RESUMO
This report represents a further update of the consensus panel criteria for the assessment of clinical response in patients with Waldenström macroglobulinaemia (WM). These criteria have been updated in light of further data demonstrating an improvement in categorical responses with new drug regimens as well as acknowledgement of the fact that such responses are predictive of overall outcome. A number of key changes are proposed but challenges do however remain and these include the variability in kinetics of immunoglobulin M (IgM) reduction with different treatment modalities and the apparent discrepancy between IgM and bone marrow/tissue response noted with some regimens. Planned sequential bone marrow assessments are encouraged in clinical trials.
Assuntos
Macroglobulinemia de Waldenstrom/tratamento farmacológico , Anticorpos Monoclonais/sangue , Anticorpos Monoclonais/uso terapêutico , Antimetabólitos/uso terapêutico , Exame de Medula Óssea/métodos , Exame de Medula Óssea/normas , Ácidos Borônicos/uso terapêutico , Bortezomib , Densitometria , Progressão da Doença , Intervalo Livre de Doença , Previsões , Hematopoese , Humanos , Cadeias Leves de Imunoglobulina/sangue , Imunoglobulina M/sangue , Imunossupressores/uso terapêutico , Neoplasia Residual , Nefelometria e Turbidimetria , Tomografia por Emissão de Pósitrons , Pirazinas/uso terapêutico , Indução de Remissão , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/sangue , Macroglobulinemia de Waldenstrom/patologiaRESUMO
In this study we used bone marrow flow cytometry and immunohistochemistry to evaluate response to fludarabine therapy in patients with Waldenström's macroglobulinemia (WM)/lymphoplasmacytic lymphoma. Responses in serum M protein were typically delayed with a median time to maximum response of 6 months following the completion of therapy (range, 0-18 months). In contrast, bone marrow responses occurred promptly in responding patients such that there were no detectable clonal B cells at the end of therapy in 55% of patients assessed. Persistent monoclonal plasma cells were, however, readily identified by CD138 immunohistochemistry, explaining the persistence of serum M protein in these patients. This simple observation has significant implications for the assessment of responses in WM as well as the design of future therapeutic strategies.
Assuntos
Medula Óssea/patologia , Vidarabina/análogos & derivados , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Feminino , Citometria de Fluxo , Humanos , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Imuno-Histoquímica , Masculino , Vidarabina/administração & dosagem , Vidarabina/uso terapêutico , Macroglobulinemia de Waldenstrom/sangueRESUMO
We report the pathologic findings in a patient with sensorimotor neuropathy associated with Waldenström's macroglobulinemia, particularly in relation to blood-nerve barrier defects. The monoclonal IgM was of kappa type and possessed anti-HNK-1 activity. A sural nerve biopsy specimen revealed severe loss of myelinated and unmyelinated nerve fibers and gaps between adjacent endothelial cells of small endoneurial vessels. Postmortem findings 3 years later included severe loss of myelinated nerve fibers and diffuse infiltration by lymphoplasmacytic B cells throughout the peripheral nervous system, sparing the central nervous system. Findings in this case suggest an immune attack against endoneurial endothelial cells with permeation of IgM into peripheral nerve tissue.