Kawai S

Cell proliferation in childhood acute leukemia. Comparison of Ki-67 and proliferating cell nuclear antigen immunocytochemical and DNA flow cytometric analysis

The proliferative activity of bone marrow leukemia cells was determined by DNA flow cytometric (FCM) analysis and labeling index (LI) of Ki‐67 monoclonal antibodies and proliferating cell nuclear antigen (PCNA) autoantibodies in 73 children with acute leukemia. LI of Ki‐67 varied greatly from patient to patient (range, 0.4% to 42.2%; mean, 18.8%) and differed significantly between acute lymphoblastic leukemia (ALL) and acute nonlymphoblastic leukemia (ANLL). In ALL, the Ki‐67 LI showed a positive correlation with the S‐phase fraction (SPF) determined by DNA FCM analysis, whereas, in ANLL, there was a discrepancy between the Ki‐67 LI and SPF. In contrast, LI of PCNA varied less among the patients (range, 57.2% to 100%; mean, 90.3%), and the value was always higher than that of the Ki‐67 L1 in individual patients. A significant relationship between PCNA LI and the percentage of blast cells was found in peripheral blood leukocytes from patients with leukemia. These results suggest that the Ki‐67 LI reflects differences in the proliferative activity depending on the subtype of the disease and that the PCNA LI is useful as a marker of proliferating cells.

Prognostic implication of cellular DNA content in acute lymphoblastic leukemia

To assess the prognostic value of the cellular DNA content measured by flow cytometry in acute lymphoblastic leukemia (ALL), we studied the pretreatment distribution of the DNA content in marrow blasts from 74 children with this disease. They were divided into standard- and high-risk groups according to their white blood cell counts and age at the time of diagnosis and were followed for up to 44 months. Abnormal DNA stemlines were detected in 26 children, and all of them had a hyperdiploid DNA content (DNA index of greater than 1.0). The duration of remission was significantly longer in those with hyperdiploid DNA stemlines than in those with diploid DNA stemlines in both risk groups. In the standard-risk group, the DNA content and common ALL antigen were significant prognostic factors, especially the former. In the high-risk group, the DNA content also showed an independent significant correlation with the clinical outcome.

Clinical Significance of Childhood Acute Myeloid Leukemias Expressing Lymphoid-Associated Antigens

The clinical significance of the expression of lymphoid-associated antigens in leukemic cells was studied in 66 children with newly diagnosed acute myeloid leukemia (AML). Among 66 AML cases, 17% were CD7-positive, 15% were CD19-positive, 8% were CD2-positive, and 5% were CD10-positive. In 23 (35%) of the 66 AML cases, at least one lymphoid-associated antigen was expressed in the leukemic cells. When the clinical features and laboratory findings were compared at diagnosis between the 23 Ly+ and the 43 Ly- AML cases, no statistically significant difference was found. The expression of CD34 was significantly more frequent in Ly+ AML cases (91%) than in Ly- AML cases (31%). Chromosomal analysis revealed t(8;21) in 6 of the 21 Ly+ AML cases examined. No other specific chromosome aberration was noted. The 3-year event-free survival rates of Ly+ AML cases and Ly- AML cases were 34% +/- 12% and 26% +/- 8%, respectively. There was no statistically significant difference between the two groups. Further studies are required to determine the prognostic significance of lymphoid-associated antigen expression.

Intramedullary Neutrophil Phagocytosis by Histiocytes in Autoimmune Neutropenia of Infancy

We describe a case of autoimmune neutropenia of infancy in which active phagocytosis of mature myeloid cells by bone marrow histiocytes was observed. This finding in the routine hematological investigation has not been reported so far and might be helpful in suggesting the diagnosis of autoimmune neutropenia of infancy, and also in understanding the pathogenesis of peripheral neutropenia in this disease.

Successful treatment of acute leukemia with t(4;11) in an infant with congenital hypothyroidism.

We describe a case of acute leukemia with t(4;11) (q21;q23) in a 3-month-old girl suffering from congenital hypothyroidism. The blast cells were cytochemically and immunologically classifiable as acute lymphoblastic leukemia of an early B-cell lineage (HLA-DR +, B4 +, CALLA-). but we treated this patient with a protocol designed mainly for acute nonlymphocytic leukemia, employing Adriamycin, vincristine, and cytosine arabinoside. Although the prognosis of this type of leukemia is known to be extremely poor, our patient is currently alive and in continuous complete remission lasting 35 months to date. This case may demonstrate a potential alternative therapeutic strategy for acute leukemia with t(4;11) as well as clinical evidence for the mixed-lineage characteristics of this condition. However, the pathogenetic role of congenital hypothyroidism in the development of acute leukemia is still uncertain.

Childhood acute megakaryoblastic leukemia with internalization of hemic cells

Two atypical cases of acute megakaryoblastic leukemia (AMKL) in infants diagnosed by immunophenotying are described. In both cases, the leukemic cells at diagnosis resembled monoblasts with reniform nuclei, fine reticular chromatin, and abundant grey-blue cytoplasm with pseudopods. In addition, these blasts frequently showed internalization of hemic cells. Therefore, the diagnosis of acute monocytic leukemia (AMOL) or malignant histiocytosis (MH) was initially suggested. However, alpha-naphthyl butyrate esterase stain was negative and immunologic studies determined megakaryocytic lineage of the blasts. Our observation in two consecutive cases of AMKL implies that there is a potential risk of misdiagnosing AMKL as AMOL or MH in infants. The incidence and significance of internalization of hemic cells by blast cells of AMKL in infancy are unknown and we cannot be certain whether these cases constitute a subgroup of AMKL in infancy.