allopurinol and Leukemia--Myelogenous--Chronic--BCR-ABL-Positive

A patient was referred with a high leukocyte count and diagnosed with chronic myelogenous leukemia (CML). Although practically asymptomatic since the time of diagnosis, he had a variable and inconsistent response to treatment. All of his bone marrow cells had a complex, three-way translocation, involving chromosomes 4, 9 and 22. Translocation of chromosome 4 to chromosome 9 was undetectable by routine cytogenetic techniques; however, by the fluorescence in situ hybridization technique, a three-way translocation was identified, 46,XY,t(4;9;22)(p16;q34;q11). Although, other chromosomes are frequently involved in complex or variant translocations with chromosome 9 and 22, participation of chromosome 4 is a very rare event. So far, two previous cases have been described in the literature with translocations involving chromosome 4p16. We present a third case of CML having similar break points whose clinical presentation is unusual.

Topics: Allopurinol; Antineoplastic Agents; Bone Marrow; Busulfan; Chromosome Banding; Chromosome Mapping; Chromosomes, Human, Pair 22; Chromosomes, Human, Pair 4; Chromosomes, Human, Pair 9; Humans; Hydroxyurea; In Situ Hybridization, Fluorescence; Karyotyping; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Translocation, Genetic

Eighty-three patients in the chronic phase of Ph1-positive chronic myelogenous leukemia (CML) have been treated with busulfan or other alkylating agents in a conventional way hitherto acknowledged. During its chronic phase, 31 cases of these 83 had received an additional intermittent therapy every 4 to 6 months, consisting of vincristine 2 mg or vindesine 3 mg per week, prednisolone 20 to 30 mg per day, and partly 6-mercaptopurine 50 to 100 mg, combined with allopurinol 200 to 300 mg per day for 2 to 3 weeks. The 50% survival of these patients using the Kaplan-Meier's method was 73, 7 months and 5-year survival was 70.2%, while those of the remaining patients were 41.2 months and 13.4%, respectively. The second nation-wide survey of long-term survivors of CML in Japan was attempted. CML totalling 195 surviving over 7 years from the initial diagnosis and 113 of CML surviving over one year from the blastic crisis had been collected by the end of March 1988. The longest survivors of the former group was for 21.3 years, while the latter 4.6 years. In addition, recent increase of the annual incidence of the above both groups was clarified. These results strongly support the progress of chemotherapy of CML in recent years.

Topics: Adolescent; Adult; Aged; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Japan; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Male; Mercaptopurine; Middle Aged; Multicenter Studies as Topic; Prednisolone; Survival Rate; Vincristine

Chronic myeloid Leukemia (CML) is a chronic myeloproliferative disorder, caused by the unregulated proliferation of granulocytes at different stages of development and maturation. Leukostasis is one of the complications of CML, causing partial or total occlusion of microvasculature with a variety of clinical manifestations, mostly ophthalmic, neurologic or respiratory. Recently, we encountered a 21-year old soldier, who complained of severe bilateral calf pain which began a few months earlier during training. He underwent complete ambulatory orthopedic evaluation which was unrevealing, and finally presented to the hospital casualty department where CML was diagnosed on the basis of an elevated WBC count and morphologic findings. Bilateral retinal hemorrhages due to leukostasis were noticed at fundoscopy. The calf pain resolved completely after leukapheresis and initial cytoreductive therapy and was in retrospect attributed to peripheral leukostasis. To the best of our knowledge this is the first report of CML presenting with bilateral calf pain due to Leukocytosis and possible leukostasis. This case report highlights the importance of differential diagnosis in cases of calf pain and the awareness of this rare manifestation of CML.

Topics: Allopurinol; Bone Marrow Examination; Dasatinib; Diagnosis, Differential; Enzyme Inhibitors; Humans; Hydroxyurea; Leg; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukocyte Count; Leukostasis; Male; Myalgia; Ophthalmoscopy; Philadelphia Chromosome; Pyrimidines; Retinal Hemorrhage; Thiazoles; Treatment Outcome; Young Adult

Topics: Accidental Falls; Adult; Allopurinol; Animals; Diagnosis, Differential; Gout Suppressants; Horses; Humans; Incidental Findings; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemoid Reaction; Male; Spleen

Visual impairment as the initial symptom of leukemia, especially chronic myeloid leukemia, is rare, occurring in approximately 3% of all leukemias in children. We describe the case of a 14-year-old boy with vision loss attributable to bilateral central retinal vein occlusion and massive retinal infiltrates. Bone marrow biopsy demonstrated the BCR-ABL translocation, and the patient was diagnosed with chronic myeloid leukemia. A major cytogenetic remission was achieved 6 months after initiation of therapy.

Topics: Adolescent; Allopurinol; Antineoplastic Agents; Benzamides; Bone Marrow; Drug Therapy, Combination; Humans; Hydroxyurea; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemic Infiltration; Male; Piperazines; Proto-Oncogene Proteins c-bcr; Pyrimidines; Retina; Retinal Neoplasms; Retinal Vein Occlusion; Vision Disorders; Visual Acuity

Topics: Adult; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Fluorescein Angiography; Humans; Hydroxyurea; Imatinib Mesylate; In Situ Hybridization, Fluorescence; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Piperazines; Pyrimidines; Retinal Neoplasms; Retinal Neovascularization

To report the use of single-dose rasburicase in an obese patient.. A 53-year-old obese African American woman weighing 136 kg (ideal body weight [IBW] 55 kg) with new-onset chronic myelomonocytic leukemia in leukocytic blast crisis was treated with hydroxyurea 5 g daily. In addition, she received allopurinol 300 mg daily for prevention of tumor lysis syndrome (TLS). The following day, allopurinol was discontinued and rasburicase was administered at a dose of 0.2 mg/kg of IBW for a serum uric acid level of 11.9 mg/dL. The patient's serum uric acid level decreased to 1.9 mg/dL 48 hours after a single dose.. Rasburicase is indicated for the initial management of elevated plasma uric acid levels in patients with hematologic and solid tumor malignancies who are at risk for TLS. This case is unique because the patient received one dose of rasburicase followed by allopurinol rather than 5 daily doses of rasburicase. Additionally, the dose was based on IBW rather than actual body weight. Efficacy of this approach is apparent from the uric acid levels and the lack of hemodialysis requirements.. A single dose of rasburicase (based on IBW) followed by allopurinol can effectively prevent TLS based on serum uric acid concentration. This approach resulted in a substantial cost savings.

Topics: Allopurinol; Dose-Response Relationship, Drug; Enzyme Inhibitors; Female; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Middle Aged; Obesity; Recombinant Proteins; Tumor Lysis Syndrome; Urate Oxidase; Uric Acid

We describe a patient with a 2-month history of right shoulder monoarthritis and fever as the presenting symptoms of a subsequent diagnosis of chronic myeloid leukemia in blast crisis. Imaging studies showed changes consistent with leukemic infiltration of the soft tissues around the right shoulder joint and the proximal humerus. Immunophenotypic and morphologic analysis of the large number of cells obtained from the synovial fluid confirmed the shoulder synovitis to be an extramedullary manifestation of myelomonocytic blast crisis of chronic myeloid leukemia. The patient was not a candidate for aggressive chemotherapy treatment because of her poor overall condition, and she had no compatible donor for allogenic bone marrow transplantation. Her painful arthropathy was refractory to standard pain management but she achieved excellent pain relief with palliative radiation therapy. We conclude that the involvement of extramedullary sites by chronic myeloid leukemia blast cells can predate hematological blast crisis in some of chronic myeloid leukemia cases. Also, painful leukemic synovitis can be managed by low dose radiotherapy in a candidate who is refractory to chemotherapy and other medical therapy.

Topics: Adult; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Blast Crisis; Combined Modality Therapy; Diagnosis, Differential; Female; Humans; Hydroxyurea; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Synovitis

Tumor lysis syndrome (TLS) is a complication associated with electrolyte abnormalities that is observed in patients with acute leukemia who are receiving intense doses of chemotherapy. Forty-one patients with acute leukemia were treated with high-dose combination chemotherapy and were evaluated for TLS. A grading system developed for the evaluation of these patients was applied. Grade I tumor lysis was observed in 22 patients, grade II TLS in 2 patients and grade III in 1 patient. All patients were treated with intravenous fluids, mannitol, allopurinol and in some patients, aluminum-based antacids. Treatment for TLS prior to intensive chemotherapy reduced morbidity and mortality associated with high-dose chemotherapy for acute leukemias.

Topics: Adolescent; Adult; Aged; Allopurinol; Antineoplastic Agents; Blast Crisis; Female; Fluid Therapy; Humans; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Male; Mannitol; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Tumor Lysis Syndrome

We report a 44 year old man who developed external ophthalmoplegia and predominantly respiratory, truncal and bulbar weakness with brisk reflexes, histological evidence of an inflammatory myopathy and a high titre of acetylcholine receptor antibodies, one month after starting hydroxyurea and allopurinol for chronic myeloid leukaemia. The temporal relationship suggests a possible association between this patient's unusual neuromuscular disorder and either the chronic myeloid leukaemia or its treatment.

Topics: Adult; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Humans; Hydroxyurea; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Myositis; Neuromuscular Diseases; Ophthalmoplegia

Topics: Adult; Aged; Allopurinol; Antineoplastic Agents; Female; Genes, myc; Genes, ras; Guanosine Triphosphate; Humans; IMP Dehydrogenase; In Vitro Techniques; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Ribavirin; Tumor Cells, Cultured

The first case in Tunisia of a 3 year old child with adult type chronic myelogenous leukemia is presented. Diagnosis was based on clinical and biological presentation and detection of Philadelphia (PH1) chromosome. Chronic myelogenous leukemia in children represents 3.8% of all cases of chronic myelogenous leukemia detected in Tunisia between 1970 and 1990. Only one 3.5 year old case was reported without PH1 chromosome.

Topics: Age Factors; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Female; Humans; Hydroxyurea; Incidence; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Tunisia

Topics: Aged; Allopurinol; Cytarabine; Drug Therapy, Combination; Humans; Hydroxyurea; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukocytosis; Male; Positive-Pressure Respiration; Postoperative Complications; Respiratory Insufficiency

Seventy-four patients in the chronic phase of Ph1-positive chronic myelogenous leukemia (CML) have been treated with busulfan or other alkylating agents in a conventional way. During its chronic phase, 24 of these 74 cases had received additional intermittent therapy every 4 to 6 months, consisting of vincristine 2 mg or vindesine 3 mg per week, prednisolone 20-30 mg per day and partly 6 mercaptopurine 50 to 100 mg, combined with allopurinol 200 to 300 mg per day for 2 to 3 weeks. The 50% survival of these patients using the Kaplan-Meier's method was 73.7 months and 5-year survival was 69.6%, against 40.5 months and 14.4%, respectively, in the remaining patients. Nine patients in the blastic or accelerated phase of Ph1-positive CML have been treated with new regimens including MCNU. All cases had been refractory for usual types of induction chemotherapy. The new regimen consisted of MCNU 50-100 mg, combined with vindesine or 6-MP plus allopurinol or prednisolone. Five out of 9 cases attained complete remission and 1 partial remission. The major adverse effect of this regimen was slight liver damage. MCNU could be regarded as an useful agent in the blastic phase as well as in the chronic phase of CML.

Topics: Adolescent; Adult; Aged; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Blast Crisis; Drug Evaluation; Female; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Accelerated Phase; Leukemia, Myeloid, Chronic-Phase; Male; Mercaptopurine; Middle Aged; Nitrosourea Compounds; Prednisolone; Remission Induction; Vincristine; Vindesine