Acute Transformation in Nonleukemic Chronic Myeloproliferative Disorders: Actuarial Probability and Main Characteristics in a Series of 218 Patients

Abstract

In a series of 218 subjects diagnosed as having nonleukemic chronic myeloproliferative disorders in a single institution within a 18-year period, 13 instances of acute transformation were registered. They corresponded to 8 out of 70 patients with idiopathic myelofibrosis (IM), 4 out of 91 with polycythemia vera (PV), and 1 out of 57 with essential thrombocythemia (ET). The actuarial probability of developing such a complication at 100 months from diagnosis reached 20.6% in IM, 8.7% in PV, and 4% in ET. Only 1 IM patient whose condition developed into acute leukemia had received prior cytolytic therapy, whereas, in contrast, all PV and ET patients showing this pattern had previously been treated with either ³²P or alkylating agents. On the other hand, acute transformation in IM generally had an insidious presentation, contrasting with its abrupt onset in most PV and ET patients. Most acute leukemias (12 out of 13) exhibited a myeloid phenotype. The patients’ median survival from diagnosis of the acute transformation was only 3 months, the development of this complication significantly shortening the patients’ overall survival.

Acute leukemia and myelodysplasia in patients with a Philadelphia chromosome negative chronic myeloproliferative disorder treated with hydroxyurea alone or with hydroxyurea after busulphan

“…The risk of spontaneous leukemic transformation in IMF is difficult to assess from the literature, as very few studies deal with the natural course of the disease when not being treated with cytoreductive and potentially leukemogenic agents. An incidence of 2-25% has been given [52][53][54], and it has been emphasized that no association has been documented between the development of AL and previous cytostatic treatment [52]. Due to the relatively small number of patients, it was not possible to analyze whether any difference existed between the various diagnostic subgroups of patients.…”

Acute myeloid leukemia (AML) having evolved from essential thrombocythemia (ET): distinctive chromosome abnormalities in patients treated with pipobroman or hydroxyurea

“…[5][6][7][8]16,17 To the best of our knowledge, this is the first cytogenetic study dealing with MDS/AML in ET patients previously treated with PI. Until now such an evolution has been described mostly in patients who had been given 32 P or alkylating agents, especially busulfan.…”

“…4 Other myelosuppressive treatments consisting of radiophosphorous ( 32 P) or alkylating agents (especially busulfan (BU)) have also been used, but it has been reported that they may increase the risk of developing acute myeloid leukemia (AML). 5,6 In fact, until recently, progression of ET to AML, preceded or not by myelodysplasia (MDS), has been observed in 3% to 4% of patients, mostly those treated with ( 32 P) or alkylating agents. 7 In 1998, however, concern also arose about the long-term safety of HU treatment: it was reported that 13% of HU-treated ET patients developed MDS/AML or solid tumors.…”

Abnormalities of GATA-1 in Megakaryocytes from Patients with Idiopathic Myelofibrosis

“…The blood film of these patients is characterized by a leuko-erythroblastic picture, with immature myeloid and erythroid cells, and by tear-drop erythrocytes. 4 The CD34 ϩ hematopoietic progenitor cells are constitutively mobilized in the peripheral blood, 5,6 and their number may be related to the severity of the disease and the risk of leukemic transformation; 6,7 the latter occurs in ϳ5 to 20% of patients, 8,9 with a dismal outcome. 8 The changes in bone marrow (BM) stroma are the result of a response of local fibroblasts, that remain polyclonal and do not derive from the neoplastic clone, 10 to cytokines, such as transforming growth factor-␤1, released by the abnormal megakaryocytes.…”