Bone marrow biopsy in adult acute lymphoblastic leukemia: morphological characteristics and contribution to the study of prognostic factors

Abstract 

Bone marrow (BM) sections were examined in 128 untreated adult patients with newly diagnosed acute lymphoblastic leukemia (ALL), seen in our institution over a 19-year period. BM biopsy was performed in order to assess the incidence, degree and prognostic significance of histological data of the disease. BM features studied were reticular fibrosis, total cellularity, residual hematopoiesis, mitotic activity, and blastic infiltration. T-cell lineage ALL were diagnosed in 23% of the cases, while B-cell lineage ALL represented 70% of the cases. There were 7% of non-T-non-B-cell lineage ALL. The percentage of BM leukemic cells was related to cellularity (P=0.02), while it was related to the disappearance of normal cell lines (P<0.0001). BM cellularity was related to the percentage of circulating leukemic cells at diagnosis (P=0.006). Residual hematopoiesis was related to a higher initial granulocyte count (P=0.04) and lower percentage of circulating blasts (P=0.04). The degree of fibrosis was inversely related to that of BM cellularity (P=0.04). All patients, but four, received standard ALL induction chemotherapy according to different successive protocols. In this whole cohort of patients, complete remission (CR) rate was 78%. Median disease-free survival (DFS) and median overall survival (OS) were 13.7 months and 20.2 months, respectively. In univariate analysis, CR rate was positively affected by mitotic activity (P=0.01) and residual hematopoiesis (P=0.008). OS was positively influenced by a higher leukemic cell mitotic activity (P=0.03) and the persistence of more than two residual normal cell lines in BM (P=0.04). Patients presenting with both of those characteristics had better outcome than patients who did not, as well as, in terms of CR (P=0.03), or DFS (P=0.002), or OS (P=0.003). T-cell lineage ALL and L3 ALL did not significantly influence those results. Our findings did not confirm that among marrow features, reticular fibrosis has any prognostic value. A multivariate analysis of both clinical and histological data was performed to test their prognostic relevance. In a model including age, immunophenotype, Philadelphia chromosome status, mitotic index, and level of normal residual hematopoiesis, the only significant predictor of CR achievement were the persistence of normal residual hematopoietic cell lines (P=0.01) and the mitotic activity of leukemic cells (P=0.002). Philadelphia chromosome status (P=0.03) and age (P<0.0001) were of prognostic value, respectively for DFS and OS.

We conclude that some characteristics of BM biopsy afford not only descriptive but also prognostic information for predicting the outcome. The persistence of normal residual hematopoiesis and intense leukemic cells mitotic activity were both factors of favorable outcome, while BM fibrosis did not display any prognostic value.

Keywords:  Bone marrow biopsy, Fibrosis, Acute lymphoblastic leukemia, Prognosis