White Cell Colony Stimulating Factors

Title XVIII of the Social Security Act §1862 (a)(1)(A) allows coverage and payment for only those services that are considered to be reasonable and necessary for the diagnosis or treatment of illness or to improve the functioning of a malformed body member.

42 CFR §411.15(k)(1) Particular services excluded from coverage are those services that are not reasonable or necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.

CMS Internet-Only Manual, Pub 100-02, Medicare Benefit Policy Manual, Chapter 15, §§50 Drugs and Biologicals and §50.4.1 Approved use of drug.

CMS Manual System, Pub 100-20, One-Time Notification, Transmittal 1542, Change Request 9284, dated September 4, 2015

White blood cell growth factors, also known as granulocyte colony stimulating factors (G-CSF), are administered to enhance recovery of blood related functions in neutropenia (low white blood count) including febrile neutropenia (FN).

CSFs are also utilized to decrease the incidence and severity of infection associated with select disease-related and drug-related myelosuppression (inhibition of bone marrow function).

G-CSF are glycoproteins which exert major control over the reproduction and maturation of certain white blood cells, which include the following U.S. Food & Drug Administration (FDA) approved products:

• Filgrastim (Neupogen^®, Amgen, Thousand Oaks, CA)
• Filgrastim-sndz biosimilar (Zarxio^®, Sandoz, Princeton, NJ)
• Pegfilgrastim (Neulasta^®, Amgen, Thousand Oaks, CA)
• Tbo-filgrastim (Granix^®, Sicor Biotech UAB/Teva Pharmaceuticals North Wales, PA)

Granulocyte-macrophage colony stimulating factor (GM-CSF) is a hematopoietic growth factor which stimulates proliferation and differentiation of hematopoietic progenitor cells.

• Sargramostim (Leukine^®, Sanofi-Aventis Bridgewater, NJ and Sanofi-Genzyme Cambridge, MA)

I. Definitions

Severe neutropenia is generally defined as an absolute neutrophil count (ANC) of less than 500 cells per ml.

Primary prophylaxis refers to administration of CSF during the first cycle of chemotherapy.

Secondary prophylaxis refers to administration of CSF during subsequent cycles of chemotherapy.

Administration of G-CSF for primary prophylaxis should not be used routinely in all chemotherapy patients receiving usual outpatient regimens. It should be reserved for those patients whose risk of FN is 20% or greater based upon chemotherapy regimen. In patients whose risk of developing FN is greater than or equal to 10% and less than 20% based on chemotherapy regimen, the use of primary prophylaxis should be reserved for those patients with 1 or more of the following risk factors for FN:

1. Age greater than 65 years;
2. Poor performance status;
3. Previous episodes of FN;
4. History of previous chemotherapy or radiation therapy;
5. After completion of combined chemoradiotherapy;
6. Bone marrow involvement by tumor producing cytopenias;
7. Preexisting neutropenia;
8. Poor nutritional status;
9. Poor renal function;
10. Liver dysfunction (i.e., elevated bilirubin);
11. The presence of open wounds or active infections;
12. Recent surgery (generally within the past 12 weeks);
13. Advanced cancer; or
14. Other serious comorbidities.

Secondary prophylaxis is considered reasonable and necessary after documented FN from a prior chemotherapy cycle (for which primary prophylaxis was not received) in which a reduction in dosage of the chemotherapeutic agents or a delay in treatment may compromise disease-free or overall survival or treatment outcome.

II. FDA Indications

A. G-CSF pegfilgrastim (Neulasta^®) and the biosimilar Fulphila™ are indicated for the following:

• Patients with Cancer Receiving Myelosuppressive Chemotherapy and/or Immunotherapy: to decrease the incidence of infection, as manifested by FN, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of severe FN.

• Patients with Hematopoietic SubSyndrome of Acute Radiation Syndrome: to increase survival in patients acutely exposed to myelosuppressive doses of radiation

Neulasta^® and biosimilars are not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

B. G-CSF tbo-filgrastim (Granix^®) is indicated for the following:

• Patients with Cancer Receiving Myelosuppressive Chemotherapy and/or Immunotherapy: to reduce the duration of severe neutropenia in adult and pediatric patients 1 month and older with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of FN.

C. G-CSF filgrastim (Neupogen^®) is indicated for the following:

• Patients with Cancer Receiving Myelosuppressive Chemotherapy and/or Immunotherapy: to decrease the incidence of infection, as manifested by FN, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of severe FN.

• Patients with Acute Myeloid Leukemia Receiving Induction and/or Consolidation Chemotherapy: to reduce the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML).

• Patients with Cancer Undergoing Bone Marrow Transplantation: to reduce the duration of neutropenia and neutropenia-related clinical sequelae, e.g., FN, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation.

• Patients Undergoing Autologous Peripheral Blood Progenitor Cell Collection and Therapy: for the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis.

• Patients with Severe Chronic Neutropenia: for chronic administration to reduce the incidence and duration of sequelae of neutropenia (e.g., fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.

• Patients with Hematopoietic Syndrome of Acute Radiation Syndrome: to increase survival in patients acutely exposed to myelosuppressive doses of radiation

D. G-CSF filgrastim-sndz biosimilar (Zarxio^®) is classified as a biosimilar and is approved for all indications included in its reference product’s (Neupogen^®) label (see above listed indications for Neupogen^®)

E. GM-CSF sargramostim (Leukine^®) differs from the above listed products in that it is a recombinant human granulocyte macrophage colony stimulating factor. GM-CSF is a hematopoietic growth factor which stimulates proliferation and differentiation of hematopoietic progenitor cells.

Sargramostim is indicated for the following:

• Following Induction Chemotherapy in Acute Myelogenous Leukemia: following induction chemotherapy in older adult patients with acute myelogenous leukemia (AML) to shorten time to neutrophil recovery and to reduce the incidence of severe and life-threatening infections and infections resulting in death. The safety and efficacy of sargramostim have not been assessed in patients with AML under 55 years of age.

• Use in Mobilization and Following Transplantation of Autologous Peripheral Blood Progentior Cells: for the mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis. Mobilization allows for the collection of increased numbers of progenitor cells capable of engraftment as compared with collection without mobilization. After myeloablative chemotherapy, the transplantation of an increased number of progenitor cells can lead to more rapid engraftment, which may result in a decreased need for supportive care. Myeloid reconstitution is further accelerated by administration of sargramostim following peripheral blood progenitor cell transplantation.

• Use in Myeloid Reconstitution After Allogeneic Bone Marrow Transplantation: for acceleration of myeloid recovery in patients undergoing allogeneic bone marrow transplantation (BMT) from HLA-matched related donors. Sargramostim has been found to be safe and effective in accelerating myeloid engraftment, reducing the incidence of bacteremia and other culture positive infections, and shortening the median duration of hospitalization.

• Use in Bone Marrow Transplantation Failure or Engraftment Delay: in patients who have undergone allogeneic or autologous BMT in whom engraftment is delayed or has failed. Sargramostim has been found to be safe and effective in prolonging survival of patients who are experiencing graft failure or engraftment delay, in the presence or absence of infection, following autologous or allogeneic BMT. Survival benefit may be relatively greater in those patients who demonstrate one or more of the following characteristics: autologous BMT failure or engraftment delay, no previous total body irradiation, malignancy other than leukemia or a multiple organ failure (MOF) score = 2. Hematologic response to sargramostim can be detected by complete blood count (CBC) with differential performed twice per week.

III. Off-Label Indications

In addition to the FDA-approved uses, coverage will be extended when any of the drugs- Filgrastim (Neupogen^®) or Filgrastim-sndz biosimilar (Zarxio^®), Pegfilgrastim (Neulasta^®), Sargramostim (GM-CSF, Leukine^®), or Tbo-Filgrastim (Granix^®) and biosimilars are used as adjunctive treatment when any of the conditions listed below are present.

Any of the following conditions may be an indication for adjunctive treatment:

1. Expected prolonged (greater than 10 days) and profound (less than 0.1 x 10⁹/L) neutropenia;
2. Age greater than 65 years;
3. Uncontrolled primary disease;
4. Pneumonia;
5. Hypotension and multi organ dysfunction (sepsis syndrome);
6. Invasive fungal infection; or
7. Hospitalized at the time of the development of fever.

Filgrastim (Neupogen^®) or Filgrastim-sndz biosimilar (Zarxio^®):

A. In an individual with acute lymphocytic leukemia (ALL) after completion of the first few days of initial induction chemotherapy or first post-remission course of chemotherapy; or

B. Use in adult individuals with AML shortly after the completion of induction or repeat induction chemotherapy, or after the completion of consolidation chemotherapy for AML; or

C. Treatment of severe neutropenia in individuals with hairy cell leukemia; or

D. In an individual with myelodysplastic syndromes (MDS) with severe neutropenia (ANC less than or equal to 500 mm3) or experiencing recurrent infection; or

E. In an individual receiving dose dense therapy (treatment given more frequently, such as every 2 weeks instead of every 3 weeks) for adjuvant treatment of breast cancer, or other malignancies for which dose dense chemotherapy is an accepted treatment option; or

F. Chronic administration to reduce the incidence and duration of sequelae of neutropenia (e.g., fever, infections, oropharyngeal ulcers) in symptomatic individuals with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia; or

G. Treatment of (non-chemotherapy) drug-induced neutropenia; or

H. Treatment of low neutrophil counts in individuals with glycogen storage disease type 1b; or

I. Treatment for neutropenia associated with human immunodeficiency virus (HIV) infection and antiretroviral therapy; or

J. In individuals receiving radiation therapy in the absence of chemotherapy if prolonged delays secondary to neutropenia are expected; or

K. After a hematopoietic progenitor stem cell transplant (HPCT/HSCT) for the following indications:

• To promote myeloid reconstitution; or

• When engraftment is delayed or has failed; or

• To mobilize progenitor cells into peripheral blood for collection by leukapheresis, as an adjunct to peripheral blood/hematopoietic stem cell transplantation (PBSCT/PHSCT); or

• Use as an alternate or adjunct to donor leukocyte infusions (DLI) in individuals with leukemic relapse after an allogeneic hematopoietic stem cell transplant.

Pegfilgrastim (Neulasta^®) and Biosimilars:

A. In an individual with ALL after completion of the first few days of initial induction chemotherapy or first post-remission course of chemotherapy; or

B. In an individual with MDS with severe neutropenia (ANC less than or equal to 500 mm3 or experiencing recurrent infection; or

C. In an individual receiving dose dense therapy (treatment given more frequently, such as every 2 weeks instead of every 3 weeks) for adjuvant treatment of breast cancer, or other malignancies for which dose dense chemotherapy is an accepted treatment option. If a patient is on a dose dense 14-day chemotherapy cycle, it would be acceptable to administer Neulasta^® outside of the 14-day before and 24-hour after rule for chemotherapy. Neulasta^® would typically be administered on the second day of a 14–day dose dense chemotherapy cycle. The medical record should clearly indicate that the patient is on a 14-day dose dense chemotherapy cycle regimen; or

D. After HPCT/HSCT for the following indications:

• To promote myeloid reconstitution; or

• When engraftment is delayed or has failed.

Sargramostim (GM-CSF, Leukine^®):

A. In an individual receiving dose dense therapy (treatment given more frequently, such as every 2 weeks instead of every 3 weeks) for adjuvant treatment of breast cancer; or

B. In an individual with ALL after completion of the first few days of initial induction chemotherapy or first post-remission course of chemotherapy; or

C. For administration shortly after the completion of induction or repeat induction chemotherapy of AML for individuals over 55 years of age; or

D. In an individual with MDS with severe neutropenia (ANC less than or equal to 500 mm3) or experiencing recurrent infection; or

E. In individuals receiving radiation therapy in the absence of chemotherapy if prolonged delays secondary to neutropenia are expected; or

F. After accidental or intentional total body radiation of myelosuppressive doses (greater than 2 Grays [Gy]) (such as Hematopoietic Syndrome of Acute Radiation Syndrome); or

G. After HPCT/HSCT for the following indications:

• To promote myeloid reconstitution; or

• When engraftment is delayed or has failed; or

• To mobilize progenitor cells into peripheral blood for collection by leukapheresis, as an adjunct to PBSCT/PHSCT; or

IV. Uses for which efficacy and safety have not been established

• Administration of G-CSF in cancer patients in order to increase chemotherapy dose-intensity except as noted above.

• Routine, continuous use of G-CSF in patients with MDS or Felty's syndrome without infections.

• Given the concerns for adverse events, avoidance of G-CSFs in patients receiving concomitant chemoradiotherapy for either head and neck cancer or lung cancer may be warranted.

• Chemo sensitization of myeloid leukemias.

• Continued use if no response is seen within 28-42 days (individuals who have failed to respond within this time frame are considered non-responders).

• Administration of G-CSF in patients with chronic aplastic anemia. Growth factors, as single agents, have not been shown to be effective in severe aplastic anemia. Their use in combination with other agents such as a cyclosporine and/or antilymphocyte globulin (ALG) is still investigational.

•For uses not meeting the criteria noted above in the LCD.

V. Coverage Requirements for Chemotherapy and/or Immunotherapy Related Uses

The patient must be receiving a drug known to be associated with the development of severe neutropenia. The drug must be covered by Medicare.

G-CSF’s and GM-CSF’s will be covered when administered under direct supervision of the physician in the office (Part B) or hospital setting (Part A). When administered by the patient or caregiver, this drug will be considered self-administered and not payable by this A/B MAC.

Pegfilgrastim is a white blood cell growth factor with labeled use to decrease the incidence of infection (as manifested by febrile neutropenia), in patients with nonmyeloid malignancies receiving myelosuppressive cancer therapy associated with a clinically significant incidence of FN.¹ The FDA label recommends administration starting at least 24 hours after the completion of chemotherapy.

To improve compliance and convenience for patients by not having to return 24 hours after chemotherapy for administration there is an interest in same day administration. A survey of physicians who administer pegfilgrastim reported that 31.6% were treated on a “same-day” schedule utilizing patient related considerations in the decision such as patient/caregiver travel distance and practice related consideration such as burden on the practice for next day administration as determining factors.²

Burris et al³ conducted a study to compare data on severe (grade 4) neutropenia duration and FN incidence in patients receiving chemotherapy with pegfilgrastim administered the same day or 24 hours after chemotherapy. These were similar, randomized, double-blind phase II noninferiority studies of patients with lymphoma or non–small-cell lung (NSCLC), breast, or ovarian cancer. Each study was analyzed separately. The primary end point in each study was cycle-1 severe neutropenia duration. Approximately 90 patients per study were randomly assigned at a ratio of 1:1 to receive pegfilgrastim 6 mg once per cycle on the day of chemotherapy or the day after (with placebo on the alternate day). In 4 studies, 272 patients received chemotherapy and 1 or more doses of pegfilgrastim (133 same day, 139 next day). Three studies (breast, lymphoma, NSCLC) enrolled an adequate number of patients for analysis. However, in the NSCLC study, the neutropenic rate was lower than expected (only 2 patients per arm experienced grade 4 neutropenia). In the breast cancer study, the mean cycle-1 severe neutropenia duration was 1.2 days (95% confidence limit [CL], 0.7 to 1.6) longer in the same-day compared with the next-day group (mean, 2.6 v 1.4 days). In the lymphoma study, the mean cycle-1 severe neutropenia duration was 0.9 days (95% CL, 0.3 to 1.4) longer in the same-day compared with the next-day group (mean, 2.1 v 1.2 days). In the breast and lymphoma studies, the ANC profile for same-day patients was earlier, deeper, and longer compared with that for next-day patients, although the results indicate that same-day administration was statistically noninferior to next-day administration according to neutropenia duration. The authors concluded that pegfilgrastim administered at least 24 hours after chemotherapy completion is recommended.

A retrospective study of patients who received chemotherapy and prophylactic same-day or next-day pegfilgrastim found that in cycle 1, 117 patients received same-day pegfilgrastim and 180 patients received next-day pegfilgrastim. FN episodes in cycle 1 occurred in 6.0% versus 6.7% of patients with same-day versus next-day pegfilgrastim, respectively (p = 0.814). Across all cycles, 8.5 and 9.4% of patients experienced >/=1 FN episode after same-day versus next-day pegfilgrastim, respectively (p = 0.793). In the breast cancer patient subgroup, FN occurred 3.2% of same-day pegfilgrastim cycles versus 1.8% of next-day pegfilgrastim cycles (p = 0.938). The authors reached the conclusion that there was no significant difference between same-day and next-day pegfilgrastim administration.⁴

McBride et. al.⁵ looked at 93 patients who received 460 cycles of CHOP-like chemotherapy. The incidence of FN and grade 3/4 chemotherapy-induced neutropenia was 5% and 16.5%, respectively. In 401 cycles, pegfilgrastim was administered same-day versus 12 cycles next-day. FN occurred in 17 cycles versus 0 cycles (p = 1.00) and grade 3/4 chemotherapy-induced neutropenia in 65 cycles (16.2%) versus 1 cycle (16.7%; p = 1.00) with same-day versus next-day pegfilgrastim administration, respectively. They concluded that pegfilgrastim may be safely administered on the same day as chemotherapy in patients with lymphoma receiving CHOP-like chemotherapy.

A systematic literature review evaluated the relative merits of same-day versus next-day dosing of pegfilgrastim. A broad Ovid MEDLINE® and Embase® literature search was conducted that examined all publications indexed before May 9, 2016, that compared same-day versus next-day pegfilgrastim administration. The first part of the systematic literature search identified 1736 publications. After elimination of duplicates, title/abstract screening was conducted on 1440 records, and full text review was conducted on 449 publications. Eleven publications met all criteria and are included in this systematic review; of these, 4 included data from randomized or single arm prospective studies, and 7 were retrospective studies. In most studies included in this review and across a variety of tumor types, administration of pegfilgrastim at least 24 h after myelosuppressive chemotherapy resulted in improved patient outcomes. The authors concluded that data from multiple publications supports administration of pegfilgrastim at least 1 day after chemotherapy.⁶

A small study of 46 patients were treated for the following malignancies: 35 (76%) epithelial ovarian, 6 (13%) primary peritoneal, and 5 (11.0%) ovarian germ cell or stromal cell carcinoma. All patients met the current guidelines of using CSF for prophylaxis against FN. A total of 269 cycles of chemotherapy were administered. All patients received pegfilgrastim within 1 hour of the completion of chemotherapy administration. Grade 1 or 2 neutropenia developed in 10 cycles (3.7%), and the mean ANC was 4926/uL (range, 1,293-24,300). No patients had febrile neutropenic episodes, hospitalizations, or antibiotic use secondary to neutropenia, nor did they have dose reductions or chemotherapy delays due to neutropenia. The authors felt that administration of pegfilgrastim on the same day as myelosuppressive chemotherapy in patients with ovarian or primary peritoneal cancer may be a convenient, safe, and effective approach.⁷

Whitworth et.al.⁸ sought to compare the safety and efficacy of day 1 pegfilgrastim administration to day 2 administration in patients with gynecologic malignancies. They retrospectively evaluated patients receiving both chemotherapy and pegfilgrastim from June 1, 2006, to August 31, 2007, for a gynecologic malignancy. After administration of chemotherapy, all patients either received 6 mg of pegfilgrastim subcutaneously on day 1 or day 2. 1226 administrations of pegfilgrastim in 230 patients were identified. 490 administrations of pegfilgrastim were given on day 1 compared to 736 on day 2. 70% of patients had ovarian cancer with a median age of 64 years (range 15-88). 79% of patients had stage III, IV, or recurrent disease and 67% were undergoing primary chemotherapy. The most common chemotherapy was docetaxel/carboplatin (53%) followed by paclitaxel/carboplatin (19%). The mean ANC nadir was 4810/mm(3) in the day 1 cohort compared to 4212/mm(3) in the day 2 cohort (p=.004). The incidence of Grade 3/4 neutropenia was similar in both groups (4.9% in day 1 vs. 5.7% in day 2; p=.63). Grade 3/4 febrile neutropenia was uncommon in both cohorts (0 episodes vs. 3 episodes; p=.41). Treatment delays were similar in both cohorts (5.9% vs. 7.5%; p=.35). Dose modifications were also similar in both cohorts (2.8% vs. 5.3%; p=.06). Their conclusion was that day 1 administration of pegfilgrastim is as effective as day 2 administration in the prevention of neutropenia in patients with gynecologic malignancies.

Some retrospective studies support safety and efficacy of same day administration, but also trend to a non-statistically significant increase in side effects with same day administration. In addition, other retrospective studies demonstrate a disadvantage to same day dosing. The National Comprehensive Cancer Network (NCCN) Guidelines Version 1.2022 state that pegfilgrastim same day administration is supported by category 1 evidence, however there is data for and against same day dosing. The FDA approved dosing schedule is still recommended by NCCN.⁹

For patients who cannot return to the clinic for next-day administration, there is an FDA-approved delivery device available that can be applied the same day as chemotherapy in order to deliver the full dose of pegfilgrastim the following day (approximately 27 hours after application).

In consideration of the above, Pegfilgrastim should continue to be given according to FDA approved dosing schedule. This A/B MAC will consider same day administration when patient/caregiver circumstances create a significant barrier to compliance, such as lack of transportation to return for dosing within recommended time frame and inability to tolerate and/or obtain the FDA approved on-body injector. This A/B MAC expects clear documentation for same day administration to be in the medical record and available upon request.

Documentation Requirements

The patient's medical record must document the medical necessity of services performed for each date of service submitted on a claim, and documentation must be available to the A/B MAC upon request.

When used for primary or secondary prophylaxis in conjunction with cancer therapy, the record must document risk factors in patients receiving agents/doses uncommonly associated with myelosuppression.

For treatment of covered chronic neutropenia, the patient's medical record must document appropriate evaluation of the cause of the neutropenia, and where appropriate, a history of recurrent fevers and/or infections. The ANC must be documented, but does not need to be submitted with the claim.

For prophylaxis of cancer therapy associate neutropenia, indicate the therapeutic drug used in the medical record.

Providers must clearly document in the medical record the time that the last dose of the cytotoxic therapy cycle ended and the time the G-CSF drug was administered.

FDA labeling of all G-CSF limits administration to 24 hours or more after the administration of the chemotherapeutic agent(s). There may be exceptions when in the clinical judgment of the physician the drug should be administered outside of the timeframe specified by the FDA labeling. In those cases, the reason for the exception should be clearly documented in the medical record.

Utilization Guidelines

Services performed for excessive frequency are not medically necessary. Frequency is considered excessive when services are performed more frequently than generally accepted by peers and the reason for additional services is not justified by documentation.

Other Medicare Administrative Contractors (MACs) Articles:

• CGS: A59126 Pegfilgrastim (Fulphila; Neulasta; Neulasta Onpro; Nyvepria; Udenyca; Ziextenzo) J2506
• Noridian: A52889 Pegfilgrastim (Neulasta) J2505

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2. Marion S, Tzivelekis S, Darden C, et al. "Same-Day" administration of pegfilgrastim following myelosuppressive chemotherapy: clinical practice and provider rationale. Support Care Cancer. 2016;24(9):3889-3896.
3. Burris HA, Belani CP, Kaufman PA, et al. Pegfilgrastim on the same day versus next day of chemotherapy in patients with breast cancer, non-small-cell lung cancer, ovarian cancer, and non-hodgkin's lymphoma: Results of four multicenter, double-blind, randomized phase II studies. J Oncol Pract. 2010;6(3):133-140.
4. Kitchen K, Mosier MC. Real-world febrile neutropenia rates with same-day versus next-day pegfilgrastim after myelosuppressive chemotherapy. Future Oncol. 2022.
5. McBride A, Alrawashdh N, Bartels T, Moore L, Persky D, Abraham I. Same-day versus next-day pegfilgrastim or pegfilgrastim-cbqv in patients with lymphoma receiving CHOP-like chemotherapy. Future Oncol. 2021;17(26):3485-3497.
6. Lyman GH, Allcott K, Garcia J, et al. The effectiveness and safety of same-day versus next-day administration of long-acting granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced neutropenia: a systematic review. Support Care Cancer. 2017;25(8):2619-2629.
7. Schuman SI, Lambrou N, Robson K, et al. Pegfilgrastim dosing on same day as myelosuppressive chemotherapy for ovarian or primary peritoneal cancer. The Journal of Supportive Oncology. 2009;7(6):225-228.
8. Whitworth JM, Matthews KS, Shipman KA, et al. The safety and efficacy of day 1 versus day 2 administration of pegfilgrastim in patients receiving myelosuppressive chemotherapy for gynecologic malignancies. Gynecologic Oncology. 2009;112(3):601-604.
9. Griffiths EA, Roy V, Alwan L, et al. NCCN Guidelines® Insights: Hematopoietic growth factors, Version 1.2022. Journal of the National Comprehensive Cancer Network: JNCCN. 2022;20(5):436-442.

• White Cell
• Colony Stimulating Factors