No abstract

Purpose: Glutathione S-transferase P1 (GSTP1) is a member of the GST enzyme superfamily that is important for the detoxification of several cytotoxic drugs and their byproducts. A single nucleotide polymorphism results in the substitution of isoleucine (Ile) to valine (Val) at codon 105, causing a metabolically less active variant of the enzyme. We assessed the impact of the GSTP1 codon 105 genotype on treatment outcome in patients with Hodgkin's lymphoma.Experimental Design: The Ile 105 Val polymorphism in the GSTP1 gene was analyzed using a PCR-RFLP technique. Ninety-seven patients with Hodgkin's lymphoma were included and associations with patient characteristics and treatment outcome were analyzed.Results: The GSTP1 Ile 105 Val polymorphism was associated in a dose-dependent fashion with an improved failure-free survival in patients with Hodgkin's lymphoma (P = 0.02). The probability of 5-year survival for patients homozygous for the 105 Val/ 105 Val GSTP1 genotype was 100%, for heterozygous patients 74% (95% confidence interval, 56-85), and for patients homozygous for the 105 Ile/ 105 Ile genotype 43% (95% confidence interval, 23-61). The Cox multivariate analysis showed that GSTP1 codon 105 genotype was an independent prognostic factor.Conclusions: The GSTP1 genotype predicts clinical outcome in patients with Hodgkin's lymphoma.

Our study indicates that cytokine genotypes predict clinical outcome in patients with HL and points to the importance of the genetic background of the host for treatment response.

All-trans retinoic acid (ATRA) has shown a synergistic activity in combination with cytosine arabinoside in vitro in the treatment of acute myeloid leukaemia (AML). In this paper we report the results of treatment with low dose cytosine arabinoside (LDAC) with or without ATRA in 28 patients with acute myeloid leukaemia aged over 60 years: 14 patients received only LDAC and the other 14 LDAC + ATRA. The patients of the 2 groups showed similar clinical features: in 10 patients AML developed after a myelodysplastic form and 4 patients presented a previous malignancy. All the patients received subcutaneous (sc) LDAC (15 mg twice a day for 14 days) and in 14 patients oral ATRA (45 mg/sqm in the same days) was added to LDAC; the courses were repeated every 4 weeks from diagnosis to relapse. The treatment was well tolerated and the patients could self-administer sc LDAC and oral ATRA at home. No statistically significant differences were observed in complete remission rate (21% vs. 50%, respectively) and resistant rate (57% vs. 29%), but the patients treated with the combination of the 2 drugs had a better time to treatment failure (15 weeks vs. 30 weeks, respectively) (P = 0.045) and a longer survival (37 weeks vs. 66 weeks) (P = 0.019). Our experience, although with a low number of patients, confirms the efficacy of ATRA in combination with sc LDAC in the treatment of AML in elderly patients.

Using immunohistochemistry, we investigated the expression of c-mpl in bone marrow megakaryocytes of 88 patients with essential thrombocythemia (ET), 6 patients with secondary thrombocytosis (ST), and 20 patients with lymphoma (controls). Considering both the pattern of expression and the staining intensity, we identified a uniform and a heterogeneous pattern of c-mplexpression. The uniform pattern was found in all the controls, all the patients with ST, and 28 of the patients with ET, with a strong staining intensity observed in most megakaryocytes (> 80%). In contrast, c-mpl expression was heterogeneous in 60 patients with ET, 18 of whom (30%) presented with thrombosis at diagnosis, a significant difference from patients with a uniform c-mpl pattern (2 of 28; 7%; P = .026). In particular, the overrepresentation of thrombotic complications in patients with a heterogeneous c-mpl expression pattern was found mainly among patients with a significant percentage (10% to 40%) of weakly stained or c-mpl–negative megakaryocytes (heterogeneous-weak pattern; 13 of 30; 43%;P = .002). Accordingly, this pattern was associated with a 6.1-fold increased risk of thrombosis compared with that of patients with a uniform c-mpl pattern. In conclusion, the presence of a heterogeneous pattern of c-mpl distribution in bone marrow megakaryocytes could be a useful diagnostic criterion in the differential diagnosis of thrombocytosis. Furthermore, detection of a significant percentage of weakly stained or c-mpl–negative megakaryocytes can identify patients with a higher risk of thrombosis.