Search

Purified populations of T and B cells were obtained from individuals with chronic lymphocytic leukemia (CLL) by the use of anti-F(ab′) 2 affinity column chromatography techniques in which twice the amount of column material used for normal separations was used for the separation of Ig − and Ig + cells from CLL patients. Furthermore, the flow rate was reduced in order to decrease the possibility that some B cells from CLL patients, containing a low density of surface Ig, would pass through without binding to the coupled Sephadex G-200. Examination of surface Ig, P23,30 antigens, and T-cell antigens in the separated populations indicated that both the Ig − and Ig + populations were highly enriched. These T cells were also tested for their response to mitogenic stimulation as well as their ability to cooperate with leukemic B cells, normal B cells, or B cells from a transformed B-cell line. T cells from leukemic patients were found to be significantly deficient in both the response to mitogens and ability to cooperate with B cells in the synthesis and secretion of immunoglobulin.

The toxicity of MOPP chemotherapy, including nausea, vomiting, hair loss, and neuropathy, can limit patient compliance. Alternative regimens employing oral alkylating agents and vinblastine have been designed to ameliorate these toxicities. The authors reviewed their experience in 24 patients with advanced-stage Hodgkin's disease who were treated with chlorambucil, vinblastine, procarbazine, and prednisone (ChlVPP). Complete responses were obtained in 92% (11/12) of previously untreated patients and in 92% (11/12) of patients who relapsed after radiation (10/10) or chemotherapy (one of two). Overall, relapse-free survival is 82% with a median duration of follow-up of 5.5 years. Toxicity was minimal with myelo-suppression being the dose-limiting toxicity. Severe nausea and vomiting occurred in only two patients and was considered secondary to procarbazine. Mild nausea occurred in six other patients. Minimal alopecia was seen in three patients and only two patients developed a mild peripheral neuropathy. The authors conclude that ChlVPP appears as effective as MOPP chemotherapy for Hodgkin's disease in comparable presentations but is a less toxic regimen. Thus, it may be useful in situations where poor compliance and patient acceptance may compromise optimal dose and frequency of drug administration.

Intracellular lysozyme (muramidase) was detected by both indirect and direct immunofluorescent microscopy in human and rat leukocytes by labeling methanol-fixed cells with the globulin fraction of immune rabbit serum prepared against the homologous lysozyme. Normal human polymorphonuclear leukocytes (PMNLs), monocytes, and cells from patients with chronic myelogenous leukemia, acute myelogenous leukemia, and acute monomyelogenous leukemia were lysozyme positive, while lymphocytes, basophils, eosinophils, and cells from patients with acute lymphatic leukemia were negative. Similarly, normal rat PMNLs, monocytes, and cells from three transplantable rat myelogenous leukemias were positive in the rat lysozyme assay, while normal rat lymphocytes and spontaneous acute mononuclear cell leukemias of two inbred strains were negative. By labeling viable cells with the purified F(ab1)2 fragment of anti-human lysozyme immunoglobulin, lysozyme could be detected on the surface of cells and surface-lysozyme-positive cells could be separated from other human bone marrow leukocytes using a fluorescence activated cell sorter. Lysozyme appears to be a potentially valuable cell-surface marker for identification and separation of myeloid, monocytic, and histiocytic cells.

This article reviews the clinical manifestations, diagnostic criteria, and treatment strategies for the acute leukemias, the myelodysplastic syndrome, Hodgkin's disease, and the non-Hodgkin's lymphomas in the elderly. These are relatively common diseases in the elderly, and age is traditionally thought to be a bad prognostic sign. The treatment of these diseases is more difficult in the elderly, but careful attention to concomitant underlying illness and general physical condition and the natural history of the diseases can result in very successful management of otherwise lethal disorders.

We performed a phase I/II study of the administration of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) to patients with aplastic anemia or myelodysplastic syndrome. Doses ranging from 15 to 480 micrograms/m2 were administered as a one-hour or four-hour intravenous infusion daily for 7 days or as a 12-hour infusion for 14 days. Temporary improvements were seen in granulocyte counts, monocyte counts, and reticulocyte counts in six of eight patients with aplastic anemia and five of seven patients with myelodysplastic syndromes. The patients with myelodysplastic syndromes had larger increases in granulocyte, monocyte, and reticulocyte counts than did those with aplastic anemia, and they also had increases in the numbers of eosinophils (two of seven), immature myeloid cells (two of seven), and myeloblasts (two of seven) that were not observed in patients with aplastic anemia. There was no reduction in erythrocyte transfusion requirements, and no effect was observed on platelet counts. There was only minimal toxicity consisting of transient low- back discomfort, anorexia, myalgias/arthralgias, and low-grade fever. Our data suggest that GM-CSF is well tolerated and is more likely to result in elevations of blood counts in patients with myelodysplasia than in patients with aplastic anemia, but the role of GM-CSF therapy in these disorders remains to be determined.

Thirty-four patients with acute promyelocytic leukemia (APL) (median age 37 years, range 20 to 69 years) received induction treatment between 1974 and 1985 with cytosine arabinoside (ara-C) and an anthracycline. Bone marrow hypercellularity was present at the time of diagnosis in all patients, although the median peripheral leukocyte count was 2,600/microL. A second course of induction therapy consisting of further ara-C and anthracycline was initiated 15 days after the start of treatment if bone marrow hypocellularity could not be documented. Karyotypic analysis of bone marrow blasts was performed on 15 of 34 patients; 11 of 15 had abnormalities in chromosomes 15 and/or 17. Twenty-nine of 34 (85%) patients had laboratory evidence of disseminated intravascular coagulopathy. Of the 29 patients surviving 14 days, 24 (83%) received a second course of induction therapy. Complete remission was achieved in 25 of 34 (74%) patients, with four of 25 (16%) requiring one course of induction chemotherapy and 21 of 25 (84%) receiving two courses. Bone marrow specimens obtained 15 days after the start of therapy from the 25 patients who eventually attained complete remission showed the continued presence of dysplastic promyelocytes in 21 cases; three specimens were technically inadequate and only one was truly devoid of promyelocytes. Seventeen of 25 (68%) patients still had persistence of abnormal bone marrow promyelocytes seven or more days after the second course of therapy. Patients in complete remission received various forms of postremission therapy. Ten of the 25 (40%) completely responding patients remain alive in continuous complete remission. Neither the absence of bone marrow hypocellularity nor the persistence of dysplastic promyelocytes during induction exerted any influence on the probability for survival. These findings confirm and extend prior reports that complete remission in APL, in contrast to other subtypes of acute nonlymphocytic leukemia (ANLL), can frequently be achieved without bone marrow aplasia. Whether this observation signifies that complete remission in APL is due to leukemic cell differentiation or selective cytotoxicity is unknown. The absence of therapy-induced bone marrow hypoplasia in APL is not an absolute indication of induction failure or a poor ultimate prognosis.

A new human megakaryocytic cell line (Dami) has been established from the blood of a patient with megakaryoblastic leukemia. The Dami cells grow primarily in suspension with a doubling time of 24 to 30 hours. By light and electron microscopy, the Dami cells range in size from 12 to 120 micron in diameter and have lobulated nuclei characteristic of megakaryocytes. At least 89% of the cells react with monoclonal antibodies against platelet glycoproteins (GP) Ib and IIB/IIIa, and glycophorin. The cells do not react with antibodies against lymphoid, monocyte, granulocyte, or macrophage antigens. Thirteen percent of the cells become polyploid, spontaneously achieving greater than 4N DNA ploidy levels. In response to phorbol myristate acetate (PMA), the proportion of cells with ploidy levels greater than 4N increased threefold and could be separated into discrete ploidy groups. PMA also increased the expression of GPIb, the GPIIb/GPIIIa complex,l and von Willebrand factor. Cytogenetic analysis revealed a human male hyperdiploid karyotype with a modal chromosome number of 54 to 64 and several consistent clonal chromosomal abnormalities. These included a partial deletion of chromosome 5 and a translocation involving chromosome 3. In contrast to other megakaryocytic cell lines in which only a small portion of the cells express the megakaryocytic phenotype, nearly all of the Dami cells express platelet glycoproteins. Thus, the Dami cells provide a superior model in which to study human megakaryocyte biochemistry and differentiation.

The use of Hodgkin's disease as a model for the evaluation and management of the non-Hodgkin's lymphomas may not be appropriate. This latter group of different syndromes and diseases differs significantly in their clinical presentation from each other as well as from Hodgkin's disease. Survival must be separated from relapse-free survival since the latter is a measure of the effectiveness of any individual therapy being applied. Localized nodal lymphoma is uncommon, but important to identify since it is potentially curable by irradiation. Stage I nodular, non-histiocytic lymphomas treated by radiation results in significant, extended, relapse-free survival. All other localized nodal lymphoma is associated with a high proportion of patients relapsing outside the treatment portal. Whole body irradiation is a useful systemic agent causing regression for an extended period of time in stage III or stage IV nodular lymphoma. Chemotherapy seems to have a limited value in nodular lymphomas, with no clear evidence that combination chemotherapy is more effective than single agents. In diffuse lymphomas, aggressive chemotherapy shows more promise, with diffuse histiocytic lymphoma having extended relapse-free survival.

A 68-yr-old male with chronic lymphocytic leukemia (CLL) presented with splenomegaly and skin infiltration but no lymphadenopathy. The peripheral blood WBC cound was 300 x 10(9)/liter, with 95% small mature- appearing lymphocytes that were E-rosette positive and EAC-rosette negative. Further characterization of the patient's cells was performed using antisera with known lymphoid sub-population specificity. Anti- p23,30, which reacts with normal circulating B cells but not with T cells or thymocytes, was unreactive with the patient's cells. Anti-311, which reacts with both thymocytes and circulating T cells, was reactive with the patient's cells. Anti-Bk, which reacts only with thymocytes and not with circulating T-cells, failed to react with the patient's cells. The enzyme terminal deoxynucleotidyl transferase, present in thymocytes but absent for circulating T-cells, was also absent from the patient's lymphoid cells. Multimarker analysis therefore showed a mature T-lymphocyte phenotype on this patient's leukemia cells. Further functional analysis will probably show that such cells represent clonal expansion of a mature T-cell subpopulation, analogous to the B-cell clonality of common-variant CLL.

A series of monoclonal antibodies reactive with normal myeloid cells at different stages of differentiation (anti-MY4, -MY7, -MY8, -Mo1, -Ia) were used to characterize the leukemic cells of 70 patients with acute myeloblastic leukemia (AML). Sixty-two of the leukemias expressed a phenotype corresponding to a recognizable immature normal myeloid cell. These 62 cases could be divided into 4 phenotype groups, corresponding approximately to the normal CFU-C (group I, 21%), myeloblast (group II, 26%), promyelocyte (group III, 8%), and promonocyte (group IV, 45%). Morphological subtyping of these leukemias tended to agree with the immunologic phenotype, particularly with more “differentiated” morphological subtypes, such as acute monocytic leukemia or acute promyelocytic leukemia. However, each phenotype group contained more than one morphological type of AML, indicating that the level of differentiation of the surface membrane of AML cells may not always be concordant with morphology. The phenotype groups were also analyzed with respect to cytochemical staining patterns, age, the presence of Auer rods, and complete remission rates. Statistically significant differences among the groups were noted in the distribution of myeloperoxidase staining, nonspecific esterase staining, and Auer rods. The complete remission rates varied from 60% (groups III and IV) to 88% (group II). These results suggest that surface marker analysis in AML may be used as a highly reproducible classification system that will provide additional information about the leukemic cells in conjunction with morphological analysis.

Presentation of Case A 68-year-old woman was admitted to the hospital because of lymphadenopathy. Her health was good until 17 years earlier, when her mouth became dry and the right parotid gland b...

Summary1. Greatly elevated serum and urine muramidase levels were observed in rats with transplanted chloroleukemia. 2. In one chloroleukemic rat with ascites, the fluid had a very high muramidase content. 3. Homogenates of chloroma cells consisting of myeloblasts and promyelocytes had very high muramidase activity. 4. In rats with acute mononuclear cell leukemia, no significant elevation of serum or urinary muramidase activity was noted, suggesting rat mononuclear leukemia is not myelogenous or monocytic in origin.

The effect of mantle irradiation therapy for Hodgkin's disease on physiologic indices of pulmonary function including lung volume, flow rates, and diffusing capacity was monitored serially in 11 patients. Lung volumes including total lung capacity (TLC) and inspiratory capacity (IC) were maximally affected at nine months but returned toward normal by 24 months. Diffusing capacity was reduced prior to radiotherapy and decreased further following treatment in more than 50% of patients. Patients with intrathoracic Hodgkin's disease had lower initial pulmonary indices which improved with tumor resolution on radiotherapy, and patients without intrathoracic disease had a comparatively greater decrease in pulmonary function following irradiation, but this was transient and recoverable.

Has the outlook for patients with multiple myeloma changed in recent years? Not much. This paper compares 81 patients followed from 1954 to 1960 with 61 patients seen from 1960 to 1967. Most of the first group received urethane, while later patients were given such agents as melphalan and cyclophosphamide. Although more patients temporarily improved on newer drugs, survival rates stayed about the same.

A small group of patients (22) with metastatic breast cancer, most of whom had advanced visceral disease, have been treated since 1973 with low-dose, multiple-drug chemotherapy: vinblastine, 0.05 mg/kg, I.V.; cyclophosphamide, 6 mg/kg P.O.; 5-fluorouracil, 500 mg. P.O., and methotrexate, 0.3 mg/kg P.O. The schedule includes the use of one drug on each of four days every week. The drugs were taken in the sequence listed on alternate days, except that dosages of methotrexate and vinblastine were consecutive. The remission rate was 68% (15/22). The median duration of remission was 30 months. The median survival time of responding patients exceeds 40 months. Of the 15 responding patients, six (40%) remain alive with a mean survival time of more than 46 months. The regimen causes minimal toxicity and has been willingly accepted by patients for as long a period as 54 months. A therapeutic advantage appears to have been achieved by this high-frequency, low-dose schedule.

A chemotherapy program used over the past 18 months in 23 previously untreated cases of adult acute granulocytic leukemia consisted of vincristine, cytosine arabinoside and daunorubicin administered over a period of three to six days. Complete remissions were attained in 55 per cent of cases. Survival time among 11 patients achieving complete remission averaged 11 months, with six patients still alive. Although efforts to maintain remission were unsuccessful, retreatment with a full course of the combined drug program reinduced complete remission in five of seven attempts. The short induction period and relatively high remission rate encourages more extensive trials with this combined chemotherapy program.

To determine the value of gallium-67 single photon emission computed tomography (SPECT) in imaging patients with lymphoma, the authors compared Ga-67 planar images and SPECT images in 40 consecutive patients, using radiologic examinations and/or medical records to confirm the presence or absence of disease. Thirty-three patients had Hodgkin disease, and seven had non-Hodgkin lymphoma. Fifty-four examinations were performed. Of 57 sites of lymphoma in the chest, planar imaging depicted 38, while SPECT depicted 55, resulting in sensitivities of 0.66 and 0.96 for planar and SPECT imaging, respectively. In eight sites, both modalities were truly negative, but SPECT was negative in four additional sites that were equivocal on planar imaging, resulting in specificities of 0.66 and 1.00 for planar and SPECT imaging, respectively. In the abdomen, the sensitivities of planar and SPECT imaging were 0.69 and 0.85, and the specificities 0.87 and 1.00, respectively. SPECT was more accurate in depicting foci of gallium-avid lymphoma in the chest and abdomen and in excluding disease when planar imaging was equivocal.

One hundred twenty-one patients with diffuse large-cell lymphoma treated with m- or M-BACOD (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone) were evaluated for pretreatment characteristics predictive for response and survival. Two characteristics, poor performance status and massive bulky disease, were negatively associated with response rate in a multivariate analysis. These two characteristics were also negatively associated with survival in multivariate analysis, as was another factor, an increased number of extranodal sites of disease. These three pretreatment characteristics were used to construct a model containing 12 categories of patients at increasing risk for relapse and shortened survival. These categories divided naturally into three broad groups of patients with respective 5-year survival rates of 68%, 55%, and 24%.

A total of 464 pathologically staged IA through IIIB Hodgkin's disease patients were evaluated for the risk of developing acute nonlymphocytic leukemia, non-Hodgkin's lymphoma, or a fatal infection after treatment with radiation therapy (RT) alone, initial combined radiation therapy and chemotherapy (CMT), or RT with MOPP administered at relapse. Patients received a standard six cycles of MOPP, and additional maintenance chemotherapy was not administered. Patients receiving total nodal irradiation (TNI) and MOPP chemotherapy have an 11.9% actuarial risk of developing a fatal complication at ten years, as compared to a 0.8% risk for lesser field irradiation and MOPP (P = .005). The risk with RT alone is 0.6%. Patients 40 years of age or older have a greater risk for complications. These data report a low risk for fatal complication with CMT when less than TNI is administered and when maintenance chemotherapy is not used.

In a series of 306 cases of myeloproliferative disorders followed over a period of 21 years, 18 cases of well-documented acute leukaemia were encountered. Leukaemias were either acute myeloblastic or myelomonocytic and occurred from 6 months to 20 years after the initial diagnosis. Onset was relatively abrupt and the course rapidly fatal with with a median survival of 4 weeks. Due to the prolonged preleukaemic phase, it was possible to carry out a variety of clinical and laboratory observations. While no consistent features were noted, dysplastic haemopoiesis, a fall in leucocyte alkaline phosphatase activity, presence of Pelger-Huet anomaly and other abnormalities suggest a disturbance in granulocytic maturation. These findings suggest that, following an initial injury to a pleuripotential haemopoietic stem cell, a prolonged 'latent' period occurs and, due to exposure to additional injurious agents or to a lack of cell regulating factors, acute leukaemia develops.

In a large series of patients with myeloid metaplasia seen over 8 years, 25 required treatment for painful splenomegaly. Splenectomy was contra-indicated in fourteen of the patients who received 21 courses of megavoltage splenic irradiation as alternative management. The dose required for long-term palliative effect was usually low, i.e. median dose 600 rad in 9 fractions. Spleen enlargement prior to treatment ranged from 2 cm to 20 cm below the costal margin. All 21 treatments produced palliation of pain and 20 (95%) resulted in reduction of spleen size: 6 complete (28%) and 14 partial (67%) responses lasted from 1 to over 73 months, and in 4 patients, over 24 months. No serious hematologic side effects were encountered. Splenic irradiation in myeloid metaplasia has been reported to be hazardous; however, our experience indicates that cautious irradiation can be a safe and useful therapeutic alternative.

Thirteen relapses occurred among 51 consecutive surgically staged patients with I, IIA, and IIIA Hodgkin disease who achieved complete remission following extended-field radiotherapy. The median disease-free interval was 14 months, but three disseminated relapses occurred at 36, 36, and 39 months. In 6 of the 13 cases, relapses occurred within treated fields. Relapse frequency was greater with advancing stage, but was not related to histology. In 9 of 12 evaluable cases the patients achieved complete remission with MOPP1 combination chemotherapy. All responders continue in complete remission a median time of 23 months after completing MOPP. This report emphasizes the need for sustained, close follow-up after radical radiotherapy and the excellent response rate of relapsed patients to MOPP combination chemotherapy.

During the past decade, the combination of an anthracycline and continuous infusion cytosine arabinoside chemotherapy has been associated with an increase in the complete response rate of patients under age 60 having acute myelocytic leukemia (AML) from 35%-55% (Carey et al. 1975; Clarkson et al. 1975) to approximately 75% (Evans et al. 1975; Gale 1979; Haghbin et al. 1977; Preisler et al. 1979; Rees and Hayhoe 1978; Yates et al. 1973). This encouraging advance, however, has not led to prolonged periods of remission and indefinite survival as seen in childhood acute lymphocytic leukemia. The median duration of complete remission in most recent studies in AML is in the range of 12-14 months (Armitage and Burns 1976; Evans et al. 1975; Haghbin et al. 1977; Moreno et al. 1977; Peterson and Bloomfield 1977; Preisler et al. 1979; Rees and Hayhoe 1978; Spiers et al. 1977). In early 1976 a therapeutic program (VAPA 10 protocol) was initiated in an attempt to overcome the causes of relapse in patients with AML. It was postulated that the high failure rate in AML patients in complete remission might be the result of inadequate cytoreduction during the maintenance period, the development of drug resistance, the presence of “sanctuaries” into which effective chemotherapy could not penetrate, and the presence of a mutant myeloid progenitor cell which over a period of time would progressively replace or even suppress the growth of the differentiated product of normal hematopoiesis. It was appreciated that if the latter possibility were true, it would be unlikely that intensive chemotherapy would have any longterm beneficial effect in patients with AML and that the only rational therapeutic option would be replacement of these progenitor cells through a maneuver such as bone marrow transplantion. Others are presently testing the utility of marrow transplantation in patients with AML shortly after complete remission is obtained (Blume et al. 1980; Powles et al. 1980; Thomas et al. 1979).

We designed a protocol to address the problem of relapse from complete remission in acute myelogenous leukemia. Patients in remission were treated for 14 months; early and later intensification of chemotherapy, sequential drug combinations, and high-dose continuous infusions of cytarabine were included. Eighty-three consecutive patients under 50 years of age were entered into this study from February 1976 to October 1979. The rate of complete remission is 70 per cent. A Kaplan–Meier analysis predicts that 49±17 per cent of patients (mean ±2 S.D.) who entered complete remission will remain free of disease at two years. Durations of complete remission for patients in the 0 to 17-year and 18 to 50-year age groups are comparable. (N Engl J Med. 1980; 303:473–8.)

Major progress in the treatment of AML has occurred during the past decade.1, 2 The higher complete remission rates for patients with AML can be attributed to advances in the application of chemotherapy, better supportive care, and carefully designed clinical trials. The median duration of complete remission and the percentage of patients surviving for 5 or more years has steadily improved. This has resulted from post-remission induction chemotherapy or chemoradiotherapy and transplantation of bone marrow from histocompatible donors.3–10 The intensity and duration of the postremission induction chemotherapy as well as the merits of marrow transplantation versus chemotherapy for the treatment of patients with AML in first remission have been the focus of recent clinical investigations.11–13

From 1970 to 1982, 157 consecutive patients with de novo acute nonlymphocytic leukemia (ANLL) were treated and followed by the Hematology Unit at the Brigham and Women’s Hospital, Boston, Massachusetts. It was in 1970, with the addition of cytosine arabinoside and daunorubicin, that remission induction (RI) rates significantly increased from 30% to greater than 50% [1]. During the past decade, major emphasis has been placed on an attempt to prolong disease-free survival with intensive chemotherapy programs and more recently with allogeneic and syngeneic bone marrow transplantation [2, 3]. Since 1970, we have attempted to treat our patients with more aggressive remission and maintenance consolidation (RC) programs.

Fifty consecutive patients with blastic chronic myelogenous leukemia were evaluated clinically, morphologically, biochemically, and therapeutically. Forty-five patients had a preceding stable phase (38 Ph +, 7 Ph -); five patients presented with de novo Ph+ blast crisis. The most frequent clinical signs of impending blast crisis were weakness, fatigue, increasing splenomegaly, anemia, thrombocytopenia, marrow fibrosis, and a rising neutrophil alkaline phosphatase. Fever (unrelated to infection), skin infiltration, lymphadenopathy, hepatomegaly, thrombocytosis, and basophilia were much less common. The development of aneuploidy occurred in less than one-half of the total group. Myeloblastic morphology at blastic transformation was most frequent with occasional lymphoblastic, promyelocytic, and undifferentiated cases seen. Terminal deoxynucleotidyl transferase was present in one-third of the patients, but had no clear-cut relationship to the morphology. Response to treatment was generally disappointing (two complete and 15 partial remissions in 45 treated patients).

In 50% of 84 ultrasonographic (US) examinations ordered for staging and restaging of non-Hodgkin lymphoma (NHL) patients, the abdomen and pelvis were not sufficiently visualized to allow diagnostic conclusions, whereas nondiagnostic studies were found in only 3% of the 102 computed tomographic (CT) examinations. Discrepancy about the presence and extent of disease below the diaphragm between US and CT occurred in 74%. The US underestimated the presence or extent of disease in nodal stations caudal to the pancreas more commonly than in other areas evaluated. Because of increased cost, patient inconvenience, and delay in therapeutic intervention due to repeat examinations, it is recommended that CT be used as the initial examination for staging, restaging, or following infradiaphragmatic disease in NHL patients.

The experience of one institution using abdominal computed tomography (CT) for staging and restaging of non-Hodgkin lymphoma (NHL) patients is reported. In 49% of abnormal examinations no significant difference in quantity of involved nodes between diffuse and nodular lymphomas appeared. High paraaortic, iliac, and mesenteric nodal sites were most commonly involved. At restaging examination, usually less extent of disease was found. Abdominal involvement could not be predicted from the presence of peripheral adenopathy. Computed tomography changed the staged during initial workup significantly in 14%. During restaging, CT detected unsuspected active disease in 43% and changed the clinical impression from limited to extensive involvement in 16%. Computed tomography proved to be useful in the management of NHL patients and is recommended as the primary imaging procedure in the abdomen in this disease.

Major progress in the treatment of acute myelogenous leukemia (AML) has occurred during the past decade. Advances in chemotherapy and supportive care have been associated with an increase in the complete remission rate of patients under the age of 60 with AML from 35%–55% [5, 7] to approximately 75% [2, 9, 16]. More importantly, the median duration of complete remission and the percentage of patients in long-term continuous complete remission has steadily improved. This has resulted from postinduction combination chemotherapy [10, 13, 18, 20] or chemoradiotherapy and transplantation of marrow from histocompatible siblings [4, 15, 21]. In 1976 the VAPA protocol was initiated to specifically improve the duration of complete remission for children and adults (< 50 years) with AML. In 1980 we reported encouraging results obtained with this approach [12, 22], and this report is an update of the study.

Adult patients with transfusional hemosiderosis were given ascorbic acid and treated with the iron chelator, desferrioxamine B. The drug was administered by continuous subcutaneous or intravenous infusions using a light weight portable constant infusion device. On this regimen, four of the five patients studied were able to excrete significant amounts of iron (greater than 35 mg/da) when receiving a daily desferrioxamine dose of 1.5 to 2.2 g. Continuous subcutaneous infusion was well tolerated and about 80 per cent as effective as intravenous therapy in chelating iron. The number of prior transfusions, the hepatic iron content and the serum ferritin levels appear to be useful in predicting which patients will respond to iron chelation therapy, especially if there is little bone marrow erythropoietic activity. One patient with ineffective erythropoiesis did not have significantly increased hepatic iron stores but responded to the administration of desferrioxamine. Continuous subcutaneously administered desferrioxamine may prove to be adaptable for long-term outpatient therapy, allowing patients with ongoing transfusion requirements to go into negative iron balance. Long-term studies will be needed to demonstrate reversal of endocrine, hepatic and cardiac dysfunction secondary to iron deposition in these patients.

Renal cell carcinoma with tumor thrombus extension into the inferior vena cava occurs in approximately 5 per cent of the cases. Despite invasion of the inferior vena cava an aggressive surgical approach for these neoplasms is recommended but prevention of a tumor thrombus pulmonary embolus during operation is necessary. Placement of a suprarenal Greenfield filter, with its ease of insertion, excellent late patency rates and minimal morbidity, has made it the procedure of choice today. Preoperative venacavography with radiopaque marking of the tumor thrombus will prevent filter displacement, malpositioning and the awkward use of intraoperative venography, while shortening operative time and minimizing patient risk.

SummaryThe transplanted rat chloroleukemia cytologically similar to human acute myelocytic leukemia is associated with markedly elevated serum and urinary muramidase levels. Current metabolic studies demonstrate excessive potassium loss in the urine and appears to be related to the degree of muramidasuria. The experimental myelogenous leukemia furnishes an excellent model for the investigation of the enzyme effect on the kidney and present studies suggest that muramidase causes a direct tubular damage.

The clinical significance of anatomic substage was assessed in 130 patients with Hodgkin's disease in pathologic stage III-A: stage III1-A includes involvement of spleen, or splenic, celiac, or portal nodes, or any combination of these; stage III2-A includes involvement of para-aortic, iliac, or mesenteric nodes, with or without upper abdominal involvement. Median follow-up was 58 months. Both 5-year disease-free survival, 74% versus 46%, and 5-year survival, 94% versus 65%, were better (P less than 0.001) in stage III1-A than in stage III2-A. In stage III1-A, 5-year disease-free survival was better in patients receiving radiotherapy and chemotherapy than in patients receiving radiotherapy alone as initial treatment, 96% versus 63%, P less than 0.003; however, 5-year survival rates in P = 0.22. For stage III2-A, both 5-year disease-free survival, 76% versus 32%, P less than 0.001, and 5-year survival, 84% versus 56%, P less than 0.03, were superior with radiotherapy-chemotherapy. Consideration of anatomic substage may aid therapeutic planning for stage III Hodgkin's disease.

Bone-marrow scintigraphy with indium chloride In 111 was performed on a patient with pure red blood cell aplasia before and after successful treatment with immunosuppressive drugs. The return of erythroid precursors to the bone marrow was accompanied by a substantial increase in the marrow uptake of 111 In. The distribution of 111 In in the posttreatment scan was indistinguishable from that of 52 Fe. These results indicate that indium chloride In 111 is a useful agent for the delineation of erythroid cellularity within bone marrow. ( Arch Intern Med 136:1169-1172, 1976)

Immunotherapy during the 1970s become a potential weapon against human cancers because of experimental beneficial results in animal models. An attempt has been made to put into clinical perspective the results of a large number of studies that have taken place over the past decade. This text consists of ten chapters broken down into disease categories such as the leukemias, lung cancer, melanoma, and breast cancer, with a final chapter dealing with new agents.Each chapter contains institutional or group clinical trials of various immunotherapy modalities. The various agents used include BCG vaccine, levamisole, interferon, Corynebacterium parvum, and irradiated malignant cells. This book is not intended as a review of clinical immunotherapy for the uninitiated, but rather presents results or representative studies in different cancers. The text is specifically designed as a reference for investigators involved with clinical cancer immunotherapy. Therefore, it has a very limited audience.The individual reports

Excerpt To the editor: In a recent paper, Mir and associates (Ann Intern Med82:54-57, 1975) propose that the hypokalemia that often occurs in association with acute myeloid leukemia may be unrelate...

Classification, diagnostic tools, and therapeutic alternatives for the malignant lymphomas present a fruitful field for research, as well as controversy, to the clinical investigator. This volume of Cancer Treatment and Research focuses on at least six major dilemmas in the study of Hodgkin's disease and non-Hodgkins lymphomas (NHLs). The individually authored 13 chapters debate issues such as (1) What is the origin of the Reed-Sternberg cell? (2) Is lymphangiography a necessary procedure in staging or has it been totally replaced by computed tomography? (3) Is radiation therapy or chemotherapy or combination of radiation therapy and chemotherapy the best treatment for limited stages of Hodgkin's disease (stages I to III)? (4) Is Rappaport's classification of the NHLs useful for the clinician in deciding on therapy? (5) Is nodular mixed NHL a subset that is more favorably treated? and (6) Should "low grade" or "favorable" NHL be treated conservatively, aggressively, or not

In a large series of adults with acute leukemia followed by the same hematology service, prior to 1970, there were only two instances of clinically apparent central nervous system involvem...

Salicylazosulfapyridine (Azulfidine), a sulfonamide, has been used extensively in the treatment of ulcerative colitis. It has been noted that sulfonamides are the most common drugs which precipitate acute hemolytic episodes in erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficient subjects. Hemolysis occurred in two erythrocyte G6PD deficient Negroes with ulcerative colitis; we suggest that the anemia complicating ulcerative colitis may in such cases be related to the therapy.

In a case of scleroderma and autoimmune hemolytic anemia, azathioprine treatment resulted in complete remission of the hemolysis despite the persistence of positive direct and indirect antiglobulin test. There were no beneficial results of the therapy on the underlying connective tissue disorder. Complications of azathioprine treatment encountered were completely reversed with termination of therapy. These concurrences, with the positive antinuclear antibody studies and rheumatoid factor, favor the autoimmune theory of pathogenesis of scleroderma.