Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study characterized the N-glycans of a humanized immunoglobulin G4 (IgG4) expressed in NS/O mouse myeloma cells and directed against the CD18 family of adhesion-promoting receptors on leukocytes. The N-glycans were released from the purified recombinant IgG by N-glycanase treatment, purified by Sephadex G50 chromatography, and fractionated by Bio-Gel P-4 chromatography into three oligosaccharide pools. Each pool was analyzed individually by glycosyl composition analysis, high-pH anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD), 600-MHz 1H-NMR spectroscopy, and electrospray-ionization mass spectrometry. In addition, each of the three pools was subfractionated by HPAEC and the isolated subfractions that contained sufficient material were hydrolyzed and analyzed for glycosyl composition by HPAEC-PAD. The overall results indicate the presence of five oligomannoside-type structures (containing 5 to 8 Man residues) which are not usually found in IgG, and the presence of eight diantennary (mostly truncated) N-acetyllactosamine-type structures which are typical of mouse and human IgGs. The N-acetyllactosamine-type structures were heterogeneous with regard to alpha(1-->6) fucosylation of the linkage GlcNAc, and the presence or absence of GlcNAc and/or Gal beta(1-->4)GlcNAc extending the core pentasaccharide (Man3GlcNAc2). No evidence was found for the presence of sialic acid or bisecting GlcNAc residues on the N-acetyllactosamine-type chains. The latter finding suggests that the N-glycans of this humanized IgG are of the mouse type.
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PMID:Structural characterization of the N-glycans of a humanized anti-CD18 murine immunoglobulin G. 790 4

Bortezomib (formerly PS-341) has significant activity in patients with relapsed multiple myeloma (MM), its efficacy is increased with the addition of dexamethasone and it demonstrates synergy with doxorubicin, thus providing the rationale for combination therapy with bortezomib, doxorubicin and dexamethasone (PAD). Patients with untreated MM received four 21-d cycles of PAD, comprising bortezomib 1.3 mg/m(2) on days 1, 4, 8 and 11, along with dexamethasone 40 mg on days 1-4, 8-11 and 15-18 during cycle 1 and days 1-4 during cycles 2-4. During days 1-4, patients also received 0, 4.5 or 9 mg/m(2) of doxorubicin at dose levels 1, 2, and 3 respectively. Following peripheral blood stem cell (PBSC) collection, patients received high-dose melphalan (MEL200) with PBSC transplantation (PBSCT). After PAD induction alone, 20 of 21 patients (95%) achieved at least a partial response (PR), including complete response (CR) in five patients (24%). Twenty of 21 had PBSC mobilized, and 18 of 20 received MEL200/PBSCT. In an intention-to-treat analysis, response rates were: CR 43%, near CR 14%, very good PR 24%, PR 14% and stable disease 5%. PAD was effective, did not prejudice subsequent PBSC collection, and should be further evaluated in prospective randomized trials.
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PMID:PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma. 1595 1

Bortezomib, doxorubicin and dexamethasone (PAD) was evaluated as induction before stem cell transplantation in newly diagnosed multiple myeloma (MM) patients, using bortezomib 1.3 mg/m(2) (PAD1, N = 21) or 1.0 mg/m(2) (PAD2, N = 20). Complete/very good partial response rates with PAD1/PAD2 were 62%/42% postinduction and 81%/53% post-transplant. Progression-free survival (29 vs. 24 months), time to re-treatment (36 vs. 29 months) and overall survival (1 year: 100% vs. 95%; 2 years: 95% vs. 73%) were statistically similar but favoured PAD1 versus PAD2. Toxicity was lower in PAD2; bortezomib dose reduction may help manage toxicities while retaining efficacy. PAD is highly active as front-line induction in MM.
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PMID:Bortezomib, doxorubicin and dexamethasone (PAD) front-line treatment of multiple myeloma: updated results after long-term follow-up. 1837 Nov 13

The most aggressive and rare manifestation of multiple myeloma is plasma cell leukaemia (PCL). While secondary form of PCL represents those heavily pretreated cases when leukaemic transformation develops terminally after intensive chemotherapy in patients with multiple myeloma, primary cases are characterized by leukaemic symptoms present at diagnosis. The secondary form has a rapid progression. The management of PCL is still unsolved. The authors present a case of a patient with non-secretory multiple myeloma who had developed plasma cell leukaemia after peripheral stem cell transplantation. PAD (bortezomib, doxorubicin, dexamethasone) treatment resulted in complete remission and 9-month survival of the patient. Previous case reports in the literature and our experience have revealed PAD protocol to be well tolerated and effective in PCL. Combination of PAD treatment with autologous and/or allogenic stem cell transplantation might further improve patients' outcome.
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PMID:[Effective PAD (bortezomib, doxorubicin, dexamethasone) treatment of a patient with plasma cell leukaemia that has developed after autologous stem cell transplantation]. 1884 14

Doxorubicin and pegylated liposomal doxorubicin are key compounds of several induction regimens used prior to autologous stem cell transplantation in patients with de novo multiple myeloma, such as vincristine, doxorubicin, dexamethasone (VAD), vincristine, pegylated liposomal doxorubicin/Doxil, dexamethasone (DVd) or PS-341/bortezomib, doxorubicin, dexamethasone (PAD). The aim of this article is to summarize the more recent data available on the efficacy of these combinations and to discuss their role as part of initial therapy.
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PMID:Combination regimens using doxorubicin and pegylated liposomal doxorubicin prior to autologous transplantation in multiple myeloma. 1958 27

PURPOSE To evaluate the effect of bortezomib as induction therapy before autologous transplantation, followed by lenalidomide as consolidation-maintenance in myeloma patients. PATIENTS AND METHODS Newly diagnosed patients age 65 to 75 years were eligible. Induction (bortezomib, doxorubicin, and dexamethasone [PAD]) included four 21-day cycles of bortezomib (1.3 mg/m(2) on days 1, 4, 8, and 11), pegylated liposomal doxorubicin (30 mg/m(2) on day 4), and dexamethasone (40 mg/d; cycle 1: days 1 to 4, 8 to 11, and 15 to 18; cycles 2 to 4: days 1 to 4). Autologous transplantation was tandem melphalan 100 mg/m(2) (MEL100) and stem-cell support. Consolidation included four 28-day cycles of lenalidomide (25 mg/d on days 1 to 21 every 28 days) plus prednisone (50 mg every other day), followed by maintenance with lenalidomide (LP-L; 10 mg/d on days 1 to 21) until relapse. Primary end points were safety (incidence of grade 3 to 4 adverse events [AEs]) and efficacy (response rate). Results A total of 102 patients were enrolled. In a per-protocol analysis, after PAD, 58% of patients had very good partial response (VGPR) or better, including 13% with complete response (CR); after MEL100, 82% of patients had at least VGPR and 38% had CR; and after LP-L, 86% of patients had at least VGPR and 66% had CR. After median follow-up time of 21 months, the 2-year progression-free survival rate was 69%, and the 2-year overall survival rate was 86%. During induction, treatment-related mortality was 3%; grade 3 to 4 AEs included thrombocytopenia (17%), neutropenia (10%), peripheral neuropathy (16%), and pneumonia (10%). During consolidation-maintenance, grade 3 to 4 AEs were neutropenia (16%), thrombocytopenia (6%), pneumonia (5%), and cutaneous rash (4%). CONCLUSION Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance, is an effective regimen.
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PMID:Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients. 2004 87

This prospective study evaluated the risk of arterial thrombosis in 195 consecutive patients aged 18 to 65 years with newly diagnosed multiple myeloma (MM). All patients were treated with 3 cycles of VAD (vincristine, doxorubicin, and dexamethasone) or TAD (thalidomide-AD) or PAD (bortezomib-AD) in national trials, followed by high-dose melphalan and autologous stem cell transplantation. For a period of 522 patient-years, 11 of the 195 patients (5.6%) developed arterial thrombosis. The highest incidence was seen during induction chemotherapy courses. Median age at onset of arterial thrombosis was 59 years (range, 43-65 years). Hypertension and smoking were significantly associated with arterial thrombosis with a relative risk of 11.7 (2.23-61.2) and 15.2 (1.78-130), respectively. Factor VIII levels (FVIII:C) correlated significantly with age (P = .02) and higher International Scoring System (ISS) stage (P = .001). A higher FVIII:C was associated with arterial thrombosis (hazard ratio [HR] = 1.85; 95% confidence interval [CI] = 0.99-3.47) after adjustment for age, ISS score, and assigned treatment arm. MM patients have an increased risk for arterial thrombotic events during and after induction chemotherapy. Hypertension, smoking, and high factor VIII levels, possibly reflecting disease activity, contribute to the risk of arterial thrombosis.
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PMID:High incidence of arterial thrombosis in young patients treated for multiple myeloma: results of a prospective cohort study. 2061 23

We conducted a phase 2 study with bortezomib, doxorubicin, and dexamethasone (PAD) followed by thalidomide and dexamethasone (TD) in patients with relapsed multiple myeloma (MM). Forty patients were enrolled between November 2005 and October 2007, with follow-up continuing until January 2009. Efficacy could be assessed in 37 patients. The overall response rate to PAD followed by TD was 83.6%: complete response 51.4%, near-complete response 13.4%, very good partial remission 5.4%, and partial response 13.4%. The median follow-up was 27 months (range 13-39). The median progression-free survival (PFS) from the start of treatment was 18 months (95% CI, 9.7-26.2 months), with a 1-year PFS rate of 56.9% and 3-year PFS rate of 25.7%. Median overall survival was 35.1 months (95% CI, 18.5-51.7), with a 1-year survival rate of 75% and 3-year survival rate of 27.3%. One hundred seventy-eight PAD cycles (median 6, range 1-6) in 38 patients were assessable for safety. The most common hematologic toxicity was thrombocytopenia, with grade 3-4 in 35.8%. Sensory neuropathy occurred at grade 2 in 26.3% and grade 3 in 10.3%. Two hundred TD treatment cycles (median 4, range 0-12 cycles) were administered. Most adverse events were of mild degree and manageable. PAD followed by TD in patients with relapsed MM is very effective and tolerable.
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PMID:Bortezomib, doxorubicin, and dexamethasone combination therapy followed by thalidomide and dexamethasone consolidation as a salvage treatment for relapsed or refractory multiple myeloma: analysis of efficacy and safety. 2034 60

The study was aimed to evaluate the adverse effects of PAD (bortezomib + adriamycin + dexamethasone) and VAD (vincristine + adriamycin + dexamethasone) as chemotherapy regimens in multiple myeloma patients. 27 and 30 patients with multiple myeloma (MM) were enrolled in PAD and VAD groups respectively. MM patients accepted 3 - 5 cycles of VAD or PAD regimens. The type, degree and occurrence time of adverse reactions during the treatment were observed. The results showed that the rash was found in two patients only in PAD group, leucocytopenia, thrombocytopenia, peripheral neuropathy, infection, fatigue, nausea, constipation, and adverse effects of cortex hormone (hypertension, glycemia, hypokalemia, hyponatremia and acne) were found in the both two groups. The thrombosis was not observed in both two groups during treatment. Although statistical analysis indicated that only the incidence of thrombocytopenia was higher in PAD group than in VAD group with statistical difference but the incidence of leucocytopenia, peripheral neuropathy and infection in PAD group were higher than those in VAD group. Rash, constipation, peripheral neuropathy could be found in the first course of chemotherapy, while the others mostly emerged after 3 courses of treatment. The main reasons for the patients who's treatment was stopped include infection and intolerable peripheral neuropathy. Although peripheral neuropathy could be found in the two groups, but the chemotherapy was stopped only in 2 patients of PAD group after 3 cycles of treatment. It is concluded that compared with conventional VAD chemotherapy, PAD may improve therapeutic effect, but it may bring more severe toxicities to the patients with multiple myeloma.
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PMID:[Adverse effects of PAD and VAD regimens in multiple myeloma patients]. 2072 22

Severe renal failure (RF) may be the first and only clinical manifestation of multiple myeloma (MM). Occasionally the disease remains long unrecognized and the patients receive renal function replacement therapy, including renal transplantation (RT). To treat MM in renal transplant recipients is a complex medical and ethical problem. The paper presents the authors' experience in treating 3 patients with MM diagnosed after RT and evolving transplant lesion. Various morphological types of grafted kidney lesion were detected. These included fibrillar glomerulonephritis, cast nephropathy, and the latter concurrent with light-chain deposition disease. RF most rapidly progressed in cast nephropathy. The natural history of the disease was unfavorable in all patients; VAD and PAD chemotherapy programs proved to be ineffective. It is concluded that RT should not be performed in patients with extended-stage MM due to the fact that there is a considerable risk for renal transplant lesion and severe infectious complications that may occur during chemotherapy. Blood and urine immunochemical studies should be conducted in all the patients who are to undergo RT.
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PMID:[Multiple myeloma in renal transplant recipients]. 2085 15


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