The addition of ara-C + TBI + ABMS to conventional consolidation therapy significantly improved remission duration and survival over those of a historical control group of patients with AML (aged < 50, AML-M3 excluded). HDT was, however, associated with significant treatment-related mortality and slow blood count recovery. The use of ara-C + TBI supported by peripheral blood progenitor cells should make the treatment safer and more widely applicable in AML.
Over a 24-year period, 137 patients were referred for management of newly diagnosed chronic lymphocytic leukemia. One hundred and nineteen patients have been reviewed in terms of response to therapy and prognostic factors for survival; 18 patients were excluded either because lymph node biopsy was not compatible with the diagnosis of CLL (11 patients), or because the lymphocyte count at presentation was < 5 x 10(9)/l (seven patients). Patients were staged retrospectively according to both the Rai and Binet Classifications. Forty-eight per cent (57/119) were deemed not to be in need of any treatment at presentation, 36 per cent (43/119) have never received any specific therapy. The majority of patients received chlorambucil alone, at a dose of 10 mg daily given for 6 weeks, followed by a 2-week interval, followed by three, 2-week cycles. The overall response rate (complete+partial remission) was 38 per cent. In terms of survival, there was a trend in favour of patients who responded to treatment in comparison with those who did not but this did not reach statistical significance (P = 0.07). Correlations with stage were highly significant, the median survivals for patients with stage A, B and C disease (Binet) were 12.5, 8 and 3.5 years respectively. On univariate analysis, the absolute lymphocyte count at presentation was the most significant prognostic factor for survival, patients presenting with an absolute lymphocyte count above 50 x 10(9)/l having a less favourable prognosis (P = 0.002). However, on multivariate analysis, older age, a low hemoglobin, low platelet count, and the presence of lymphadenopathy and fever at presentation correlated adversely with survival. Overall, 40 patients died as a consequence of CLL or from disease-related causes, 34/40 dying of infection. Twenty-one patients developed second cancers. With a median follow-up of 13 years, these results confirm that the two staging systems can separate patients into prognostic groups, however in practice, there is heterogeneity of outcome within stage. New approaches are urgently needed.
Between 1969 and 1999, 420 patients (age > 60 years) with newly diagnosed AML were managed at St Bartholomew's Hospital (SBH), London, UK. Sixty-nine percent of patients received therapy with curative intent Eighty-eight patients (31%) of the latter achieved complete remission (CR), representing an overall CR rate of 21%. Treatment failure due to early death (ED) and resistant disease (RD) occurred in 50 and 19%, respectively. With median follow up of 11 years, actuarial survivals at 1,3 and 5 years were 20, 7 and 4%, respectively, the median survival of the entire cohort was 2 months. For patients who achieved CR, median survival was significantly better than that of patients in whom treatment failed (14 vs. 6 months). Over the 30 years, CR rate and the relative incidence of RD both increased from 13 to 45%, and 3 to 27%, respectively, whilst ED rate reduced from 84 to 27%. Multivariate analysis showed that treatment era, hepatosplenomegaly and increasing age predicted for reduced CR rate and OS. Although elderly patients with AML are characterised by a poor response to intensive chemotherapy, significant improvements in supportive care and the delivery of intensive treatment have led to improved CR rates and OS. New therapeutic strategies and a greater awareness of prognostic factors may further improve clinical outcome in this important group of patients.
Seventy-two patients with acute promyelocytic leukemia (APML) were treated at St.Bartholomew's Hospital (SBH) over a 25-year period. Improvements in supportive care and the use of more intensive chemotherapy have led to an increase in the complete remission rate from 14 to 58%. Similarly, the median survival has increased from 3 weeks to 2 years; the median duration of remission, which was 7 months in 1974, has not yet been reached. There was also a significant difference in survival from first recurrence, compared with that of patients with other subtypes of acute myeloid leukemia. RT-PCR analysis on bone marrow samples from 14 patients confirmed the presence of the PML/RARA fusion; 13 of the 14 patients achieved 'molecular remission' after therapy. The one patient who remained persistently positive experienced recurrence within 4 months. In seven of the eight patients in whom the disease recurred, the translocation was identified by RT-PCR at the time of relapse, whilst in one patient it was noted 4 months prior to morphological recurrence. These results illustrate the improvement in prognosis that occurred over a 25-year period in patients with APML treated at a single centre.
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