Cancer Treatment Today » Neupogen

Prophylactic myeloid growth factors before chemotherapy in the elderly – pro

M Levin, MD — Wed, 17 Jul 2013 17:22:47 +0000

Standard guidelines recommend prophylactic Neulasta or Neupogen for patients who are treated with chemotherapy regimens that produce a greater than 20% risk of febrile neutropenia. These guidelines do not apply to the elderly. Elderly patients are at a higher risk of febrile neutropenia following chemotherapy, with worse morbidity and mortality rates. However, good prospective trial data are lacking with respect to elderly cancer patients due to their relative exclusion from randomized clinical trials, which therefore limits specific recommendations relative to this patient group. An earlier Task Force(2003) said: “In several specific malignancies, there is a clear need for further well- designed studies and clinically applicable tools to assist the identification of elderly patients who will benefit most from prophylactic G-CSF.” More recently, a study in the elderly by Rahan et al found that: “PPG-CSF use is associated with reductions in in-patient healthcare utilization. These findings have implications for ASCO guidelines and Medicare coverage policies for PPG-CSF administration in elderly breast cancer patients.” Studies by Romileu and Balducci et la support prophylactic GCSF therapy and a review by Aspro et al in 2010 recommends it. It would be fair to say that the field is shifting toward generally recommending prophylactic growth factors in the elderly.

Repetto L . Greater risks of chemotherapy toxicity in elderly patients with cancer. J Support Care Oncol 2003;1 Suppl 2:18-24.

J. de Naurois et al,Management of febrile neutropenia: ESMO Clinical Practice Guidelines Ann Oncol (2010) 21 (suppl 5): v252-v256.

EORTC Cancer in the Elderly Task Force guidelines for the use of
colony-stimulating factors in elderly patients with cancer, 2003, http://www.hompedin.org/download/paper/EORTGuideline.pdf

ERajan SS, Lyman GH, Stearns SC, Carpenter WR.ffect of primary prophylactic granulocyte-colony stimulating factor use on incidence of neutropenia hospitalizations for elderly early-stage breast cancer patients receiving chemotherapy.Med Care. 2011 Jul;49(7):649-57.

Romieu G, Clemens M, Mahlberg R, Fargeot P, Constenla M, Schutte M, Easton V, Skacel T, Bacon P, Brugger W. Pegfilgrastim supports delivery of FEC-100 chemotherapy in elderly patients with high risk breast cancer: a randomized phase 2 trial. Crit Rev Oncol Hematol. 2007;64:64–72.

Balducci L, Al-Halawani H, Charu V, Tam J, Shahin S, Dreiling L, Erchler WB. Elderly cancer patients receiving chemotherapy benefit from first-cycle pegfilgrastim. Oncologist. 2007;12:1416–1424.

Matti Aapro et al, Prophylaxis of chemotherapy-induced febrile neutropenia with granulocyte colony-stimulating factors: where are we now? Support Care Cancer. 2010 May; 18(5): 529–541.

See Lay version here

Neupogen for Gleevec induced neutropenia – pro

M Levin, MD — Fri, 07 Dec 2012 14:52:25 +0000

Many chemotherapeutic drugs cause neutropenia and guidelines now uniformly recommend G-CSF(granulocyte growth stimulating factors) prophylactically and therapeutically for chemotherapy. However, non-chemo drugs can also cause neutropenia. Among them are bcr-abl directed drugs used for CML, such as Gleevec. Depending on the stage, up to 70% of the patients treated with imatinib for CML experience an NCI grade 3 or 4 neutropenia or thrombocytopenia during Imatinib therapy. A number of reports indicate that Neupogen can overcome neutropenia, allowing maintenence of dose and schedule of imatinib. NCCN in version 2.2013 recommends GSCF in combination with imatinib in patients with refractory neutropenia. In Asia beramine si being investigatede for this purpose.

Zaucha JM, Wyrowinska E, Prejzner W, Calbecka M, Hellmann A. Imatinib-associated neutropenia may not be overcome by filgrastim treatment in patients with blastic phase of chronic myeloid leukaemia.Clin Lab Haematol. 2006 Jun;28(3):208-10.

D Heim et al, G-CSF for Imatinib-induced neutropenia. Leukemia (2003) 17, 805–807.

nccn. org, CML 2012

Zhao Y, Tan Y, Wu G, Liu L, Wang Y, Luo Y, Shi J, Huang H. Berbamine overcomes imatinib-induced neutropenia and permits cytogenetic responses in Chinese patients with chronic-phase chronic myeloid leukemia.Int J Hematol. 2011 Aug;94(2):156-62.

For Lay version see here

For Neupogen for interferon induced neutropenia see here

Mozobil with Neupogen – pro

admin — Sat, 01 Sep 2012 20:38:46 +0000

Mozobil is a new drug designed to mobilize stem cells from the bone marrow into the bloodstream, where they can be collected. Previous alkylation therapy, radiotherapy and low collection day platelet count are predictive of poor collection yields. Neupogen, which is commonly given prior to stem cell harvesting, stimulates the body to make white blood cells. When given together, Mozobil and Neupogen have been shown to increase harvest efficiency prior to autologous peripheral stem cell transplantation. I am not aware of any data that Neupogen alone can be used to predict response to the combintaton of Mozobil and Neupogen.

The original trial was a Phase III study which randomly allocated patients with NHL scheduled to receive an autologous transplant to have stem cells collected after Neupogen alone or Neupogen plus Mozobil. They reported that 59% of patients receiving Neupogen plus Mozobil achieved the goal of harvesting 6 million CD34+ cells/kg from the peripheral blood in 4 or fewer aphereses compared to 20% for the Neupogen alone group. In addition, 87% of patients receiving Neupogen plus Mozobil achieved the minimum quantity of CD34+ cells required for transplantation (2 million/kg) compared to 47% in the Neupogen alone group. It was also reported that combination therapy was also more successful in achieving secondary endpoints such as: number of days to achieve target CD 34+ cell numbers, success of engraftment, number of days needed to engraft and durability of engraftment for the first 100 days. Other studies also suggest that Mozobil is an effective agent for mobilization of stem cells when administered as a single agent. A recent study also suggests that Mozobil and Neupogen mobilizes more lymphocytes than Neupogen alone which may decrease post-transplant relapses. This was also confirmed in myeloma patients.

Considering marked superiority of combined therapy to Neupogen alone, I do not consider a trial of Neupogen alone to be clinically appropriate if Mozobil and Neupogen are available.

Neulasta and neupogen for acute myeloid leukemia: An Update – pro

admin — Sat, 01 Sep 2012 20:37:41 +0000

Myeloid growth factors granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been extensively studied in acute leukemias. Whether administered before, during, or after chemotherapy for acute myeloid and acute lymphoblastic leukemias, these agents reduce the duration of neutropenia and appear to be safe and well tolerated. Despite consistently demonstrating a shorter duration of neutropenia, multiple, prospective, randomized trials have documented only modest benefits in terms of reduction in the incidence and severity of infections, without substantial gains or impact in complete remission, overall survival, and disease-free survival rates. Growth factors have also been used to recruit quiescent leukemia cells into the S phase of the cell cycle to increase their susceptibility to chemotherapy with the goal to reduce relapse and resistance. Randomized trials to evaluate this priming strategy have consistently demonstrated an improvement in terms of disease-free or event free survival in the intermediate risk group of patients with acute myeloid leukemia, but no overall survival benefit. G-CSF is usually well tolerated and medullary bone pain is the most frequently reported side-effect. Other less common adverse effects include headaches, generalized musculoskeletal pain, and exacerbation of underlying inflammatory skin disease. Neulasta is not used routinely in acute myeloid leukemia but is not harmful if used appropriately. A recent guideline says: “Similarly there is insufficient evidence to support routine use of G-colony stimulating factor (CSF) or granulocyte macrophage (GM)-CSF with induction chemotherapy in patients over 60 years of age, although this may be appropriate if it is desirable to reduce hospitalisation or antibiotic usage”.

Milligan DW, Grimwade D, Cullis JO, Bond L, Swirsky D, Craddock C, Kell J, Homewood J, Campbell K, McGinley S, Wheatley K, Jackson G. Guidelines on the management of acute myeloid leukaemia in adults. London (UK): British Society of Haematology (BSH); 2005 May 23. 77 p. [202 references]

Neutropenia rate of docetaxel/ cyclophoshamide regimen – pro

admin — Sat, 01 Sep 2012 20:36:18 +0000

The issue in is whether the docetaxel/ cyclophashamide regimen has a febrile neutropenia rate of 20% or more when used in the usual manner in adjuvant treatmetn of breast cancer. The issue is solely whether the docetaxel/ cyclophashamide regimen has a febrile neutrropenai rate of 20% or more when used in the usual manner in adjuvant treatment of breast cancer. The original Journal of Clinical Onology paper(Dec 1 206)reported a febrile nutropenia rate of 5%, whereas there is also a figure of 41% drawn from a paper reporting solid tumors in a phase I setting.

However, a more recent reviews have put the risk of febrile neutropenia with this regimen as high a 33%. This accords with actual clinical experience of practicing oncologists. The disrepancy seems to be explainable by the setting. In the university setting, for unclear reasons, there is less febrile nutropenia with this regimen than in the community. I therefore think that G-CSF prophyalxis is appropriate according to the NCCN and ASCO guidelines. These set G-CSF use as appropriate for febrile neutropenia risk of 20% or more.

T. Vandenberg, BA MD, J. Younus, MD, and S. Al-Khayyat, MD Febrile neutropenia rates with adjuvant docetaxel and cyclophosphamide chemotherapy in early breast cancer: discrepancy between published reports and community practice—a retrospective analysis Curr Oncol. 2010 April; 17(2): 2–3.
However, more recent reviews have put the risk of febrile neutropenia with this regimen as high a 33%. This accords with actual clinical experience of practicing oncologists. The disrepancy seems to be explainable by the setting. In the university setting, for unclear reasons, there is less febrile nutropenia with this regimen than in the community. I therefore agree with the client’s methodological point but remain of the opinion that G-CSF prophyalxis is appropraite according to the NCCN and ASCO guidelines.
T. Vandenberg, BA MD, J. Younus, MD, and S. Al-Khayyat, MD Febrile neutropenia rates with adjuvant docetaxel and cyclophosphamide chemotherapy in early breast cancer: discrepancy between published reports and community practice—a retrospective analysis Curr Oncol. 2010 April; 17(2): 2–3.

Myeloid Growth Factor Guidelines and Folforinox – pro

M Levin, MD — Mon, 27 Aug 2012 18:23:04 +0000

The use of G-CSF after the administration of chemotherapy may be in several settings:

“Primary prophylaxis,” when neutropenia is expected to occur following a course of chemotherapy, but the patient has never experienced it.
“Secondary prophylaxis,” when the patient had a neutropenic fever in a previous course of similar chemotherapy and is thus expected to do so again.
“Supportive” in the attempt to shorten the duration of severe chemotherapy-induced neutropenia in patients without fever (“afebrile neutropenia”).(Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;52:e56–e93. ).

Administration of G-CSF is generally not recommended for routine treatment in patients with established fever and neutropenia. ASCO and ASH guidelines recommend routine use of Neulasta® or Neupogen (filgrastim) for patients with an overall risk of FN of 20% or greater. The NCCN guidelines state that for patients with a febrile neutropenia risk of 10% to 20%, prophylactic colony-stimulating factor use should be considered based on the treatment intent and the importance of chemotherapy dose delivery on schedule.Previous studies have suggested that prophylactic Neulasta can reduce the incidence of hospitalizations, decrease FN and allow better delivery of protocol doses of chemotherapy. The recommended dosage of Neulasta® is a single subcutaneous injection of 6 mg administered once per chemotherapy cycle. Neulasta® should not be administered in the period between 14 days before and 24 hours after administration of cytotoxic chemotherapy.

The supportive data was generated from 8 randomized clinical trials and 3 observational studies conducted between 1998 and 2005.

NCCN, Supportive Chemotherapy 2019

Thomas J. Smith, Kari Bohlke, Gary H. Lyman, Kenneth R. Carson, Jeffrey Crawford, Scott J. Cross, Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. Journal of Clinical Oncology 33, no. 28 (October 2015) 3199-3212.

Lyman GH, Kleiner JM. Summary and comparison of myeloid growth factor guidelines in patients receiving cancer chemotherapy. Cancer Treat Res. 2011;157:145-65.

Some specific regimens.

The reported rates of febrile neutropenia differ between studies of the TC(Taxotere/Cytoxan) studies. The Jones et al study, noted a trend toward more febrile neutropenia (FN; 5% v 2.5%, P = .07) in the TC group. A 2009 study(Soong et al) reported FN rates of up to 50%. While true rates of FN are beign assessed, I consider Neulasta appropriate for the TC regimen.

A recent study(Vandenberg et al) found that patients older than 65 had a 40% risk of febrile neutropenia with the AC regimen.

Carboplatin/paclitaxel result in a very low incidence of grade 4 neutropenia

Markman J, Zanotti K, Webster K, Belinson J, Peterson G, Kulp B, Markman M.Experience with the management of neutropenia in gynecologic cancer patients receiving carboplatin-based chemotherapy. Gynecol Oncol. 2004 Feb;92(2):592-5.

The recent 2005 ASCO guideline added that patients treated with palliative intent for metastatic disease should have thir dose reduced rather than use myeloid growth factors.

Désirée Caselli et al,Biosimilars in the management of neutropenia: focus on filgrastim.Biologics. 2016; 10: 1722.

Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;52:e56e93.

Christopher R. Flowers, Jerome Seidenfeld, Eric J. Bow, Clare Karten, Charise Gleason, Douglas K. Hawley, Nicole M. Kuderer, Amelia A. Langston, Kieren A. Marr, Kenneth V.I. Rolston and Scott D. Ramsey Antimicrobial Prophylaxis and Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology Clinical Practice Guidelin JCO January 14, 2013

Thomas J. Smith, Kari Bohlke, Gary H. Lyman, Kenneth R. Carson, Jeffrey Crawford, Scott J. Cross, John M. Goldberg, James L. Khatcheressian, Natasha B. Leighl, Cheryl L. Perkins, George Somlo, James L. Wade, Antoinette J. Wozniak and James O. Armitage, Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. JCO July 13, 2015

NCCN Supportive Care, Neutropenia, 2016.

Management of febrile neutropenia: ESMO Clinical Practice Guidelines Ann Oncol (2010) 21 (suppl 5): v252-v256.

Clark OAC, Lyman G, Castro AA, Clark LGO, Djulbegovic B. Colony stimulating factors for chemotherapy induced febrile neutropenia. Cochrane Database of Systematic Reviews 2000, Issue 4. Art. No.: CD003039

Adams, Jared R., Angelotta, Cara, Bennett, Charles L.
When the Risk of Febrile Neutropenia Is 20%, Prophylactic Colony-Stimulating Factor Use Is Clinically Effective, but Is It Cost-Effective? J Clin Oncol 2006 24: 2975-2977

Smith TJ, Khatcheressian J, Lyman GH: 2006 update of recommendations for the use of white blood cell growth factors: An evidence-based, clinical practice guideline. J Clin Oncol 24:3187-3205, 2006

Lyman GH: Guidelines of the National Comprehensive Cancer Network on the use of myeloid growth factors with cancer chemotherapy: A review of the evidence. J Natl Compr Canc Netw 3:557-571, 2005

D. Soong et al, High Rate of Febrile Neutropenia in Patients With Operable Breast Cancer Receiving Docetaxel and Cyclophosphamide, JCO September 10, 2009 vol. 27 no. 26 e101-e102

Alimta and carboplatin in second line studies have a risk of febrile neutropenia of 2.7-3.4%.

Ardizzoni A, Tiseo M, Boni L, et al: Pemetrexed versus pemetrexed and carboplatin as second-line chemotherapy in advanced nonsmall-cell lung cancer (NSCLC): Results of GOIRC 02-2006 randomized phase II study and pooled analysis with NVALT7 trial. J Clin Oncol 30:4501-4507, 2012.

2. Smit EF, Burgers SA, Biesma B, et al: Randomized phase II and pharmacogenetic study of pemetrexed compared with pemetrexed plus carboplatin in pretreated patients with advanced nonsmall-cell lung cancer.

Taxotere and Cytoxan

The prevalence of febrile neutropenia in this regimen was specifically looked at from a regulatory perspective. Historically, reported rates of FN without prophylactic G-CSF range from 5% in the phase III trial to as high as 50% in retrospective chart reviews for TC regimen. Guidelines recommend GCSF propjylaxis when febrile neutropenia exceeds 20%. As G-CSF was not covered by Ontario provincial cancer funding agency for primary prophylaxis of FN with TC chemotherapy, local investigators sought to determine the incidence of FN with TC chemotherapy in two comprehensive cancer centres in Ontario, Canada. Methods: Patients who received adjuvant TC chemotherapy between January 1, 2008 and December 31, 2012 were identified through the pharmacy databases. Electronic charts were retrospectively reviewed to abstract patient characteristics, treatment details including G-CSF use, and incidence of FN. : Preliminary results from one institution demonstrate that 187 patients were treated with TC over the study period. Of the 74 (40%) patients who did not receive primary G-CSF prophylaxis, 23 (31%) developed FN requiring hospitalization and treatment with intravenous antibiotics. However, none of the 113 patients who received primary G-CSF prophylaxis (funded by the patient or a third party payer) developed FN. Putative risk factors for FN in the absence of G-CSF including age, BSA, BMI, and pre-treatment absolute neutrophil count were examined and will be reported. Conclusions: The FN rate associated with TC chemotherapy exceeds 30%, higher than that reported in the clinical trial. They concluded: As per ASCO guidelines, primary G-CSF prophylaxis should be given with TC chemotherapy, and in Canada this should be covered by provincial cancer funding agencies.

Joanne Linda Yu, Michael Kurin, Mark Pasetka, Srikala S. Sridhar, Ellen Warner; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada; Odette Cancer Centre, Sunnybrook Health Sciences Centre; University of Toronto, Toronto, ON, Canada; Princess Margaret Hospital, Toronto, ON, Canada, Febrile neutropenia with adjuvant docetaxel and cyclophosphamide (TC) chemotherapy for breast cancer. Clin Oncol 31, 2013 (suppl; abstr e17523)

Foforinox had a febrile neutropenia rate reported of 24% by Weycker et al, and Neulasta is appropriate per guidelines. Yamada Y, Fujii H, Watanabe D, et al. Grade 3–4 neutropenia occurs more frequently in patients treated with FOLFIRINOX than gemcitabine (45.7% versus 21.0%, p < 0.001). A high incidence of grade 3–4 neutropenia (77.8%) has also been observed in Japanese patients receiving FOLFIRINOX for metastatic pancreatic cancer.
Severe Neutropenia is Associated with Better Clinical Outcomes in Patients with Advanced Pancreatic Cancer Who Receive Modified FOLFIRINOX Therapy. Cancers (Basel). 2018;10(11):454. Published 2018 Nov 16. doi:10.3390/cancers10110454
"Supportive care in cancer: official journal of the Multinational Association of Supportive Care in Cancer." href="https://www.ncbi.nlm.nih.gov/pubmed/25082364">Support Care Cancer. 2014 Dec;22(12):3275-85.

Yamada Y, Fujii H, Watanabe D, et al. Severe Neutropenia is Associated with Better Clinical Outcomes in Patients with Advanced Pancreatic Cancer Who Receive Modified FOLFIRINOX Therapy. Cancers (Basel). 2018;10(11):454. Published 2018 Nov 16. doi:10.3390/cancers10110454

Rituximab induced neutropenia – pro

M Levin, MD — Mon, 27 Aug 2012 17:04:25 +0000

Neutropenia has been well reported with Rituxan in CLL. In these reports it ws usually associated with agressive regimens that incorpoorted Rituxan. The use of intensive primary chemotherapy regimen was a risk factor. Neutropenia was generally self-limited and not associated with severe infections. I did not find any reports of using G-CSF to treat this condition and in the absence of dicumented infection, it may not be of any benefit. Since an immunologic mechanism, suc as induction of anti-neutrophil antiboides can be potentially invovled, Rituxan should be discontinued, especially in the maintenance situations, in which benefit is still uncertain.

Voog, Eric, Morschhauser, Franck, Solal-Celigny, Philippe, Benyunes, Mark C., Multani, Pratik S., Saunders, Andrew
Neutropenia in Patients Treated with Rituximab
N Engl J Med 2003 348: 2691-2694

Nitta, E, Izutsu, K, Sato, T, Ota, Y, Takeuchi, K, Kamijo, A, Takahashi, K, Oshima, K, Kanda, Y, Chiba, S, Motokura, T, Kurokawa, M (2007). A high incidence of late-onset neutropenia following rituximab-containing chemotherapy as a primary treatment of CD20-positive B-cell lymphoma: a single-institution study. Ann Oncol 18: 364-369

Marotte, H, Paintaud, G, Watier, H, Miossec, P (2008). Rituximab-related late-onset neutropenia in a patient with severe rheumatoid arthritis. Ann Rheum Dis 67: 893-894

Severe Congential Neutropenia and Stem Cell Transplantation – pro

M Levin, MD — Tue, 07 Aug 2012 02:56:45 +0000

Severe congenital neutropenia (SCN) is a constellation of syndromes consisting of arrested myeloid development resulting in neutropenia. The mainstay of treatment is G-CSF. It is not, however, a curative treatment. Approximately 90% of patients respond to GCSF administration with a subsequent decrease in sepsis-related mortality to almost 1% per year during the first decade of life, with a cumulative incidence of 21% of progression to acute leukemia following 10 years of GCSF. Recently updated North American registry data suggest a relative plateau in the hematologic malignancy risk after 10–15 years. It remains controversial if prolonged GCSF therapy predisposes to malignant transformation.

Allogeneic sem cell transplantation is curative. Zeidler et al. reported 11 SCN patients without malignancy who received HSCT; 8 received sibling-matched transplants (5 BMT, 1 cord, 1 BMT and cord, 1 PBSC) and 10 received myeloablative conditioning with busulfan/cyclophosphamide ± ATG, thiotepa, or melphalan. All patients receiving myeloablative conditioning engrafted regardless of source although 40% of tested patients had graft chimerism (30%–84% donor) at 6–12 months post-transplant. Acute GVHD grade II–IV was present in 2 of the unrelated BMT recipients. Overall survival of the 10 patients receiving myeloablative regimens was 80% at median follow-up of 10 months. The French SCN registry reported HSCT outcomes on 5 SCN patients without malignant transformation. Donors included unrelated cords (2) and unrelated bone marrows (2), and related bone marrow (1). All received myeloablative regimens with 80% engraftment and 40% mortality due to infection at one year post-transplant. In contrast, 18 Japanese patients with SCN without malignant transformation underwent transplantation from sibling-matched (9) or matched-unrelated donors (9) following myeloablative conditioning in 12 cases and non-myeloablative in the remaining 6 patients. Although four patients encountered primary graft failure (including two sibling matched donor transplants) and received a second transplant, 16 of the 18 patients are considered disease-free with a median follow-up of 6 years.

It appears form reproted series and cases that it is far better to transplant before AML or MDS develop.

Transplantation is indicated for patients unresponsive to GCSF and should be strongly considered for mild responders to high doses of GCSF given this group’s risk of malignancy and the disparity between transplant survival prior to malignant transformation compared to afterwards.

Sung W. Choi, John Levine Indications for hematopoietic cell transplantation for children with severe congenital neutropenia Pediatric Transplantation Volume 14, Issue 8, pages 937–939, December 2010

Kenji Morimoto et al, Transplantation for Congenital Bone Marrow Failure Syndromes Bone Marrow Research
Volume 2011 (2011), Article ID 849387, 7 pages

P. S. Rosenberg, B. P. Alter, and B. P. Alter, “The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy,” Blood, vol. 107, no. 12, pp. 4628–4635, 2006.

P. S. Rosenberg, C. Zeidler, and C. Zeidler, “Stable long-term risk of leukaemia in patients with severe congenital neutropenia maintained on G-CSF therapy: short report,” British Journal of Haematology, vol. 150, no. 2, pp. 196–199, 2010.

M. H. Freedman, M. A. Bonilla, and M. A. Bonilla, “Myelodysplasia syndrome and acute myeloid leukemia in patients with congenital neutropenia receiving G-CSF therapy,” Blood, vol. 96, no. 2, pp. 429–436, 2000.

C. Zeidler, K. Welte, and K. Welte, “Stem cell transplantation in patients with severe congenital neutropenia without evidence of leukemic transformation,” Blood, vol. 95, no. 4, pp. 1195–1198, 2000.

C. Ferry, M. Ouachée, and M. Ouachée, “Hematopoietic stem cell transplantation in severe congenital neutropenia: experience of the French SCN register,” Bone Marrow Transplantation, vol. 35, no. 1, pp. 45–50, 2005.

K. Oshima, R. Hanada, R. Kobayashi, K. Kato, Y. Nagatoshi, K. Tabuchi, and S. Kato, “Hematopoietic stem cell transplantation in patients with severe congenital neutropenia: an analysis of 18 Japanese cases,” Pediatric Transplantation, vol. 14, no. 5, pp. 657–663, 2010.

S. W. Choi, L. A. Boxer, and L. A. Boxer, “Stem cell transplantation in patients with severe congenital neutropenia with evidence of leukemic transformation,” Bone Marrow Transplantation, vol. 35, no. 5, pp. 473–477, 2005

Chronic Neutropenia and Neupogen – pro

M Levin, MD — Tue, 07 Aug 2012 02:47:02 +0000

Severe chronic neutropenia is a general term that applies to both congenital and acquired cases. Kostmann syndrome is a subtype of chronic neutropenia with onset in early childhood with an autosomal recessive pattern of development. It can have an immune basis. The mainstay of treatment is G-CSF and the member has done well on it. It is not, however, a curative treatment. Approximately 90% of patients respond to GCSF administration with a subsequent decrease in sepsis-related mortality to almost 1% per year during the first decade of life, with a cumulative incidence of 21% of progression to acute leukemia following 10 years of GCSF. Recently updated North American registry data suggest a relative plateau in the hematologic malignancy risk after 10–15 years. It remains controversial if prolonged GCSF therapy predisposes to malignant transformation. However, when it causes infections, short term Neupogen therapy is appropriate.

David C. Dale, Laurence A. Boxer Guidelines for pediatric management of severe chronic neutropenia American Journal of Hematology Volume 87, Issue 2, page 133, February 2012

Read the Layperson version here.

Neupogen: Dose – pro

M Levin, MD — Wed, 20 Jun 2012 11:57:46 +0000

NCCN, ASCO and ASH guidelines recommend routine use of Neulasta® or Neupogen (filgrastim) for patients with an overall risk of FN of 20% or greater. Previous studies have suggested that these drugs can reduce the incidence of hospitalizations, decrease Febrile Neutropenia and allow better delivery of protocol doses of chemotherapy. The supportive data was generated from 8 randomized clinical trials and 3 observational studies conducted between 1998 and 2005.

NEUPOGEN® (filgrastim) is indicated to decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anti- cancer drugs associated with a significant incidence of severe neutropenia with fever , as dose dense chemotherapy for lymphoma would be. The recommended starting dose of NEUPOGEN® (filgrastim) is 5 mcg/kg/day‚ administered as a single daily injection by SC bolus injection‚ by short IV infusion (15 to 30 minutes)‚ or by continuous SC or continuous IV infusion. A CBC and platelet count should be obtained before instituting NEUPOGEN® (filgrastim) therapy‚ and monitored twice weekly during therapy. Doses may be increased in increments of 5 mcg/kg for each chemotherapy cycle‚ according to the duration and severity of the ANC nadir.

Whereas 10 days of therapy may be, in fact, necessary, the indication is for doses to be adjusted based on ANC and WBC. SImilaryl, NCCN on MGF-C says that Neupogen should be used until nadir recoveryu and does not state a defined number of doses.