Translocation (2;11)(q37;q23) in therapy-related myelodysplastic syndrome after treatment for acute promyelocytic leukemia.

Treatment of acute promyelocytic leukemia (APL) with a combination of anthracycline-based chemotherapy and all-trans retinoic acid (ATRA) leads to very high rates of complete remission and survival. There are only a limited number of publications on the development of therapy-related myelodysplastic syndrome (MDS) or acute myeloid leukemia during follow-up of APL. Although drugs targeting at DNA-topoisomerase II characteristically induce translocations involving 11q23, this was seldom seen in patients treated for APL. We report on a patient initially diagnosed with APL. Response to therapy was monitored by fluorescence in situ hybridization (FISH) and reverse-transcriptase polymerase chain reaction for the PML-RARalpha rearrangement. Consecutive samples showed a swift and complete reduction of PML-RARalpha rearranged cells. Twenty months after diagnosis, however, conventional cytogenetics revealed a complex karyotype with a translocation involving 11q23 and loss of chromosomes 7q and Xq. FISH analysis with the MLL probe identified 2q37 (harboring the SEPT2 gene) as the translocation partner of chromosome 11. We consider the rather unique t(2;11)(q37;q23) as the primary event causing therapy-related MDS in our patient. This case stresses the importance of conventional karyotyping to be performed on a regular basis in all treated APL patients for the early detection of chromosomal aberrations that indicate the development of therapy-related MDS or acute myeloid leukemia.

Is there still an indication for nursing patients with prolonged neutropenia in protective isolation?. An evidence-based nursing and medical study of 4 years experience for nursing patients with neutropenia without isolation.

UNLABELLED: Patients with severe neutropenia due to high-dose chemotherapy and/or total-body irradiation are at risk of serious infections and are frequently nursed in strict protective isolation. This is a costly procedure and results in a psychological burden for the patient and its significance has been debated for a long time. The introduction of very potent systemic antibiotics, antibiotic prophylaxis, haematopoietic growth factors and peripheral stem cell transplantation might have decreased the need for it. We performed a systematic literature review and conducted a medical/nursing guideline study. In the literature we searched especially for prospective randomised studies. Only six were found, these were prospective randomised studies and contradicted each other on the usefulness of protective isolation. In an initiative aimed at promoting evidence-based care, we conducted a combined medical and nursing guideline study consisting of three parts: (1) inventory of (inter) national guidelines; (2) analysis of potential sources of infection; and (3) follow-up study post-implementation of new guidelines. RESULTS: (1) The practices in different centres in Europe appeared to vary widely. (2) Micro-organisms spread easily, especially if hands are not adequately dried. Isolation does not prevent this. Based on these findings we decided to stop protective isolation. This change of policy was combined with a campaign for optimal hygiene and introduction of hand alcohol. (3) We monitored the incidence of febrile neutropenia, infections and use of systemic antibiotics and antifungals in a 3-year period without protective isolation and compared this with the findings in the preceding 3 years with isolation. No significant differences in infections and mortality were found. We concluded that abandoning protective isolation combined with increased hygienic measures in nursing of patients with severe neutropenia does not increase the risk of infections, but improves the quality of care and patient satisfaction and reduces costs.

Results of a HOVON/SAKK donor versus no-donor analysis of myeloablative HLA-identical sibling stem cell transplantation in first remission acute myeloid leukemia in young and middle-aged adults: benefits for whom?

The Dutch-Belgian Hemato-Oncology Cooperative Group and the Swiss Group for Clinical Cancer Research (HOVON-SAKK) collaborative study group evaluated outcome of patients (pts) with acute myeloid leukemia (AML) in first remission (CR1) entered in 3 consecutive studies according to a donor versus no-donor comparison. Between 1987 and 2004, 2287 pts were entered in these studies of whom 1032 pts (45%) without FAB M3 or t(15;17) were in CR1 after 2 cycles of chemotherapy, received consolidation treatment, and were younger than 55 years of age and therefore eligible for allogeneic hematopoietic stem cell transplantation (allo-SCT). An HLA-identical sibling donor was available for 326 pts (32%), whereas 599 pts (58%) lacked such a donor, and information was not available in 107 pts. Compliance with allo-SCT was 82% (268 of 326). Cumulative incidences of relapse were, respectively, 32% versus 59% for pts with versus those without a donor (P < .001). Despite more treatment-related mortality (TRM) in the donor group (21% versus 4%, P < .001), disease-free survival (DFS) appeared significantly better in the donor group (48% +/- 3% versus 37% +/- 2% in the no-donor group, P < .001). Following risk-group analysis, DFS was significantly better for pts with a donor and an intermediate- (P = .01) or poor-risk profile (P = .003) and also better in pts younger than 40 years of age (P < .001). We evaluated our results and those of the previous MRC, BGMT, and EORTC studies in a meta-analysis, which revealed a significant benefit of 12% in overall survival (OS) by donor availability for all patients with AML in CR1 without a favorable cytogenetic profile.

Randomized comparison of low-dose versus high-dose interferon-alfa in chronic myeloid leukemia: prospective collaboration of 3 joint trials by the MRC and HOVON groups.

The optimal dose of interferon-alfa (IFN) for chronic myeloid leukemia (CML) is unknown. Retrospective analyses suggest that low doses are as effective as high doses, with less toxicity and fewer patients abandoning the drug. The Dutch Hemato-Oncology Association (HOVON) and British Medical Research Council (MRC) cooperative groups jointly performed randomized trials in newly diagnosed CML patients, comparing high-dose IFN (5 MIU/m(2) daily) with low-dose (3 MIU, 5 times a week). Both arms allowed additional hydroxyurea to keep the white blood cell count lower than 5 x 10(9)/L. Quality of life data were collected in a subset of patients. Between 1993 and 2001, 407 patients were randomized. At a median follow-up of 53 months, there were no significant differences in overall survival (odds ratio = 1.09, 95% confidence interval, 0.81-1.46), progression-free survival, and complete hematologic or major cytogenetic responses. Fewer patients in the low-dose group abandoned IFN for reasons other than transplant or progressive disease (P =.002, 58% vs 72% at 5 years). Quality of life data showed comparable results in both arms for most factors. There is no evidence of benefit for high-dose IFN compared with low-dose for the treatment of CML. Therefore, when IFN is combined with other drugs, low-dose IFN is advised, to minimize toxicity and costs.