Myelodysplasia syndrome and acute myeloid leukemia in patients with congenital neutropenia receiving G-CSF therapy.

Granulocyte colony-stimulating factor (G-CSF) has had a major impact on management of "severe chronic neutropenia," a collective term referring to congenital, idiopathic, or cyclic neutropenia. Almost all patients respond to G-CSF with increased neutrophils, reduced infections, and improved survival. Some responders with congenital neutropenia have developed myelodysplastic syndrome and acute myeloblastic leukemia (MDS/AML), which raises the question of the role of G-CSF in pathogenesis. The Severe Chronic Neutropenia International Registry (SCNIR), Seattle, WA, has data on 696 neutropenic patients, including 352 patients with congenital neutropenia, treated with G-CSF from 1987 to present. Treatment and patient demographic data were analyzed. The 352 congenital patients were observed for a mean of 6 years (range, 0.1-11 years) while being treated. Of these patients, 31 developed MDS/AML, for a crude rate of malignant transformation of nearly 9%. None of the 344 patients with idiopathic or cyclic neutropenia developed MDS/AML. Transformation was associated with acquired marrow cytogenetic clonal changes: 18 patients developed a partial or complete loss of chromosome 7, and 9 patients manifested abnormalities of chromosome 21 (usually trisomy 21). For each yearly treatment interval, the annual rate of MDS/AML development was less than 2%. No significant relationships between age at onset of MDS/AML and patient gender, G-CSF dose, or treatment duration were found (P >.15). In addition to the 31 patients who developed MDS/AML, the SCNIR also has data on 9 additional neutropenic patients whose bone marrow studies show cytogenetic clonal changes but the patients are without transformation to MDS/AML. Although our data does not support a cause-and-effect relationship between development of MDS/AML and G-CSF therapy or other patient demographics, we cannot exclude a direct contribution of G-CSF in the pathogenesis of MDS/AML. This issue is unclear because MDS/AML was not seen in cyclic or idiopathic neutropenia. Improved survival of congenital neutropenia patients receiving G-CSF therapy may allow time for the expression of the leukemic predisposition that characterizes the natural history of these disorders. However, other factors related to G-CSF may also be operative in the setting of congenital neutropenia. (Blood. 2000;96:429-436)

Memories of half a life ago.

A study of the recollections of childhood of a 12-year-old girl is placed in the context of developmental perceptions of time. Specifically, the transition from wishful to more realistic perceptions of the future is discussed, along with the growing capacity of the older child to incorporate experiences of the past into the present. The role of time perception in the formation of identity is presented from the perspective of psychological maturation and the growing comprehension of social roles and personal competence.

On studying the young.

The process of studying youth culture is examined in terms of the consequence of the social and imaginative worlds of young people and those who study them. The impressions of the young, thus found, ultimately reveal to us insights into our own past, the relationship of generations, and the meaning of maturation. The ambivalence demonstrated by so many young people is discussed along with the difficulties this produces for observations of youth. Finally, mention is made of the importance of recognizing that studies of youth accentuate the tentativeness with which the results of social psychological studies must be held, and of resisting the temptation either to dehumanize young people through social scientific inquiries, or to overromanticize them to the extent that they themselves begin to question their own worth.