Flow cytometric detection of CD10 (cALLA) on peripheral blood B lymphocytes of neonates.

CD10 (cALLA) was detected on the surface of CD19-positive circulating lymphocytes in the peripheral blood of 32/50 neonates tested. These cells are presumed to represent immature B cells, commonly referred to as haematogones, previously undescribed in peripheral blood. The CD10+/CD19+ cells expressed lower levels of CD22 consistent with these cells being immature B lymphocytes. The presence of CD10+/CD19+ cells in the blood was not significantly correlated with a leucoerythroblastic picture, adjusted gestational age, or the presence in blood smears of medium-to-large lymphocytes with an immature appearance that morphologically resembled classic bone-marrow haematogones.

Myeloid malignancies induced by alkylating agents in Nf1 mice.

Therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML and MDS) are severe late complications of treatment with genotoxic chemotherapeutic agents. Children with neurofibromatosis type 1 (NF1) are predisposed to malignant myeloid disorders that are associated with inactivation of the NF1 tumor suppressor gene in the leukemic clone. Recent clinical data suggest that NF1 might be also associated with an increased risk of t-AML after treatment with alkyating agents. To test this hypothesis, we administered cyclophosphamide or etoposide to cohorts of wild-type and heterozygous Nf1 knockout mice. Cyclophosphamide exposure cooperated strongly with heterozygous inactivation of Nf1 in myeloid leukemogenesis, while etoposide did not. Somatic loss of the normal Nf1 allele correlated with clinical disease and was more common in 129/Sv mice than in 129/Sv x C57BL/6 animals. Leukemic cells showing loss of heterozygosity at Nf1 retained a structural allele on each chromosome 11 homolog. These studies establish a novel in vivo model of alkylator-induced myeloid malignancy that will facilitate mechanistic and translational studies.

Myelodysplastic and myeloproliferative disorders of childhood: a study of 167 patients.

Myelodysplastic syndromes (MDS) and myeloproliferative syndromes (MPS) of childhood are a heterogeneous group of clonal disorders of hematopoiesis with overlapping clinical features and inconsistent nomenclature. Although a number of genetic conditions have been associated with MDS and MPS, the overall contribution of inherited predispositions is uncertain. We report a retrospective study examining clinical features, genetic associations, and outcomes in 167 children with MDS and MPS. Of these patients, 48 had an associated constitutional disorder. One hundred one patients had adult-type myelodysplastic syndrome (A-MDS), 60 had juvenile myelomonocytic leukemia (JMML), and 6 infants with Down syndrome had a transient myeloproliferative syndrome (TMS). JMML was characterized by young age at onset and prominent hepatosplenomegaly, whereas patients with A-MDS were older and had little or no organomegaly. The most common cytogenetic abnormalities were monosomy 7 or del(7q) (53 cases); this was common both in patients with JMML and those with A-MDS. Leukemic transformation was observed in 32% of patients, usually within 2 years of diagnosis. Survival was 25% at 16 years. Favorable prognostic features at diagnosis included age less than 2 years and a hemoglobin F level of less than 10%. Older patients tended to present with an adult-type MDS that is accommodated within the French-American-British system. In contrast, infants and young children typically developed unique disorders with overlapping features of MDS and MPS. Although the type and intensity of therapy varied markedly in this study, the overall outcome was poor except in patients with TMS.

Lacrimal gland lymphoma: a cytomorphologic and immunophenotypic study.

The cytomorphology of lacrimal gland lymphoma has not been specifically described. Herein we present six cases of histologically proven lacrimal gland lymphoma which we analyzed using fine-needle aspiration cytology, cell suspension immunophenotype analysis, and immunoglobulin gene rearrangement studies. Fine-needle aspiration cytology revealed atypical populations of cells comprised of either monomorphic small round lymphocytes with or without plasmacytoid features (4 cases), a mixed population of small and large irregular lymphocytes (1 case), or a population of large irregular lymphocytes (1 case). The initial cytologic diagnosis was malignant lymphoma in all six cases. Cell suspension immunophenotype analysis demonstrated that the lesions were composed predominantly of B-cells that expressed monotypic surface immunoglobulin. Three cases demonstrated an immunoglobulin heavy chain gene rearrangement. The atypical cytologic features and the abnormal immunophenotype were consistently predictive of malignant lymphoma. Given that these lesions are small and biopsy material is often limited, fine-needle aspiration offers the advantage of providing tissue that is ideal for cytologic and cell suspension immunophenotype evaluation, obviating the need to provide surgical biopsy material for this purpose. We conclude that fine-needle aspiration can identify malignant lymphoid lesions of the lacrimal gland and may serve as a valuable adjunct in the assessment of these lesions. Additional study is warranted to determine whether fine-needle aspiration can reliably distinguish between benign and malignant lymphoid proliferations of the lacrimal gland.

Effect of recombinant human granulocyte-macrophage colony-stimulating factor on hematopoietic reconstitution after high-dose chemotherapy and autologous bone marrow transplantation.

Recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) has been reported to increase the leukocyte count in subhuman primates subjected to total-body irradiation and in patients with the acquired immunodeficiency syndrome. We administered this substance to 19 patients with breast cancer or melanoma treated with high-dose combination chemotherapy and autologous bone marrow support. Groups of three or four patients were treated with 2.0, 4.0, 8.0, 16.0, or 32.0 micrograms per kilogram of body weight per day of glycosylated rHuGM-CSF by continuous intravenous infusion for 14 days, beginning three hours after bone marrow infusion. Total leukocyte and granulocyte recovery was accelerated in these patients as compared with 24 historical controls matched for age, diagnosis, and treatment. Leukocyte counts (mean +/- SD) obtained 14 days after transplantation were 1511 +/- 1003 per microliter in patients given 2 to 8 micrograms per kilogram per day, 2575 +/- 2304 in those given 16 micrograms, and 3120 +/- 1744 in those given 32 micrograms, as compared with 863 +/- 645 per microliter in the controls. No consistent effect on platelet counts was noted. Toxic effects were generally mild and not clearly dose-related in patients given 2 to 16 micrograms per kilogram per day. Edema, weight gain, or myalgias occurred in all patients given 32 micrograms per kilogram; marked weight gain, generalized edema, pleural effusions, and hypotension developed in two patients, one of whom also had acute renal failure. Our results indicate that rHuGM-CSF can accelerate myeloid recovery after high-dose chemotherapy and autologous bone marrow transplantation, over a range of doses that can be tolerated. In this setting the ability to increase the dose is limited by the development of myalgias and fluid retention.

Occlusion of the basilar artery within a fracture of the clivus. Case report.

Following a 15-foot fall from a roof, a 70-year-old man became comatose and developed signs of pontine dysfunction. There was a severely comminuted fracture of the distal left femur suggesting that he had landed in an upright position. It was clinically unclear whether the fall was secondary to a pontine infarct; however, an autopsy revealed a fracture of the clivus which had entrapped and occluded the basilar artery, causing death. These findings, and those in similar cases, suggest that this entity results from a force transmitted in an axial direction.

Patients with myotonic dystrophy, a possible segmental progeroid syndrome, and Duchenne muscular dystrophy have fibroblasts with normal limits for in vitro lifespan and growth characteristics.

Myotonic dystrophy (MyD) has been suggested to be a segmental progeroid syndrome in man, as this syndrome has some clinical manifestations of premature aging. Fibroblasts from patients with other progeroid syndromes have been shown to have diminished in vitro lifespans or growth characteristics; therefore, it was of interest to study cellular senescence in fibroblasts from patients with MyD. Fibroblast cultures from patients with Duchenne muscular dystrophy (DMD) were used as additional controls, as premature aging is not associated with this genetic disorder. Primary skin fibroblast cultures obtained from patients with MyD or DMD and from age-sex matched controls were grown in DMEM plus 10% FBS. The in vitro lifespan was determined by either a 1:4 split ratio or with a constant initial inoculum of 1 times 10(4) cells/cm2, followed by determination of the final density at weekly intervals. Our results demonstrate that there is no difference in the limits of the in vitro lifespan for either the MyD or DMD fibroblast strains compared to the controls. Likewise, no difference could be detected in the growth characteristics of these cells. The only observable difference was that the pooled age-matched controls and MyD cultures had a shorter in vitro lifespan than the DMD group and their pooled controls, a finding expected because of the age of the patients in each group. Unlike the other progeroid syndromes, MyD fibroblasts have normal limits for in vitro lifespan. MyD is probably not closely related to the other premature aging syndromes, although there is an increasing phenotypic expression as a function of age.