Monosomal karyotype in adult acute myeloid leukemia: prognostic impact and outcome after different treatment strategies.

We aimed to determine the prognostic impact of monosomal karyotype (MK) in acute myeloid leukemia (AML) in the context of the current World Health Organization (WHO) classification and to evaluate the outcome of MK(+) patients after allogeneic HSCT. Of 1058 patients with abnormal cytogenetics, 319 (30%) were MK MK(+). MK(+) patients were significantly older (P = .0001), had lower white blood counts (P = .0006), and lower percentages of BM blasts (P = .0004); MK was associated with the presence of -5/5q-, -7, 7q-, abnl(12p), abnl(17p), -18/18q-, -20/20q-, inv(3)/t(3;3), complex karyotype (CK), and myelodysplasia (MDS)-related cytogenetic abnormalities (P < .0001, each); and NPM1 mutations (P < .0001), FLT3 internal tandem duplications (P < .0001), and tyrosine kinase domain mutations (P = .02) were less frequent in MK(+). Response to induction therapy and overall survival in MK(+) patients were dismal with a complete remission rate of 32.5% and a 4-year survival of 9%. MK retained its prognostic impact in AML with CK, AML with MDS-related cytogenetic abnormalities, and in a revised definition (MK-R) excluding cases with recurrent genetic abnormalities according to WHO classification and those with derivative chromosomes not leading to true monosomies. In younger patients, allogeneic HSCT from matched related and unrelated donors resulted in a limited improvement of overall survival.

The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML.

To study the characteristics and clinical impact of therapy-related acute myeloid leukemia (t-AML). 200 patients (7.0%) had t-AML and 2653 de novo AML (93%). Patients with t-AML were older (P < .0001) and they had lower white blood counts (P = .003) compared with de novo AML patients; t-AML patients had abnormal cytogenetics more frequently, with overrepresentation of 11q23 translocations as well as adverse cytogenetics, including complex and monosomal karyotypes, and with underrepresentation of intermediate-risk karyotypes (P < .0001); t-AML patients had NPM1 mutations (P < .0001) and FLT3 internal tandem duplications (P = .0005) less frequently. Younger age at diagnosis of primary malignancy and treatment with intercalating agents as well as topoisomerase II inhibitors were associated with shorter latency periods to the occurrence of t-AML. In multivariable analyses, t-AML was an adverse prognostic factor for death in complete remission but not relapse in younger intensively treated patients (P < .0001 and P = .39, respectively), relapse but not death in complete remission in older, less intensively treated patients (P = .02 and P = .22, respectively) and overall survival in younger intensively treated patients (P = .01). In more intensively treated younger adults, treatment-related toxicity had a major negative impact on outcome, possibly reflecting cumulative toxicity of cancer treatment.

Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma.

PURPOSE: R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is standard care for aggressive B-cell lymphoma. A prospective trial was conducted to investigate the role of additive radiotherapy (RT) to bulky and extralymphatic disease. PATIENTS AND METHODS: The best arm of the RICOVER-60 trial (6×R-CHOP-14+2R [R-CHOP administered once every 2 weeks plus two additional applications of rituximab] plus involved-field RT [36 Gy] to sites of initial bulky [≥ 7.5 cm] disease and extralymphatic involvement) was compared with a cohort receiving the same immunochemotherapy but without RT in an amendment to the RICOVER-60 trial (RICOVER-noRTh) in a prospective fashion. RESULTS: After a median observation time of 39 months, 164 of 166 RICOVER-noRTh patients were evaluable. In a multivariable analysis of the intention-to-treat population adjusting for International Prognostic Index risk factors and age (> 70 years), event-free survival (EFS) of patients with bulky disease was inferior without additive RT (hazard ratio [HR], 2.1; 95% CI, 1.3 to 3.5; P = .005), with trends for inferior progression-free (PFS; HR, 1.8; 95% CI, 1.0 to 3.3; P = .058) and overall survival (OS; HR, 1.6; 95% CI, 0.9 to 3.1; P = .127). In a per-protocol analysis with 11 patients in RICOVER-noRTh excluded for receiving unplanned RT, multivariable analysis revealed HRs of 2.7 (95% CI, 1.3 to 5.9; P = .011) for EFS, 4.4 (95% CI, 1.8 to 10.6; P = .001) for PFS, and 4.3 (95% CI, 1.7 to 11.1; P = .002) for OS for patients not receiving RT to bulky disease. CONCLUSION: Additive RT to bulky sites abrogates bulky disease as a risk factor and improves outcome of elderly patients with aggressive B-cell lymphoma. Whether RT can be spared in patients with (metabolic) complete remission after immunochemotherapy must be addressed in appropriately designed prospective trials.