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

Immune reconstitution may be delayed after CD34-selected compared with unmanipulated autologous peripheral blood stem cell transplantation (PBSCT), resulting in a theoretically increased risk of infections. In a case-control matched study we compared the incidence of infection in 25 recipients of CD34-selected PBSC (CD34 group) and 75 recipients of unmanipulated PBSC (PBSC group) transplants. The population included 52 males and 48 females suffering from non-Hodgkin's lymphoma (n = 32), Hodgkin's disease (n = 8), multiple myeloma (n = 40) or breast cancer (n = 20). Neutrophil engraftment was comparable in the two groups. The actuarial incidence of infection was similar in the two groups (56% vs. 49% at day 30, and 70% vs. 64% at 1 yr respectively). The proportion of patients with 1, 2 or 3 infections, the number of infectious event per patient (1.32 vs. 1.04; NS), the number of infections before day 15 or 30, between days 31 and 100 or after day 100, the risk of varicella-zoster virus or cytomegalovirus infection or disease, or the use of antibiotic or antifungal therapy, were not increased in the CD34 compared with the PBSC group. The main agents responsible for infection were bacteria, particularly gram-positive cocci, in both groups. Bacteremia accounted for 33% of all infectious events in the CD34 group vs. 16% in the PBSC group (P < 0.05). Fungal infections were rare. In conclusion, our results do not support the notion that CD34-selection of the graft is associated with an increased rate of infection after autologous PBSC transplantation. The role of extended infection prophylaxis should be evaluated.
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PMID:Infections after CD34-selected or unmanipulated autologous hematopoietic stem cell transplantation. 1640 30

Reactivation of varicella zoster virus (VZV) is a common event after stem cell transplantation (SCT). When activated in the abdominal cavity, the infection may be life threatening. Visceral presentation with VZV infection is uncommon, although probably an under-diagnosed event in post-SCT patients. The interval from onset of abdominal pain to the development of skin eruptions may delay the initiation of specific antiviral therapy and symptoms may be incorrectly diagnosed as surgical disease or graft-versus-host disease. We describe the case of a 53-year-old man who had undergone stem cell autograft for multiple myeloma and developed visceral VZV infection with hepatitis, melaena and subileus 7 months later.
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PMID:Visceral varicella zoster virus infection after stem cell transplantation: a possible cause of severe abdominal pain. 1648 31

We report the incidence of varicella zoster virus (VZV) and herpes simplex virus (HSV) infection in patients with multiple myeloma and colon cancer who were treated with arsenic trioxide for their disease. In this report, we discuss the effects of arsenic on immune system, and suggest arsenic compounds as a possible predisposing factor for viral reactivation in these patients.
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PMID:The incidence of recurrent herpes simplex and herpes zoster infection during treatment with arsenic trioxide. 1648 89

The present study evaluated cellular and humoral immune parameters in myeloma patients, focusing on the effect of treatment and the risk of opportunistic infections. Peripheral blood lymphocyte subsets and serum levels of nonmyeloma immunoglobulins (Ig) were analysed in 480 blood samples from 77 myeloma patients. Untreated myeloma patients exhibited significantly reduced CD4+/45RO+, CD19+, CD3+/HLA-DR+, and natural killer (NK) cells, as well as nonmyeloma IgA, IgG and IgM. Conventional-dose chemotherapy resulted in significantly reduced CD4+ and even further decline of CD4+/CD45RO+ and CD19+ cells, most notably in relapsed patients. Additional thalidomide treatment had no significant effects on these parameters. Following high-dose chemotherapy (HD-CTX), prolonged immunosuppression was observed. Although CD8+, NK, CD19+ and CD+/CD45RO+ cells recovered to normal values within 60, 90, 360 and 720 days, respectively, CD4+ counts remained reduced even thereafter. Nine opportunistic infections were observed, including five cytomegalovirus (CMV) diseases, one Pneumocystis carinii pneumonia (PCP) and three varicella zoster virus infections with CMV diseases and PCP occurring exclusively after HD-CTX. Opportunistic infections were correlated with severely reduced CD4+, as well as CD4+/CD45RO+ and CD19+ counts. Thus, myeloma patients display cellular and humoral immunodeficiencies, which increase following conventional as well as HD-CTX, and constitute an important predisposing factor for opportunistic infections.
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PMID:Immune parameters in multiple myeloma patients: influence of treatment and correlation with opportunistic infections. 1696 69

Bortezomib, a proteasome inhibitor, has been used for patients with refractory and relapsed multiple myeloma, lymphoma and leukemia. We used bortezomib in ten refractory or relapsed patients (seven of multiple myeloma, two of lymphoma and one of acute myeloblastic leukemia). Six out of ten (60%) patients developed varicella herpes zoster after the complete of one cycle of bortezomib. The incidence of varicella herpes zoster was higher than reported in the literature. It may be due to immunosuppression caused by the combination of high-dose dexamethasone or other drugs. We considered that prophylactic antiviral medication could be used in predisposed patients to reduce the incidence of varicella herpes zoster.
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PMID:The high incidence of varicella herpes zoster with the use of bortezomib in 10 patients. 1713 26

The present study analyses the influence of high-dose chemotherapy (HD) and autologous stem cell transplantation on natural and vaccine induced specific immunity in multiple myeloma patients. Peripheral blood was collected from six multiple myeloma (MM) patients at serial time points in connection with treatment and during a follow-up period of 3 months. T-cell response to cytomegalovirus (CMV), varicella zoster virus (VZV) and tetanus toxoid (TT) was determined by flow cytometry analysis for CD69, TNFalpha, IFNgamma, IL-4 expression and cell proliferation. At diagnosis and prior to induction chemotherapy TNFalpha expressing T cells in 5/6 patients were found specific for CMV, 3/6 for VZV and 4/6 for TT. Serial analyses during treatment conclude impaired immune response, however, 3 months post-transplantation all but one patient had regained cytokine expressing CD8(+) T cells specific for CMV, VZV and TT. The highest percentages of cytokine responding T cells were observed after stimulation with CMV antigen. A striking observation was the low cytokine reactivity (close to zero) measured in G-CSF mobilized blood at the time of leukapheresis. In spite of a general reduction of the CD4/CD8 ratio following transplantation, recovery of antigen specific CD4(+) T cells reactivity generally occurred prior to CD8(+) recovery and often to a higher level. In conclusion, the study demonstrates that natural as well as vaccine induced specific immunity present prior to HD was regained after stem cell transplantation, hence identifying a possible window for future vaccination trials.
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PMID:Antigen-specific T-cell immunity in multiple myeloma patients is restored following high-dose therapy: implications for timing of vaccination. 1785 May 92

A 65-year-old Japanese male was diagnosed as multiple myeloma with Bence Jones kappa type, clinical stage IIIA. His disease status reached partial remission after chemotherapy. Thereafter, he received tandem transplantation, consisting of high-dose chemotherapy with autologous stem cell transplantation (ASCT), followed by unrelated cord blood transplantation (U-CBT). U-CBT with a reduced-intensity conditioning regimen (RI-CBT) was performed in August 2003. HLA mismatch between the patient and the CBT donor was present at two serological loci (B and DR). A total nucleated CBT cell dose of 2.45 x 10(7)/kg body weight was infused on day 0. Graft-vs.-host disease (GVHD) prophylaxis consisted of cyclosporine A and short-term methotrexate. Neutrophil engraftment (>0.5 x 10(9)/l) was obtained on day 46. He developed positive cytomegalovirus antigenemia, grade II acute GVHD involving skin and liver, varicella-zoster virus infection, septic shock, hemorrhagic cystitis caused by adenovirus and acute hepatitis B virus infection after U-CBT. We retrospectively analyzed T-cell receptor (TCR) repertoire diversity and found that TCR repertoire diversity decreased continuously after U-CBT. Therefore, low-TCR repertoire diversity in this patient appears to be associated with various infections caused by immunodeficiency.
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PMID:Chimerism and T-cell receptor repertoire analysis after unrelated cord blood transplantation with a reduced-intensity conditioning regimen following autologous stem cell transplantation for multiple myeloma. 1819 Apr 73

Bortezomib, a proteasome inhibitor, has been used for patients with refractory multiple myeloma. We present a 58-year old man who had IgG-gamma-type multiple myeloma, refractory for MP (melphalan-predonisolone) and VAD (vincrisitine-doxorubicin-dexamethasone) therapy. He was complicated with reactivation of varicella-zoster virus (VZV) 4 weeks before bortezomib administration. Two weeks of consolidation treatment with standard dose valaciclovir caused VZV infection to settle down and, after a further 2 weeks, VZV remission was confirmed. Bortezomib was started at a dose of 1.3 mg/m2 with prophylactic use of valaciclovir for VZV reactivation, post-herpetic neuralgia exacerbated the following day and grade 3 neuralgia developed the following week without recurrence of skin eruption. Neuralgia improved after the cessation of bortezomib with various supportive treatments and interventions. Although the reactivation of VZV was suspicious, no apparent skin lesions were observed. Although the mechanisms of post-herpetic neuralgia and chemotherapy-induced neuropathy are different, bortezomib might enhance post-herpetic neuralgia independent of the manner of viral reactivation.
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PMID:[Aggravated post-herpetic neuralgia due to bortezomib]. 1857 10

The appropriate induction therapy before and the role of maintenance therapy after auto-SCT for patients with multiple myeloma remain areas of active investigation. We conducted a study in 40 patients with bortezomib given sequentially pre-auto-SCT and as maintenance therapy post auto-SCT. Pre-transplant bortezomib was administered for two cycles followed by high-dose melphalan 200 mg/m(2) with auto-SCT of G-CSF-mobilized PBMCs. Post transplant bortezomib was administered weekly for 5 out of 6 weeks for six cycles. No adverse effects were observed on stem cell mobilization or engraftment. An overall response rate of 83% with a CR+very good partial remission (VGPR) of 50% was observed with this approach. Three-year Kaplan-Meier estimates of disease-free survival and overall survival (OS) were 38.2 and 63.1%, respectively. Bortezomib reduced CD8(+) cytotoxic T cell and CD56(+) natural killer cell PBL subsets and was clinically associated with high rates of viral reactivation to varicella zoster.
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PMID:Bortezomib administered pre-auto-SCT and as maintenance therapy post transplant for multiple myeloma: a single institution phase II study. 1902 64

We report a 54-year-old man who developed visceral varicella-zoster virus (VZV) infection after autologous peripheral blood stem cell transplantation (auto-PBSCT) without using immunosuppressive agents for multiple myeloma. He suffered from severe abdominal pain 2 months after auto-PBSCT, and morphine chloride was needed to control it. Since the characteristic skin rash of VZV infection appeared over his entire body on the seventh hospital day, aciclovir was immediately started with favorable results. It is extremely difficult to diagnose VZV infection when severe abdominal pain proceeds and the eruptions characteristic of VZV infections are absent. This may also result in devastating delays in effective antiviral treatment. The increase in fat density around the celiac trunk and the root of the superior mesenteric artery on computed tomography shown in this case may has contributed to the correct diagnosis of visceral VZV infection.
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PMID:[Case of visceral varicella-zoster virus infection after autologous peripheral blood stem cell transplantation in which severe abdominal pain preceded the skin rash]. 2113 64


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