RESUMO
This retrospective analysis was conducted in 64 patients diagnosed with type I cryoglobulinaemia (CG) followed at two French centres. Median follow-up was 6·75 years. CG was IgG in 60% and IgM in 40% of all cases and was asymptomatic in 16 patients (25%). Cold-triggered ischaemic skin manifestations were observed in 33 patients (51%). Neurological manifestations were observed in 15 patients and renal manifestations in 13. Most of the patients with necrotic purpura (14/16, P = 0·009) and renal manifestations (11/13, P = 0·057) had IgG CG. IgG CG was associated with monoclonal gammopathy of undetermined significance (MGUS), myeloma, chronic lymphocytic leukaemia and lymphoplasmocytic lymphoma in 18, 13, 5 and 2 patients, respectively. IgM CG was associated with MGUS and Waldenström macroglobulinaemia in 8 and 18 cases, respectively. One third of patients did not receive any specific treatment. Various treatments, including rituximab, were administered to 25/31 patients with IgG CG and 6/25 patients with IgM CG due to CG-related symptoms. Rituximab was ineffective in all cases associated with a predominantly plasmacytic proliferation. To conclude, type I CG has specific clinico-biological characteristics compared to type II CG. Furthermore, there are differences in terms of related manifestations between type I IgG and type I IgM CG.
Assuntos
Anticorpos Monoclonais Murinos/administração & dosagem , Antineoplásicos/administração & dosagem , Crioglobulinemia , Imunoglobulina G/sangue , Paraproteinemias , Macroglobulinemia de Waldenstrom , Idoso , Anticorpos Monoclonais Murinos/efeitos adversos , Antineoplásicos/efeitos adversos , Crioglobulinemia/sangue , Crioglobulinemia/tratamento farmacológico , Crioglobulinemia/patologia , Feminino , Seguimentos , Humanos , Isquemia/sangue , Isquemia/tratamento farmacológico , Isquemia/patologia , Rim/patologia , Nefropatias/sangue , Nefropatias/tratamento farmacológico , Nefropatias/patologia , Masculino , Paraproteinemias/sangue , Paraproteinemias/tratamento farmacológico , Paraproteinemias/patologia , Estudos Retrospectivos , Rituximab , Pele/irrigação sanguínea , Pele/patologia , Dermatopatias/sangue , Dermatopatias/tratamento farmacológico , Dermatopatias/patologia , Macroglobulinemia de Waldenstrom/sangue , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/patologiaRESUMO
BACKGROUND: Neutrophilic dermatoses refer to a group of cutaneous inflammatory disorders characterized by neutrophilic infiltration of the skin. Neutrophilic dermatoses have been reported in association with various conditions including autoimmune diseases, inflammatory bowel diseases, and neoplasia. In the later condition, myeloproliferative disorders and monoclonal gammopathy (monoclonal immunoglobulin [MIg]) are the most frequent. Only few data are available in case of neutrophilic dermatoses associated with MIg regarding the pathophysiology and the clinical outcome. OBJECTIVE: We sought to gain further insight into clinical and biological aspects of neutrophilic dermatoses associated with MIg. METHODS: We report a retrospective series of 26 patients with neutrophilic dermatoses associated with MIg focusing on clinical and biological aspects, with a study of a large panel of cytokines, chemokines, and adhesion molecules. RESULTS: This study reveals an association between MIg IgA isotype and neutrophilic dermatoses, and a specific inflammatory pattern including elevated interleukin 6, vascular endothelial growth factor, monocyte chemotactic protein-1, epidermal growth factor, and intercellular adhesion molecule-1. LIMITATIONS: This is a retrospective study from a single institution with a limited number of participants. CONCLUSION: Our data highlight a strong association between IgA isotype and neutrophilic dermatoses, and the existence of a specific inflammatory profile involving several molecules.
Assuntos
Imunoglobulina A/imunologia , Isotipos de Imunoglobulinas/imunologia , Paraproteinemias/complicações , Paraproteinemias/imunologia , Dermatopatias/complicações , Dermatopatias/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Moléculas de Adesão Celular/sangue , Quimiocinas/sangue , Citocinas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Paraproteinemias/diagnóstico , Estudos Retrospectivos , Dermatopatias/diagnósticoRESUMO
Xanthomas are a common manifestation of lipid metabolism disorders. They include hyperlipemic xanthoma, normolipemic xanthoma, and a related condition, necrobiotic xanthogranuloma (NXG). All 3 forms can be associated with monoclonal immunoglobulin (MIg). In an attempt to improve diagnosis, understanding, and treatment of this association, we retrospectively analyzed a personal series of 24 patients (2 hyperlipemic xanthoma, 11 normolipemic xanthoma, and 11 NXG) and 230 well-documented reports from the literature. With the exception of the nodules and plaques featured in NXG, the clinical presentation of xanthomatous lesions usually resembled that seen in common hyperlipidemic forms and could not be used to suspect MIg-associated xanthomas. Extracutaneous sites were not rare. The MIg was an IgG in 80% of cases. Myeloma was diagnosed in 35%. Hypocomplementemia with low C4 fraction was present in 80% of studied patients. Low C1 inhibitor serum levels were found in 53%. Cryoglobulinemia was detected in 27%. These abnormalities suggest immune complex formation because of interactions between the MIg and lipoproteins and argue in favor of a causal link between MIg and xanthomas. Monoclonal gammopathy therapy could thus be an option. Indeed, among the patients who received chemotherapy, hematologic remission was accompanied by improvement in xanthoma lesions in several cases.
Assuntos
Paraproteinemias/complicações , Paraproteinemias/terapia , Xantomatose/complicações , Xantomatose/terapia , Humanos , Paraproteinemias/diagnóstico , Paraproteinemias/patologia , Estudos Retrospectivos , Pele/patologia , Xantomatose/diagnóstico , Xantomatose/patologiaRESUMO
Schnitzler syndrome is a rare plasma cell disorder the pathogenesis of which is still not fully understood. We evaluated the circulating levels of four major angiogenic cytokines (VEGF, angiogenin, angiopoietin-1 and angiopoietin-2) and six bone remodeling markers (sRANKL, osteoprotegerin, dickkopf-1, CTX, osteocalcin and bone-specific alkaline phosphatase-bALP) in 13 patients with Schnitzler syndrome. At diagnosis, patients had elevated angiogenic cytokines. The mean VEGF levels were almost 3.5-fold higher in Schnitzler syndrome compared to controls, while 10 of 13 patients had higher VEGF than the upper control value. Successful treatment led to a significant reduction in VEGF. Patients with Schnitzler syndrome had increased bone formation (high bALP, osteocalcin and osteoprotegerin) which was not balanced by an increase in bone resorption (normal CTX and sRANKL). These data support a role for VEGF as a new minor criterion in the diagnosis and follow up of Schnitzler syndrome, while the uncoupling of bone remodeling in favor of bone formation justifies the presence of bone densification.
Assuntos
Proteínas Angiogênicas/sangue , Antígenos de Diferenciação/sangue , Imunoglobulina M , Neovascularização Fisiológica , Osteogênese , Síndrome de Schnitzler/sangue , Urticária/sangue , Adulto , Idoso , Reabsorção Óssea/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Schnitzler/complicações , Síndrome de Schnitzler/patologia , Urticária/complicações , Urticária/patologiaRESUMO
BACKGROUND: Common variable immunodeficiency (CVID) is a primary immune deficiency defined by defective antibody production. In most series, a small proportion of patients present with opportunistic infections (OIs). METHODS: The French DEFI study has enrolled patients with primary hypogammaglobulinemia and allows a detailed clinical and immunologic description of patients with previous OIs and/or at risk for OIs. RESULTS: Among 313 patients with CVID, 28 patients (8.9%) presented with late-onset combined immune deficiency (LOCID), defined by the occurrence of an OI and/or a CD4(+) T cell count <200 x 10(6) cells/L, and were compared with the remaining 285 patients with CVID. The patients with LOCID more frequently belonged to consanguineous families (29% vs 8%; P = .004). They differed from patients with CVID with a higher prevalence of splenomegaly (64% vs 31%), granuloma (43% vs 10%), gastrointestinal disease (75% vs 42%), and lymphoma (29% vs 4%). Even on immunoglobulin substitution, they required more frequent antibiotics administration and hospitalization. Lymphocyte counts were lower, with a marked decrease in CD4(+) T cell counts (158 x 10(6) vs 604 x 10(6) cells/L; P < .001) and a severe defect in naive CD45RA(+)CCR7(+)CD4(+) T cell counts (<20% of total CD4(+) T cells in 71% of patients with LOCID vs 37% of patients with CVID; P = .001). The CD19(+) B cell compartment was also significantly decreased (20 x 10(6) vs 102 x 10(6) cells/L; P < .001). CONCLUSIONS: LOCID differs from classic CVID in its clinical and immunologic characteristics. Systematic T cell phenotype may help to discriminate such patients from those with CVID. Identification of this phenotype should result in a more fitted diagnostic and therapeutic approach of infections and could provide insights for genetic diagnosis.
Assuntos
Imunodeficiência de Variável Comum/complicações , Imunodeficiência de Variável Comum/imunologia , Linfócitos T/imunologia , Linfócitos T/patologia , Adulto , Agamaglobulinemia/imunologia , Agamaglobulinemia/patologia , Idade de Início , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/etiologia , Infecções Oportunistas/imunologia , Adulto JovemRESUMO
BACKGROUND: A 55-year-old woman with no remarkable medical history presented to a neurology ward with a 17-week history of rapidly progressive gait difficulties that confined her to a wheelchair. INVESTIGATIONS: Electroneuromyography, immunoelectrophoresis, bone radiography, lesion-targeted bone-marrow examination, blood tests. DIAGNOSIS: Neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. MANAGEMENT: High-dose chemotherapy and autologous hematopoietic stem-cell transplantation.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndrome POEMS/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Síndrome POEMS/fisiopatologiaRESUMO
BACKGROUND: Schnitzler syndrome is characterized by chronic urticarial rash and monoclonal IgM gammopathy and is sometimes associated with periodic fever, arthralgias, and bone pain. Current treatment is unsatisfactory. OBSERVATIONS: Eleven patients with Schnitzler syndrome were treated with oral pefloxacin mesylate (800 mg/d). In 10 patients, we observed a dramatic and sustained improvement of urticarial and systemic manifestations. Corticosteroid therapy could be stopped or reduced in 6 patients. In 9 patients, pefloxacin was administered for more than 6 months (Assuntos
Anti-Infecciosos/uso terapêutico
, Pefloxacina/uso terapêutico
, Síndrome de Schnitzler/tratamento farmacológico
, Adulto
, Idoso
, Idoso de 80 Anos ou mais
, Anti-Infecciosos/administração & dosagem
, Estudos de Coortes
, Quimioterapia Combinada
, Glucocorticoides/administração & dosagem
, Humanos
, Pessoa de Meia-Idade
, Pefloxacina/administração & dosagem
, Estudos Retrospectivos
, Resultado do Tratamento
RESUMO
PURPOSE: To study the impact of high-dose therapy (HDT) with autologous stem-cell support in patients with symptomatic multiple myeloma (MM) between the ages of 55 and 65 years. PATIENTS AND METHODS: One hundred ninety patients between 55 and 65 years old who had newly diagnosed stage II or III MM were randomly assigned to receive either conventional chemotherapy (CCT; ie, monthly courses of a regimen of vincristine, melphalan, cyclophosphamide, and prednisone) or HDT and autologous blood stem-cell transplantation (using either melphalan alone 200 mg/m(2) intravenous [IV] or melphalan 140 mg/m(2) IV plus busulfan 16 mg/kg orally as pretransplantation cytoreduction). RESULTS: Within a median follow-up of 120 months, median event-free survival (EFS) times were 25 and 19 months in the HDT and CCT groups, respectively. Median overall survival (OS) time was 47.8 months in the HDT group compared with 47.6 months in the CCT group. A trend to better EFS (P = .07) was observed in favor of HDT, whereas OS curves were not statistically different (P = .91). The period of time without symptoms, treatment, and treatment toxicity (TwiSTT) was significantly longer for the HDT patients than for the CCT patients (P = .03). CONCLUSION: With a median follow-up time of approximately 10 years, this randomized trial confirmed a benefit of HDT in terms of EFS and TwiSTT but did not provide evidence for superiority of HDT over CCT in OS of patients aged 55 to 65 years with symptomatic newly diagnosed MM.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Transplante de Células-Tronco de Sangue Periférico , Fatores Etários , Idoso , Bussulfano/administração & dosagem , Ciclofosfamida/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Transplante Autólogo , Resultado do Tratamento , Vincristina/administração & dosagemAssuntos
Alergia e Imunologia/história , Anticorpos Antinucleares/imunologia , Doença das Cadeias Pesadas/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Anticorpos Antinucleares/história , Anticorpos Antinucleares/isolamento & purificação , França , História do Século XX , Humanos , Papel do MédicoAssuntos
Remissão Espontânea , Síndrome de Schnitzler/diagnóstico , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Paraproteinemias/diagnóstico , Prednisona/uso terapêutico , Síndrome de Schnitzler/tratamento farmacológico , Apneia Obstrutiva do Sono/diagnóstico , Úlcera Gástrica/diagnósticoRESUMO
Waldenström's macroglobulinemia associates a serum monoclonal IgM and a lymphoplasmacytic infiltration of bone marrow, spleen, lymph nodes and various organs. Clinical symptoms are related either to the lymphoid disorder or to the physico-chemical characteristics or antibody activity of the monoclonal IgM. Visceral infiltration may target stomach small bowel, lungs, exocrine glands or skin. Major complications include bone marrow failure, auto-immune cytopenia, occurrence of large cell lymphoma and infections (related either to the humoral immunodeficiency or to chemotherapy). Asymptomatic macroglobulinemia does not deserve any treatment. Otherwise, alkylating agents or nucleoside analogues are first line agents. The benefit of monoclonal antibodies, high dose chemotherapy followed by auto or allogenic stem cell graft is currently assessed.
Assuntos
Macroglobulinemia de Waldenstrom , Fatores Etários , Humanos , Imunoglobulina M/sangue , Plasmócitos/patologia , Prognóstico , Fatores Sexuais , Macroglobulinemia de Waldenstrom/complicações , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/tratamento farmacológicoRESUMO
BACKGROUND: The association between primary hyperparathyroidism (PHPT) and monoclonal gammopathy has been reported, but whether it is fortuitous remains unsettled. We conducted a prospective study to determine the prevalence of monoclonal gammopathies in patients with surgically proved PHPT. METHODS: In 101 consecutive patients with PHPT, serum immunoglobulins were systematically studied using agarose gel electrophoresis and immunofixation before and, when appropriate, after parathyroid surgery. The PHPT population was compared with a control series of patients with other diseases requiring surgery and with a group of patients with benign disease of the thyroid gland matched for age and sex to the PHPT population. RESULTS: Monoclonal immunoglobulin was detected in 10 (10%) of 101 patients with PHPT (including 2 with multiple myeloma) compared with 2 (2%) of 127 patients who underwent other surgery (P =.005) and 3 (3%) of 101 patients with benign thyroid diseases (P =.04). CONCLUSIONS: The prevalence of monoclonal gammopathies is high in patients with PHPT. At minimum, sensitive serum protein electrophoresis should be performed routinely in all patients with PHPT. Conversely, in patients with monoclonal gammopathy who have hypercalcemia but no other symptoms of progressive disease, clinicians must seek PHPT.
Assuntos
Hiperparatireoidismo/complicações , Paraproteinemias/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hiperparatireoidismo/sangue , Hiperparatireoidismo/cirurgia , Imunoglobulinas/sangue , Masculino , Pessoa de Meia-Idade , Paraproteinemias/sangue , Estudos ProspectivosRESUMO
BACKGROUND: Long-term anti-cytomegalovirus (CMV) treatments in immunocompromised patients are hampered by resistance to antiviral drugs. Longitudinal changes in the resistance genotype may depend on changes in selective pressure and the complexity of CMV isolates. OBJECTIVE: To evaluate longitudinal changes in the CMV resistance genotype and phenotype along with strain-specific variability in a patient with non-Hodgkin's lymphoma in whom successive anti-CMV treatments failed. STUDY DESIGN: The resistance phenotype and genotype of seven CMV isolates collected from one patient during a 2-year follow-up period were retrospectively analysed. In parallel, we used glycoprotein B (gB) genotyping, and a- and UL10-13-sequence analysis to study CMV interstrain variability. RESULTS: The patient was infected by at least three CMV strains plus variants of the parental strains. Resistance to ganciclovir, cidofovir and foscarnet was successively detected during the follow-up period. UL97 protein kinase changes responsible for resistance to ganciclovir were initially detected at residues 591 and 592, and then at position 594. Decreased sensitivity to foscarnet coincided with the appearance of amino acid substitution N495K in DNA polymerase, whereas cross-resistance to ganciclovir and cidofovir was due to the L501I substitution. CONCLUSIONS: The CMV isolates obtained from our patient were complex mixtures of strains. Changes in resistance genotypes depended on resistance selective pressure and were not linked to interstrain variation.
Assuntos
Infecções por Citomegalovirus/virologia , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Citosina/análogos & derivados , Evolução Molecular , Linfoma de Células T/complicações , Epidemiologia Molecular , Organofosfonatos , Idoso , Antivirais/farmacologia , Antivirais/uso terapêutico , Cidofovir , Infecções por Citomegalovirus/tratamento farmacológico , Citosina/farmacologia , Citosina/uso terapêutico , DNA Viral/análise , DNA Viral/química , DNA Viral/isolamento & purificação , Farmacorresistência Viral/genética , Feminino , Foscarnet/farmacologia , Foscarnet/uso terapêutico , Ganciclovir/farmacologia , Ganciclovir/uso terapêutico , Humanos , Mutação de Sentido Incorreto , Compostos Organofosforados/farmacologia , Compostos Organofosforados/uso terapêutico , Polimorfismo de Fragmento de Restrição , Análise de Sequência de DNARESUMO
Human T-cell lymphotropic virus type 1 associated adult T-cell leukemia/lymphoma carries a very poor prognosis due to its intrinsic resistance to chemotherapy. Although zidovudine (AZT) and alpha-interferon (IFN) yield some responses and improve ATL prognosis, alternative therapies are needed. Arsenic trioxide (As) dramatically synergizes with IFN to induce growth arrest and apoptosis of ATL leukemia cells in vitro. These results prompted us to initiate a phase II trial of As/IFN combination in seven patients with relapsed/refractory ATL (four acute and three lymphoma). Four patients exhibited a clear initial response (one complete remission and three partial remissions). Yet, the treatment was discontinued after a median of 22 days because of toxicity (three patients) or subsequent progression (four patients). Six patients eventually died from progressive disease (five patients) or infection (one patient), but the remaining patient is still alive and disease free at 32 months. Pharmacokinetic studies showed that maximum arsenic blood levels (median 0.46 microM) were slowly achieved (8-15 days). In conclusion, arsenic/IFN treatment is feasible and exhibits an anti-leukemia effect in very poor prognosis ATL patients despite a significant toxicity. Future studies should assess the best timing for arsenic therapy: frontline with IFN/AZT or as maintenance after induction.
Assuntos
Antineoplásicos/administração & dosagem , Arsenicais/administração & dosagem , Vírus Linfotrópico T Tipo 1 Humano/efeitos dos fármacos , Interferon-alfa/administração & dosagem , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Óxidos/administração & dosagem , Adulto , Fármacos Anti-HIV/administração & dosagem , Trióxido de Arsênio , Feminino , Humanos , Injeções Intravenosas , Leucemia-Linfoma de Células T do Adulto/patologia , Leucemia-Linfoma de Células T do Adulto/virologia , Pessoa de Meia-Idade , Prognóstico , Recidiva , Resultado do Tratamento , Zidovudina/administração & dosagemRESUMO
The t(4;14) translocation, found in 15% of multiple myeloma (MM), indicates a poor prognosis. Clinico-biological features associated with this severe outcome and the impact of novel agents are unknown. We report a series of 102 consecutive patients with t(4;14) MM. The median age was 56 years. The isotype was IgA in 42%, and the median serum ß(2)-microglobulin was 2.3 mg/L. FGFR3 expression was lacking in 20 (19%) cases. Monoclonal gammopathy of undetermined significance (MGUS) or smoldering MM (sMM) was found in 26 patients (25%). Seven (27%) became symptomatic in a median time of 9 months. Fifty-six of 76 patients with symptomatic MM received high-dose therapy (HDT). The overall response rate (ORR) was 93% (22% CR, 44% VGPR), and the median progression-free survival (PFS) was 12 months. Twenty-four (37%) patients experienced aggressive relapse. Post-second-line ORR was 51% and the median PFS was 7 months, with a trend for longer PFS in patients treated with a bortezomib-based regimen. Median overall survival after HDT was 31 months. t(4;14) is detected in patients with MGUS/sMM and this does not require immediate chemotherapy. Patients with t(4;14) MM have a high ORR after HDT, contrasting with a short PFS and aggressive relapses, and, despite novel agents, still have a poor prognosis.
Assuntos
Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 4/genética , Mieloma Múltiplo/genética , Recidiva Local de Neoplasia/genética , Translocação Genética/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Ácidos Borônicos/uso terapêutico , Bortezomib , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Prospectivos , Pirazinas/uso terapêutico , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Terapia de Salvação , Taxa de SobrevidaAssuntos
Crioglobulinemia/epidemiologia , Úlcera da Perna/complicações , Fosfato de Vidarabina/análogos & derivados , Adulto , Idoso , Crioglobulinemia/complicações , Crioglobulinemia/terapia , Ciclofosfamida/administração & dosagem , Feminino , França/epidemiologia , Humanos , Infusões Intravenosas , Interferon-alfa/administração & dosagem , Úlcera da Perna/patologia , Úlcera da Perna/terapia , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Troca Plasmática , Prednisona/administração & dosagem , Estudos Retrospectivos , Fosfato de Vidarabina/administração & dosagem , CicatrizaçãoRESUMO
We treated 5 patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome and multifocal bone lesions or diffuse bone marrow plasmacytic infiltration with high-dose therapy (HDT) and autologous blood stem cell transplantation. In all cases, the treatment produced remission of plasma cell proliferation associated with marked improvement in the patients' performance status, neurologic symptoms, and other manifestations of the syndrome. HDT with stem cell support should be investigated further as a therapeutic option in patients with POEMS syndrome and disseminated plasma cell dyscrasia.
Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Síndrome POEMS/terapia , Adulto , Células Clonais/imunologia , Células Clonais/patologia , Terapia Combinada , Relação Dose-Resposta a Droga , Feminino , Humanos , Imunoglobulinas/sangue , Imunoglobulinas/urina , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/etiologia , Síndrome POEMS/complicações , Síndrome POEMS/patologia , Plasmócitos/imunologia , Plasmócitos/patologia , Indução de Remissão , Transplante Autólogo , Resultado do TratamentoRESUMO
BACKGROUND: Multiple myeloma (MM) itself is not considered to be responsible for fever and is not usually listed among the causes of fever of unknown origin (FUO). METHODS: We report three cases of MM presenting with specific fever that we analyze in combination with the three previously published cases. RESULTS: MM could easily be suspected in most, but not all, cases, emphasizing that bone marrow aspiration should be a part of 'standard' FUO investigations. All patients underwent extensive, sometimes potentially harmful, investigations. Conventional treatment of MM produced a sustained improvement in the temperature curve and inflammatory syndrome in all cases within a few months. Fever recurred during nearly all relapses. Six patients died, one after a disease course of more than 8 years. CONCLUSIONS: This series shows that MM may present as a FUO and that useless and hazardous investigations may be avoided given the possibility of specific fever in this disease. Chemotherapy must be considered without much delay after a reasonable work-up to eliminate any associated process, especially infections.
RESUMO
OBJECTIVES: Pharmacological concentrations of arsenic trioxide (ATO) and organic arsenic melarsoprol induce apoptosis in malignant plasma cells. In an attempt to further document the interest of the arsenic in vivo, we treated severe combined immunodeficient (SCID) mice transplanted with human myeloma cells by ATO or melarsoprol. METHODS: Fifty-two SCID mice were irradiated before intraperitoneal (i.p.) injection of plasma cells from five myeloma patients. Engraftment was assessed by serial measurement of the human monoclonal immunoglobulin G (HuMIgG) concentration in mouse serum. Treatment with ATO (10 microg/g i.p. 5 d a week), melarsoprol (30 microg/g i.p. 5 d a week) or phosphate buffer saline was started when a sustained growth of the tumor cells was demonstrated. RESULTS: Seventeen mice developed the human tumor. A significant decrease in HuMIgG amounts was observed in three of five mice of the ATO group, including two that achieved an apparent complete remission persisting up to 5 months after ATO discontinuation. In these mice, no human plasma cells were detected in tissue samples collected postmortem. Soluble human interleukin-6 receptor amount, measured in mice sera as a surrogate marker of the plasma cell proliferation, varied in parallel with HuMIgG concentration. A significant difference in survival was observed between control and ATO treated mice (113 and 158 d, respectively; P = 0.01) whereas no difference could be evidenced in control and melarsoprol groups. CONCLUSION: Present study confirms in vivo the in vitro effects of ATO on myeloma cells. Delayed relapses were observed suggesting that prolonged or maintenance therapy has to be considered in future clinical trials. Whether or not this will translate into clinically relevant effect of the drug in myeloma patients deserves further consideration.
Assuntos
Arsenicais/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Óxidos/farmacologia , Animais , Trióxido de Arsênio , Arsenicais/farmacocinética , Divisão Celular/efeitos dos fármacos , Humanos , Imunoglobulina G/sangue , Melarsoprol/farmacologia , Camundongos , Camundongos SCID , Transplante de Neoplasias/métodos , Neoplasias Experimentais/tratamento farmacológico , Óxidos/farmacocinética , Plasmócitos/citologia , Plasmócitos/efeitos dos fármacos , Receptores de Interleucina-6/sangue , Análise de Sobrevida , Distribuição Tecidual , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Immunodeficiency following autologous CD34+-purified peripheral blood stem cell (PBSC) transplantation could be related to T-cell depletion of the graft or impaired T-cell reconstitution due to thymus irradiation. Aiming to assess the role of irradiated thymus in T-cell repopulation, we studied 32 adults with multiple myeloma, randomly assigned to receive high-dose therapy including total body irradiation (TBI) followed by autologous transplantation with either unselected or CD34+-selected PBSCs. The median number of reinfused CD3+ cells was lower in the selected group (0.03 versus 14 x 10(6)/kg; P =.002). Lymphocyte subset counts were evaluated from month 3 to 24 after grafting. Naive CD4+ T cells were characterized both by phenotype and by quantification of T-cell receptor rearrangement excision circles (TRECs). The reconstitution of CD3+ and CD4+ T cells was significantly delayed in the CD34+-selected group, but eventually led to counts similar to those found in the unselected group after month 12. Mechanism of reconstitution differed, however, between both groups. Indeed, a marked increase in the naive CD62L+CD45RA+CD4+ subset was observed in the selected group, but not in the unselected group in which half of the CD45RA+CD4+ T cells appear to be CD62L-. Age was identified as an independent adverse factor for CD4+ and CD62L+CD45RA+CD4+ T-cell reconstitution. Our results provide evidence that infusing PBSCs depleted of T cells after TBI in adults delays T-cell reconstitution but accelerates thymic regeneration.