Page 126 - Essential Haematology

112 / Chapter 8 White cells: Granulocytes and monocytes

as a ‘ reserve pool ’ or storage compartment. Th e pegylated (PEG) G - CSF can be given once in
bone marrow normally contains more myeloid cells 7 – 14 days. Some of the indications are as follows:

than erythroid cells in the ratio of 2 : 1 to 12 : 1, the
• Post - chemotherapy, radiotherapy or stem cell trans-
largest proportion being neutrophils and metamy-
plantation In these situations, G - CSF accelerates
elocytes. In the stable or normal state, the bone
granulocytic recovery and shortens the period of
marrow storage compartment contains 10 – 15 times

neutropenia (Fig. 8.5 ). This may translate into a
the number of granulocytes found in the peripheral
reduction of length of time in hospital, antibiotic
blood.
usage and frequency of infection but periods of
Following their release from the bone marrow,
extreme neutropenia after intensive chemother-
granulocytes spend only 6 – 10 hours in the circula-
apy cannot be prevented.
tion before moving into the tissues where they
• Acute myeloid leukaemia As in other haemato-
perform their phagocytic function. In the blood-
logical malignancies treated with intensive chem-
stream there are two pools usually of about equal
otherapy G - CSF has been used to reduce
size: the circulating pool (included in the blood
infections, hospital stay and antibiotic usage.
count) and the marginating pool (not included in

There is no evidence that G - CSF injections can

the blood count). They spend on average 4 – 5 days
precipitate relapse of the disease.
in the tissues before they are destroyed during
• Myelodysplasia G - CSF has been given alone or in

defensive action or as the result of senescence.
conjunction with erythropoietin in an attempt to
improve bone marrow function (without acceler-
Control of g ranulopoiesis: m yeloid ating leukaemic transformation).
g rowth f actors • Lymphomas G - CSF is given to reduce infection,
delay in giving chemotherapy and hospitalization

The granulocyte series arises from bone marrow
after chemotherapy. A single injection of pegylated
progenitor cells which are increasingly specialized.
G - CSF immediately after chemotherapy is often
Many growth factors are involved in this matura-
used.
tion process including interleukin - 1 (IL - 1), IL - 3,
• Severe neutropenia Both congenital and acquired
IL - 5 (for eosinophils), IL - 6, IL - 11, granulocyte –
neutropenia, including cyclical and drug - induced
macrophage colony - stimulating factor (GM - CSF),
neutropenia, have been found to respond well to
granulocyte CSF (G - CSF) and monocyte CSF (M -
G - CSF.

CSF) (see Fig. 1.7 ). The growth factors stimulate

• Severe infection G - CSF has been used as an adju-

proliferation and differentiation and also aff ect the
vant to antimicrobial therapy.
function of the mature cells on which they act (e.g.
• Peripheral blood stem cell harvesting G - CSF is
phagocytosis, superoxide generation and cytotoxic-
used to increase the number of circulating multipo-
ity in the case of neutrophils; phagocytosis, cytotox-
tent progenitors, improving the harvest of
icity and production of other cytokines by
sufficient peripheral blood stem cells for

monocytes) (Fig. 1.6 ).
transplantation.
Increased granulocyte and monocyte produc-
tion in response to an infection is induced by Monocytes
increased production of growth factors from stromal
cells and T lymphocytes, stimulated by endotoxin, Monocytes spend only a short time in the marrow
IL - 1 or tumour necrosis factor (TNF) (Fig. 8.4 ). and, after circulating for 20 – 40 hours, leave the
blood to enter the tissues where they mature and
carry out their principal functions. Th eir extravas-

Clinical a pplications of G - CSF

cular lifespan after their transformation to macro-
Clinical administration of G - CSF intravenously phages (histiocytes) may be as long as several months
or subcutaneously produces a rise in circulating or even years. They may assume specifi c functions

neutrophils. G - CSF is used in clinical practice. in different tissues (e.g. skin, gut, liver) (Fig. 8.6 ).

Short - acting G - CSF is given daily. A longer acting One particularly important lineage is that of