ACUTE LYMPHOBLASTIC-LEUKEMIA WITH SEVERE SKELETAL INVOLVEMENT - A SUBSET OF CHILDHOOD LEUKEMIA WITH A GOOD PROGNOSIS

Skeletal radiographic abnormalities are common in children with acute lymphoblastic leukemia (ALL). The impact of severe skeletal involvemen t (SI) on survival and the correlation between Si and biological marke rs were analyzed. Therefore, radiographs and medical charts of 106 ALL patients who received a skeletal survey at the time of diagnosis and were treated at the University Children's Hospital Wurzburg between 19 74 and 1995 were reviewed. On the basis of the skeletal survey, SI was quantified using a score. Fifty-nine patients (55%) showed radiograph ic abnormalities defined as metaphyseal banding (48%), periosteal reac tions (11%), osteolysis (33%), osteosclerosis (31%), or osteopenia (22 %). Children with severe SI (n = 32) presented with a higher rate of s evere radiographic abnormalities such as geographic destructive osteol ysis (37%; P < .001) and periosteal reactions (28%; P < .05) compared with children with moderate SI (0% and 4 %, respectively). Patients wi th severe SI showed a lower peripheral blast count (P < .05) at diagno sis. a more frequent ''prednisone good response'' (P < .05), and a hig her survival rate (83 +/- 7%; P < .05) than patients without SI (54 +/ - 9%). Patients with moderate SI (n = 27) showed a higher hemoglobin c oncentration (P < .05), an enlargement of liver (P < .05) and spleen ( P < .01), a higher BFM risk factor (P < .01), but still a higher survi val rate (73 +/- 11%) than patients without SI (NS). Patients with sev ere SI had a higher (P < .001) DNA content of leukemic cells as measur ed by DNA index (DI) than patients without SI. Thirty-one percent of p atients with severe SI, 22% of patients with moderate SI, and no patie nt without SI had a DI > 1.16. No patient with a DI < 1.0 presented wi th severe SI. The number of radiographic abnormalities in patients wit h SI correlated with the DI (rho: 0.46; P < .001). However, patients w ith euploidy (DI = 1) and severe SI also had a higher (P = .05) surviv al rate (70 +/- 18% n = 15) than euploid patients without SI (49 +/- 1 1%; n = 24). Of the patients with severe SI, 78% had common ALL and 22 % had an ALL type other than common ALL (P < .05). In patients with AL L types different from common ALL, severe SI was also associated with higher survival rates. We conclude that on the basis of clinical featu res, two distinct subgroups could be identified in terms of SI. Patien ts with clinically relevant severe SI had a better prognosis, a higher DI, and more frequently a common ALL than patients without SI. Howeve r, the impact of severe SI on prognosis was independent of DI and type of leukemia.