How to manage compromised hematopoietic bone marrow function?

From the Guidelines

Management of compromised hematopoietic bone marrow function should prioritize the use of azacitidine in patients with higher-risk myelodysplastic syndromes (MDS) without major comorbidities not immediately eligible for allogeneic stem cell transplantation (allo-SCT) 1. The primary treatment strategies for compromised hematopoietic bone marrow function include:

• Hematopoietic growth factors such as erythropoietin (EPO) for anemia
• Granulocyte colony-stimulating factor (G-CSF) for neutropenia
• Thrombopoietin receptor agonists like eltrombopag or romiplostim for thrombocytopenia
• Blood product transfusions for immediate support, with red blood cell transfusions recommended when hemoglobin falls below 7-8 g/dL, and platelet transfusions when counts drop below 10,000/μL or 50,000/μL before invasive procedures
• Immunosuppressive therapy with agents like cyclosporine and anti-thymocyte globulin for immune-mediated bone marrow suppression
• Allo-SCT for severe cases, which offers potential cure Supportive care includes:
• Infection prophylaxis with antimicrobials like levofloxacin 500 mg daily during severe neutropenia
• Nutritional support
• Careful medication management to avoid bone marrow-toxic drugs These interventions work by either stimulating the remaining functional bone marrow cells to increase production, replacing deficient blood components, suppressing harmful immune responses, or completely replacing the damaged bone marrow with healthy donor cells 1. In patients with lower-risk MDS, erythropoiesis-stimulating agents (ESAs) like EPO alpha are recommended for the first-line treatment of anemia 1. For transfusion-dependent anemia of lower-risk MDS with del(5q), lenalidomide (LEN) is the most effective drug 1. After ESA failure, luspatercept is recommended for anemia in RBC transfusion-dependent MDS-RS patients 1. Prophylactic platelet transfusion should be administered to patients with thrombocytopenia resulting from impaired bone marrow function to reduce the risk of hemorrhage when the platelet count falls below a predefined threshold level 1.

From the FDA Drug Label

NEUPOGEN is a leukocyte growth factor indicated to Reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ e.g. ‚ febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation (BMT) (1.3) Mobilize autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis (1.4) Reduce the incidence and duration of sequelae of severe neutropenia (e.g. ‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia (1.5) Increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome) (1.6)

To manage compromised hematopoietic bone marrow function, the use of filgrastim is indicated for several purposes, including:

• Reducing the duration of neutropenia and its related clinical sequelae in patients undergoing bone marrow transplantation 2
• Mobilizing autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis 2
• Reducing the incidence and duration of sequelae of severe neutropenia in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia 2
• Increasing survival in patients acutely exposed to myelosuppressive doses of radiation 2 Key considerations for managing compromised hematopoietic bone marrow function include:
• Dose adjustments: The recommended starting dose of filgrastim is 5 mcg/kg/day for patients with cancer receiving myelosuppressive chemotherapy or induction and/or consolidation chemotherapy for AML 2
• Administration: Filgrastim can be administered subcutaneously or intravenously, with the specific route and duration of administration depending on the patient's condition and response to treatment 2

From the Research

Management of Compromised Hematopoietic Bone Marrow Function

To manage compromised hematopoietic bone marrow function, several strategies can be employed, including:

• The use of filgrastim-stimulated bone marrow (G-BM) as an alternative allograft, which may be associated with prompt hematopoietic recovery and less chronic graft-versus-host disease (cGVHD) 3
• The administration of pegfilgrastim, a granulocyte colony-stimulating factor (G-CSF), to reduce the incidence and duration of chemotherapy-induced febrile neutropenia (FN) 4
• The use of filgrastim-mobilized peripheral blood progenitor cells (PBPC) or bone marrow transplantation for treating leukemia, with PBPC transplantation associated with a higher incidence of chronic GVHD 5

Hematopoietic Stem Cell Transplantation

Hematopoietic stem cell transplantation (HSCT) is a treatment option for various hematologic malignancies, and the choice of graft source (bone marrow or peripheral blood) can impact outcomes, including:

• The incidence and severity of chronic GVHD, with bone marrow transplantation associated with a lower risk of chronic GVHD 3, 5
• The risk of relapse or disease progression, with no significant difference between bone marrow and peripheral blood transplantation 3

Bone Marrow Hematopoietic Niche

The bone marrow hematopoietic niche plays a crucial role in maintaining hematopoietic stem cell (HSC) pluripotency and self-renewal, and its adaptation to infection can impact hematopoiesis, with:

• Infections affecting the bone marrow hematopoietic niche and its response to infectious stress still not fully understood 6
• The use of G-CSFs, such as filgrastim, to mobilize hematopoietic stem cells and prevent neutropenia-related infections 7

Safety and Efficacy of Filgrastim

Filgrastim has been shown to be effective in preventing neutropenia-related infections and mobilizing hematopoietic stem cells, with:

• A systematic literature review confirming its efficacy and safety in chemotherapy-induced neutropenia (CIN) and other indications 7
• Bone pain being a commonly reported adverse event associated with filgrastim use 7