Development of acute lympboblastic leukemia in a patient with increased hematogones after toxic bone marrow damage

Abstract

To the best of our knowledge we describe the first case showing the association of increased B cell precursors/hematogones in a regenerating post-toxic bone marrow with subsequent development of a B-ALL. Since all immunohistochemical/moleculargenetic anaylses have failed to identify the initial malignant leukemic clone, we suggest a close-meshed follow-up of such cases to identify potential mechanisms for the malignant transformation of B-cell precursors/hematogones and to prevent further fatal courses.

Keywords: B-ALL; Bone marrow; hematogones; toxic damage.

Figure 1

Peripheral blood smear (1a) and bone marrow biopsy (1b) from December 2008 showing a distinct pancytopenia (1,6×10⁶/μl red blood cells (RBC), 0,5×10³/μl WBC (white blood cells) and 7,8×10⁴/μl PLT (platelets)) as well as classical histological aspects of toxic bone marrow damage with vanished and edematous marrow areas (1b). Approximately 5% loosely distributed TDT positive bone marrow cells were identified by immunohistochemistry (IH) (inset 1b) and double immunofluo-rescence staining (DIF) (1c) without coexpression of the cell adhesion molecule CD54 [1], [2] (1c) and detection of a polyclonal rearrangement of the FR3a/2a-IgH genlocus (inset lc).

Figure 2

In March 2009 both normalized blood values (2a) with regular blood cells in peripheral blood smear (2a) and regularly maturating hematopoiesis in nor-mocellular bone bone marrow spaces (2b) were detectable. By contrast ∼20% TDT positive cells were found by IH (inset 2b) with partial coexpression of TDT and CD54 in DIF (2c) and detection of a prominent peak in the amplification of Fr3a/IgH rearrangement (inset 2c) corresponding to a clonal rearrangement/cell population on a still existing polyclonal background (2c inset).

Figure 3

In May 2009 a distinct leucocytosis (3a; 45×10³/μl) became apparent with abundant blasts in peripheral blood (3a) and bone marrow (3b). In IH (inset 3b) and DIF (3c) the blasts were strongly positive for TDT and showed a homogenous coexpression of TDT and CD54 (3c) as well as a prominent monoclonal rearrangement of the Fr3a/IgH genlocus (inset 3c).