Advances in the treatment of chronic lymphocytic leukemia (CLL)

CLL is a chronic lymphoproliferative disorder which is characterized by the proliferation of a CD5 positive B cell clone. At diagnosis most patients are in early stage of the disease (stage A). It is well established that an early treatment in stage A is not associated with a survival advantage. Therefore, the disease should be treated only when signs of progression are present. The standard initial therapy is chlorambucil +/- prednisone. By this treatment remissions (mostly partial remissions) are achieved in about half of the patients. Fludarabine, a purine analogue, is more effective than chlorambucil as initial treatment (75% remissions, 27% complete remissions, 33 months progression free survival). However, the overall survival is not prolonged when compared to chlorambucil treatment. Fludarabine has a high efficacy in patients with recurrent disease, in particular in those who are resistant to alkylating agents. The allogeneic and autologous stem cell transplantation is an experimental treatment which may be indicated in younger patients who show a response to conventional treatment. With both procedures hematological remissions are frequently achieved and in some of the patients long lasting molecular remissions were obtained. Currently, it is unknown whether patients can be cured by stem cell transplantation and longer follow-up will be necessary to clarify this question. Monoclonal B-cell antibodies are effective in vivo and partial remissions can be obtained in chemotherapy refractory patients. Antibodies have a high efficacy in clearing lymphoma cells from peripheral blood and bone marrow but are less effective on the organomegaly.     

The use of transfer factors in the treatment of multiple sclerosis: a case report

A 23-year-old woman suffering from multiple sclerosis (MS) was given a course of 6 injections (0.5 U) of mumps transfer factor (TF) at 2-weekly intervals. The patient's symptoms improved dramatically and during the 10 months since treatment was instituted, no exacerbations have occurred. The possible aetiological role of paramyxoviruses in MS and the use of TF in the treatment of the disease are discussed. MS is however, a disease of exacerbations and spontaneous remissions, and despite our promising findings in this patient we wish to refrain from hailing mumps TF as a possible cure for this notorious disease.     

Long-term follow-up of patients with subacute sclerosing panencephalitis treated with intraventricular alpha-interferon

We treated 22 patients with subacute sclerosing panencephalitis (SSPE) with intraventricular alpha-interferon (alpha-IFN) and oral inosiplex between 1986 and 1991. The follow-up for 56 to 108 months demonstrates a higher survival rate in these patients compared with those who did not receive alpha-IFN. However, eight of 11 patients whose condition improved after alpha-IFN treatment and five of five patients whose condition stabilized after alpha-IFN experienced neurologic deterioration 6 to 90 months after treatment; three of 11 and four of five died. The use of inosiplex did not influence the prognosis. Re-administration of the same regimen was not effective in one patient. Treatment-induced remissions in SSPE can be temporary, analogous to spontaneous remissions. Longer treatment with higher doses, or combinations of drugs, may be required.     

Effectiveness of the use of immunological methods in clinical laboratory diagnosis

The efficacy of treatment of stomatological manifestations and visceral diseases in patients with Sjogren's disease (syndrome) by therapeutic complexes including plasmapheresis is assessed. Plasmapheresis was administered to 7 inpatients in an intermittent mode with exfusion of up to 1 liter of plasma per session. A course consisted of one to three sessions, the total duration of treatment was three to four weeks. The efficacy of plasmapheresis in a complex of therapeutic measures was assessed from the time course of the clinical picture, results of studies of the function of salivary glands, and parameters of metabolic processes and immunity. Plasmapheresis helped attain long remissions and improved the general status of the patients, this being paralleled by a positive time course of local symptoms of the disease and the principal homeostasis parameters.     

Carotenoid intake in the German National Food Consumption Survey

The patient with surgically incurable melanoma presents a difficult problem for the medical oncologist. Single chemotherapeutic agents at conventional doses produce bona fide but infrequent remissions. The most active single agent for the treatment of metastatic melanoma is dacarbazine (DTIC). Until recently, combinations of drugs yielded no real improvement over treatment with the individual components. The combination of DTIC + carmustine (BCNU) + cisplatin + tamoxifen (the "Dartmouth regimen") appears to be more effective than DTIC alone, but prospective randomized trials comparing the two are still in progress. The contribution of tamoxifen to the observed results continues to be evaluated. Biological agents, such as interferon and interleukin-2, have lower overall response rates compared to chemotherapy regimens, but response duration appears to be longer. Chemotherapy combined with biotherapy offers the promise of higher response rates and long-term durable remissions. The results from high-dose regimens that use autologous bone marrow or peripheral stem cell support have not been sufficient to justify the added toxicity. Although advanced melanoma often is not curable with systemic therapy, the considered use of currently available regimens can induce clinically significant remissions and, possibly, prolong life in some patients.     

Personal and social factors associated with the remission of psychiatric symptoms

Most studies of "spontaneous remission" involve samples of untreated psychiatric patients. This selection process limits the generalizability of findings to the population of persons with neurotic disturbances. This report concerns a community sample of people with neurotic disorders. Fifty subjects were followed up for five years, using both clinical and quantitative techniques. Almost half lost their symptoms during this time. Various sociodemographic factors, personality assets, and liabilities contribute to the process through which such remissions occur.     

Phase 1 trial of transforming growth factor beta 2 in chronic progressive MS

Transforming growth factor (TGF)-beta2 is a pleiotropic cytokine associated with remissions in multiple sclerosis (MS) and amelioration of allergic encephalomyelitis. We assessed the safety of TGF-beta2 in an open-label trial of 11 patients with secondary progressive (SP) MS. Five patients had a reversible decline in the glomerular filtration rate. There was no change in expanded disability status scale or MRI lesions during treatment. Systemic TGF-beta2 may be associated with reversible nephrotoxicity, and further investigation of its therapeutic potential in MS should be performed with caution.     

Kaposi's sarcoma following long-term immunosuppressive therapy: clinical, histologic, and ultrastructural study

Multifocal Kaposi's sarcoma in a patient with chronic myeloid leukemia treated with busulfan, a cytostatic and suppressive drug, is reviewed. After five years of treatment, during which temporary remissions occurred, the patient experienced a relapse of leukemia and a considerable immune deficiency. This was expressed by a decrease in the ratio of CD4/CD8 lymphocytes in the peripheral blood. The relation of Kaposi's sarcoma with leukemia, as well as with the state of immunity in this case, does not evoke any doubts. Verification of oncologic treatment brought about a remission of leukemia, an improvement in the patient's immune state, as well as an inhibition of new foci of the Kaposi's sarcoma in the skin in the course of a few months of follow-up evaluation.     

Occurrence of Loma cf. salmonae in brook, brown and rainbow trout from Buford trout hatchery, Georgia, USA

We retrospectively analysed the long-term treatment results (median 8 years) of 31 patients with macroprolactinoma. 17 patients were treated by pituitary surgery (group 1) followed by long-term dopamine agonist therapy whereas 14 patients received long-term dopamine agonist therapy alone (group 2). 2 patients of group 1 and 1 patient of group 2 had external pituitary irradiation because of progressive disease. The two groups were comparable with respect to age, gender and initial prolactin (PRL) levels. At the end of the observation period dopamine agonist dosage could be reduced by 50% in group 1 and by 39.3% in group 2. Pituitary function did not change substantially during therapy. Complete remissions (no visible tumour in CT or MRI, normal PRL levels under current dopamine agonist medication) were achieved in 23.5% of group 1 vs. 21.4% of group 2, partial remissions (reduction of PRL and tumour size) in 35.3% vs. 64.3%, stable disease in 23.5% vs. 7.1% and progressive disease in 17.7% vs. 7.1% (differences not significant). Visual field defects showed 28.4% remissions (complete and partial) in group 1 versus 50% in group 2. Dopamine agonist therapy could be stopped definitively in only 1 patient of group 2 with an invasive macroprolactinoma. Initial surgical reduction of tumour load followed by medical therapy does not seem to guarantee a better long-term outcome than dopamine agonist therapy alone if the patient responds to and tolerates dopamine agonist therapy. Surgery should be reserved for non-responders, drug-intolerant or non-compliant patients, and for those with acute severe neurological compromise.     

Detection of Salmonella in animal protein by Rappaport-Vassiliadis broth using indirect impediometry

To determine if glipizide could enhance remission induction in new onset type 1 diabetes compared to intensive insulin treatment alone, 27 patients with type 1 diabetes were intensively treated in an open randomized trial with subcutaneous injections for one month. The insulin was randomly either discontinued (Group A) or the insulin discontinued and glipizide begun (Group B) Three patients in Group A (22%) and 7 in Group B (54%, p < .05) underwent insulin-free remissions for 10.3 +/- 4.4 and 8.7 +/- 2.6 months, respectively (p = NS). Mean blood glucose levels during insulin treatment were lower in patients entering remissions (94 +/- 3 mg/dl versus 102 +/- 5 mg/dl, p < 0.05). C-peptide levels were performed 0, 4, 8, and 24 weeks after insulin treatment. When all patients were examined, mean stimulated C-peptide levels at 4 weeks (0.58 +/- 0.09 pm/ml) were increased compared to time 0 (0.32 +/- 0.05 pm/ml, p < 0.02). Patients not entering remission had higher 4-week stimulated values (0.67 +/- 0.12 pm/ml) compared to time 0 values (0.29 +/- 0.06 pm/ml, p < .01), whereas remission patients' mean C-peptide levels remained similar at 0, 4, 8 and 24 weeks. These data indicate that a) insulin treatment plus glipizide induces higher rates of remission compared to intensive insulin treatment alone, b) the intensity of initial metabolic control may be an important determinant for remission induction, and c) endogenous insulin secretion is not associated with remission induction, suggesting that glipizide alters insulin sensitivity or is immunomodulatory in the context of new onset type 1 diabetes.     

Liver pathology in juvenile chronic polyarthritis

Besides lymphodenopathy and splenomegaly, hepatomegaly may also be detected in 25-50% of children with juvenile rheumatoid arthritis. This is particularly evident in patients with complete Still's syndrome. The hepatomegaly increases during relapse situations and disappears during remissions. Transient icterus, elevation of aminotransferases and delayed bromsulfalein excretion have been reported, particularly in patients with complete Still's syndrome, and indicate impairment of liver function. Liver biopsies have been performed only rarely and show nonspecific infiltrations of portal fields with lymphocytes and, in a few cases, "autoimmune" hepatitis and even cirrhosis with portal hypertension. Plasma cell hepatitis with affection of joints can be readily differentiated from juvenile rheumatoid arthritis: the synovitis is merely transiet and disappears with institution of steroid therapy. As in the adult, severe liver dysfunction leads to remission of arthritis. Amyloidosis should be considered in every case of long-lasting hepatomegaly.     

Total body irradiation of chronic lymphocytic leukemia. Relationship between therapeutic response and prognosis

There is lack of evidence to date that treatment of chronic lymphocytic leukemia (CLL) alters the natural history of disease or influences survival. In the present series, total body irradiation (TBI) produced a range of therapeutic responses among patients with active, progressive CLL. One-third of patients experienced virtually complete clinical and hematologic remissions with the initial course of TBI. These patients did not differ from the less complete responders with respect to age or sex, degree of lymphocytosis in the peripheral blood, incidence of anemia and/or thrombocytopenia, or the frequency of constitutional symptoms. However, the patients with complete remissions noted a return to normal performance status, had fewer serious infections, demonstrated recovery from depressed immunoglobulin levels, and had significantly longer survival. These data indicate that TBI is capable of inducing remissions which modify the course of disease in patients with CLL and that prognosis has a direct correlation with the response to therapy.     

Preventive therapy of opiate addiction with naltrexone

The trial included 120 patients with opiates addiction: the study group (60 patients) and a control one (60 individuals) which were similar in sex, age and clinical peculiarities of the disease. Naltrexon was administered prophylactically to the patients of the study group during 6 months and longer, while the patients of the control group didn't receive naltrexon. Simultaneously, a program of common therapy and rehabilitation concerning both groups was performed during 6 months. It was established that application of naltrexon decreased probability of relapse of drug abuse, facilitated an inclusion of a patient into a program of therapy and rehabilitation, increased a number and quality of remissions as well as it also decreased a tendency to alcohol and sedative drugs administration. Naltrexon had no side effects and was well tolerated by the patients. 8 follow-up cases of treatment with metadone in some foreign clinics are presented. These observations and literary data show that prophylactic properties of metadone are less pronounced as compared with naltrexon.     

Acquired factor VIII inhibitors--successful treatment with an oral outpatient regimen

A rare cause of a spontaneous, life threatening coagulopathy in adults is the development of autoantibodies to factor VIII. We recently had the opportunity to treat seven patients with this disorder. After stabilization, they were given a regimen consisting of prednisone and oral cyclophosphamide. All patients had a complete response to treatment. The median time to response was three weeks. Durable remissions were achieved, making this oral regimen an acceptable treatment for this disorder.     

Pneumatic lithotripsy applied through deflected working channel of miniureteroscope: results in 143 patients

OBJECTIVE: Transdermal nicotine appears to be of benefit in the short-term treatment of patients with ulcerative colitis. The aim of this study was to determine its long-term effects. DESIGN: A randomized, comparative study. PATIENTS AND METHODS: Patients with mild to moderate clinical relapses of left-sided ulcerative colitis during maintenance treatment with mesalamine 1 g b.i.d. were allocated to an additional treatment with either transdermal nicotine or prednisone for 5 weeks. The first consecutive 15 patients per group, with clinical and endoscopic signs of remission, were followed up for 6 months, while continuing mesalamine maintenance treatment. RESULTS: Relapses of active colitis were observed in 20% of patients formerly treated with nicotine and in 60% of patients in the prednisone group (P = 0.027). Relapses occurred earlier in the latter group. CONCLUSION: Our results confirm that nicotine is useful in cases of ulcerative colitis with mild or moderate activity and suggest that remissions induced by nicotine may last longer than those obtained with oral corticosteroids.     

Treatment strategy of high malignancy non-Hodgkin lymphomas

While radiotherapy is not justified as a single-modality approach in high-grade non-Hodgkin's lymphoma, standard therapy consists of chemotherapy with the CHOP regimen, which induces complete remissions in ca. 2/3 of the patients, with or without additional radiotherapy. Since the majority of these remissions do not last, dose escalations up to myeloablative ranges using hematopoietic stem cell support are being evaluated especially in young patients with bad risk factors. The trials of the German Non-Hodgkin's Lymphoma Consensus Trial group determine the value of a consolidating high-dose chemotherapy in young patients with high-risk profile, while dose intensifications of the CHOP regimen by two-week regimens and/or the incorporation of etoposide are being evaluated in all other treatment groups.     

Results of long-term (over 10 years) lithium therapy

The effectiveness of long term lithium prophylaxis has been studied in thirty patients with bipolar affective disorder. The study covered only these patients receiving prophylactic lithium treatment for at least 10 years, who demonstrated positive response to lithium during the initial five years of the therapy. Standard medical documentation was analyzed for the time-course of the illness within the whole observation period (number, duration and character of remissions) as well as for the history of lithium therapy (serum lithium concentrations, regularity of medical checks, breaks in the lithium treatment). The effectiveness of lithium prophylaxis has been found to diminish with time in as many as 40% of patients subjected to the prolonged lithium therapy, as evidenced by an increased number of recurrences in this group. The explanation for this phenomenon is not clear, particularly that the change in the responsiveness to lithium has been found not to correlate with age, duration of illness, duration of lithium therapy, incidence of somatic diseases and history of lithium treatment (serum lithium concentrations, breaks in the treatment).     

The efficacy of inhaled corticosteroids in the management of non asthmatic chronic airflow obstruction

AIMS: The aims of this investigation were to evaluate the efficacy of regular inhaled beclomethasone in the control of symptoms and lung function with non-asthmatic smoking related obstructive pulmonary disease and to evaluate the relationship between clinical responses to a short course of oral prednisone and longer term outcomes using inhaled steroid. METHODS: The study was a randomised, double blind, placebo controlled, crossover investigation in 18 patients. The active treatment was inhaled beclomethasone 1000 micrograms given twice daily for three months by metered dose inhaler. At the end of each treatment period, patients received oral prednisone 30 mg/day for ten days. The two treatment phases were separated by a one month washout interval. Peak flow rates, symptom scores and "rescue" bronchodilator use were recorded twice daily. Lung function (FEV1, FVC and lung volumes) and bronchial hyperresponsiveness (PC20 methacholine) were measured at monthly visits. The number of exacerbations requiring intervention therapy were also recorded. RESULTS: There were no consistent benefits attributable to beclomethasone. Lung function was not significantly better as a result of active treatment. Sputum production improved but other symptom scores were similar during active and placebo therapy. Three patients exhibited an increase in FEV1 of 15% or more during active treatment but did not do so when oral prednisone was administered immediately after the period of placebo treatment. A further three patients showed an improvement in FEV1 of 15% or more with oral prednisone but failed to improve during treatment with inhaled beclomethasone. The predictive value of the "trial of steroid" was 0% and 81.3% for positive and negative outcomes respectively. CONCLUSIONS: Our results indicate that in non-asthmatic chronic obstructive pulmonary disease inhaled corticosteroid fails to achieve significant improvements in either lung function or symptoms. The response to a "trial of steroid" using oral prednisone is not clinically helpful in selecting the small number of patients who may subsequently benefit from this form of therapy.     

Treatment of common ocular allergic disorders; a comparison of lodoxamide and NAAGA

PURPOSE: The optimal treatment of AIDS-related NHL (ARL) has yet to be defined. The purpose of this study was 1) to evaluate the efficacy and toxicity of the CNOP-regimen (cyclophosphamide, mitoxantrone, vincristine, and prednison) in combination with G-CSF; and 2) to study the effect of this regimen on HIV-1 viral replication. PATIENTS AND METHODS: A phase II study was performed in 21 previously untreated patients with ARL. RESULTS: Based on intention to treat, the response rate was 43%: four complete and five partial remissions. Median survival was only five months. Only one patient had an opportunistic infection during treatment; three patients had localized infections and one episode of septicaemia was seen. Remarkably, during treatment, in 94% of cases p24 antigen levels either remained undetectable or showed a substantial decrease, even though antiretroviral therapy had been discontinued just prior to the first cycle of chemotherapy in all patients. HIV-1 RNA load decreased or remained unchanged in 82% of patients and increased in three patients. CONCLUSIONS: Our data demonstrate, 1) that the CNOP-regimen in combination with G-CSF, although associated with a low risk of both opportunistic and bacterial infections, can not be recommended in the treatment of ARL; but 2) that G-CSF can be used safely to sustain haematopoiesis in patients with ARL treated with chemotherapy.     

Systemic therapy of low malignancy non-Hodgkin lymphomas

Substantial progress has been achieved in eludicating the molecular mechanisms of malignant transformation, in establishing therapeutic standards and in evaluating innovative treatment strategies in patients with low grade Non-Hodgkin's Lymphoma. Correlation of genetic aberrations and immunologic marker profiles to histopathological entities and the clinical course has lead to a new transatlantic lymphoma classification. Today, application of 6-8 courses of moderately intensive induction polychemotherapy induces partial or complete remissions in 80% of patients in stage III or IV. Longterm maintenance therapy with interferon alpha significantly prolongs progression free survival. Current multicenter trials evaluate the curative potential of high-dose chemotherapy with autologous stem cell transplantation. Recently, several new approaches including new cytostatic drugs, immunotherapy with monoclonal antibodies and gene therapy with antisense oligonucleotides have been developed and have achieved remissions in pretreated patients. In the future, intensification of chemotherapy and the new treatment options may offer the potential for cure in patients with low malignant Non-Hodgkins Lymphoma.