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Hyperhaploid clones (24-34 chromosomes) were identified in 33 patients with multiple myeloma (MM), identifying a novel numerical cytogenetic subgroup. Strikingly, all hyperhaploid karyotypes were found to harbor monosomy 17p, the single most important risk stratification lesion in MM. A catastrophic loss of nearly a haploid set of chromosomes results in disomies of chromosomes 3, 5, 7, 9, 11, 15, 18, 19, and 21, the same basic set of odd-numbered chromosomes found in trisomy in hyperdiploid myeloma. All other autosomes are found in monosomy, resulting in additional clinically relevant monosomies of 1p, 6q, 13q, and 16q. Hypotriploid subclones (58-68 chromosomes) were also identified in 11 of the 33 patients and represent a duplication of the hyperhaploid clone. Analysis of clones utilizing interphase fluorescence in-situ hybridization (iFISH), metaphase FISH, and spectral karyotyping identified either monosomy 17 or del17p in all patients. Amplification of 1q21 was identified in eight patients, demonstrating an additional high-risk marker. Importantly, our findings indicate that current iFISH strategies may be uninformative or ambiguous in the detection of these clones, suggesting this patient subgroup maybe under-reported. Overall survival for patients with hyperhaploid clones was poor, with a five-year survival rate of 23.1%. These findings identify a distinct numerical subgroup with cytogenetically defined high-risk disease.

Nausea and vomiting are significant side effects in bone marrow transplant (BMT) patients who receive high-dose preparative regimens. Higher than conventional ondansetron doses and continuous infusion might improve emetic control, because of the high doses and combinations of chemotherapy (CT) used in this setting. Our objective was to conduct a prospective, randomized study comparing two different administration methods of high-dose ondansetron during a BMT preparative regimen in breast cancer patients. Patients were eligible if they were nonpregnant women over 18 but under 65 years of age, undergoing highly emetogenic CT in preparation for autologous BMT. All patients received ondansetron as an intermittent (INT = 24 mg i.v. q 12 h/day) or continuous intravenous infusion (CIV = 8 mg i.v. loading dose followed by a continuous infusion of 2 mg/h per day). A total of 66 patients were enrolled in the study (n = 34, INT; n = 32, CIV). There was no statistical difference between treatment groups in the worst grade of emesis for the entire study period (P = 0.49). Greater than 90% of all patients were graded as failures (> or = 5 emetic episodes or need for rescue antiemetics). Complete control (no vomiting episodes) and complete plus major control (1-2 emetic episodes) per day ranged from 8% to 85% and 11% to 91%, respectively. There was no significant difference between the treatment arms in: grade of emesis, episodes of vomiting and retching, nausea scores, and mean number of rescue medications administered. There were no differences in efficacy when high-dose ondansetron was given as CIV or INT for the control of nausea and vomiting in breast cancer patients undergoing high-dose CT for autologous BMT. Ondansetron alone was not adequate to provide sustained control of CT-induced nausea and vomiting over the entire 5-day study period. A combination of antiemetics targeting various mechanisms of CT-induced nausea and vomiting may be necessary to improve response rates.

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Introduction: When enrollment in SAMMPRIS was stopped, the 30-day rate of stroke or death and the 1-year rate of the primary endpoint in the medical arm were 5.8% and 12.2%, respectively. The comparative rates in patients in WASID who met the SAMMPRIS entry criteria were 10.6% and 21.9%. While the lower rates in the SAMMPRIS trial have been attributed to aggressive medical management, an alternative hypothesis is that SAMMPRIS patients may have been at lower risk due to a lower burden of vascular risk factors. Methods: We compared risk factors at study entry in the 227 patients in the medical arm of SAMMPRIS with the 143 patients in WASID who met the SAMMPRIS entry criteria. Results: Compared with WASID patients, SAMMPRIS patients were younger (mean age 59.5 years vs. 62.5 years; p=0.009) but had higher percentages of hypertension (89% vs. 76%; p<0.001)*, hyperlipidemia (89% vs 69%; p<0.001)*, stenosis in the 80-99% range (55% vs. 35%; p<0.001), anterior circulation stenosis (68% vs. 48%; p<0.001), white race (71% vs. 61%; p=0.06), and on an antithrombotic agent at the time of the qualifying event (62% vs. 52%; p=0.08). SAMMPRIS patients had higher mean systolic blood pressure (146.8 mmHg vs. 139.1, p< 0.001), higher body mass index (30.7 kg/m 2 vs. 29.4, p=0.045) but lower LDL (98 mg/dl vs. 125, p<0.001). There were no significant differences in the frequency of female gender, stroke as the qualifying event, diabetes, smoking, history of previous stroke, time from qualifying event to study entry, and history of CAD. Conclusion: Compared to WASID patients meeting the SAMMPRIS entrance criteria, SAMMPRIS patients were slightly younger but had a higher burden of other important vascular risk factors including severity of stenosis, which was the most important predictor of subsequent stroke in WASID. These data suggest that the improved prognosis in the medical arm of SAMMPRIS compared with WASID patients is related to the aggressive medical management used in SAMMPRIS and not to a lower burden of risk factors in SAMMPRIS patients. * the increased frequency of hypertension and hyperlipidemia in SAMMPRIS might reflect the change in the JNC definition of hypertension after the start of WASID and the fact that many more patients are prescribed statins now than when WASID was done