Durable second complete remissions with oral melphalan in hypocellular Acute Myeloid Leukemia and Refractory Anemia with Excess Blast with normal karyotype relapsing after intensive chemotherapy.

We treated six patients who had relapsed after intensive chemotherapy, presenting initially with AML or RAEB, a hypocellular marrow and normal karyotype, and who were deemed unsuitable for re-induction with intensive chemotherapy, with low dose oral melphalan. Three of six patients achieved complete hematological response with no significant toxicity and with a duration of 12, 8 and 3+ months respectively. These three patients had received only two prior courses of chemotherapy each, in contrast to non-responders who were more heavily pre-treated. Low dose melphalan is highly effective therapy for this rare subtype of AML/RAEB, even in relapsed disease with limited prior chemotherapy.

Survival of patients with hematological malignancy admitted to the intensive care unit: prognostic factors and outcome compared to unselected medical intensive care unit admissions, a parallel group study.

Improved survival in patients with hematological malignancy (HM) admitted to the intensive care unit (ICU) has largely been reported in uncontrolled cohorts from single academic institutions. We compared hospital mortality between 147 patients with HM and 147 general medical admissions to five non-specialist ICUs. The proportion of patients surviving to hospital discharge was significantly worse in patients with HM (27% vs. 56%; p < 0.001). Six-month and 1-year survival in patients with HM was 21% and 18%, respectively. HM, greater age, mechanical ventilation (MV) and acute physiology and chronic health evaluation (APACHE) II score were independent predictors of poor outcome. For patients with HM, culture proven infection, age, MV and inotropes were negative predictors. Disease-specific factors including hematological diagnosis, neutropenia, remission status, prior stem cell transplant, time from diagnosis to admission and degree of prior treatment were not predictive. Overall survival of patients with HM was worse than that recently reported from specialist units.

Chronic lymphocytic leukaemia is a risk factor for venous thromboembolism.

Venous thromboembolism (VTE) is a major cause of morbidity and mortality in cancer patients. The literature is sparse on the incidence in the most common lymphoid malignancy, chronic lymphocytic leukaemia (CLL). We calculated the incidence rates for VTE in an unselected UK CLL clinic population at 1.45% per patient year. This represents a tenfold increase over previously published estimates of incidence in the general population and a twofold increase over that of the local hospital inpatient population. In our cohort, the risk of VTE was related to stage C disease. Clinicians should be aware that CLL patients are at risk of VTE.

Defining the pathogenic role of telomerase mutations in myelodysplastic syndrome and acute myeloid leukemia.

The primary pathology in many cases of myelodysplasia (MDS) and acute myeloid leukemia (AML) remains unknown. In some cases, two or more affected members have been identified in the same family. To date, mutations in two genes have been directly implicated: the hematopoietic transcription factors RUNX1 (runt-related transcription factor 1) and CEBPA (CCATT-box enhancer binding protein alpha). However, there are also other familial cases of MDS/AML where the genetic basis remains unknown. Both MDS, and to a lesser extent AML, have been observed in cases of the bone marrow failure syndrome dyskeratosis congenita, in which telomerase mutations have been identified. Recently, an increased incidence of telomerase reverse transcriptase mutations has been reported in a series of de novo AML. We have now identified novel mutations in the telomerase RNA (TERC) or telomerase reverse transcriptase component (TERT) within 4 of 20 families presenting with familial MDS/AML. Functional analysis has demonstrated that all mutations adversely impact on telomerase activity in vitro, and affected individuals have short telomeres. These families, in conjunction with a review of previously published cases, help to further define the pathological role of telomerase mutations in MDS/AML and have implications for the biology, treatment and screening regimen of de novo cases.