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At least 1,243 records · Page 69Linked to original sources
PubMed2002

Angioimmunoblastic lymphadenopathy (AILD) may respond to thalidomide treatment: two case reports.

The histological morphology of AILD-type T-cell lymphoma shows proliferation of small, arborizing high endothelial venules. Patients typically have generalized lymphadenopathy, fever, weight loss, skin rash, polyclonal hypergammaglobulinemia and autoimmune phenomena, and are susceptible to infections. The clinical course is usually aggressive. About 30% of patients have an initial remission on steroids alone, but most require some form of cytotoxic chemotherapy. Median survival ranges from 15 to 24 months, and it appears that the disease cannot be cured. We have used anti-angiogenetic therapy with thalidomide in two AILD patients and observed remarkable responses.

Adolescent↗
PubMed2004

Discordant response or progression in patients with myeloma treated with thalidomide-based regimens.

UNLABELLED: Thalidomide-based regimens (TBR) are now widely used for the treatment of refractory multiple myeloma and have shown significant activity in newly diagnosed patients. In some patients with secretory disease, we observed discrepancies between the reduction of the monoclonal protein levels and the plasma cell infiltration in the bone marrow and/or extramedullary sites of relapse after treatment with TBR. The purpose of this study was to assess the incidence and analysis of this phenomenon in all myeloma patients treated with TBR in our Institution. PATIENTS AND METHODS: We studied all patients who received TBRs and had a follow up time of at least 6 months. Partial response (PR) was defined as at least 50% reduction of serum myeloma protein and soft tissue plasmacytomas and/or > 90% reduction of Bence Jones protein excretion and minor response as a > 25% reduction of the serum myeloma protein or > 50% reduction of the Bence Jones myeloma protein. RESULTS: Between July 1999 and July 2002 we treated 94 patients with advanced myeloma and 9 patients with newly diagnosed disease with TBR. Sixty-seven patients (66%) achieved either partial or minor response. In 4 patients (3 with advanced and 1 with newly diagnosed myeloma) the bone marrow was heavily infiltrated by plasma cells, despite a decrease of the paraprotein levels ranging from 38% to 68%. This discordance between monoclonal protein levels and bone marrow plasmacytosis was noted in 6% of patients rated as responders and in 11% of responding patients who actually had a repeat bone marrow assessment. Furthermore 6 responding patients, after achieving a PR which lasted between 5 and 9 months, relapsed with bone marrow (all cases), and extramedullary (2 cases) plasmacytosis, without increase of serum and/or urine monoclonal protein. This hyposecretory conversion was noted in 12.5% of relapsing patients. CONCLUSION: Our data indicate that after treatment with TBR some patients with myeloma show discordant responses of the monoclonal protein levels and the bone marrow or extramedullary plasmacytosis. If our data are confirmed, they may have practical implications for assessment of response and follow up of patients treated with TBR.

Adult↗
PubMed2004

Treatment of relapsed/refractory multiple myeloma with thalidomide-based regimens: identification of prognostic factors.

We evaluated the predictive value of several parameters, including the International Staging System (ISS) for myeloma, in patients with advanced disease treated with thalidomide-based regimens (TBR). We analyzed 119 patients, from 3 phase II studies. Patients with pretreatment beta2 microglobulin<3.5 mg/l and albumin 3.5 g/dl were scored ISS stage 1, patients with beta2 microglobulin<3.5 mg/l and albumin<3.5 g/dl or beta2 microglobulin 3.5-5.5 mg/l regardless of albumin levels were scored ISS stage 2, patients with beta2 microglobulin>5.5 mg/l ISS stage 3. ISS stage was 1, 2 and 3 in 45, 32 and 23% of patients respectively. Seventy-four patients (62%) achieved at least partial response. Median progression-free and overall survival were 8 months and 19.5 months respectively. ISS stage, serum LDH and performance status were independent predictive factors for survival. Based on these 3 variables a scoring system was developed with survival times of 38.1, 28.8 and 5.8 months for scores 0, 1 and 2 respectively. The ISS staging system was highly predictive for overall survival of patients with advanced myeloma treated with TBR. With the addition of performance status and serum LDH, a simple scoring system was developed which may help select patients likely to benefit from TBR.

Adult↗
PubMed2006

Low dose Velcade, thalidomide and dexamethasone (LD-VTD): an effective regimen for relapsed and refractory multiple myeloma patients.

From January 2004, R/R MM cases referred to the Institution received LD-VTD regimen. Patients, irrespective of age, PS and life expectancy, were enrolled in the study once they had a measurable disease. Planned therapy: Velcade 1.0 mg m(-2) i.v. twice weekly for 2 weeks of a 28-day cycle for up to 6 cycles, oral Dexamethasone 24 mg on the day of and the day following each Velcade dose and Thalidomide 100 mg each evening. DVT prophylaxis with warfarin to maintain international normalized ratio between 2.0-3.0 was planned in all patients. As of 1 June 2005, 18 were the treated patients: median age 63 years, median time from diagnosis 5.8 years, a median of 4 previous therapy lines. Seventeen were the valuable patients and 9 (53%) were the responders: 2 CR, 6 PR, 1 MR. Six were the stable disease and 2 the progressive ones. Median time to best response was 2 months. Toxicity was negligible. No case of DVT was recorded. Except for the first cycle, subsequent cycles were delivered on an outpatient basis. After a median follow-up of 11 months, 12 patients were alive and 5 died (3 disease progression, 1 heart failure, 1 intestinal bleeding). Thus, the LD-VTD regimen applied appears feasible and effective in elderly and heavily pre-treated R/R myeloma patients.

Aged↗
PubMed2006

The combination of cyclophosphomide, thalidomide and dexamethasone is an effective alternative to cyclophosphamide - vincristine - doxorubicin - methylprednisolone as induction chemotherapy prior to autologous transplantation for multiple myeloma: a case-matched analysis.

A retrospective case-matched study was conducted to compare the oral regimen CTD (cyclophosphamide - thalidomide - dexamethasone) and infusional CVAMP (cyclophosphamide - vincristine - doxorubicin - methylprednisolone) as induction therapy followed by autologous peripheral blood stem-cell transplantation (PBSCT) for newly diagnosed multiple myeloma patients. The response rate after three cycles of treatment was statistically higher with CTD (n = 27) compared to CVAMP (n = 27) (89% vs. 56%, P = 0.016). Toxicity studies showed more neutropenia (grade 3/4) (4% vs. 60%, P = 0.0002) with CVAMP and more thrombotic episodes with CTD (11% vs. 4%). CTD may emerge as the superior induction regimen prior to PBSCT, in terms of high efficacy and better tolerability.

Adult↗
PubMed2006

Prognostic factors for the efficacy of thalidomide in the treatment of multiple myeloma: a clinical study of 110 patients in China.

Thalidomide (Thal) has been used for a few years as salvage treatment for patients with multiple myeloma (MM). However, the response rate in Chinese patients treated with Thal has not been determined and the prognostic factors for response rate (RR), progression-free survival (PFS) and overall survival (OS) not yet well identified. This study enrolled 110 Chinese patients with MM who received either Thal alone, Thal plus dexamethasone (Thal + Dex) or Thal plus conventional chemotherapy (Thal + CC). Their laboratory and clinical parameters were retrospectively analysed. The overall RR was 63.6% (complete response rate 6.4%, partial response rate 57.3%). Patients aged < 65 years, time from diagnosis to the start of Thal treatment < 6 months or combined therapy had a significantly higher RR (p < 0.05). In univariate analysis, age < 65years predicted a longer PFS (p = 0.008). Age < 65 years, serum creatinine < 176.8 micromol L-1 and serum beta 2 microglobulin (beta2M) < 3.5 mg L-1 were associated with longer OS (p = 0.028, 0.045 and 0.019, respectively). Multi-factor analysis suggested that serum beta2M was the only independent prognostic factor for OS (p = 0.025).

Aged↗
PubMed1991

Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes.

Thalidomide selectively inhibits the production of human monocyte tumor necrosis factor alpha (TNF-alpha) when these cells are triggered with lipopolysaccharide and other agonists in culture. 40% inhibition occurs at the clinically achievable dose of the drug of 1 micrograms/ml. In contrast, the amount of total protein and individual proteins labeled with [35S]methionine and expressed on SDS-PAGE are not influenced. The amounts of interleukin 1 beta (IL-1 beta), IL-6, and granulocyte/macrophage colony-stimulating factor produced by monocytes remain unaltered. The selectivity of this drug may be useful in determining the role of TNF-alpha in vivo and modulating its toxic effects in a clinical setting.

Blood Proteins↗
PubMed2000

Inflammatory pseudotumor causing small bowel obstruction and mimicking lymphoma in a patient with AIDS: clinical improvement after initiation of thalidomide treatment.

A patient with AIDS was diagnosed with inflammatory pseudotumor with small bowel involvement. After receiving thalidomide treatment, serum tumor necrosis factor (TNF) and soluble TNF receptor II levels normalized, his constitutional and gastrointestinal symptoms diminished, and the mass lesion shrunk.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Successful treatment of idiopathic colitis and proctitis using thalidomide in persons infected with human immunodeficiency virus.

Gastrointestinal ulcerations in persons infected with HIV have many causes, the most common being opportunistic infections and neoplasms. Recently, idiopathic ulcerative lesions of the colon and rectum have been described. Two cases are reported of idiopathic colonic and anorectal inflammation and ulceration which failed traditional therapies but responded to thalidomide with complete clinical and histologic resolution.

Adult↗
PubMed1999

Influence of cyclodextrins on the in vitro corneal permeability and in vivo ocular distribution of thalidomide.

The aim of the present study has been to develop aqueous Thalidomide (THA) eye drops in order to minimize systemic side effects and to improve bioavailability following topical application. Cyclodextrins (CDs), suitable vehicles to improve aqueous solubility of THA, were evaluated with regard to their ability to influence in vitro corneal permeability of THA. Additionally, rabbit eyes received either THA-suspension (0.04%) (THA-SP) or THA (0.04%)/hydroxypropyl-beta-cyclodextrin (HP-beta-CD) (12.5%) solution (THA-CD). In vitro corneal permeation studies demonstrated that the absolute amount of THA permeated could not be increased by means of CDs. The percentile release of THA was extensively decreased using saturated THA/CD solutions. Following loading doses of either THA-CD or THA-SP onto the rabbit eye, significantly increased aqueous humor levels were obtained for THA-CD 30 min (THA-CD:THA-SP=4.6:1) and 60 min (THA-CD:THA-SP=3.1:1) post instillation (p<0.05). In the iris-ciliary body, significantly increased THA levels were obtained using THA suspension (THA-CD(60 min):THA-SP(60 min)=1:6.1) (p<0.05). In the cornea, conjunctiva, vitreous and sclera, differences between the THA tissue levels were not statistically significant. Cyclodextrins might be a useful tool to formulate aqueous THA eye drop solutions and modify intraocular drug bioavailability.

Angiogenesis Inhibitors↗
PubMed1996

Regression of AIDS-related Kaposi's sarcoma during therapy with thalidomide.

A 14-year-old girl with HIV infection and subcutaneous Kaposi's sarcoma (KS) received thalidomide therapy for oral ulcers, resulting in regression of KS lesions, disappearance of KS-associated herpesvirus (KSHV) DNA from blood, and reduced viral load in tumor tissue. Administration of grauntocyte colony-stimulating factor resulted in clinical exacerbation of KS and reappearance of KSHV DNA in blood.

Adolescent↗
PubMed2001

Management of Kaposi sarcoma: the role of interferon and thalidomide.

Kaposi sarcoma (KS) remains the most commonly diagnosed cancer in HIV-infected patients. Although several chemotherapeutic agents have proven effective in controlling KS, the growing understanding of the factors contributing to the development of KS has provided a stronger rationale for using noncytotoxic agents that influence the mechanisms involved in KS pathogenesis. Two such agents, interferon and thalidomide, have shown activity against KS in clinical trials and have the potential to influence multiple steps believed to be important in KS development and progression. Studies are ongoing to explore the optimal way to use these agents and their mechanisms of action.

Antiviral Agents↗
PubMed1986

Treatment and prevention of acute graft-versus-host disease with thalidomide in a rat model.

We have investigated the immunosuppressive effects of thalidomide (Thal) in a bone marrow transplant (BMT) model for graft-versus-host disease (GVHD). Lewis rats received RT1-incompatible marrow transplants from ACI rats after total-body irradiation. Twenty-two of twenty-three rats with established severe acute GVHD were successfully treated with Thal. Thal was given for therapy by gavage at 50 mg/kg/day or 100 mg/kg/day for 40 days after GVHD was clinically and histologically present. Fourteen of twenty-two received prophylaxis successfully with Thal at a dose of 50 mg/kg/day or 100 mg/kg/day. Acute GVHD did not develop after the drug was stopped. Three animals treated for severe GVHD later developed chronic GVHD. Chimerism was shown by permanent acceptance of ACI skin grafts and rejection of third-party skin grafts. Lymphocytes from Thal-treated animals likewise did not respond to Lewis or ACI cells in mixed lymphocyte culture but responded to third-party BN lymphocytes. Thal appears to be a potent new agent for therapy and prophylaxis of GVHD.

Animals↗
PubMed1991

Lupus erythematosus profundus with partial C4 deficiency responding to thalidomide.

A female patient with disfiguring lupus erythematosus profundus (LEP) from the age of 13 years was found to have an isolated partial C4 deficiency, with reduced levels of both allotypes, C4A and C4B. A genetic basis for the hypocomplementaemia was confirmed by a family study of complement and HLA types which revealed heterozygous null alleles for C4A and C4B in the proband. Marked improvement in her cutaneous lesions occurred with thalidomide.

Adolescent↗
PubMed2006

Doxorubicin and dexamethasone followed by thalidomide and dexamethasone is an effective well tolerated initial therapy for multiple myeloma.

Among the drug combinations designed for the initial treatment of multiple myeloma, none has been unequivocally shown to be superior. However, a regimen leading to a high response rate and a low incidence of adverse events is highly desirable. We report the results of a phase II clinical trial involving 45 patients with Durie-Salmon stage II and III multiple myeloma. Doxorubicin and dexamethasone were given for 2 or 3 months followed by thalidomide and dexamethasone for 2 months (AD-TD regimen) with prophylactic antibiotics and daily aspirin (81 mg/d). Among the 42 patients whose response could be assessed, 38 responded to therapy (90.5%). The intent-to-treat response rate was 84.4% with seven complete responses (CR 15.5%), nine near complete responses (nCR 20.0%), and 22 partial responses (PR 48.9%). Two patients had stable disease (4.4%), and two progression of disease (4.4%). Normalization of the free light chain ratio after one or two cycles of treatment was highly predictive of achievement of CR or nCR. Patients tolerated the treatment well although five patients developed thromboembolic complications (11%). AD-TD administered with low dose aspirin for deep vein thrombosis prophylaxis was well tolerated and yielded a high response rate with minimal treatment-related morbidity.

Adult↗
PubMed2006

Von Willebrand's disease and angiodysplasia treated with thalidomide.

A 54-year-old man with type IIB VWD and severe angiodysplasia had such a large blood loss from the bowel that it was difficult to keep up with transfusion requirements. Treatment with factor eight concentrate barely slowed the loss. D.D.A.V.P., Octreotide, and recombinant activated Factor VII, tried separately, were ineffective. The use of Thalidomide at a dose of 150 mg daily has rendered him free from blood loss for the last six months and we suggest would be worth a trial in similar cases.

Angiodysplasia↗
PubMed1985

Thalidomide therapy. An open trial.

In an open trial, 35 patients suffering from a variety of dermatologic conditions were treated with thalidomide. The drug was shown to be a valuable addition to the therapeutic armamentarium; however, the occurrence of a peripheral neuropathy will limit its use just as its teratogenic side effects have done for many years.

Adult↗
PubMed2005

Reduced somatosensory hand representation in thalidomide-induced dysmelia as revealed by fMRI.

The concept of cerebral plasticity suggests that the hand representation in somatosensory cortex is abnormal in congenital malformation disorders. To investigate this issue we studied 11 subjects with different degrees of upper extremity dysmelia due to thalidomide embryopathy in comparison to 10 control subjects. In the affected subjects fingers are typically missing in radio-ulnar order beginning with the thumb. Haemodynamic responses to electrical stimulation of the radial-most and ulnar-most fingers were measured in each subject using functional magnetic resonance tomography. The size of the hand area in the primary somatosensory cortex was estimated by calculating the Euclidian distance between corresponding activation peaks on the lateral postcentral gyrus. The cortical somatosensory hand representation was found to be significantly smaller in dysmelic subjects as compared with the control subjects (P <0.001). The shrinkage of the hand area was not proportional to the number of missing fingers. Furthermore, the cortical representation of the ulnar fingers in the dysmelic subjects was shifted towards the cortical thumb representation of the control group. We suggest that the unproportional reduction of the hand area together with the observed shift may reflect use-dependent rather than malformation-induced reorganization of the somatosensory hand area.

Adult↗