Page 1 - Illustrated Pathology of the Bone Marrow

14
Post-therapy bone marrow changes
Introduction
A variety of therapy regimens and toxin exposures can
cause bone marrow changes. Post-therapy evaluation of
the marrow may be useful to evaluate for residual disease,
to assess the degree of marrow ablation, or to look for signs may initially be composed only of erythroid cells or a mix
of marrow recovery. While proper marrow evaluation after
therapy in individual patients requires knowledge of the
type of prior therapy and original disease, some changes
after therapy are common to all cases and vary primarily
by the degree of marrow ablation.
General marrow changes after
myeloablative therapy
There are many similarities in the marrow findings fol-
lowing high-dose chemotherapy or combined chemother-
apy and radiation, as is often used in preparation for
hematopoietic stem cell transplantation, and even after
toxin or drug injuries to the marrow (Sale & Buckner 1988;
van den Berg et al., 1989, 1990; Michelson et al., 1993;
Wilkins et al., 1993). Common bone marrow changes after
myeloablative therapy are summarized in Table 14.1. In
the first week after the most severe types of injuries, the
marrow shows complete aplasia with a complete or near-
complete absence of normal hematopoietic elements and
marrow fat. There is marked edema with dilated marrow
sinuses, intramedullary hemorrhages, and scattered stro-
mal cells, histiocytes, lymphocytes, and plasma cells. The
histiocytes may contain cellular remnants, and fibrinoid
necrosis may be prominent. Zonal areas of tumor necro-
sis may also be present, although myeloablative therapy is
often given in the absence of prior marrow disease. After
the first week, a mild reticulin fibrosis develops and the
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reappearance of fat cells, often multilobulated, is the first
evidence of marrow recovery (Fig. 14.1). Although the mar-
row remains markedly hypocellular, focal hematopoietic
elements begin to appear in association with fat, usually in
the second week after treatment. The regenerative islands
of granulocyte precursors and erythroid cells, and both
cell types can usually be identified after two weeks. By the
third week, regenerating megakaryocytes, often hypolo-
bated and in clusters, can usually be identified. Marrow
regeneration in any age group, but most prominent in chil-
dren, may also be associated with an increase in small
lymphoid cells with a precursor B-cell immunopheno-
type, termed hematogones. These cells which show a spec-
trum of B-cell maturation are usually found admixed with
other maturing marrow elements. As the marrow cellular-
ity increases, the early reticulin fibrosis resolves and the
marrow may become transiently hypercellular.
After recovery from hematopoietic stem cell transplanta-
tion, the marrow cellularity may remain patchy and below
the pre-transplant cellularity, essentially establishing a new
baseline cellularity for the post-transplant state (Fig. 14.2).
Another unique general feature of the post-transplant mar-
row is a change in the maturation architecture of the mar-
row. While islands of regenerating marrow elements are
normally located adjacent to bony trabeculae, the post-
transplant marrow may show such islands away from bone,
mimicking the so-called abnormal localization of imma-
ture cell precursors (ALIP) of myelodysplasia. Increases
in siderotic iron are also common in post-transplantation
states (Macon et al., 1995), which may include the tran-
sient presence of ringed sideroblasts, and should not be
interpreted as evidence of myelodysplasia.
Patients with delayed engraftment or post-therapy bone
marrow failure show signs of aplasia for several weeks,