To assess the clinical heterogeneity among patients with acute lymphoblastic leukemia (ALL) and various 11q23 abnormalities, we analyzed data on 497 infants, children and young adults treated between 1983 and 1995 by 11 cooperative groups and single institutions. The substantial sample size allowed separate analyses according to age younger or older than 12 months for the various cytogenetic subsets. Infants with t(4;11) ALL had an especially dismal prognosis when their disease was characterized by a poor early response to prednisone (P = 0.0005 for overall comparison; 5-year event-free survival (EFS), 0 vs 237 712% s.e. for those with good response), or age less than 3 months (P = 0.0003, 5-year EFS, 57 75% vs 23.47 74% for those over 3 months). A poor prednisone response also appeared to confer a worse outcome for older children with t(4;11) ALL. Hematopoietic stem cell transplantation failed to improve outcome in either age group. Among patients with t(11;19) ALL, those with a T-lineage immunophenotype, who were all over 1 year of age, had a better outcome than patients over 1 year of age with B-lineage ALL (overall comparison, P = 0.065; 5-year EFS, 887 713 vs 46714%). In the heterogeneous subgroup with del(11)(q23), National Cancer Institute-Rome risk criteria based on age and leukocyte count had prognostic significance (P = 0.04 for overall comparison; 5-year EFS, 647 78% (high risk) vs 837 76% (standard risk)). This study illustrates the marked clinical heterogeneity among and within subgroups of infants or older children with ALL and specific 11q23 abnormalities, and identifies patients at particularly high risk of failure who may benefit from innovative therapy.

We reviewed the data of children with high-stage primitive neuroectodermal tumors (medulloblastomas) who were treated on Children's Cancer Group-921 protocol to evaluate the correlation between tumor resection and prognosis. Patients enrolled in the study had either tumors that were operatively categorized to be Chang tumor stage 3b or 4, postoperative residual tumors > 1.5 cm2, or evidence of tumor dissemination (Chang metastasis Stages [M Stages] 1-4) at diagnosis. Resections were analyzed in two ways, as follows: 1) by the extent of resection (percent of the tumor that was removed), as estimated by the treating neurosurgeon; and 2) by the extent of residual tumor (how much of the tumor was left), as estimated from postoperative scans. Two hundred and three children were enrolled in the study with institutional diagnoses of primitive neuroectodermal tumors-medulloblastomas; diagnoses were confirmed by central neuropathological review in 188 patients. Progression-free survival (PFS) at 5 years was 54% (standard error, 5%). As in previous Children's Cancer Group studies, age and M stage correlated with survival; PFS was significantly lower in children 1.5 to 3.0 years old at diagnosis and in those with any evidence of tumor dissemination (M Stage 1-4). On univariate analysis, neither extent of resection nor extent of residual tumor correlated with PFS. However, adjusting for other factors, extent of residual tumor was important; PFS was 20% (standard error, 14%) better at 5 years in children with no dissemination (M Stage 0) who had< 1.5 cm2 of residual tumor (P = 0.065) and was 24% (standard error, 14%) better at 5 years in children > 3 years old with no tumor dissemination (M Stage 0) and with < 1.5 cm2 residual tumor (P = 0.033). On the basis of our observations, we conclude that extent of tumor resection, as estimated by the neurosurgeon, does not correlate with outcome but that extent of residual tumor does correlate with prognosis in certain children (those who are > 3 years old, with no tumor dissemination). In contrast to age and M stage, the major factors associated with outcome, residual tumor is an important variable in outcome, one that neurosurgeons can control.

TIC injections extended throughout the intensification and maintenance periods are superior to IDM pulses for prevention of CNS leukemia. Our results with TIC seem comparable with those achieved with other contemporary methods of CNS preventative therapy. Thus, extended TIC affords a reasonable alternative to CNS irradiation plus upfront IT MTX for patients with B-progenitor ALL.

The best therapy for patients with histiocytosis X with disease involvement other than isolated bone lesions but without organ dysfunction is unclear. This retrospective study was undertaken to define the natural history of this group of patients. In 25 of the 92 studied patients, there was no progression of the disease after diagnosis. In 53 surviving patients, the disease either continuously progressed (40) or recurred intermittently (13). The onset of last disease activity was 24 months or less for 55% of these children. A fatal outcome occurred in 14 children. All of these children developed organ dysfunction and 11/14 died during or before the second year of disease. These three different outcomes could not be predicted from the parameters evaluated; however, the disease that never abated but was continuously active was associated with a suboptimal outcome, and the development of organ dysfunction was a grave prognostic sign.