Search

A case of acute undifferentiated myelocytic leukemic with trisomy 4 is described. The patient is a 61-year-old woman who developed leukemia 4 1 2 years after receiving radiation therapy for uterine carcinoma. Many leukemic cells exhibited hand-mirror configuration after the bone marrow aspirate was left at room temperature overnight. The relationship between trisomy 4 and hand-mirror cells in acute myelocytic leukemia is unknown.

Serum from 21 patients with lymphoblastic leukemia, five with myeloblastic leukemia and 30 age matched control subjects tested for thymic hormone activity in an assay that measures the induction of T cell surface antigen. This activity was subnormal in serum from 10 of 16 patients with untreated lymphoblastic leukemia (p less than 0.001) but was within the normal range when the leukemia was in remission. Low inductive activity was associated with an inhibitor of T cell induction which was less than 30,000 daltons in molecular size and interfered with induction by purified thymopoietin plus a high concentration of ubiquitin or by normal serum alone.

The relation between the quantified French-American-British cooperative study (FAB) classification and presenting features was studied in 123 adult patients (greater than or equal to 15 years) with acute myeloid leukemia. Myeloblastic leukemia with maturation (M2) patients with a high maturation index (M2a) were older, compared to the other myeloblastic subgroups, while promyelocytic leukemia (M3) patients were younger than those with M2 or M2a. Differences between various leukemia types were found in the occurrence of a preceding myelodysplastic syndrome, leukocyte count, and platelet count. In both monoblastic leukemia (M5) and myeloblastic leukemia (M1-3) a smaller degree of maturation seemed to be related to a larger tumor mass. The effect of chemotherapy was analyzed in a group of 64 patients. Comparison between immature (M1) and more mature (M2) myeloblastic leukemia suggested a longer duration of first complete remission and a longer survival in M2. The findings of this study may imply that the degree of maturation determines tumor mass and the success of chemotherapy.

A large dose of equine antilymphocytic globulin (ALG, 120 mg/kg/day) was given intravenously to four patients with myeloblastic leukemia. Leukemic myeloblasts from each patient were lysed by the ALG in vitro, in the presence of the same patient's serum complement. In each patient, ALG infusion was followed by a reduction in the count of circulating leukemic myeloblasts, and a fall in the serum levels of C3 and C4 complement. It is likely that complement-mediated lysis of circulating leukemic myeloblasts occurred in these patients, as a result of ALG administration.

Three-hundred and ninety-nine patients with acute leukemia examined during the period 1947-1964 were divided into three sequential series and their survival, from diagnosis to death, was compared. A statistically significant increase in duration of survival for myeloblastic leukemia from a median of 2 to 5 months occurred between series I and series III. This is the first convincing evidence that 6-mercaptopurine therapy influences survival in myeloblastic leukemia. A steady increase in median survival of patients with lymphoblastic leukemia from 4 to 8 to 12 months was found in the three series. The results of analysis of these series are compared to other reported series. The hypothesis —that the longer survivals reported for patients treated in hematology clinics compared to that of patients selected from population areas reflects patient selection—was examined and appeared unlikely.

The longevity, reckoned from the symptomatic onset of acute leukemia as well as from the initiation of treatment, of a group of 89 cases including children and adults, treated in this clinic since March, 1954, was found to exceed that of a similar group of 78 patients treated in preceding years in the same clinic. The median survival of all cases considered as a unit was increased from three to six months, as measured from the date treatment was begun. The change was found to be statistically significant as well as clinically important. The longer survival found in the 1954-57 series correlated with the greater use of three, rather than only two, chemotherapeutic agents. On analysis, improved survival was statistically proven only for individuals with lymphoblastic leukemia; for these, the median survival was 10 months after the symptomatic onset of leukemia and 7½ months after the start of treatment. Within this group, there was an even greater improvement for those whose leukocyte values immediately prior to the initiation of therapy were less than 10,000 per cu.mm.; half of these patients lived more than 12 months after treatment was begun. The reason for the exceptional longevity of patients with the lower pre-treatment leukocyte values is unknown. It appears that one can attribute at least part of the improvement to therapy. The type of statistical analysis used presents the minimum figures for improvement in median survival. When the ultimate longevity is known for the 17 per cent of the cases surviving at the closing date of the study an additional small increment may be found. The relative inefficacy of chemotherapy in myeloblastic leukemia should be a signal for greater screening of new agents in this type of tumor.

A case with a prolonged period of blood disorder preceding the terminal development of myeloblastic leukemia is reported in some detail. The preleukemic period was characterized by anemia, neutropenia and thrombocytopenia. It extended over a period of almost nine years but was punctuated by a period of remission lasting four and one half years. In the initial phase, the marrow was hypoplastic but during the later stages, it was hyperplastic. Brief reference is made to somewhat similar cases that have been recorded and to the ideas expressed by the authors of these reports. It is suggested that further investigation is needed to determine whether the initial blood disease occurring in such cases is irrevocably linked to the subsequent leukemia.

Four cases of severe refractory anemia with an enormous increase of demonstrable free iron in the normoblasts are reported. Three cases were of unknown etiology and of benign course but in the fourth the anemia was probably related to rheumatoid arthritis or to the onset of myeloblastic leukemia. The significance of the sideroblastic bone marrow in these cases is discussed and the opinion expressed in the literature—that it indicates a defect in hemoglobin synthesis is subscribed to. Thus, it is believed that the anemia in these cases is due to degenerative changes in the bone marrow which also have some morphologic manifestations. The disturbance of marrow activity is probably best reflected in the reticulocyte counts.

A detailed study (phase contrast, bright field and electron microscopy) of the primitive leukemic cells from a patient with atypical myeloblastic leukemia has been presented. An unusual mucopolysaccharide-containing vacuole has been observed and characterized both morphologically and histochemically. In addition, this study has yielded considerable information concerning the structure and chemical composition of the fibrillar formations, fat droplets and the alterations in erythrocytes following their ingestion by the leukemic cells. Intramitochondrial structural alterations have been observed and characterized in many of the primitive myeloblasts. Changes in the mitochondria and endoplasmic reticulum may reflect impaired or altered metabolism in these abnormal leukemic cells.

A 63 year old Caucasian woman presented with myeloblastic leukemia and a hyperdiploid C group chromosome change in 10 per cent of marrow metaphases. Treatment with cytotoxic agents resulted in an increased percentage (52 per cent) of these hyperdiploid marrow cells. Furthermore, the marrow continued to show leukemic features morphologically and in culture. Despite the indications of persistence or progression of the hyperdiploid, putatively leukemic line at cessation of chemotherapy and for a period of time thereafter, remission was achieved and blood and marrow cell numbers one year after cessation of all treatment are normal. The hyperdiploid line is no longer detectable. This case raises questions concerning the mechanism whereby remission is attained in some cases of acute leukemia and is discussed in terms of the restoration of normal hemopoiesis eliminating the leukemic process.

A patient with coexistent Gaucher disease and Philadelphia positive chronic granulocytic leukemia (CGL), who subsequently developed myeloblastic leukemia, is described. The diagnosis of CGL was established according to standard clinical, morphological, biochemical, and cytogenetic data, while the diagnosis of true Gaucher disease was based on biochemical data and the presence of Gaucher cells with typical ultrastructural features in the bone marrow and spleen. Enzyme studies showed low activity of ceramide-β-glucosidase in the patient's peripheral blood leukocytes, skin fibroblasts, and splenic tissue and the presence of increased amounts of ceramide-β-glucoside in the spleen. This case is reported in order to draw attention to the possible coexistence of these two diseases in the same patient, as opposed to the well-recognized finding of “Gaucher-like” cells in the bone marrow of patients with CGL. Enzyme studies enable distinction between these two situations.

A PATHOGENIC relation between aplastic anemia and myeloblastic leukemia has long been suspected. It is well known that certain agents capable of producing aplastic anemia in man can also induce leukemia. Prime examples are benzene1 , 2 and irradiation.3 , 4 In addition, cases of leukemia developing during the course of hereditary hypoplastic syndromes have been recorded.5 , 6 The broad-spectrum antibiotic chloramphenicol7 8 9 has become the most commonly cited cause of acquired aplastic anemia. To date, only 1 case report of acute myeloblastic leukemia following aplasia secondary to chloramphenicol administration has been published.10 The purpose of this communication is to present 2 additional cases of chloramphenicol-induced . . .

SummarySerial suspension cell cultures have been established from the peripheral blood of 3 out of 3 patients with high-count acute lymphoblastic or myeloblastic leukemia. A period of latency from 4 to 10 weeks, during which the cultures were regularly refed, preceded the start of multiplication. The techniques for initiation and maintenance of the cultures are described as well as observations made during these procedures. Preliminary attempts at virus isolation from all of the cultures were negative. Evidence suggesting a possible latent virus infection in one of the serial cultures is presented.

SURVIVAL in myeloblastic leukemia of adults has not appreciably changed since the advent of chemotherapy. As pointed out by Gunz et al.,1 the progress of the disease may be quite variable, but it usually follows a rapidly downhill course, with death ensuing within several weeks to months. A few patients, however, may live in apparent symbiosis with their disease for periods of up to several years. These cases, unfortunately, are uncommon. Recently, several reports have appeared suggesting that aggressive chemotherapy with combinations of agents may prolong life in this disease.2 3 4 To evaluate these studies in the light of our own . . .