for mobilization, G-CSF has been favored for this purpose. The use of concurrent filgrastim or filgrastim-sndz and sargramostim is a category 2B recommendation. For select patients with NHL or multiple myeloma, filgrastim, filgrastim-sndz, or tbo-filgrastim can be given followed by plerixafor.
Mobilization with Growth Factors in the Allogeneic Setting
Initially, there were concerns about mobilization in the allogeneic setting due to normal donor toxicity and the risk for graft-versus-host disease (GVHD) in the recipient, but studies have demonstrated G-CSF to be well-tolerated by donors without an effect on long-term survival. The use of plerixafor in normal donors is currently under study. Tbo-filgrastim has also been shown to mobilize PBPC for allogeneic transplantation in both healthy donors and in patients with multiple myeloma and lymphoma, but the data are limited, and mobilization is not listed as an approved indication. Studies of filgrastim-sndz have been predominately in the settings of autologous PBPC mobilization and in support of count recovery after transplant, whereas data are sparse in the allogeneic setting. The smaller studies in allogeneic progenitor cell donors have suggested that there are no short-term safety issues; however, the long-term data are not yet available. A single retrospective study of filgrastim-sndz in comparison to filgrastim for mobilization in normal donors reported that 3 out of 18 donors mobilization in the filgrastim-sndz group failed without any mobilization failures in the filgrastim group. Neutrophil and platelet count recovery after allogeneic transplant were similar in both arms. The World Marrow Donor Association recommends against the use of filgrastim biosimilars in unrelated donors based on extrapolation from autologous transplant data.
The NCCN Panel recommends single-agent filgrastim (category 2A, preferred), filgrastim-sndz (category 2B), or tbo-filgrastim (category 2B) for allogeneic hematopoietic cell mobilization and for granulocyte transfusion. The addition of plerixafor in selection patients is a category 2B recommendation.
Growth Factors as Part of Supportive Care After Transplant
Consensus is lacking on the use of growth factors in the post-transplant setting. G-CSF administration after high-dose chemotherapy and autologous PBPC transplantation has been shown to expedite neutrophil recovery in prospective randomized trials. However, results were mixed on the impact of G-CSF on duration of hospital stay, infections, and survival. A systematic review comparing filgrastim and pegfilgrastim in the autologous setting, including a randomized trial of 80 patients, concluded that the two are at least equally effective.
Similarly, data are conflicting on G-CSF as a supportive care measure for allogeneic transplant recipients, with some studies associating G-CSF with worse clinical outcome. However, it has been used routinely to alleviate the delayed recovery of blood counts after umbilical cord blood transplant, because there is a significant delay in the rate and kinetics of neutrophil and platelet engraftment after cord blood transplant as compared to marrow or mobilized PBPC grafts. GM-CSF has been demonstrated to promote hematopoietic recovery after autologous hematopoietic cell transplantation or delayed autologous engraftment. GM-CSF therapy has been shown to improve treatment outcome in patients with hematologic malignancies who previously had graft failure following bone marrow transplant. GM-CSF has also been administered to patients with hematologic malignancies leading to decreased neutropenia, decreased morbidity, and decreased hospitalization during autologous hematopoietic cell transplant.
The NCCN Panel recommends consideration of MGFs in the supportive care setting post-autologous hematopoietic cell transplant. Filgrastim, filgrastim-sndz, tbo-filgrastim, pegfilgrastim, and sargramostim (all category 2A) can be considered in the supportive care setting.
Dosing and Administration
For dosing information, see Myeloid Growth Factors in Mobilization and Post Hematopoietic Cell Transplant in the algorithm.