慢性髓性白血病的危险因素探讨

对38例不同病期的慢性髓性白血病患者骨髓进行DNA链损伤(%D值)、DNA-非整倍体及流式细胞仪细胞膜抗原CD15与HLA-DR测定。结果显示三种参数能较可靠地预示病情进展。DNA-非整倍体的存在及DNA链损伤加重,均为CML急变的高危指标。CD15与HLA-DR比值测定简易可靠。其比值倒置先于细胞形态学的恶化,应定期追踪复查。     

影响慢性粒细胞白血病长期生存的因素临床分析

本文把存活5年以上的23例慢粒患者与同期生存时间少于5年的40例慢粒患者的临床特点进行了对照分析;发现生存期较长病例的脾肿大较轻,其首次缓解持续时间较长,而白细胞较高的患者,预后并不一定差。     

慢性粒细胞白血病的骨髓组织病理学研究

应用国产塑料包埋剂对23例慢粒慢性期患者进行了骨髓塑包切片的组织病理学研究,证明慢粒属于异质性疾病,分两类组织学亚型:即以粒系细胞极度增殖为主的粒细胞(GRAN)型和以粒系细胞—巨核细胞混合性增殖,且伴巨核细胞多形性与异位的粒细胞/巨核细胞(GRAN/MEG)型。本文对两型的其它组织学特点一并进行了讨论。     

Comparison of Chromosome Constitution in Chronic Myelocytic Leukemia and Other Myeloproliferative Disorders

The frequency of the Ph¹ chromosome in freshly aspirated marrow cells of14 patients with typical chronic myelocytic leukemia processed by a "directtechnic" without resort to culture or colchicine was significantly higher (>75 per cent) than that observed in the cultured blood cells (< 35 per cent)of the same subjects. The karyotypic abnormally of the abbreviated G-groupchromosome would appear not to be related to therapy, since the frequencywith which it occurred was not materially affected by treatment (including radiation). The Ph¹ chromosome was not observed in any of the metaphases ofblood or marrow of 12 subjects who had developed a leukemia-like picturecomplicating either myelofibrosis, polycythemia vera or myeloid metaplasia. Anew chromosome abnormality—a shortened D-group chromosome—was observed with about the same frequency in the blood and marrow metaphases ofa female patient with treated chronic myelocytic leukemia. This new karyotypicabnormality was associated with the highest frequency of the Ph¹ chromosomein cultured blood cells in the group studied. The Ph¹ chromosome was observed in the metaphases of a patient with the blastic phase of chronic myelocytic leukemia. The variations of the morphology of the Ph¹ chromosome arediscussed and illustrated, especially in relation to the Y-chromosome. In fourpatients with an atypical picture of CML, the Ph¹ chromosome was not observed either in the marrow or cultured blood.

Submitted on April 25, 1962 Accepted on June 7, 1962     

A Longitudinal Comparison of Antibodies to Epstein-Barr Virus and Clinical Parameters in Chronic Lymphocytic Leukemia and Chronic Myelocytic Leukemia

Elevated titers to the Epstein-Barr virushave previously been reported in a number of lymphoproliferative diseases, including Burkitt’s lymphoma, infectiousmononucleosis, and Hodgkin’s disease.This study also demonstrates a significantly higher titer against EBV in agroup of patients with chronic lymphoproliferative disease (CLL) than in agroup of patients with chronic myeloproliferative disease (CML) or normal individuals. No significant antibody changeswere detected in the 20 CML patientsor 23 of the 24 CLL patients who werefollowed for a period of time up to 5 yr.It appears that the elevated EBV titersseen in patients with CLL reflect anevent or process occurring prior to theonset of disease or in the very earlystages rather than a nonspecific riseparalleling the increase in total-bodylymphocytes.

Submitted on March 22, 1971 Revised on May 18, 1971 Accepted on May 19, 1971     

Chronic Myelocytic Leukemia with Two Philadelphia Chromosomes and Prominent Peripheral Lymphadenopathy

1. Three adults with CML, 2 Ph¹ chromosomes, and marked peripherallymphadenopathy are described.

2. In each instance node enlargement was thought to be due to leukemicinfiltration rather than a supervenient lymphomatous process.

3. Marked adenopathy is an unfavorable prognostic sign in CML, particularly if caused by myeloblastic infiltration. Such infiltration can precede myeloblastic involvement of the peripheral blood and bone marrow.

4. Karyotype analysis and touch preparations of extramedullary tumor tissuein CML will aid in accurate diagnosis and may help to answer more basicquestions regarding the pathogenesis of this malignancy.

Submitted on July 5, 1966 Accepted on October 13, 1966     

Leukocyte Lysozyme Activity in Myelocytic Leukemia

Leukocyte and serum lysozyme activity was determined in nine patientswith acute myeloblastic or chronic myelocytic leukemia and in 20 normalcontrol subjects. Biochemical assay and quantitative estimation of leukocytelysozyme activity in the patients demonstrated a parallel in general betweenthe maturity of the granulocytes and their lysozyme content. Such determinations appear to provide a quantitative index of the extent of the leukemicprocess in the peripheral granulocytes and therefore should be of value as aguide to prognosis in these disorders.

Submitted on February 7, 1967 Accepted on April 21, 1967     

Daunorubicin Metabolism in Acute Myelocytic Leukemia

Daunorubicin reductase is a cytoplasmic enzyme that converts daunorubicin to a principal metabolite, daunorubicinol, in the presence of NADPH.This enzyme, found in mammalian tissues and studied in rat tissue preparations and normal human blood components, is also present in humanleukemic myeloblasts. The enzymesfrom both normal and leukemic leukocytes require NADPH for activity, havesimilar kinetics and substrate saturation characteristics, and have a K_m, of1.7 x 10^-4 M. When daunorubicin reductase levels in leukemic myeloblastsare related to the clinical response todaunorubicin therapy, we find that patients with a high enzyme level respond favorably to daunorubicin therapy with either a complete or partialremission, whereas those patients witha lower enzyme level experience eitherno response or die during therapy.These observations suggest that thelevel of daunorubicin reductase in theleukemic myeloblast may be importantin determining the susceptibility ofthat cell to daunorubicin. Moreover,the measurement of daunorubicin reductase level may have prognosticvalue regarding the clinical responseto daunorubicin therapy.

Submitted on August 19, 1971 Revised on October 7, 1971 Accepted on November 8, 1971     

Peripheral Leukocyte Kinetic Studies of Acute Leukemia in Relapse and Remission and Chronic Myelocytic Leukemia in Blastic Crisis

Peripheral blood leukocyte dynamics were investigated in a group of patientswith acute leukemia both in relapse and remission and in chronic granulocyticleukemia in blastic crisis. In acute leukemia in relapse and in chronic granulocytic leukemia in blastic crisis, labeled blast cells appeared promptly with apeak at one to two days. Secondary peaks occurred 40-70 hours following thefirst peaks with labeled blasts usually the predominant labeled cell in bothpeaks. The time interval between these successive waves of labeled blastscould represent a generation time. The leukocyte specific activity patterns obtained in patients in blastic crisis resembled some of the patterns of patientswith acute leukemia.

The leukocyte kinetic patterns in patients with acute leukemia consideredto be in complete remission were usually normal. However, in some patientsin bone marrow remission only, an abnormal early peak was present usuallycomposed of labeled abnormal cells released early into the peripheral circulation. In the presence of a known leukemic infiltrate, alteration of the normalleukocyte kinetic curve apparently depended upon release of these leukemiccells into the circulating blood.

Submitted on August 29, 1967 Accepted on November 8, 1967     

Leukocyte Transfusions: Function of Transfused Granulocytes from Donors with Chronic Myelocytic Leukemia

The in vivo function of chronic myelocytic leukemia (CML) leukocytes transfused into infected patients with severeneutropenia was evaluated and the results in four representative patients arereported. The intravascular survival, extravascular migration, and phagocyticcapacity of these cells appeared normalin two patients without preformed leukoagglutinins. In two other patients whohad only small transient increments incirculating granulocytes and severe transfusion reactions, preformed leukoagglutinins were found. The poor granulocyterecoveries in these patients with antibodycould probably be explained by splenicsequestration of the transfused cells.These studies provide evidence supporting the use of CML leukocyte transfusions in patients without preformedleukocyte antibodies.

Submitted on March 25, 1970 Revised on May 1, 1970 Accepted on May 8, 1970     

Busulfan in the Treatment of Chronic Myelocytic Leukemia. The Effect of Long Term Intermittent Therapy

1. The observations made during the administration of 114 courses of busulfan to 30 patients over a period of seven years are recorded. The responses toinitial courses of therapy corresponded with those reported previously. Withrepeated courses of therapy, subjective improvement, the decline in thenumber of leukocytes, decrease of anemia and the subsidence of physicalsigns of the disease were as satisfactory as during the first course but tendedto appear later. Patients were ambulatory and most were symptomatically andobjectively improved during and after repeated courses as compared to theirstatus beforehand.

2. Remissions were longest when the leukocyte values were 10,000 per cu.mm., or less, at the time busulfan was discontinued. Among such patients,remissions of six months or longer were seen in 85 per cent after the initialcourse of busulfan but in only 19 per cent after fifth or later courses.

3. Evidence of partial resistance to busulfan was seen in some cases aftermultiple courses of treatment. Complete resistance occurred in 15 patients upondevelopment of the acute, myeloblastic phase of chronic myelocytic leukemia.When busulfan failed, 6-mercaptopurine and colcemide were temporarily ofvalue; x-ray was not of benefit. After the onset of the acute phase. the mediansurvival was three months. This mode of termination is probably no morefrequent (50 per cent of cases) since the advent of busulfan therapy thanbefore.

4. If anemia was not relieved, or a large spleen was not reduced 50 per centin size following a course of therapy, the prognosis was poor and the acutephase imminent.

5. Thrombocytopenia in early, untreated cases was not necessarily a badsign, nor was the use of busulfan precluded because of it. However, whenthrombocytopenia appeared in a previously treated patient, without otherevidence indicating busulfan toxicity, or when it occurred in a patient withthree or more years of known disease, it usually presaged the development ofthe terminal acute phase.

6. Side effects of busulfan were significant in only one patient; this manreceived 8 milligrams daily, double the usual dose, for eight months anddeveloped glossitis, anhydrosis and alopecia totalis. The major hazard in theuse of the drug was the occurrence of pancytopenia. This could be related toexcessive dosage.

7. Morbidity was clearly decreased. Longevity (median 42 months) wasgreater than in Minot’s untreated cases (median 31 months) and at least asgreat as that achieved by treatment with radioactive phosphorus and x-ray(median 32-41 months). Repeated courses of busulfan are considered to offeran effective and practical palliative form of therapy for chronic myclocyticleukemia, up to the time of appearance of the terminal acute myeloblasticphase.

Submitted on August 29, 1960 Accepted on October 15, 1960     

Leukocyte Labeling With 51Chromium. II. Leukocyte Kinetics in Chronic Myelocytic Leukemia

Sequential or simultaneous leukocytekinetic studies using radioactive diisopropylfluorophosphate and radiochromate (⁵¹Cr) yielded similar or identicalblood leukocyte disappearance curvesin seven patients with chronic myelocytic leukemia (CML). Body surface⁵¹Cr counting regularly showed a risein the spleen counting rate during thefirst hours after infusions of granulocytepopulations of mixed maturity. Epinephrine-induced leukocytosis was associated with a fall in the spleen countingrate, lesser decreases over the liver andmarrow, rises in the heart and lungcounting rates, and an unchanged bloodleukocyte disappearance curve. Thesechanges are consistent with the mobilization by epinephrine of a marginalgranulocyte pool (MGP), which is largely localized in the spleen and is in equilibrium with the circulating pool. Immature CML granulocyte fractions werecleared from the blood more rapidlythan mixed cell populations. The immature cells failed to equilibrate withthe splenic MGP, and instead accumulated in the marrow and later recirculated into the blood as mature cells.These findings indicate that the delayedand variably contoured blood granulocyte disappearance curves found inCML are composites resulting from therecirculation of immature granulocytesin the presence of an enlarged totalblood pool of mature cells.

Submitted on January 4, 1971 Revised on March 11, 1971 Accepted on March 26, 1971     

Serial In Vitro Marrow Culture in Acute Myelocytic Leukemia

The in vitro granulocyte colony-formingability of bone marrow from 19 patientswith acute myelocytic leukemia (AML) wasstudied at the time of initial diagnosis andserially. Initially 18 of the 19 patients grewscant numbers of colonies, one producedlarge numbers of colonies. When clinicalremission was attained and leukemic blastsin the marrow were reduced to <5%, colonyforming ability usually returned to normal.Eight such patients who achieved clinicalremission were serially studied during remission. Normal in vitro colony formationensued in five of the eight patients studied.Three patients did not produce normalnumbers of colonies, and it was noted thatthese patients relapsed within 2 mo. Therepeated observation of normal numbers ofgranulocyte colonies appears to distinguishpatients whose remissions are stable fromthose patients who relapse quickly.

Submitted on September 28, 1972 Revised on May 4, 1973 Accepted on May 7, 1973     

粒系白血病细胞核仁组成区变化的初步研究

作者应用AgNOR染色技术,对41例急性粒细胞白血病、慢性粒细胞白血病及正常骨髓组织内幼稚粒细胞核内NOR颗粒的数量进行观察和对比分析。结果表明,正常组(N组8.01±0.36)、急粒组(AML组14、69±0.40)及侵粒组(CML组11.68±0.53)三者之间相互比较,差异均有极显著性意义(P<0.001)。提示AgNOR技术不仅是一个了解白血病细胞周期的简便易行的有效手段,而且可能是一个白血病辅助定量诊断的新方法。