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Hematologic diseases may affect the nervous system. Abnormalities in the cellular components, impaired flow, abnormal clotting, or tendency to bleed may all produce neurologic symptoms and signs. A systematic approach to these etiologies is important.
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The prophylactic and therapeutic effects of the oral administration of amphotericin B (AMPH) to patients with deep mycosis associated with hematologic diseases were evaluated in an investigation including determination of serum concentrations of the antibiotic. Prophylactic effects were examined in 111 subjects, and the efficacy rates averaged 83.8% at daily doses from 1,200 to 4,800 mg. The efficacy was significantly higher at a dose of 2,400 mg/day than at a dose of 1,200 mg/day (P less than 0.05). The efficacy rate tended to be higher when the length of administration period was 1 month or more. The percentage of the number of days of fever by neutrophil count was significantly less at a daily dose of 2,400 mg than at 1,200 mg in patients with neutrophil count of 1,000 cells/mm3 or less (P less than 0.001). The safety was evaluated in 131 subjects, and adverse effects were found in only 2 cases of nausea for an incidence rate of 1.5%. Therapeutic effects were studied in 12 cases, and efficacy rates averaged 58.3% at daily doses from 2,400 to 7,200 mg. Adverse effects consisted of 1 case of diarrhea among 15 subjects who were evaluated for the safety for an incidence rate of 6.7%. The serum concentrations of the antibiotic were examined in 60 of the prophylactic and therapeutic subjects. Average concentrations of AMPH at 4 hours after the first daily dose of 1,200, 2,400 and 4,800 mg were 0.040, 0.053 and 0.078 micrograms/ml, respectively. Concentrations gradually increased thereafter and reached averages of 0.089, 0.090 and 0.132 micrograms/ml, respectively, for the 3 dose levels on the 7th day. These results indicated that there were no serious adverse effects and serum concentrations were above the Candida MIC values at daily prophylactic and therapeutic doses of 1,200 to 7,200 mg of AMPH. Based on these findings, this drug can be expected to show prophylactic and therapeutic effects with safety in cases of deep mycosis.
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Malignant hematologic diseases are severe illnesses for which complex forms of treatment are used and to which a great variety of metabolic changes are anticipated. Both lymphomas and leukemias, as well as chemotherapy, can induce abnormalities in thyroid hormone metabolism without overt disease, thus leading to what is known as euthyroid sick syndrome (ESS). In the present report, 25 patients with lymphomas and leukemias were studied to evaluate the effect of chemotherapy on thyroid hormone concentration. After chemotherapy, the most frequent and significant alteration was a decrease in serum triiodothyronine concentration.
A 22-year-old man who was admitted to our respiratory division complaining of fever and cough of 1 month's duration had been diagnosed with myelodysplastic syndrome 5 years earlier. On admission, radiological findings showed bilateral diffuse small nodular shadows. Although the results of an acid-fast bacilli examination of blood, sputum, and urine samples were all negative, we initiated antituberculous therapy for suspected miliary tuberculosis because the histological diagnosis from a bone marrow biopsy was epitheloid granuloma. The abnormalities on his chest radiographs improved, but his left cervical lymph nodes became swollen. The histological result of a lymph node biopsy revealed epitheloid granuloma with caseating necrosis. The DNA-DNA hybridization result of a resected lymph node culture indicated Mycobacterium avium. The final diagnosis was disseminated Mycobacterium avium complex (MAC) disease. Both leukocytopenia and thrombocytopenia had been noted in the patient's 19-year-old younger brother, who had been living in the same home 5 years earlier, and for whom a diagnosis of myelodysplastic syndrome was made from bone marrow aspiration on admission. An infiltration shadow with nodular shadows was noted in the right upper lung field on a chest radiograph. A bronchoscopic examination revealed pulmonary MAC disease. As for the route of infection, although we investigated restriction fragment length polymorphism (RFLP), a different pattern was found in the two brothers. We suspect that they were infected by different species of Mycobacterium avium in the same environment rather than by droplet infection from the younger brother to the older brother.
Upon establishing new out-patient services at the Clinical Centre, Clinic of Hematology has set up a new diagnostic and therapeutic department which is popularly named "Hematologic Daily Hospital". In way, the work at the Clinic of Hematology has been completely changed, since a new activity in the out-patient management of hematologic patients has been initiated. In the course of 8-hour working time numerous various diagnostic and therapeutic interventions are being performed in "Hematologic Daily Hospital", such as: a detailed survey of the patients, biologic material is taken and sent to various analyses, sternal and other functions are performed, cytologic analyses of punctates obtained, patients are referred to radiologic, ultrasonographic, CT and other surveys, administration of parenteral therapy of corresponding solution with or without cytostatics, blood and blood derivate transfusion as well as the application of various forms of apheresis. Data on the number and kinds of services applied are presented in this paper with the insight on the organization of work. Such an organization of work has made diagnostic of hematologic patients faster and has contributed to a simpler employment of therapy.
Six patients with hematological disease complicated by intracranial hemorrhage were surgically treated in the last 2 years. In this study, in order to clarify indication for operation and perioperative management, 6 cases were classified into 2 groups. The details of each group were as follows: Group 1 was defined by the fact that the underlying hematological disease had not yet been controlled. (One case was ITP and the others were 2 AML cases). Group 2 was defined by the fact that the underlying hematological disease was well controlled. (One case was CML, one case was ATL and one case was ITP). A tendency to bleed was corrected in all patients of group 1 in the perioperative period. In the AML cases, prevention of infection was mandatory because both AML cases had been in remission, and no serious postoperative complication had occurred. The outcome of short term treatment was excellent in all but one case, in whom the recurrence of subdural hematoma caused death during the period 1 month after operation. On the other hand, no cases classified in group 2 needed specific hematological perioperative management and the short term treatment outcome was excellent. Since intracranial hemorrhage related to hematological disease has often been fatal, those patients were treated conservatively in most cases. However, from our analyses, we were able to emphasize that most intracranial hemorrhage related to hematological disease might be treated surgically and with good result, if the underlying hematological disease has entered the remission period.
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Clinical and bacteriological data of 145 inpatients with septicemia, treated at the hospital of Chiba University School of Medicine from 1972 to 1987, were reviewed by dividing them into three stages. (stages I: 1972-76, stage II: 1978-82, stage III: 1983-87) Patients with underlying diseases have been increasing: 91.8% of the total patients in stage III. Among the patients with underlying diseases, malignant and hematological diseases occupied about 60%, and in the other diseases, congenital heart diseases have been increasing in number. As to the organisms isolated, gram positive bacteria have increased, while gram negative bacteria have decreased. In stage III, the rate of gram positive organisms and gram negative ones accounted for 43.1% and 41.2% of all the isolates from the septic patients with malignant & hematological diseases, respectively. In patients with malignant & hematological diseases, alpha-streptococcus, coagulase-negative staphylococcus, and Fusobacterium sp. have been increasing, whereas, Escherichia coli, Enterobacter sp., Klebsiella sp., and Pseudomonas aeruginosa decreasing. In patients with other underlying diseases, S. aureus, CNS, and non Fermenters have been increasing. Among the patients without underlying diseases, gram positive bacteria accounted for the major part. The decrease of gram negative organisms in patients with malignant and hematological diseases may partially depend on the introduction of polymixin B as the drug of gut decontamination. The outcome of septicemia in the patients with malignant & hematological diseases has been markedly improving through all the three stages. During stage III, episode mortality and case mortality rate proved to be 23% and 31%, respectively. The introduction of the third generation cephems has decreased the mortality rate for gram negative organisms and contributed to the improvement of the total prognosis. The prognosis was worst in the case of P. aeruginosa, showing a mortality rate of 50% during stage III. Coincidence rate of blood and other cultures have been largest in the case of P. aeruginosa, so, the drug sensitivity of the strain cultured from other sites is sometimes useful in the choice of antibiotics.
Patients with hematological diseases undergoing diagnostic or therapeutic splenectomy are at increased risk of pneumococcal infections. Vaccination is a straightforward option in preventing these infections. A well-defined cohort of splenectomized patients with hematological disorders was followed according to response to 23-valent pneumococcal capsular polysaccharide (Pneumovax N) vaccination. A total of 76 splenectomized patients (Hodgkin lymphoma, HL 26, non-Hodgkin lymphoma, NHL 19, immune-mediated cytopenias 28, and others 3) with a median age of 52 years (range 18-82 years) were included. Pneumococcal polysaccharide (PS) antibodies were determined using an enzyme-linked immunosorbent assay before vaccination, at peak, and follow-up. A poor response to vaccination was observed in 21 (28%) patients and a good response in 55 (72%), respectively. During the follow-up period of 7.5 years (range 3.5-10.5 years) after vaccination, and despite repeated revaccination in many cases, a total of five episodes (in three patients) of pneumococcal infections were reported, all confined to the poor responder group. Revaccination did not improve antibody levels in this group. The median age at vaccination was significantly higher in the group of poor responders (p=0.0006). None of the following factors could predict a poor antibody response: gender, disease activity or aggressiveness in hematological malignancies, previous radiotherapy and/or chemotherapy, time between splenectomy and pneumococcal vaccination, time between chemotherapy/radiotherapy and study pneumococcal vaccination (1 year), or the presence of hypogammaglobulinemia. In conclusion, a substantial proportion of splenectomized patients with hematological diseases mounted a poor PS antibody response and remained at risk for pneumococcal infections despite vaccination. In the absence of apt indirect clinical predictors of antibody response, with the exception of age, measurement of antibody levels seems to be a feasible method for early identification of this patient subgroup. Poor responders do not benefit from revaccination, and should be offered other prophylactic measures.
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Prenatal diagnosis of hematologic diseases can now be performed with fetal blood, fetal amniotic fluid cell DNA, and fetal chorionic villi DNA. Some hemoglobinopathies can be detected by all three methods, and the choice will depend on the available obstetric and laboratory techniques, as well as the time of presentation of the pregnancy. Hopefully, further development of molecular probes and techniques will soon expand these options to all of the globin disorders. Detection of coagulation disorders in utero currently requires samples of pure fetal blood. Gene cloning is accomplished for some (factor IX and antithrombin III) and is underway for others (factor VIII), and further investigation is necessary to determine whether deficiencies in these gene products are due to gene deletion or to mutant genes linked to polymorphic restriction enzyme sites of diagnostic use. Thus, molecular biology may be applied to prenatal diagnosis of the clotting problems, but this has not yet been accomplished. Disorders affecting the number and/or function of erythrocytes, leukocytes, and platelets can be diagnosed by analysis of fetal blood. Blood samples will continue to be required until more is known about the molecular biology of hematopoiesis. Syndromes that can be diagnosed by chromosome studies should be revealed in cultures of amniotic fluid cells, fetal blood lymphocytes, and chorionic villi cells. Cultured cells can be examined for karyotypes, Y-chromatin, spontaneous or induced chromosome breakage, DNA repair, SCEs, and translocations. The techniques for culturing amniotic cells and fetal blood white cells are established, and those for growing cells from chorionic villi are improving rapidly. Direct preparations of cells from villi only may suffice for some of the above analyses. The study of hematologic disease in utero has thus come full circle, from the use of amniotic cells to determine the sex in X-linked disorders, to fetal blood sampling for the analysis of gene products, then back to amniocentesis for DNA, and now earlier in gestation to chorionic villi. All of this has occurred in less than ten years, and it is anticipated that developments in the next ten years will be equally dramatic. The future should bring all prenatal testing into the first trimester, use molecular probes, and provide for both early diagnosis and early treatment of genetic hematologic disease.
Patients with hematological malignancies or recipients of hematopoietic stem cell transplants may develop myriad pulmonary manifestations, as a complication of either the disease or the diverse agents used to treat the disease. Clinical, radiographic, and physiological features of drug-induced and radiation-induced pulmonary injury are often difficult to distinguish from other causes of pulmonary infiltrates (e.g., infections, pulmonary edema, alveolar hemorrhage, etc.). Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) is essential to exclude infectious etiologies. In some cases, surgical lung biopsies are required to establish a specific etiological diagnosis. This review discusses the myriad causes of lung injury/toxicity that may afflict patients with hematological malignancies or transplant recipients, and presents diagnostic and therapeutic approaches.
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