Predictive tests for shunting normal pressure hydrocephalus – pro

Patients with acute myeloid leukemia (AML) are often neutropenic becasue of leukemia and they also experience profound neutropenia following induction and/or consolidation chemotherapy, which may result in serious, potentially life-threatening, infection. Prophylactic use of myeloid growth factors reduces the severity and duration of neutropenia. Pegylated filgrastim (pegfilgrastim), or Neulasta, has the same mechanism of action as the first generation agent filgrastim, but has markedly reduced renal clearance, with neutrophil-mediated clearance being the major route of elimination. It, therefore, requires only a single dose.

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. 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. This was confirmed by a meta-analysis(Wang et al).

G-CSF is usually well tolerated and medullary bone pain is the most frequently reported side-effect. Sierra et al and Bosi et al demonstrated that Neulasta and Neupgen have the same efficacy. Other less common adverse effects include headaches, generalized musculoskeletal pain, and exacerbation of underlying inflammatory skin disease. A 2005 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”.

 

Jorge Sierra et al, A single dose of pegfilgrastim compared with daily filgrastim for supporting neutrophil recovery in patients treated for low-to-intermediate risk acute myeloid leukemia: results from a randomized, double-blind, phase 2 trial BMC Cancer. 2008; 8: 195.

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]

Bosi A, Szer J, Kassis J, et al. A Multicentre, Double-Blind, Randomized, Phase 2 Trial Comparing Pegfilgrastim with Filgrastim as an Adjunct to Chemotherapy for Acute Myeloid Leukaemia (AML). Proceedings from the 46th annual meeting of the American Society of Hematology (ASH). December 2004. Abstract # 866.

Wang J, An L, Chen S, et al. Prophylactic use of granulocyte colony-stimulating factor after chemotherapy does not affect survival rate in acute myeloid leukemia: A meta-analysis. Acta Haematol. 2009;121(4):223-226.

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