Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone marrow specimens by 4-color flow cytometry

Abstract

Bone marrow hematogones (B-lymphocyte precursors) may cause problems in diagnosis because of their morphologic and immunophenotypic similarities to neoplastic lymphoblasts. The purposes of this prospective, multiparametric flow cytometry study were to quantify hematogones across age groups and a spectrum of clinical conditions, to identify factors that affect the relative quantity of hematogones, and to compare their immunophenotype with that of neoplastic lymphoblasts. A total of 662 consecutive marrow specimens were analyzed for hematogones using one of two 4-color antibody combinations; hematogones were identified in 528 (79.8%). There was a significant decline in hematogones with increasing age (P < .001), but a broad range was found at all ages and many adults had a relatively high number. Specimens processed by density gradient had a higher mean percent hematogones than those processed by erythrocyte lysis (P < .001). There was a direct decline in hematogones with increasing marrow involvement with neoplastic cells. A total of 8% of the 662 specimens contained 5% or more hematogones: 24.6% of specimens from patients aged less than 16 years and 6.3% from those 16 and older (P < .000 01).

Expansion of B cell precursors after unrelated cord blood transplantation for an adult patient

“…3,5 Morphological evaluation of BM smears confirmed that at the level of 5% or more hematogones were conspicuous and likely to be confused with ALL relapse as reported previously. 3 However, their immunophenotypic features, reported in Table 2, were always consistent with typical B cell precursors. Taking into consideration immunophenotypic features, chimerism status, MRD results and X chromosome inactivation analysis, B cell precursor expansion appeared clearly as non-malignant state.…”

“…2 Hematogones exhibit a typical complex spectrum of lymphoid antigen differentiation extending from early B cell precursors to mature surface immunoglobulin-bearing B cells, lack aberrant antigen expression and do not exhibit clonal immunoglobulin or TCR gene rearrangements. 2,3 Their increase has been observed in marrow regenerative states following chemotherapy or BM transplantation and may cause diagnostic confusion particularly after treatment for ALL because of hematogones' similarities to neoplastic lymphoblasts. 3 Expansion of hematogones may be persistent, for 2 years after completion of chemotherapy for ALL and for more than 1 year following BM transplantation.…”

“…2,3 Their increase has been observed in marrow regenerative states following chemotherapy or BM transplantation and may cause diagnostic confusion particularly after treatment for ALL because of hematogones' similarities to neoplastic lymphoblasts. 3 Expansion of hematogones may be persistent, for 2 years after completion of chemotherapy for ALL and for more than 1 year following BM transplantation. 4,5 No clear description of their increase after CB transplantation has been reported until now.…”

Donor cell leukemia after umbilical cord blood transplantation: recurrent or de novo? The importance of diagnosis for therapeutic decision making

“…distinguishing leukemia from hematogones [13]. In our case, the bone marrow was occupied by nearby 85% blasts, indicating a possible malignant state.…”

Abnormally expanded pro‐B hematogones associated with congenital cytomegalovirus infection

“…Their presence has been noted in children with different hematological (red blood aplasia, SchwachmanDiamond syndrome, amegakaryocytic thrombocytopenia, hereditary spherocytosis) and nonhematological (retinoblastoma, viral infections, HIV, Gaucher disease, Ewing's sarcoma) disorders [1,2]. Their morphology and immunophenotype (CD19, CD10, CD34 surface antigen, and nuclear terminal deoxynucleotidyl transferase/TdT positive) is similar to that of B-precursor cells [3,4]. Occasionally, an hematogone increase may mimic acute lymphoblastic leukemia (ALL), raising diagnostic problems [5].…”