The achievement of complete response (CR) after high-dose therapy/autologous stem cell transplantation (HDT/ASCT) is a surrogate for prolonged survival in multiple myeloma; however, patients who lose their CR status within 1 year of HDT/ASCT (unsustained CR) have poor prognosis. Thus, the identification of these patients is highly relevant. Here, we investigate which prognostic markers can predict unsustained CR in a series of 241 patients in CR at day ؉100 after HDT/ASCT who were enrolled in the Spanish GEM2000 (n ‫؍‬ 140) and GEM2005 < 65y (n ‫؍‬ 101) trials. Twenty-nine (12%) of the 241 patients showed unsustained CR and a dismal outcome (median overall survival 39 months). The presence of baseline high-risk cytogenetics by FISH (hazard ratio 17.3; P ‫؍‬ .002) and persistent minimal residual disease by multiparameter flow cytometry at day ؉100 after HDT/ASCT (hazard ratio 8.0; P ‫؍‬ .005) were the only independent factors that predicted unsustained CR. Thus, these 2 parameters may help to identify patients in CR at risk of early progression after HDT/ASCT in whom novel treatments should be investigated. (Blood. 2012;119(3):687-691) IntroductionThe incorporation of high-dose therapy/autologous stem cell transplantation (HDT/ASCT) and novel agents in the treatment of young patients with multiple myeloma (MM) has markedly improved the achievement of complete response (CR). 1,2 There are now extensive data in the setting of HDT/ASCT showing that achievement of CR is associated with prolonged survival. 3 Although this is well accepted, the long-term clinical outcome of MM patients who achieve CR is still heterogeneous, 4 and 2 important observations must be made: (1) some patients who revert to a monoclonal gammopathy of undetermined significance (MGUS) stage after therapy experience similar prolonged survival as patients in CR 5 ; and (2) a small fraction of patients unexpectedly lose their CR status during the first year after HDT/ASCT and experience a dismal survival rate. 6,7 In fact, survival of patients with unsustained CR is even poorer than for those not achieving CR. 6,7 Herein, we sought to identify prognostic markers predictive of unsustained CR after HDT/ASCT. MethodsThe study included 241 MM patients diagnosed according to International Myeloma Working Group criteria. 8 Patients were included in 2 consecutive PETHEMA/GEM (Programa para el Estudio de la Terapéutica en Hemopatías Malignas/Grupo Español de Mieloma) trials: GEM2000 (VBMCP [vincristine, carmustine, melphalan, cyclophosphamide, and prednisone]/VBAD [vincristine, carmustine, doxorubicin, and dexamethasone] followed by HDT/ASCT and 2 years of maintenance with interferon and prednisone; n ϭ 140) and GEM2005 Ͻ 65y (randomized induction with the same chemotherapy plus bortezomib in the last 2 cycles or thalidomide/dexamethasone or bortezomib/thalidomide/dexamethasone followed by HDT/ASCT, and 3 years of maintenance with interferon-␣2b or thalidomide or thalidomide/bortezomib; n ϭ 101). All case subjects were in CR at day ϩ100 after HDT/ASCT, def...

cooperative study group Achieving complete remission (CR) in multiple myeloma (MM) translates into extended survival, but two subgroups of patients fall outside this paradigm: cases with unsustained CR, and patients that do not achieve CR but return into a monoclonal gammopathy of undetermined significance (MGUS)-like status with long-term survival. Here, we describe a novel automated flow cytometric classification focused on the analysis of the plasma-cell compartment to identify among newly diagnosed symptomatic MM patients (N ¼ 698) cases with a baseline MGUS-like profile, by comparing them to MGUS (N ¼ 497) patients and validating the classification model in 114 smoldering MM patients. Overall, 59 symptomatic MM patients (8%) showed an MGUS-like profile. Despite achieving similar CR rates after high-dose therapy/autologous stem cell transplantation vs other MM patients, MGUS-like cases had unprecedented longer time-to-progression (TTP) and overall survival (OS; B60% at 10 years; Po0.001). Importantly, MGUS-like MM patients failing to achieve CR showed similar TTP (P ¼ 0.81) and OS (P ¼ 0.24) vs cases attaining CR. This automated classification also identified MGUS patients with shorter TTP (P ¼ 0.001, hazard ratio: 5.53) and ultra-high-risk smoldering MM (median TTP, 15 months). In summary, we have developed a biomarker that identifies a subset of symptomatic MM patients with an occult MGUS-like signature and an excellent outcome, independently of the depth of response.

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Invasive fungal infections (IFIs) have become high prevalence in patients with hematologic malignancies. Drug-based strategies for IFIs include various approaches such as prophylactic, empiric, preemptive, and directed treatment. Prophylaxis is an attractive strategy in high-risk patients, given the lack of reliable diagnostics and the high mortality rate associated with IFIs. Prophylaxis includes the use of antifungal drugs in all patients at risk. An ideal antifungal compound for prophylaxis should have a potent and broad activity, be available both orally and intravenously, and have a low toxicity profile. Voriconazole fulfills all these criteria. The clinical efficacy of voriconazole against the majority of fungal pathogens makes it potentially very useful for the prevention of IFIs in patients with hematologic malignancies. Voriconazole appears to be very effective for the primary and secondary prevention of IFIs in these patients and recipients of allogeneic hematopoietic stem-cell transplantation. Randomized controlled trials evaluating voriconazole as primary antifungal prophylaxis in patients with neutropenia treated for a variety of hematologic malignancies have been performed, confirming its value as a prophylactic agent. Voriconazole is generally safe and well tolerated; however, its use is also associated with a number of concerns. In most patients with hematologic malignancies there is the potential for pharmacokinetic drug-drug interactions given that voriconazole is metabolized through the P450 cytochrome system.

Primary cerebral lymphoma (Primary CNS Lymphoma, PCNSL) is an aggressive non-Hodgkin lymphoma that originates in the central nervous system without evidence of lymphoma in any other localization at the time of diagnosis. Primary cerebral lymphomas are less well-known and are characterized than their homologues the systemic lymphomas, as they are an entity whose frequency was scarce until a few decades ago. However, the great rise in incidence that this pathology has undergone over the last three decades, and which is still unexplained, makes more studies necessary to better understand the etiopathology of this entity. Thanks to the new systems of treatment, the prognosis of this pathology has improved significantly in recent years. Nonetheless, treatment of primary cerebral lymphoma continues to give rise to numerous controversies at present due to its high neurotoxicity in patients over 60 years of age, a group of patients frequently affected by this pathology. To resolve these and other questions it is necessary to deep in the study of primary cerebral lymphoma and to carry out high quality clinical trials.