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The New England Journal of Medicine Jan 1984We treated seven patients who had progressive hairy-cell leukemia with daily doses of 3 million units of partially pure alpha (leukocyte) interferon by the intramuscular...
We treated seven patients who had progressive hairy-cell leukemia with daily doses of 3 million units of partially pure alpha (leukocyte) interferon by the intramuscular route. Three patients had a complete remission, and four had a partial remission, according to strict criteria for a response. After treatment, bone-marrow aspirates showed an absence of leukemia cells in three patients and 5 per cent or fewer in three others. Normalization of subnormal peripheral-blood values occurred in six of six patients with anemia, in seven of seven with granulocytopenia, and in four of four with thrombocytopenia. Remissions have been maintained for over 6 to over 10 months. Alpha interferon appears to be highly effective in patients with hairy-cell leukemia.
Topics: Adult; Blood Cell Count; Bone Marrow; Female; Humans; Infections; Injections, Intramuscular; Interferon Type I; Leukemia, Hairy Cell; Male; Middle Aged
PubMed: 6689734
DOI: 10.1056/NEJM198401053100104 -
Terapevticheskii Arkhiv 2017To analyze the clinical and morphological manifestations of membranous nephropathy (MN) and to evaluate the efficiency of its therapy.
AIM
To analyze the clinical and morphological manifestations of membranous nephropathy (MN) and to evaluate the efficiency of its therapy.
MATERIAL AND METHODS
MN cases in 2009 to 2016 were retrospectively detected with a subsequent analysis of patients with primary MN (PMN). The titer of IgG-autoantibodies to phospholipase A2 receptor (anti-PLA2R Ab) was determined by an indirect immunofluorescence assay. Treatment outcomes, such as the time course of changes in proteinuria, nephrotic syndrome (NS), and the development of complete and partial remissions (CR and PR), were assessed.
RESULTS
MN was detected in 201 cases; the secondary etiology of the disease was established in 24.9%. The prevalence of MN among morphologically confirmed glomerulopathies was 14%; that of PMN was 10.4%. The median period to diagnosis PMN was 8 (5; 19) months. 150 patients with PMN (66.7% were men; age was 50±15 years) were distributed according to the following morphological stages: Stages I (23.9%), II (48.5%), III (26.1%), and IV (1.5%). Elevated anti-PLA2R Ab levels were found in 51.6% of cases; NS in the presence of proteinuria was detected in 85.6% of patients. An estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m2 was seen in 25% of cases. Treatment outcomes were evaluated in 80 cases; the median follow-up period was 19 (8; 40) months. 68% of cases had CR (32%) or PR (36%) with a median follow-up of 26 (13; 44) months. Spontaneous CRs or PRs were observed in 7.5% of the patients. Multivariate analysis showed that the probability of CR or PR increased 3.2-fold in the use of cyclophosphamide and/or cyclosporine and decreased as eGFR dropped.
CONCLUSION
In Russia, PMN is a common type of glomerulopathy, the specific features of which should include the low rates of spontaneous remissions and detection of anti-PLA2R Abs. For renal protection, the majority of patients with PMN require timely diagnosis and treatment; individualization of the choice of treatment and its enhanced efficiency call for further investigations.
Topics: Adult; Aged; Female; Glomerulonephritis, Membranous; Humans; Male; Middle Aged; Prevalence; Russia
PubMed: 28745685
DOI: 10.17116/terarkh201789621-29 -
Advances in Nephrology From the Necker... 1988We undertook a review of the literature concerning idiopathic NS in the adult (with MGL or due to FSGS) in an effort to assess the results obtained with corticosteroid... (Clinical Trial)
Clinical Trial Comparative Study Review
We undertook a review of the literature concerning idiopathic NS in the adult (with MGL or due to FSGS) in an effort to assess the results obtained with corticosteroid and/or conventional immunosuppressive treatments. We found few usable published works and we were left with an impression of great imprecision. This imprecision stems both from frequently deficient definition of glomerular lesions and from different evaluations of responses to treatment. The almost total absence of controlled series, due to the rarity of nephrosis in the adult, hinders any firm conclusions with regard to the effect of treatments. It limits evaluation to mere tendencies, formulated in such vague terms as "complete remission," "partial remission," and "treatment failure," in a disease whose natural history is sometimes so whimsical that the same clinical case, over a period of years, can be both a success and a failure of the same treatment. In the adult, there is a significant difference in the incidence of complete remissions obtained by corticosteroids according to whether the NS is due to MGL or to FSGS. Nevertheless, the published data are difficult to interpret because dosage and length of treatment vary among authors. A high percentage of corticoresistant, corticodependent, or multirelapsing nephroses responds to immunosuppressive treatment. Efficacy has been documented for three drugs. Chlorambucil is easy to use but entails some long-term oncogenic hazards. Cyclophosphamide has more short-term side effects, but its long-term risk of malignancy appears less. Both of these alkylating agents may definitively compromise fertility. Azathioprine, easy to use but prescribed surprisingly little in NS, may have considerable advantages over alkylating drugs, which would justify reconsidering its use in nephrosis. An open, cooperative study was launched to determine the efficacy and the tolerance of cyclosporine in 45 patients who had been considered as failures of corticosteroid and/or conventional immunosuppressive therapy. The preliminary results of this trial showed that two thirds of the patients with cases of MGL and half of those with FSGS had total or partial remission after long-term treatment with cyclosporine. It is not yet known whether this may eventually lead to lasting remission after treatment is progressively tapered to a stop, or only represent reappearance of low-dose corticosensitivity. In case of dependence on this new immunosuppressive drug, long-term tolerance remains to be determined.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Clinical Trials as Topic; Cyclosporins; Drug Resistance; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Glucocorticoids; Humans; Immunosuppressive Agents; Nephrosis, Lipoid; Recurrence
PubMed: 3124536
DOI: No ID Found -
Acta Haematologica 1993All-trans-retinoic acid (ATRA) has demonstrated in vivo and in vitro that it could differentiate leukemic cells in acute promyelocytic leukemia (APL). ATRA yields... (Review)
Review
All-trans-retinoic acid (ATRA) has demonstrated in vivo and in vitro that it could differentiate leukemic cells in acute promyelocytic leukemia (APL). ATRA yields complete remission (CR) rates of approximately 90% in newly diagnosed and first relapsing APL, in APL resistant to one or two courses of chemotherapy, whereas patients in second and subsequent remissions often have only partial remissions. The use of ATRA in APL is associated with two major drawbacks: (1) the risk of rapidly rising leukocyte counts, leading to the 'retinoic acid syndrome' which may be fatal if the increase in leukocytes is not reversed and (2) almost universal relapse, if no intensive chemotherapy is administered after CR achievement. Preliminary results, however, suggest that ATRA followed by intensive chemotherapy has improved the outcome of newly diagnosed APL, by slightly increasing the CR rate but also by reducing the risk of relapse, as compared to chemotherapy alone.
Topics: Humans; Leukemia, Promyelocytic, Acute; Neoplasm Recurrence, Local; Polymerase Chain Reaction; Remission Induction; Tretinoin
PubMed: 8475669
DOI: 10.1159/000204581 -
Cancer Jan 1985Serum albumin levels were measured by electrophoresis in 552 evaluable patients with Hodgkin's disease. Determinations were made on all patients at onset, on 224 after...
Serum albumin levels were measured by electrophoresis in 552 evaluable patients with Hodgkin's disease. Determinations were made on all patients at onset, on 224 after induction therapy and on 78 in relapse after remissions of variable length. At onset a discrete hypoalbuminemia was evident, inversely related to stage and more marked in symptomatic cases and elder patients. Little or no differences in albumin levels were found with relation to histologic subtypes, sex and presence of weight loss or hepatic damage. Posttherapeutic normalization of serum albumin occurred only after achievement of complete remission and failed after partial remission, while a new clear decrease became evident in relapse. On the basis of 799 albumin measurements during active disease and in remission, the albumin/alpha 2-globulin ratio demonstrated a clear and useful clinical advantage over either albumin or alpha 2-globulin fractions alone as indicator of active disease and relapse. If defective synthesis is the most accepted mechanism for hypoalbuminemia in Hodgkin's disease, these results suggest a casual factor somehow related to the tumoral mass.
Topics: Adult; Age Factors; Alpha-Globulins; Electrophoresis, Cellulose Acetate; Female; Hodgkin Disease; Humans; Male; Serum Albumin
PubMed: 2578086
DOI: 10.1002/1097-0142(19850115)55:2<389::aid-cncr2820550216>3.0.co;2-f -
Journal of Clinical Oncology : Official... May 1990Twenty-five patients with metastatic melanoma were treated with a therapeutic vaccine ("theraccine") consisting of allogeneic melanoma lysates and a novel adjuvant,...
Twenty-five patients with metastatic melanoma were treated with a therapeutic vaccine ("theraccine") consisting of allogeneic melanoma lysates and a novel adjuvant, DETOX (Ribi ImmunoChem Research, Inc, Hamilton, MT). Each patient received 200 antigenic units (20 x 10(6) tumor cell equivalents) subcutaneously on weeks 1, 2, 3, 4, and 6. Clinical responses included one complete remission, three partial remissions, and a long-term (17-month) stability. Two other patients had mixed responses, with partial remissions of numerous subcutaneous nodules. Sites of responsive disease included primarily the skin, but ileal, breast, and a liver metastasis also responded. Removal of residual lesions in patients with partial remissions, whose other lesions had disappeared during treatment, led to long disease-free survivals. The median duration of remission was 17 months, with four of the five responders alive for at least 24 months after treatment. An increase in precursors of cytolytic T cells (CTLs) correlated with clinical outcome, when complete, partial, and mixed responses and long-term stability were considered. The CTLs recognized melanoma-associated antigens on many cell lines, but not other types of tumor or normal lymphocytes. Skin-test reactivity to melanoma antigens and serum antibodies against the melanoma cells was unrelated to clinical response. Toxicity was minimal, restricted largely to minor soreness at the site of injection. Only five patients, four of whom were treated with repeated courses, developed severe granulomas. These results confirm that active-specific immunization with allogeneic lysates of melanoma administered with the adjuvant DETOX can induce immunity to melanoma, and can induce regressions of disease in a proportion of patients with metastatic disease with little toxicity.
Topics: Adjuvants, Immunologic; Adult; Aged; Aged, 80 and over; Antibodies, Neoplasm; Antigens, Neoplasm; Cell Wall Skeleton; Cytotoxicity, Immunologic; Female; Humans; Hypersensitivity, Delayed; Immunotherapy; Leukocyte Count; Lipid A; Male; Melanoma; Middle Aged; Mucoproteins; Mycolic Acids; Remission Induction; Skin Neoplasms; Skin Tests; Survival Rate; T-Lymphocytes, Cytotoxic
PubMed: 2139701
DOI: 10.1200/JCO.1990.8.5.856 -
Epilepsy Research Feb 2015To analyze the predictors of spontaneous transient seizure remission for ≥1 year in patients with drug-resistant epilepsy (DRE) due to mesial temporal sclerosis (MTS). (Comparative Study)
Comparative Study
PURPOSE
To analyze the predictors of spontaneous transient seizure remission for ≥1 year in patients with drug-resistant epilepsy (DRE) due to mesial temporal sclerosis (MTS).
METHODS
This analysis included 38 patients with DRE (M:F = 20:18, age: 31.7 ± 10.9 years) diagnosed with unilateral MTS (right:left = 16:22). Group I ('remission' group) comprised of patients with seizure remission (M:F = 10:8, age: 32.8 ± 12.3 years, mean seizure free period: 2.2 ± 1.1 years; median: 2.1 years). Group II ('non-remission' group) comprised of age and gender matched 20 patients (M:F = 10:10, age: 30.7 ± 9.7 years) with unilateral MTS who never had seizure remission and subsequently underwent epilepsy surgery. Groups I and II were compared to find the predictors associated with transient seizure remission.
RESULTS
The age at onset of seizures in group I was 13.2 ± 11.8 years and in group II was 12.0 ± 7.6 years. The duration of seizure was: group I - 19.7 ± 12.5 years and group II - 19.3 ± 7.7 years. Past history of seizure remissions (p < 0.001), frequent periods of remissions (p < 0.001), first remission within a year of onset of seizures (p = 0.04) and normal EEG (p = 0.04) were the important clinical predictors associated with seizure remission in this cohort. Fifteen patients in group I (83.3%) experienced remission following either change in AED (p ≤ 0.001) or increase in AED dosages (p < 0.001). There was no difference between the two groups regarding the type of semiology (partial vs. secondarily generalized) (p = 0.50), family history of seizures (p = 1.0), side of the lesion (p = 0.34), history of febrile seizures (p = 1.0) and the number of AEDs used (p = 0.53).
CONCLUSION
The present study unfolds, some of the clinically relevant predictors associated with transient seizure remission in patients with DRE and MTS. Future molecular and network studies are required to understand its mechanism.
Topics: Adult; Anticonvulsants; Brain; Comorbidity; Drug Resistance; Electroencephalography; Epilepsy, Temporal Lobe; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Mental Disorders; Prognosis; Remission, Spontaneous; Sclerosis; Seizures; Temporal Lobe
PubMed: 25616456
DOI: 10.1016/j.eplepsyres.2014.11.018 -
Blood Nov 1993We investigated whether recombinant alpha 2b interferon (r alpha 2bIFN) would reduce the proportion of bone marrow Philadelphia chromosome (Ph) cells in chronic-phase... (Clinical Trial)
Clinical Trial
Prolonged subcutaneous administration of recombinant alpha 2b interferon in patients with previously untreated Philadelphia chromosome-positive chronic-phase chronic myelogenous leukemia: effect on remission duration and survival: Cancer and Leukemia Group B study 8583.
We investigated whether recombinant alpha 2b interferon (r alpha 2bIFN) would reduce the proportion of bone marrow Philadelphia chromosome (Ph) cells in chronic-phase chronic myelogenous leukemia (CML) by treating 107 previously untreated patients daily with r alpha 2bIFN at 5 x 10(6)IU/m2 subcutaneously. Patients with complete remission, partial remission, or partial hematologic remission received treatment until progression; those with progressive disease were taken off study and observed for survival. Sixty-three (59%) of the patients achieved at least a partial hematologic remission (24 complete remissions and 39 partial remissions). The median time to response for the 63 responders was 3.4 months, with a median duration of remission of 52 months and with 81% of responders continuing in remission beyond 12 months. The median survival for the 107 patients was 66 months. Of 78 patients with cytogenetic follow-up data, 31 (40%) achieved a partial cytogenetic response (n = 17) or a complete cytogenetic response (n = 14). The percentage of cytogenetic responders among all patients was 29% (31 of 107 patients). The median time to first cytogenetic response was 9 months. A major dose reduction of r alpha 2bIFN (> or = 50%) was required at some time during treatment in 38% of patients, 26% required 10% to 49% dose reductions, and 36% had minor dose reductions of < or = 10%. No association was observed between dose received and the attainment of a cytogenetic response. None of the usual prognostic factors (sex, race, performance status, weight loss, time from diagnosis to treatment, hepatosplenomegaly, age, symptoms, hemoglobin, or platelet, blast, basophil, or white blood cell count) were significantly related to survival. These data provide confirmation that major cytogenetic responses to prolonged administration of subcutaneous r alpha 2bIFN occur in 20% to 38% (95% confidence interval) of chronic-phase Ph-positive patients. Although it is hypothesized that patients achieving major cytogenetic responses to r alpha 2bIFN should have prolonged remission duration and survival compared with nonresponders, analyses of the effect of cytogenetic responders by both "landmark" and time-dependent covariate techniques fail to provide statistically significant evidence for an effect of cytogenetic response on remission duration or survival. This may be due in part to an effect size insufficiently large to be detected with the number of patients treated in this study. Thus, confirmation of remission duration or survival benefit, if any, of r alpha 2bIFN therapy in Ph-positive chronic-phase CML must await the outcome of randomized trials comparing IFN with conventional agents.
Topics: Adolescent; Adult; Aged; Female; Humans; Interferon alpha-2; Interferon-alpha; Karyotyping; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Male; Middle Aged; Prognosis; Recombinant Proteins; Remission Induction; Survival Rate; Time Factors
PubMed: 8219189
DOI: No ID Found -
Annals of the Rheumatic Diseases Jul 2009Conventional therapy of Wegener's granulomatosis with cyclophosphamide and corticosteroids is limited by incomplete remissions and a high relapse rate. The efficacy and... (Clinical Trial)
Clinical Trial
OBJECTIVES
Conventional therapy of Wegener's granulomatosis with cyclophosphamide and corticosteroids is limited by incomplete remissions and a high relapse rate. The efficacy and safety of an alternative immunosuppressive drug, deoxyspergualin, was evaluated in patients with relapsing or refractory disease.
METHODS
A prospective, international, multicentre, single-limb, open-label study. Entry required active Wegener's granulomatosis with a Birmingham vasculitis activity score (BVAS) > or =4 and previous therapy with cyclophosphamide or methotrexate. Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status. Deoxyspergualin, 0.5 mg/kg per day, was self-administered by subcutaneous injection in six cycles of 21 days with a 7-day washout between cycles. Cycles were stopped early for white blood count less than 4000 cells/mm(3). The primary endpoint was complete remission (BVAS 0 for at least 2 months) or partial remission (BVAS <50% of entry score). After the sixth cycle azathioprine was commenced and follow-up continued for 6 months.
RESULTS
42/44 patients (95%) achieved at least partial remission and 20/44 (45%) achieved complete remission. BVAS fell from 12 (4-25), median (range) at baseline to 2 (0-14) at the end of the study (p<0.001). Prednisolone doses were reduced from 20 to 8 mg/day (p<0.001). Relapses occurred in 18 (43%) patients after a median of 170 (44-316) days after achieving remission. Severe or life-threatening (> or = grade 3) treatment-related adverse events occurred in 24 (53%) patients mostly due to leucopaenias.
CONCLUSIONS
Deoxyspergualin achieved a high rate of disease remission and permitted prednisolone reduction in refractory or relapsing Wegener's granulomatosis. Adverse events were common but rarely led to treatment discontinuation.
Topics: Adult; Aged; Female; Granulomatosis with Polyangiitis; Guanidines; Humans; Immunosuppressive Agents; Male; Middle Aged; Prospective Studies; Recurrence; Remission Induction; Treatment Outcome; Young Adult
PubMed: 18713783
DOI: 10.1136/ard.2008.092429 -
Urologic Oncology 2010Former systemic therapy for metastatic renal cell cancer (mRCC) based on immunomodulation could achieve complete remissions (CR) in only some patients. Angiogenic...
BACKGROUND
Former systemic therapy for metastatic renal cell cancer (mRCC) based on immunomodulation could achieve complete remissions (CR) in only some patients. Angiogenic therapy with sunitinib, sorafenib, and temsirolimus changed the paradigm of treating mRCC based on a doubled progression-free survival (PFS) and 10% to 30% of patients achieving partial remission (PR). Unfortunately, CR is rarely seen. Within our patients we could achieve some CR, which we are presenting in this study.
PATIENTS AND METHODS
We assessed 194 consecutive patients of an institutional database that were treated for mRCC with either sorafenib or sunitinib between 05/2006 and 12/2007. Restaging with repeated high-resolution computed tomography (CT) of thorax and abdomen was performed in an 8 to 10 weeks interval. Five patients who achieved CR in repeated CT under therapy are included in this analysis.
RESULTS
Of the patients in whom we achieved CR, two were female and three were male. Median age was 63.2 years (range 52-70). All patients had clear cell histology. In three of the five patients, CR was achieved by surgery after partial remission, and in two patients it was achieved by sole medical therapy. All patients remained in CR until now with a median duration of CR of 24 months (range 24-29 months). One patient still is on therapy, while four patients do not receive any systemic treatment.
CONCLUSIONS
We proof long-term confirmed CR in mRCC achieved by anti-angiogenic therapy alone or in combination with surgery. Combining surgery and anti-angiogenic therapy based on sorafenib and sunitinib could render patients free of disease even after repeated cycles of systemic treatment.
Topics: Aged; Angiogenesis Inhibitors; Benzenesulfonates; Carcinoma, Renal Cell; Combined Modality Therapy; Female; Humans; Indoles; Kidney Neoplasms; Male; Middle Aged; Nephrectomy; Niacinamide; Phenylurea Compounds; Pyridines; Pyrroles; Remission Induction; Sorafenib; Sunitinib
PubMed: 19576802
DOI: 10.1016/j.urolonc.2009.03.033