Acute Myelogenous Leukemia Concurrent With Untreated Chronic Lymphocytic Leukemia

We report a case of acute myelogenous leukemia (AML) concurrent with untreated chronic lymphocytic leukemia (CLL). An 84-year-old Japanese man was admitted to the Chihaya Hospital with persistent high-grade fever. Morphologic observation of peripheral blood and bone marrow smears revealed a proliferation of blasts and lymphocytosis with small and mature phenotypes. Immunophenotyping of the blast cells revealed CD13+, CD33+, CD34+, and HLA-DR+, and that of the lymphocytes revealed CD5+, CD19+, CD20+, and lambda+ on the cell surface. The peripheral lymphocytes revealed an IgH gene rearrangement. Chromosome analysis of 20 metaphase cells from bone marrow showed numerous abnormalities, containing +8,+11,+21. The patient's disease was diagnosed as AML with trilineage dysplasia concurrent with CLL. The simultaneous occurrence of AML and CLL is extremely rare but should not be overlooked as a possible underlying cause of lymphocyte abnormalities in AML patients.     

Imatinib Mesylate in the Treatment of Chronic Myelogenous Leukemia

Imatinib mesylate binds to the inactive conformation of BCR-ABL tyrosine kinase, suppressing the Philadelphia chromosome-positive clone in chronic myelogenous leukemia (CML). Clinical studies of imatinib have yielded impressive results in the treatment of all phases of CML. With the higher rates of complete cytogenetic response with imatinib, molecular monitoring of disease has become mandatory in assessing response and determining prognosis. The practical aspects of the treatment of CML with imatinib are discussed. The emergence of imatinib resistance, albeit in a small percentage of patients, has prompted an evaluation of innovative treatment strategies.     

Cyclic Leukocyte Oscillations in Chronic Myelogenous Leukemia During Hydroxyurea Therapy

Cyclic fluctuations of the leukocyte and platelet counts were observed in fivepatients with chronic myelogenous leukemia during treatment with hydroxyurea. The cyclic periods ranged from 30 to 50 days, were similar in eachindividual, but the peak-to-trough values of single cycles varied in magnitude.A second biorhythm was a cyclic undulation of the leukocyte count withheights of the peaks at nine-to-20-month intervals. Rhythmic variations of theplatelet counts were also observed; the period and phase of the cycle beingthe same as that of the leukocyte cycle. No cyclic oscillations were noted inthe hemoglobin or reticulocyte counts. The recognition of the phenomenonmay aid in the use of hydroxyurea or other chemotherapeutic agents in thecontrol of myelogenous leukemia. Chronopharmacology may more accuratelydevelop the use of antitumor agents by its investigation of drug effects onbiologic characteristics as a function of biologic timing.

Submitted on December 19, 1969 Accepted on January 15, 1970     

Double-Unit Unrelated Cord Blood Transplantation for Chronic Myelogenous Leukemia

Two patients with advanced renal cell carcinoma underwent allogeneic hematopoietic stem cell transplantation and received cyclosporine (CSP) as part of their immunosuppressive therapy. Despite adequate renal function, both patients developed hyperkalemia. CSP was the only pharmaceutical agent to which this electrolyte abnormality could be attributed. Evaluation of renal tubule function suggested that CSP-associated isolated hyperkalemia resulted from tubular resistance to aldosterone. We propose that the presence of a single functional kidney may be a risk factor for isolated hyperkalemia due to CSP.     

Similarities of the Erythrocytes in Juvenile Chronic Myelogenous Leukemia to Fetal Erythrocytes

A 4-yr-old boy was studied whoshowed typical findings of juvenilechronic myelogenous leukemia, including massive hepatosplenomegaly,thrombocytopenia, low leukocyte alkaline phosphatase, and absence of aPhiladelphia chromosome. The erythrocytes of the patient exhibited manycharacteristic features of erythrocytesof newborn infants: the fetal hemoglobin concentration was greatly elevated (72%); the oxygen dissociationcurve of the whole blood was displaced to the left of the curve fromnormal adult blood; the hemoglobinA₂ level and the erythrocyte I antigentiter were reduced; and a structuralanalysis of the -chain of the fetalhemoglobin showed the glycine to alanine ratio in -136 to be typical of theneonatal pattern. These findings support the suggestion that juvenilechronic myelogenous leukemia is accompanied by reversion to a fetal pattern of erythropoiesis.

Submitted on November 1, 1971 Revised on December 20, 1971 Accepted on December 22, 1971     

The Distribution of the Philadelphia Chromosome in Patients with Chronic Myelogenous Leukemia

Thirteen patients with chronic myelogenous leukemia continued to havethe Ph¹ chromosomes in 90-100 per cent dividing marrow cells during drug-induced clinical remissions. The Ph¹ chromosome was present in erythroidas well as granulocytic marrow cells, and possibly in megakaryocytes.

The presence of Ph¹ chromosomes was also studied in cultures of peripheralblood. In six patients in relapse, 40 per cent of metaphases contained the Ph¹chromosome, and the percentage of these cells corresponded roughly to therelative frequency of immature granulocytes in the blood. In contrast, duringremission, few or no Ph¹ chromosomes were found in peripheral blood cultures, presumably because in the absence of immature granulocytes the dividing cells in the cultures originate from lymphocytes, as they do in normalblood.

It is suggested that the Ph¹ chromosome usually arises in a precursor cellcommon to the erythroid, granulocytic, and megakaryocytic, but not thelymphoid series of hemopoietic cells.

Submitted on April 5, 1963 Accepted on June 30, 1963     

Myelogenous Leukemia in the Rat

Observations on growth and other characteristics of subcutaneously transplanted chloroleukemia in non-inbred rats have been described in this report.This chloroleukemia cytologically is an acute or subacute, not chronic, myelogenous leukemia. Because of serious immunologic differences, the experimentalusefulness of subtransferred chloroleukemia is greatly limited. However,myelogenous leukemia in the rat, induced by chemical agents or ionizing radiation, may offer a valuable approach to the study of leukemogenic mechanisms.

Submitted on June 23, 1961 Accepted on August 18, 1961     

Biological Effects of Repeated Leukapheresis of Patients With Chronic Myelogenous Leukemia

Fifteen patients with chronic myelogenousleukemia were managed only with repeated leukapheresis for up to 26 mo. Ateach procedure approximately 10 liters ofblood were processed with a continuous-flow blood cell separator over a 3-hr period. Five patients had intermittent leukapheresis (1-2 procedures/wk), and ten ofthem had one or more series of intensiveleukapheresis (4-5 procedures/wk). Addition of hydroxyethyl starch to the extracorporeal circuit was found to increase theremoval of leukocytes fourfold. With intensive leukapheresis the leukocyte countdecreased 80%, and the platelet count decreased 54% (mean values). With intermittent leukapheresis the correspondingfigures were 70% and 35%. Thrombocytopenia was never clinically significant. All15 patients experienced symptomatic improvement, and those with organomegalyhad decrease in the size of the spleen andliver. Leukapheresis was not associatedwith morbidity, except that anemia became more severe and required periodictransfusions of packed red blood cells.Patients managed with leukapheresis didnot enter bone marrow remission, andtransformation of CML into blastic crisiswas not prevented or delayed.

Submitted on February 17, 1973 Revised on April 30, 1973 Accepted on May 14, 1973     

Imatinib Mesylate in Combination with Other Chemotherapeutic Agents for Chronic Myelogenous Leukemia

Imatinib therapy is an important contribution to the management of patients with chronic myelogenous leukemia (CML). Despite high rates of hematologic and cytogenetic responses to imatinib therapy, the emergence of resistance to imatinib has been recognized as a major problem in the treatment of CML. Experimental and clinical studies suggest that imatinib as a single drug may not be sufficient to eradicate BCR-ABL-positive stem cells. Therefore, whether combinations of imatinib with other agents can increase the length of molecular remission and whether such combinations can prolong survival should be determined by large-scale clinical studies. In this review, we discuss efficacious combinations for future clinical trials. These regimens combine imatinib with conventional chemotherapeutic agents or with inhibitors of other signal transduction molecules that may be preferentially activated in CML cells.     

Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in A Child: A Case Report

Philadelphia chromosome (Ph¹)-positive Chronic Myelogenous Leukemia (CML) in a child below the age of 3 years is extremely rare. We have reported such a case in a 3 year old male child. Peripheral blood smear revealed features of CML and karyotypic study showed (Ph¹) positivity. Biologic behaviour and prognosis are similar to that of adult-type of CML.     

The Costs and Cost-Effectiveness of Unrelated Donor Bone Marrow Transplantation for Chronic Phase Chronic Myelogenous Leukemia

Unrelated donor transplantation prolongs survival in some patientswith chronic myelogenous leukemia (CML) in chronic phase. However,there are growing concerns about the intensive resources required forthis procedure given health care budget constraints. To address thisissue, we conducted a study of the costs and cost-effectiveness ofunrelated donor transplantation for chronic phase CML. The costs oftransplantation were derived from 157 patients from the Brigham andWomen's Hospital (BWH) and the Fred Hutchinson Cancer Research Center(FHCRC). Estimates of the effectiveness of transplantation were takenfrom our previous work using data from the International Bone MarrowTransplant Registry and the National Marrow Donor Program.The median cost of the first 6 months of care including donoridentification, marrow collection, patient hospitalization fortransplantation and all outpatient medications and readmissions through6 months postmarrow infusion was $178,500 (range, $85,000 to $462,400)and the mean was $196,200. Mean costs for patients surviving beyond 6 months posttransplant were significantly lower than for patients dyingwithin that period ($189,700 v $211,000, respectively,P = .03). Posttransplant follow-up costs were high formonths 6 to 18, then decreased. The incremental cost-effectiveness oftransplantation within 1 year of diagnosis versus -interferon therapy without transplant in the base case of a 35-year-old patient was $51,800/quality-adjusted life year (QALY) gained. Sensitivity analysis showed that most ratios were between $50,000 to $100,000/QALY or within the intermediate zone of acceptable cost-effectiveness ratios.     

HA＋马利兰／HA方案初治慢性粒细胞白血病疗效观察

12例初诊的慢性粒细胞白血病(CML)接受HA+马利兰/HA方案化疗.三尖杉酯硷 2～3mg/d,阿糖胞苷100～200ng/d,7～10天为1疗程.7例在停HA后即连用马利兰4～8mg/d×5～8天.1疗程未达CR者间隔2～3周开始第2疗程直至CR.结果;1疗程CR率66.6%,有效率100%;2疗程CR率100%;达CR中位时间30天.其中2例ph_1;阳性率治疗前后对比下降平均为48.6%.提示:HA+马利兰/HA方案缓解率及有效率明显高于单一马利兰;显效快,达CR迅速,作用轻.HA+马利兰较HA能加速CML获CR.对慢性期CML细胞遗传学有较好改善.     

应用COX模型判断慢性粒细胞白血病患者的预后

应用国际慢性粒细胞白血病(CML)预后研究协作组建立的Cox模型对35例CML患者进行了回顾性分析,高危患者占80％,3年生存率35.7％,中危患者占20％,生存期均超过3年,无1例低危组,提示该模型在我国也有一定的实用价值。在判断CML预后的几个危险因素中,脾脏大小是最重要的,红细胞压积对46岁以下患者预后影响也较大。外周血中原始细胞百分数及血小板计数在高中危组之间差异并不显著。