Thalidomide plus dexamethasone as a maintenance therapy after autologous hematopoietic stem cell transplantation improves progression-free survival in multiple myeloma

Despite the good response of stem cell transplant (SCT) in the treatment of multiple myeloma (MM), most patients relapse or do not achieve complete remission, suggesting that additional treatment is needed. We assessed the impact of thalidomide in maintenance after SCT in untreated patients with MM. A hundred and eight patients (<70 years old) were randomized to receive maintenance with dexamethasone (arm A; n = 52) or dexamethasone with thalidomide (arm B; n = 56; 200 mg daily) for 12 months or until disease progression. After a median follow-up of 27 months, an intention to treat analysis showed a 2-year progression-free survival (PFS) of 30% in arm A (95% CI 2238) and 64% in arm B (95% CI 5771; P = 0.002), with median PFS of 19 months and 36 months, respectively. In patients who did not achieve at least a very good partial response, the PFS at 2 years was significantly higher when in use of thalidomide (19 vs. 59%; P = 0.002). Overall survival at 2 years was not significantly improved (70 vs. 85% in arm A and arm B, respectively; P = 0.27). The addition of thalidomide to dexamethasone as maintenance improved the PFS mainly in patients who did not respond to treatment after SCT. Am. J. Hematol. (c) 2012 Wiley Periodicals, Inc.FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)CNPq (Conselho Nacional do Desenvolvimento Cientifico e Tecnologico)Conselho Nacional do Desenvolvimento Cientifico e Tecnologico (CNPq)FAPERJ (Fundacao de Apoio a Pesquisa do Estado do Rio de Janeiro)FAPERJ (Fundacao de Apoio a Pesquisa do Estado do Rio de Janeiro

Alterações moleculares no Mieloma Múltiplo Molecular abnormalities in Multiple Myeloma

Nos últimos anos tem acontecido uma revolução no conhecimento dos mecanismos moleculares envolvidos na patogênese do mieloma múltiplo, principalmente devido à incorporação de técnicas de citogenética molecular (hibridização in situ fluorescente - FISH) e biologia molecular (Reação em cadeia da polimerase - PCR, hibridização genômica comparativa baseada em microarranjos - aCGH e microarranjos de RNA). Estas técnicas permitem estudar as células em interfase e detectar alterações cromossômicas crípticas, superando assim problemas metodológicos relacionados à análise por citogenética convencional. Por outro lado, a complexidade metodológica relacionada com a realização das técnicas de FISH e biologia molecular tem impossibilitado que sejam amplamente utilizadas na rotina laboratorial. Este trabalho tem como objetivo fazer uma revisão das principais vias moleculares alteradas no mieloma múltiplo, o seu valor prognóstico e a sua utilização na estratificação dos pacientes em diferentes grupos de risco. São detalhadas diferentes abordagens metodológicas e uma ênfase especial é dada em relação à importância da análise se restringir exclusivamente às células plasmocitárias. Por último, discutimos uma série de prioridades e estratégias de estudo na rotina laboratorial.<br>In recent years, we have seen an explosion in knowledge on genetic and cytogenetic mechanisms involved in the pathogenesis of multiple myeloma, mainly due to the incorporation of molecular tools in its study (fluorescence in situ hybridization - FISH, Real time PCR and RNA microarrays). These tools have enabled the study of cells in interphase and to detect cryptic chromosomal abnormalities, replacing cytogenetic techniques. The technical complexities associated with the performance of these tests, however, have limited their widespread applicability in routine clinical practice. The aim of this work is to review the present status of our knowledge of the pathogenetic pathways of the disease, the prognostic value of the main chromosomal abnormalities and its role in risk stratification of multiple myeloma patients. We detail technical aspects, emphasizing the importance to restrict analysis to myeloma cells. Finally, we discuss different strategies and recommendations for the adoption of routine molecular genetic testing

Thalidomide plus dexamethasone as a maintenance therapy after autologous hematopoietic stem cell transplantation improves progression-free survival in multiple myeloma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Despite the good response of stem cell transplant (SCT) in the treatment of multiple myeloma (MM), most patients relapse or do not achieve complete remission, suggesting that additional treatment is needed. We assessed the impact of thalidomide in maintenance after SCT in untreated patients with MM. A hundred and eight patients (<70 years old) were randomized to receive maintenance with dexamethasone (arm A; n = 52) or dexamethasone with thalidomide (arm B; n = 56; 200 mg daily) for 12 months or until disease progression. After a median follow-up of 27 months, an intention to treat analysis showed a 2-year progression-free survival (PFS) of 30% in arm A (95% CI 2238) and 64% in arm B (95% CI 5771; P = 0.002), with median PFS of 19 months and 36 months, respectively. In patients who did not achieve at least a very good partial response, the PFS at 2 years was significantly higher when in use of thalidomide (19 vs. 59%; P = 0.002). Overall survival at 2 years was not significantly improved (70 vs. 85% in arm A and arm B, respectively; P = 0.27). The addition of thalidomide to dexamethasone as maintenance improved the PFS mainly in patients who did not respond to treatment after SCT. Am. J. Hematol. (c) 2012 Wiley Periodicals, Inc.8710948952Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPERJ (Fundacao de Apoio a Pesquisa do Estado do Rio de Janeiro)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq