Page 5 - Illustrated Pathology of the Bone Marrow

128 Post-therapy bone marrow changes
Table 14.3. Changes associated with recombinant
granulocyte colony-stimulating growth factor (G-CSF)
and granulocyte–macrophage colony-stimulating growth
factor (GM-CSF).
Peripheral blood changes
Neutrophilia
Granulocyte left shift
Toxic granulation
Dohle bodies
Hypogranular neutrophils
Vacuolated neutrophils
Giant neutrophils
Increase in large granular lymphocytes
Eosinophilia
Transient blast cells
Circulating nucleated red blood cells
Early bone marrow changes
Granulocytic hyperplasia with increase numbers
of promyelocytes and myelocytes
Transient blast cell increase
Toxic granulation of granulocytes
Enlarged promyelocytes and myelocytes
Increased mitotic activity of granulocyte precursors
Biopsy hypocellularity with left-shifted granulocytic precursors tions that are not accompanied by an increase in promyelo-
Late bone marrow changes
Binucleated promyelocytes
Marrow neutrophilia
Marrow eosinophilia
Toxic granulation
Variable biopsy cellularity
Growth factor changes
Growth factors are now administered for a variety of rea-
sons, including enhancing bone marrow recovery after
chemotherapy and priming the marrow or peripheral blood
prior to stem cell collection (Armitage, 1998). It is essential
that administration of these agents be included in the clin-
ical history of any bone marrow sample. The most com-
monly administered growth factors are human recombi-
nant granulocyte colony-stimulating factor (G-CSF) and
granulocyte–macrophage colony-stimulating factor (GM-
CSF). Both peripheral blood and bone marrow alterations
occur with these drugs (Kerrigan et al., 1989; Campbell
et al., 1992; Ryder et al., 1992; Schmitz et al., 1994; Mey-
erson et al., 1998) (Table 14.3).
Both agents cause a peripheral blood leukocytosis with a
granulocyte left shift. Toxic granulation and Dohle bodies
are often present and may give the appearance of a reactive
proliferation. Enlarged neutrophils or neutrophils with vac-
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AB
Figure 14.6. Colony-stimulating factor effects, after G-CSF
administration. (A) Core biopsy shows a marked degree of
neutrophilic hyperplasia. (B) Marrow aspirate smear displays the
characteristic “maturation arrest” at the promyelocyte/early
myelocyte stage which is seen during the early regenerative phase
in patients with hypoplastic marrow treated with this cytokine.
uolated cytoplasm may also occur. The bone marrow shows
a granulocytic hyperplasia which, depending on the timing
of bone marrow examination, may display a complete spec-
trum of granulocytic maturation, may give the appearance
of maturation arrest (Fig. 14.6), or may show a predom-
inance of segmented neutrophils. The maturation arrest
type changes that occur just after administration of the
growth factor offer the most diagnostic problems and may
be confused with recurrent leukemia or myelodysplasia. A
predominance of promyelocytes and myelocytes is usually
present. In rare cases, bone marrow and even peripheral
blood blast cells may exceed 5% (Meyerson et al., 1998),
but this increase is usually accompanied by an increase in
promyelocytes (Harris et al., 1994). The transient increase
in blast cells from growth factor administration should have
even higher numbers of promyelocytes, and blast prolifera-
cytes should be considered highly suspicious for leukemia
and not simply attributed to growth factor changes.
In a patient with a history of acute myeloid leukemia, it
may not be possible to entirely exclude the possibility of
residual leukemia in the setting of an increase in blast cells,
and cytogenetic studies or evaluation for a prior aberrant
leukemia immunophenotype may be useful in that set-
ting. The promyelocytes that occur with G-CSF and GM-
CSF therapy usually have prominent perinuclear hofs, and
this feature should be a clue to the possibility of growth
factor administration. These cells differ from those of
acute promyelocytic leukemia (Innes et al., 1987); the latter