-
Blood Jan 1998Treatment with alkylating agents or radiophosphorous (32P) has been shown to carry a certain leukemogenic risk in myeloproliferative disorders (MPDs), including...
Treatment with alkylating agents or radiophosphorous (32P) has been shown to carry a certain leukemogenic risk in myeloproliferative disorders (MPDs), including essential thrombocytemia (ET). The leukemogenic risk associated to treatment with hydroxyurea in ET, on the other hand, is generally considered to be relatively low. Between 1970 and 1991, we diagnosed ET in 357 patients, who were monitored until 1996. One or several therapeutic agents had been administered to 326 patients, including hydroxyurea (HU) in 251 (as only treatment in 201), pipobroman in 43, busulfan in 41, and 32P in 40. With a median follow-up duration of 98 months, 17 patients (4.5%) had progressed to acute myeloid leukemia (AML; six cases) or myelodysplastic syndrome (MDS; 11 cases). Fourteen of these patients had received HU, as sole treatment in seven cases, and preceded or followed by other treatment in seven cases, mainly pipobroman (five cases). The remaining three leukemic progressions occurred in patients treated with 32P (two cases) and busulfan (one case). The incidence of AML and MDS after treatment, using 32P alone and 32P with other agents, busulfan alone and with other agents, HU alone and with others agents, and pipobroman alone and with other agents was 7% and 9%, 3% and 17%, 3.5% and 14%, and 0% and 16%, respectively. Thirteen of 17 patients who progressed to AML or MDS had successful cytogenetic analysis. Seven of them had rearrangements of chromosome 17 (unbalanced translocation, partial or complete deletion, isochromosome 17q) that resulted in 17p deletion. They also had a typical form of dysgranulopoiesis combining pseudo Pelger Hüet hypolobulation and vacuoles in neutrophils, and p53 mutation, as previously described in AML and MDS with 17p deletion. Those seven patients had all received HU, as the only therapeutic agent in three, and followed by pipobroman in three. The three patients who had received no HU and progressed to AML or MDS had no 17p deletion. A review of the literature found cytogenetic analysis in 35 cases of AML and MDS occurring after ET, 11 of whom had been treated with HU alone. Five of 35 patients had rearrangements that resulted in 17p deletion. Four of them had been treated with HU alone. These results show that treatment with HU alone is associated with a leukemic risk of approximately 3.5%. A high proportion of AML and MDS occurring in ET treated with HU (alone or possibly followed by pipobroman) have morphologic, cytogenetic, and molecular characteristics of the 17p- syndrome. These findings suggest that widespread and prolonged use of HU in ET may have to be reconsidered in some situations, such as asymptomatic ET.
Topics: Adult; Aged; Antisickling Agents; Chromosomes, Human, Pair 17; Female; Gene Deletion; Humans; Hydroxyurea; Leukemia, Myeloid; Male; Middle Aged; Myelodysplastic Syndromes; Thrombocytosis
PubMed: 9427717
DOI: No ID Found -
The Journal of Investigative Dermatology Jun 2016
Topics: Aged; Antineoplastic Agents; Carcinoma, Squamous Cell; Female; Genes, ras; Humans; Indoles; Pipobroman; Protein Multimerization; Proto-Oncogene Proteins B-raf; Skin Neoplasms; Sulfonamides; Vemurafenib
PubMed: 26854489
DOI: 10.1016/j.jid.2015.12.047 -
Deutsches Arzteblatt International Jan 2008
PubMed: 19633773
DOI: 10.3238/arztebl.2008.0071d -
British Journal of Haematology Nov 2003Essential thrombocythaemia (ET) is usually considered an indolent disease, but it may progress during its natural course into acute leukaemia (AL); however, an influence...
Essential thrombocythaemia (ET) is usually considered an indolent disease, but it may progress during its natural course into acute leukaemia (AL); however, an influence of myelosuppressive agents in the blastic transformation of ET cannot be excluded. We performed a retrospective study to assess the incidence of AL in ET patients treated with pipobroman (PB) as first-line therapy. One hundred and sixty-four patients with ET were managed with PB at a dose of 1 mg/kg/d until a stable platelet count below 400 x 10(9)/l was achieved. Maintenance therapy was given at a planned dose ranging between 0.2 and 1 mg/kg/d according to platelet count, in all cases, with a median daily dose of 25 mg (range 7-75 mg/d). The median treatment time was 100 months (range 25-243 months). The patients were evaluated for the occurrence of AL and/or secondary malignancies and survival end-points. AL was observed in nine patients (5.5%) after a median treatment time of 153 months (range 79-227 months). The overall survival (OS) and the event-free survival (EFS) at 120 months were 95% and 97%, whereas at 180 months, they were 84% and 76% respectively. In conclusion, this retrospective analysis shows a low incidence of AL in a large group of patients consecutively treated with PB as first-line chemotherapy. Therefore, an investigation of the role of myelosuppressive agents in the blastic transformation of ET would be of interest.
Topics: Adult; Aged; Aged, 80 and over; Alkylating Agents; Disease Progression; Female; Humans; Leukemia; Male; Middle Aged; Pipobroman; Retrospective Studies; Thrombocythemia, Essential
PubMed: 14617017
DOI: 10.1046/j.1365-2141.2003.04542.x -
British Medical Journal Nov 1968
Topics: Asparaginase; Busulfan; Chlorambucil; Cyclophosphamide; Cytarabine; Humans; Hydroxyurea; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Pipobroman; Prednisolone; Vincristine
PubMed: 5246597
DOI: No ID Found -
Blood Apr 2005Progression to acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) is a possible evolution of polycythemia vera (PV), but whether some patients are at increased...
Progression to acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) is a possible evolution of polycythemia vera (PV), but whether some patients are at increased natural risk for this complication and how much the contribution of pharmacologic cytoreduction can affect the natural course of the disease remain uncertain. The European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) prospective project included 1638 patients with PV. AML/MDS was diagnosed in 22 patients after a median of 2.5 years from recruitment in the study and a median of 8.4 years from the diagnosis of PV. Variables associated with progression to AML/MDS were assessed using different models of multivariate analysis. Older age was confirmed as the main independent risk factor (hazard ratio [HR], 4.30; 95% confidence interval [95% CI], 1.16-15.94; P = .0294), whereas overall disease duration failed to reach statistical significance (more than 10 years: HR, 1.91; 95% CI, 0.64-5.69; P = .2466). Exposure to P32, busulphan, and pipobroman (HR, 5.46; 95% CI, 1.84-16.25; P = .0023), but not to hydroxyurea (HU) alone (HR, 0.86; 95% CI, 0.26-2.88; P = .8021), had an independent role in producing an excess risk for progression to AML/MDS compared with treatment with phlebotomy or interferon.
Topics: Acute Disease; Adult; Aged; Aspirin; Databases, Factual; Disease Progression; Disease-Free Survival; Female; Humans; Leukemia, Myeloid; Male; Middle Aged; Multivariate Analysis; Platelet Aggregation Inhibitors; Polycythemia Vera; Prospective Studies; Risk Factors
PubMed: 15585653
DOI: 10.1182/blood-2004-09-3426 -
Blood Aug 1998
Comparative Study
Topics: Acute Disease; Antineoplastic Agents, Alkylating; Bone Marrow; Busulfan; Chromosome Aberrations; Chromosomes, Human, Pair 17; Diagnosis, Differential; Disease Progression; Humans; Hydroxyurea; Incidence; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Myelodysplastic Syndromes; Pipobroman; Polycythemia Vera; Research Design; Retrospective Studies; Risk; Thrombocythemia, Essential
PubMed: 9694740
DOI: No ID Found -
Blood Sep 1998
Topics: Antineoplastic Agents; Humans; Hydroxyurea; Leukemia; Pipobroman; Polycythemia Vera
PubMed: 9716616
DOI: No ID Found