melphalan and Polycythemia-Vera

Topics: Bloodletting; Busulfan; Chlorambucil; Cyclophosphamide; Humans; Injections, Intravenous; International Cooperation; Melphalan; Phosphorus Radioisotopes; Polycythemia Vera

Topics: Allopurinol; Bloodletting; Chlorambucil; Erythropoiesis; Gout; Humans; Melphalan; Phosphorus Radioisotopes; Polycythemia Vera; Uric Acid

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

Ten years after being diagnosed with polycythemia vera, a 55-year-old woman required frequent blood transfusion due to secondary myelofibrosis. She underwent reduced-intensity stem cell transplantation (RIST) from an HLA-identical sibling donor. Since mixed chimerae were identified in the peripheral blood at day 35, cyclosporine was withdrawn. At day 73, she developed acute graft-versus-host disease of the liver, while simultaneous resolution of splenomegaly occurred and complete donor chimerism in the peripheral blood was achieved. Frequent red blood cell transfusion was required until day 300 after transplantation. Thus, RIST for an older patient with secondary myelofibrosis was successful without severe treatment-related morbidity. This case suggests that RIST could be an effective treatment modality for secondary myelofibrosis.

Topics: Female; Graft vs Host Disease; Humans; Janus Kinase 2; Melphalan; Middle Aged; Polycythemia Vera; Primary Myelofibrosis; Stem Cell Transplantation; Transplantation Conditioning; Treatment Outcome; Vidarabine

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

Topics: Bone Marrow; Busulfan; Chlorambucil; Cyclophosphamide; Humans; Melphalan; Phosphorus Radioisotopes; Polycythemia Vera

The unsaturated B12 binding capacity (UBBC) of the serum and the binding capacity of each of the 3 vitamin B12 binders--the transcobalamins (TC) I, II and III were determined in 21 patients with polycythaemia vera (PV) during the course of the disease and following treatment, using the recently described charged cellulose filter technique. High serum UBBC due to elevated serum TCIII was found in all patients. TCI was moderately elevated in patients who had leucocytosis with a shift to the left. The changes in serum TCIII and UBBC correlated with the activity of the disease. Chemotherapy resulted in a decrease in TCIII and UBBC. The decrease in TCIII and UBBC folowing chemotherapy may be observed before a decrease in the haematocrit and the leucocyte count occurs. Activation of the disease may be assessed by the elevation of TCIII and UBBC. The onset of acute myeloblastic crisis in 1 patient was associated with a decrease in TCIII and TCI levels and a rise in serum TCII. The determination of TCIII and UBBC may be helpful in differentiating true from secondary polycythaemia.

Topics: Blood Proteins; Busulfan; Humans; Leukemia, Myeloid, Acute; Melphalan; Polycythemia Vera; Protein Binding; Transcobalamins; Vitamin B 12

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

Topics: Humans; Melphalan; Polycythemia Vera

Topics: Antineoplastic Agents; Benzene; Bone Marrow Diseases; Chloramphenicol; Cyclophosphamide; Dose-Response Relationship, Radiation; Humans; Immunosuppressive Agents; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Radiation-Induced; Melphalan; Multiple Myeloma; Phenylbutazone; Phenytoin; Polycythemia Vera

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: Antibiotics, Antineoplastic; Busulfan; Chlorambucil; Chromosome Aberrations; Chromosome Disorders; Humans; Leukemia; Melphalan; Phosphorus Isotopes; Polycythemia Vera

Topics: Blood Cell Count; Bloodletting; Humans; Melphalan; Polycythemia Vera; Remission, Spontaneous

Topics: Chlorambucil; Humans; Hydroxyurea; Melphalan; Phosphorus Isotopes; Polycythemia Vera; Remission, Spontaneous; Time Factors

Topics: Adolescent; Blood Coagulation Disorders; Blood Platelets; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, 16-18; Disseminated Intravascular Coagulation; Humans; Immunoglobulin A; Immunologic Deficiency Syndromes; Karyotyping; Male; Melphalan; Polycythemia Vera

Topics: Aged; Anemia, Sideroblastic; Blood Platelets; Female; Hemoglobinometry; Humans; Leukocyte Count; Leukopenia; Male; Melphalan; Polycythemia Vera; Primary Myelofibrosis

Topics: Humans; Leukopenia; Melphalan; Polycythemia Vera; Splenomegaly; Thrombocytopenia

Topics: Aged; Blood Cell Count; Blood Proteins; Bone Marrow; Cyclophosphamide; Female; Globulins; Gold Isotopes; Hemoglobins; Humans; In Vitro Techniques; Male; Melphalan; Middle Aged; Multiple Myeloma; Polycythemia Vera; Radionuclide Imaging