Imatinib mesylate therapy in chronic myeloid leukemia patients in stable complete cytogenetic response after interferon-alpha results in any high complete molecular response.

To determine the impact on minimal residual disease by switching to imatinib chronic phase chronic myeloid leukaemia (CP-CML) patients responsive to interferon-alpha (IFNα), in stable complete cytogenetic response (CCR) but with persistent PCR positivity. Twenty-six Philadelphia positive (Ph+) CML patients in stable CCR after IFNα but persistently positive at PCR analysis during this treatment, were given imatinib mesylate at standard dose. At enrolment into the study, median IFN treatment and CCR duration were 88 months (range 15–202) and 73 months (range 10–148), respectively. Imatinib treatment resulted in a progressive and consistent decline of the residual disease as measured by quantitative PCR (RQ-PCR) in all but one of the 26 patients; at the end of follow-up, after a median of 32 months (range 21–49) of treatment, a major molecular response (BCR/ABL levels <0.1) was reached in 20 patients (77%), and BCR/ABL transcripts were undetectable in 13 (50%). The achievement of molecular response was significantly correlated with post-IFN baseline transcript level (mean 1.194 for patients achieving complete molecular response versus 18.97 for those who did not; p < 0.001), but not with other clinical/biological disease characteristics. These results indicate that patients induced into CCR by IFN treatment represent a subset with very favourable prognosis, which can significantly improve molecular response with imatinib and further support investigative treatment schedules combining these two drugs

A long-term study of young patients with essential Thrombocythemia treated with anagrelide.

BACKGROUND AND OBJECTIVES: Essential thrombocythemia (ET) can be complicated by life-threatening thrombosis and has a risk of converting into acute leukemia. Cytoreductive therapy may reduce the risk of thromboembolic complications. Herein, we report the results of a long-term study of patients with ET treated with anagrelide to control thrombocytosis. DESIGN AND METHODS: Thirty-nine (34 evaluable) patients (median age, 33 years; 24 previously untreated) were enrolled between 1989-1996; the mean platelet count prior to therapy was 1197x10(9)/L. Only 9 out of 34 evaluable patients were at high risk of thrombosis (platelet count more than 1500x10(9)/L). The initial dose of anagrelide (0.5 mg/bid for 7 days) was increased by 0.5 mg/day (maximum dose: 3 mg/day) until a response was seen. RESULTS: A complete response (platelets 1 month) was seen in 15 /34 (44%) patients and a partial response (platelets 450-600x10(9)/L for >1 month) was seen in 17/34 ( 50%), so that the some kind of response was seen in 32/34 (94%) of the patients at a median time of 4.2 months after starting treatment. Seventeen patients (50%) are still being treated and have achieved platelet control for a maximum follow-up of 12.5 years. Late onset anemia occurred in 4/39 patients. Three out of 39 patients (8%) had cardiac disorders. INTERPRETATION AND CONCLUSIONS: Anagrelide appears suitable for controlling thrombocytosis in ET patients over the long-term. This drug may be used in patients younger than 60 years, with the exclusion of women of child-bearing potential and subjects aged 40-60 years with a history of major thrombotic events. Anagrelide should not be administered to patients with cardiac disorders, and a careful approach to patients should include monitoring of heart function before and during treatment

Incidence and prognostic significance of autoantibodies against erythrocytes and platelets in chronic lymphocytic leukemia (CLL).

Antiglobulin Test (AT), and Dixon Tests (DT) have been studied in 100 patients with CLL. Thirty-five patients were Rai stage 0 and I, 19 patients stage 2, 13 patients stage 3 and 33 patients stage 4. Twelve patients showed a Red Blood Cells Autoantibodies (RBCAb) positivity; a positivity (direct, indirect, or both) of DT was present in 74% of patients. The presence of autoantibodies against erythrocytes and platelets did not influence survival curves, but anemia and thrombocytopenia are risk factors for survival, independently of the presence of an autoimmune disorder. Nine patients RBCAb positive and DT positive showed the worst survival curve, five out of these were anemic and one thrombocytopenic and anemic

Effect of chemotherapy for acute myelogenous leukemia on hematopoietic and fibroblast marrow progenitors

Since reduced marrow cellularity and prolonged pancytopenia following autologous bone marrow transplantation (ABMT) have been frequently observed in patients with acute myelogenous leukemia (AML) included in the AML10 GIMEMA/EORTC trial, the question was raised to what extent hematopoietic and microenvironmental progenitor cells were involved in these patients, Marrow hematopoietic progenitors were investigated by a short-term methylcellulose assay quantitating multipotent CFU-Mix, erythroid BFU-E and granulocyte-macrophage CFU-GM, as well as a long-term assay quantitating long-term culture-initiating cells (LTC-IC), The marrow microenvironment was studied by evaluating the incidence of fibro-blastoid progenitors (CFU-F) and the capacity of stromal layers to support allogeneic hematopoietic progenitors, As compared to normal controls (n = 57), AML patients (n = 26) showed a statistically significant reduction of the mean (+/- s.e.m.) number of CFU-Mix (5.3 +/- 0.6 vs 0.8 +/- 0.2, P less than or equal to 0.0001), BFU-E (68 +/- 5 vs 20 +/- 4, P less than or equal to 0.0001), CFU-GM (198 +/- 11 vs 144 +/- 15, P less than or equal to 0.008), and LTC-IC (302 +/- 46 vs 50 +/- 8, P less than or equal to 0.001), The mean (+/- s.e.m.) incidence of marrow CFU-F was not significantly reduced as compared to normal control (48 +/- 6 vs 52 +/- 7, P less than or equal to 0.73). Seventeen AML stromal layers were tested for their capacity to support the growth of allogeneic hematopoietic progenitors, Seven samples failed to support any progenitor cell growth, seven had a significantly lower supportive activity as compared to normal stromal layers (13 +/- 5 vs 249 +/- 56, P less than or equal to 0.002), whereas three cultures could not be analyzed due to contamination, In conclusion, induction and consolidation regimens used in AML patients of the AML10 protocol induce a markedly defective in vitro growth of primitive hematopoietic progenitors and a severe functional defect of marrow stroma, The association of hematopoietic with microenvironmental damage might play a key role in the delayed hematopoietic regeneration observed following ABMT in patients of the AML10 trial

Spontaneous remission in adult patients with de novo myelodysplastic syndrome: a possible event.

I.F.