melphalan and Thrombocythemia--Essential

The case of a patient with the diagnosis of essential thrombocythemia is presented. Following treatment with melphalan during three years the patient presented clinical and radiologic data of pulmonary fibrosis. Thoracotomy with lung biopsy histologically proving fibrosis was performed. The patient developed a true histiocytic lymphoma afterwards. The rarity of pulmonary fibrosis induced by melphalan and the exceptional association of essential thrombocythemia and histiocytic lymphoma is emphasized. The characteristics of the latter disease, diagnostic difficulties and possible treatment are commented upon.

Topics: Adult; Biopsy; Female; Humans; Lung; Lymphoma, Large B-Cell, Diffuse; Melphalan; Pulmonary Fibrosis; Thoracic Neoplasms; Thrombocythemia, Essential; Time Factors

Thirty-one patients with essential thrombocythemia were randomized to receive either melphalan or radioactive phosphorus as myelosuppressive therapy. Twenty-seven patients were evaluable for response. Of 13 patients treated with melphalan, 11 had a complete response (platelet count less than 450,000/mm3) at 3 and 6 months. This response rate was significantly better than the response to radioactive phosphorus. The response rates were similar at 12 months. No significant toxicity was observed with either regimen.

Topics: Aged; Clinical Trials as Topic; Female; Follow-Up Studies; Humans; Male; Melphalan; Middle Aged; Myeloproliferative Disorders; Phosphorus Radioisotopes; Polycythemia Vera; Thrombocythemia, Essential

Topics: Aged; Antimetabolites, Antineoplastic; Azacitidine; Blast Crisis; Female; Humans; Hydroxyurea; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Male; Melphalan; Middle Aged; Mutation; Myeloproliferative Disorders; Pipobroman; Polycythemia Vera; Primary Myelofibrosis; Prognosis; Remission Induction; Retrospective Studies; Thrombocythemia, Essential; Treatment Outcome

In myelofibrosis, the introduction of reduced-intensity conditioning (RIC) preceding allogeneic stem cell transplantation (SCT) resulted in lower transplant-related mortality rates compared with myeloablative conditioning. However, lowering the intensity of conditioning may increase the risk of graft failure in myelofibrosis, although hitherto this has not been indisputably proven. We here report the outcome of 53 patients who underwent allogeneic SCT with different conditioning regimens (RIC and non-myeloablative (NMA)) in three transplantation centers in the Netherlands. The cumulative incidence of graft failure within 60 days after SCT was high (28%), and this was primarily associated with the intensity of the conditioning regimen. Cumulative neutrophil engraftment at 60 days was lower in patients who received NMA conditioning compared with those who received RIC (56% vs 84%, P=0.03). Furthermore, of six patients who received a second transplantation after graft failure, the three patients with RIC regimens subsequently engrafted, whereas the three patients who received a second NMA regimen did not. This study indicates that in myelofibrosis, NMA regimens result in high engraftment failure rates. We propose the use of more intensive conditioning regimens, incorporating busulfan or melphalan.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Calreticulin; Combined Modality Therapy; Cord Blood Stem Cell Transplantation; Cyclophosphamide; Disease Progression; Female; Graft Survival; Humans; Janus Kinase 2; Male; Melphalan; Middle Aged; Myeloablative Agonists; Neutrophils; Peripheral Blood Stem Cell Transplantation; Polycythemia Vera; Primary Myelofibrosis; Receptors, Thrombopoietin; Retrospective Studies; Thrombocythemia, Essential; Transplantation Conditioning; Treatment Outcome; Vidarabine; Whole-Body Irradiation; Young Adult

Topics: Bone Marrow; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Hydroxyurea; Janus Kinase 2; Melphalan; Middle Aged; Multiple Myeloma; Mutation; Myeloablative Agonists; Platelet Count; Thrombocythemia, Essential; Treatment Outcome

Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by an indolent clinical course, with a median survival exceeding 20 years. A minority of patients undergo thrombohemorrhagic complications, which might be prevented by cytoreductive treatment in high risk categories. Alkylating agents (ALK) have been demonstrated to increase the risk of acute leukemia and myelodysplastic syndromes in patients with myeloproliferative disorders, whereas the potential oncogenicity of hydroxyurea (HU) remains a matter of debate. In this study, we retrospectively investigated long-term development of hematological and non-hematological second malignancies in 331 patients with ET, analyzing possible associations with chemotherapy treatments. Median follow-up was 108 months. Of the 194 patients who were treated with chemotherapy, 116 (60%) received only HU, 38 (19.5%) only ALK (busulfan or melphalan) and 40 (20.5%) ALK followed by HU. After a median time of 87 months from the diagnosis of ET, 43 patients developed a second malignancy, hematological in 15 and non-hematological in 28, for an overall cumulative incidence of 13%. According to the type of treatment, second malignancies were documented in 11.2% of patients treated with only HU, in 26.3% of patients who received only ALK, and in 25% of those treated with ALK followed by HU. Ten cases (7.3%) were recorded among the 137 patients who did not receive any treatment. Our analysis revealed a significant association between treatment with alkylating agents and an increased risk of developing second hematological malignancies, whereas no such association was detected with regard to treatment with hydroxyurea single agent in our ET population. In addition, different treatment strategies did not affect the risk of developing second solid cancers.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alkylating Agents; Busulfan; Drug Therapy, Combination; Female; Follow-Up Studies; Hematologic Neoplasms; Humans; Hydroxyurea; Male; Melphalan; Middle Aged; Neoplasms, Second Primary; Retrospective Studies; Thrombocythemia, Essential; Young Adult

In polycythemia vera (PV), treatment with chlorambucil and radioactive phosphorus (p32) increases the risk of leukemic transformation from 1% to 13-14%. This risk has been estimated to be 1-5.9% with hydroxyurea (HU) therapy. When compared with historical controls, the risk with use of HU does not appear to be statistically significant. The leukemogenic risk of HU therapy in essential thrombocytosis (ET) and in myelofibrosis with myeloid metaplasia (MMM) is unknown. HU remains the main myelotoxic agent in the treatment of PV, ET, and MMM. We studied 64 patients with these three disorders, seen at our institution during 1993-1995. The patients were studied for their clinical characteristics at diagnosis, therapies received, and development of myelodysplasia or acute leukemia (MDS/AL). Forty-two had PV, 15 ET, and 6 MMM, and 1 had an unclassified myeloproliferative disorder. Of the 42 patients with PV, 18 were treated with phlebotomy alone, 16 with HU alone, 2 with p32, 2 with multiple myelotoxic agents, and 2 with interferon-alpha (IFN-alpha). Two patients from the phlebotomy-treated group, one from the HU-treated group, and 1 from the multiple myelotoxic agent-treated group developed MDS/AL. In the larger group, 11 received no treatment or aspirin alone, 18 were treated with phlebotomy alone, 25 with HU, 5 with multiple myelotoxic agents, 2 with p32, 2 with IFN-alpha, and 1 with melphalan. Study of the entire group of 64 patients showed that only one additional patient (total of 5 out of 64) developed MDS/AL. This patient had been treated with HU alone. Statistical analysis did not show any association between clinical characteristics at diagnosis, or HU therapy, and development of MDS/AL (P=0.5). Thus, our data provide no evidence suggestive of increased risk of transformation to MDS/AL with HU therapy in PV, ET, and MMM. Larger, prospective studies are needed to study this issue further.

Topics: Acute Disease; Anemia, Refractory, with Excess of Blasts; Busulfan; Cell Transformation, Neoplastic; Chlorambucil; Cohort Studies; Disease Progression; Drug Therapy, Combination; Enzyme Inhibitors; Female; Humans; Hydroxyurea; Incidence; Interferon-alpha; Leukemia; Leukemia, Radiation-Induced; Male; Melphalan; Middle Aged; Phlebotomy; Phosphorus Radioisotopes; Polycythemia Vera; Preleukemia; Primary Myelofibrosis; Retrospective Studies; Ribonucleotide Reductases; Risk; Thrombocythemia, Essential

Leukemic transformation in essential thrombocythemia (ET) is rare. We describe a patient with ET which transformed to megakaryoblastic leukemia with myelofibrosis after treatment with melphalan for 8 years. His course after transformation smouldered for 20 months without antileukemic chemotherapy. A 61-year-old man was referred by a local doctor to Niigata University Hospital due to nasal bleeding in June 1984. Complete blood count (CBC) was as follows; hemoglobin 12.4 g/dl, platelets 268.8 x 10(4)/microliters, and white blood cells 11,900/microliters, with differentials of 39% PMN, 1% basophils, 2% eosinophils, 4% monocytes, and 13% lymphocytes. Bone marrow examination revealed hyperplasia of megakaryocytes without increase of reticulin fibers. Neutrophil alkaline phosphatase activity and karyotype of marrow cells were normal. ET was diagnosed. He was followed up by local doctor. The platelet count was controlled at a level of approximately 40 x 10(4)/microliters with melphalan for eight years. In January 1992 he developed pain in his lower extremities. He was admitted to our hospital on May 29, 1992. CBC was as follows; hemoglobin 8.9 g/dl, platelets 14.3 x 10(4)/microliters, and white blood cells 3,500/microliters, with differentials of 25% PMN, 5% monocytes, 28% lymphocytes, and 24% blasts. Bone marrow aspiration was unsuccessful and bone marrow biopsy revealed increases in fibroblasts and collagen fibers. Circulating blasts were positive for CD4, CD7, CD25, CD13, CD33, CD34, and HLA-DR and partly positive for CD41 and CD36. In ultrastructural cytochemistry blasts were positive for platelet peroxidase but negative for myeloperoxidase. Cytogenetic study revealed 46, XY, +der (1) t(1:7) (p11;q11) in all of five metaphases. He was diagnosed with megakaryoblastic leukemia accompanied by myelofibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Blast Crisis; Humans; Leukemia, Megakaryoblastic, Acute; Male; Melphalan; Primary Myelofibrosis; Thrombocythemia, Essential

Topics: Acute Disease; Female; Humans; Leukemia; Melphalan; Middle Aged; Myelodysplastic Syndromes; Thrombocythemia, Essential

178 episodes of essential thrombocytosis with symptoms of haemorrhage or thrombosis, were treated in 15 patients with melphalan (5 mg/m2 orally during 4 d). An average reduction in the platelet count of 77% was achieved by oral melphalan in 14 responding patients. 1 patient appeared to be refractory to oral therapy, but a decrease of the thrombocyte count was achieved after intravenous administration of melphalan. All responding patients experienced a relief of the thrombocytosis-associated clinical symptoms. Reduction of the thrombocyte count persisted for 3-4 wk.

Topics: Adolescent; Adult; Aged; Drug Administration Schedule; Female; Humans; Male; Melphalan; Middle Aged; Thrombocythemia, Essential; Thrombocytosis; Thrombosis

Essential thrombocythemia is a clonal myeloproliferative disorder, characterized predominantly by a markedly elevated platelet count without known cause. We report a case that was recognized during investigation of a transient ischemic attack, and review the neurologic findings in 33 patients with unequivocal essential thrombocythemia under prospective study by the Polycythemia Vera Study Group. Twenty-one patients had neurologic manifestations at some point during their course, including headache (13 patients), paresthesiae (10), posterior cerebral circulatory ischemia (9), anterior cerebral circulatory ischemia (6), visual disturbances (6) and epileptic seizures (2). All patients with neurologic symptoms responded satisfactorily to treatment, although continuous or repeated treatment was often required. Therapeutic recommendations include plateletpheresis for major thrombo-hemorrhagic phenomena, or megakaryocyte suppression with radioactive phosphorus, alkylating agents (such as melphalan), or hydroxyurea; minor symptoms may respond to platelet antiaggregating agents.

Topics: Adult; Epilepsy; Female; Headache; Humans; Ischemic Attack, Transient; Melphalan; Paresthesia; Platelet Count; Plateletpheresis; Prospective Studies; Thrombocythemia, Essential; Vision Disorders

Primary thrombocythemia is a myeloproliferative disease characterized by a sustained and marked increase in platelet count. The platelet number rises in excess of 1000 X 10(9)/l. Adult patients present with recurrent hemorrhages, thrombotic episodes and microvascular disturbances. It is a relatively benign disease and rarely reported in children. We describe two patients with a thrombocythaemia. The first, a 13 1/2 year old boy, had no complaints. A thrombocythemia (2167 X 10(9)/l) and splenomegaly were found by chance. He was treated with melfalan. Acetylsalicilic acid and dipyridamol were added as anti-coagulants. The second patient, a 12 year old girl, was submitted to a splenectomy at the age of 10, because of a traumatic rupture. Sixteen months later she was admitted to our hospital with symptoms of thrombotic as well as bleeding tendency. Periferal microvascular disturbances and symptoms on the basis of impaired cerebro-vascular bloodflow were found. The number of platelets was 5083 X 10(9)/l. She was treated in the same way as the first patient. Symptoms disappeared as soon as the number of platelets decreased. In both patients periferal blood and bonemarrow examination as well as platelet function, measured by aggregation studies, were abnormal. Consideration of the literature on children and our own case I indicate that this disease in the younger patient may exist without undue risk of complications. One might consider treatment with anti-aggregating agents only.

Topics: Adolescent; Aspirin; Child; Dipyridamole; Drug Therapy, Combination; Female; Humans; Male; Melphalan; Platelet Aggregation; Platelet Count; Thrombocythemia, Essential; Thrombocytosis

The various myeloproliferative diseases have different symptoms, therapeutic problems, and prognoses. The most common of these disorders appears to be agnogenic myeloid metaplasia, which primarily affects older persons. The five-year survival rate at the Mayo Clinic for these patients is 58%, and the prognosis depends on the presence of symptoms, anemia, and thrombocytopenia and on the size of the liver. Androgen therapy is often necessary to control anemia, and splenectomy may be indicated.

Topics: Adult; Aged; Chlorambucil; Female; Humans; Male; Melphalan; Middle Aged; Myeloproliferative Disorders; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Thrombocythemia, Essential

A report is presented on two patients with the very rare combination of thrombocythaemia and multiple myeloma. Both patients displayed an increase in monoclonal immunoglobulin in the serum, an increased amount of plasma cells in the bone marrow, and multiple osteolytic lesions in the skeleton, along with a platelet count exceeding 1 mill./mm3, haemorrhagic diathesis, and thromboembolic complications. In case 1, both diseases reacted favourably to treatment with melphalan during a 36-month follow-up. In case 2, the thrombocythaemia had been brought under control with busulphan prior to the diagnosis of myeloma. The latter patient died before initiation of treatment of the myeloma. The signifacance of the combination is discussed.

Topics: Aged; Blood Cell Count; Blood Platelets; Bone Marrow Cells; Busulfan; Female; Follow-Up Studies; Humans; Immunoglobulin A; Immunoglobulin G; Male; Melphalan; Multiple Myeloma; Plasma Cells; Thrombocythemia, Essential

Topics: Adenocarcinoma; Aged; Anemia, Sideroblastic; Cecal Neoplasms; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Radioisotope Teletherapy; Spinal Neoplasms; Thrombocythemia, Essential

Topics: Adult; Aged; Blood Coagulation Tests; Bone Marrow Examination; Busulfan; Follow-Up Studies; Gastrointestinal Hemorrhage; Hemorrhage; Hepatomegaly; Humans; Male; Melphalan; Middle Aged; Oral Hemorrhage; Phosphorus Isotopes; Pipobroman; Polycythemia Vera; Splenomegaly; Thrombocythemia, Essential; Thrombosis; Tooth Extraction

Topics: Blood Platelets; Heparin; Humans; Male; Melphalan; Middle Aged; Thrombocythemia, Essential

Topics: Adult; Aged; Blood Cell Count; Blood Platelets; Bone Marrow Examination; Female; Hematemesis; Hematocrit; Hemoglobinometry; Humans; Leukocytosis; Male; Megakaryocytes; Melena; Melphalan; Middle Aged; Postoperative Complications; Splenectomy; Thrombocythemia, Essential; Thrombocytosis