Page 3 - Illustrated Pathology of the Bone Marrow

126 Post-therapy bone marrow changes

Table 14.2. Useful features in the differential diagnosis of
hematogones and residual or recurrent precursor B-cell acute
lymphoblastic leukemia.

Feature Hematogones Leukemia

Homogeneous nuclear chromatin + −
Maturation spectrum + −
Most cells smaller than a maturing + −

granulocyte − +
Nucleoli − +
Precursor B-cell clusters on biopsy − +/−
Aberrant antigen expression − +/−
Peripheral blood involvement

cellularity for remission. The new criteria also have cat- Figure 14.3. Residual acute lymphoblastic leukemia with
egories of “cytogenetic complete remission,” “molecular post-treatment hematogone hyperplasia. Note the difference
complete remission,” and “morphologic complete remis- between the residual blasts (large, irregular nuclei, vacuolation)
sion with incomplete blood count recovery.” This later cat- and the hematogones (small, dense mature chromatin, round
egory is for patients that remain neutropenic or thrombo- nuclear contours). The distinction can be difficult, however, and
cytopenic after chemotherapy. flow cytometry or immunohistochemistry may be helpful.

Despite these new criteria, regenerative bone marrow Figure 14.4. Post-therapy acute promyelocytic leukemia.
blast cell increases of 5% or more may occur, especially with Numerous residual promyelocytes are present, some of which
the common use of growth factors. Therefore, the simple are atypical in appearance.
use of a blast cell count is not sufficient for accurately deter-
mining the presence or absence of disease. Correlation with that are similar to other acute myeloid leukemias. Some
the original blast cell morphology and immunophenotype patients, however, are treated primarily with ATRA and do
can be extremely helpful in this differential diagnosis. not develop post-therapy aplasia (Kantarjian et al., 1985).
The marrow may remain hypercellular, with elevated num-
A similar dilemma occurs in the differential diagno- bers of promyelocytes (Fig. 14.4). These cells will usually
sis between residual or recurrent acute lymphoblastic undergo a slow maturation secondary to the therapy. There-
leukemia and hematogones (Table 14.2). Hematogones are fore, the type of therapy should be known, as the presence of
polytypic B-cell progenitors that usually show a spectrum sheets of promyelocytes may not indicate treatment failure.
of morphologic and immunophenotypic B-cell matura- These patients should be followed closely with additional
tion, comparable to lymphoblasts (Fig. 14.3). In contrast marrow examinations and cytogenetic studies, to confirm
to residual/recurrent leukemia, hematogones do not show
aberrant antigen expression, usually do not involve the
peripheral blood, and do not show prominent nucleoli.
Therefore, the immunophenotypic detection of an aber-
rant leukemia clone or molecular testing for clonality may
be useful in this differential diagnosis. Immunohistochem-
ical study of the bone marrow biopsy may also be helpful in
this setting. Detection of CD34- or TdT-positive immature
cell clusters on the biopsy is helpful (Rimsza et al., 1998),
because regenerating blasts and hematogones do not nor-
mally form large clusters.

Acute promyelocytic leukemia

Most patients with acute promyelocytic leukemia receive
both all-trans-retinoic acid (ATRA) and combination
chemotherapy, and show post-therapy marrow changes

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