Channel-forming discharges typically are associated with recurrence intervals less than five years and usually less than two years. However, the actual frequency of occurrence of these discharges is often several times more frequent than the statistical expectation. This result was confirmed by using the Log-Pearson Type 3 statistical method to analyze measured annual series of instantaneous peaks and peak daily means for 150 catchments in six states in the North Central Region of the United States. Discharge records ranged from 39 to 102 years and catchment sizes ranged from 29 to 6475 km 2 . For each state, mean values of the ratio of the calculated to the expected occurrences exceeded 1.0, for recurrence intervals from two years to 100 years with R-squared values varying from 0.64 to 0.97, respectively. However, catchment-by-catchment variability was too large for the relationships for each state to be useful. We propose a method, called Full Daily Distribution (FDD), which used all of the daily values for the available period of records. The approach provided ratios of calculated to expected occurrences that were approximately 1.0. For recurrence intervals less than five years, the FDD calculated discharges were much greater than those obtained by using the Log-Pearson Type 3 approach with annual series of instantaneous peaks or peak daily means. The method can also calculate discharges for recurrence intervals less than one year. The study indicates a need to enhance the Log-Pearson Type 3 method to provide better estimates of channel-forming discharges and that the proposed FDD could be a useful tool to this purpose.

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Previous banded metaphase cytogenetic studies of CLL identified deletions of 13q, 11q, 17p and 6q and trisomy 12 as recurring aberrations; all except del(6q) have well-recognized prognostic significance. The association of other cytogenetic abnormalities with these recurring aberrations has not been previously described. To more completely characterize our patients with CLL, we performed banded metaphase cytogenetics and fluorescence in situ hybridization (FISH) on 539 patients with previously untreated as well as relapsed CLL. By banded metaphase analysis 236 cases were abnormal, 282 were normal (≥20 metaphases and no abnormal clone identified) and 21 were culture failures. Of the 236 abnormal cases, 30 had a sole numerical sex chromosome abnormality, which may not represent the malignant clone. 89 cases had complex karyotypes (≥ 3 unrelated abnormalities), and 147 had simple abnormalities. Losses (451 total, 116 whole chromosome, 47 of which were sex chromosomes, and 335 partial losses) were much more common than gains (132 total, 110 whole chromosome, 68 +12, 13 +X or Y, only 29 other whole chromosome gains, and 22 partial chromosome gains). 130 balanced rearrangements occurred; most frequently involving chromosomes 14 and 1 (15 and 14 balanced rearrangements, respectively). As previously reported, +12, del(13q), del(11q), del(17p) and del(6q) occurred frequently (34.3%, 14.4%, 16.5%, 22.9%, and 10.2% of cases, respectively). Other frequent losses involved 14q, 9p, 3p and 18p (8.5%, 6.8%, 6.4% and 5.9% of cases, respectively). Partial chromosome losses usually resulted from apparent unbalanced translocations, suggesting frequent non-reciprocal interchromosomal rearrangements that may represent a unique form of chromosomal instability. We recently have begun examining the clinical significance of secondary abnormalities occurring with common aberrations in CLL. Of interest, all patients with t(14;18)(q32;q21) and 7 of 10 patients with trisomy 18 also had trisomy 12. All 4 patients with t(14;18) CLL had atypical immunophenotypes with only one developing symptomatic disease requiring therapy. A similar atypical immunophentype was found in 5 of 7 pts with co-existent trisomy 12 and 18, and only one of these patients has progressed to require treatment. In contrast, 36 of the remaining 57 pts with trisomy 12 have developed progressive disease requiring therapy. Overall, our studies show that multiple chromosomal aberrations in addition to those commonly reported occur in CLL. Chromosomal losses are more common than gains, and unbalanced rearrangements are more frequent than balanced rearrangements. The unbalanced rearrangements are frequently interchromosomal and may indicate a unique type of chromosomal instability. Unlike the other common cytogenetic aberrations in CLL, trisomy 12 appears to be associated with secondary aberrations including t(14;18) and trisomy 18 that may define a different more favorable clinical pathologic history than observed in trisomy 12 patients without these secondary aberrations.

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