Clinical features and survival of 338 multiple myeloma patients treated with hematopoietic stem cell transplantation or conventional chemotherapy.

Therapeutic approaches against multiple myeloma (MM) have largely changed during the past decade. Hematopoietic stem cell transplantation (HSCT) and licensing of immunomodulators and proteasome inhibitors have resulted in better response and increased overall survival rates compared to previous conventional therapies. To assess the impact that these new strategies have had on outcome of patients with symptomatic MM in Spain, we conducted an epidemiological retrospective analysis of 338 newly diagnosed patients with stage II-III MM who started first-line treatment over a 2-yr period (2003-2005) by collecting data from their medical records. Most patients had been diagnosed with secretory MM (94.4%), 41.7% stage II and 58.3% stage III. The presence of bone lesions (72.2%), as well as anemia (79.8%) and elevated beta2-microglobulin levels (62.3%), was a common finding; in contrast, hypercalcemia and elevated serum creatinine were less frequent (25% each). First-line treatment had consisted of either conventional chemotherapy (62%) or induction treatment plus autologous HSCT (38%), as per standard clinical practice. HSCT not only resulted in greater objective response rates (93% vs. 50%), but also contributed to a significant increase in 3-yr survival (85% vs. 49.7%; 95% CI, range 77-91 vs. 41-58; P < 0.001). Overall, 55% of patients presented treatment-related adverse events, mainly hematological. Toxicity rates were higher among patients treated with alkylating-based regimens and in those undergoing transplantation. In conclusion, data analysis shows an adequate balance between increased response rates and safety that supports the use of up-front high-dose HSCT therapy in younger patients. Most importantly, this study provides further confirmation that the introduction of HSCT has significantly prolonged survival of patients with MM.

Cryptochrome-1 expression: a new prognostic marker in B-cell chronic lymphocytic leukemia.

Chronic lymphocytic leukemia is an adult-onset leukemia with a heterogeneous clinical behavior. When chronic lymphocytic leukemia cases were divided on the basis of IgV(H) mutational status, widely differing clinical courses were revealed. Since IgV(H) sequencing is difficult to perform in a routine diagnostic laboratory, finding a surrogate for IgV(H) mutational status seems an important priority. In the present study, we proposed the use of Cryptochrome-1 as a new prognostic marker in early-stage chronic lymphocytic leukemia. Seventy patients (Binet stage A, without treatment) were included in the study. We correlated Cryptochrome-1 mRNA with well established prognostic markers such as IgV(H) mutations, ZAP70, LPL or CD38 expression and chromosomal abnormalities. High Cryptochrome-1 expression correlated with IgV(H) unmutated samples. In addition, Cryptochrome-1 was a valuable predictor of disease progression in early-stage chronic lymphocytic leukemia, therefore it can be introduced in clinical practice with the advantage of a simplified method of quantification.

Fluorescence in situ hybridization improves the detection of 5q31 deletion in myelodysplastic syndromes without cytogenetic evidence of 5q-.

BACKGROUND: More than 50% of patients with myelodysplastic syndromes present cytogenetic aberrations at diagnosis. Partial or complete deletion of the long arm of chromosome 5 is the most frequent abnormality. The aim of this study was to apply fluorescence in situ hybridization of 5q31 in patients diagnosed with de novo myelodysplastic syndromes in whom conventional banding cytogenetics study had shown a normal karyotype, absence of metaphases or an abnormal karyotype without evidence of del(5q). DESIGN AND METHODS: We performed fluorescence in situ hybridization of 5q31 in 716 patients, divided into two groups: group A patients (n=637) in whom the 5q deletion had not been detected at diagnosis by conventional banding cytogenetics and group B patients (n=79), in whom cytogenetic analysis had revealed the 5q deletion (positive control group). RESULTS: In group A (n=637), the 5q deletion was detected by fluorescence in situ hybridization in 38 cases (5.96%). The majority of positive cases were diagnosed as having the 5q- syndrome. The deletion was mainly observed in cases in which the cytogenetics study had shown no metaphases or an aberrant karyotype with chromosome 5 involved. In group B (n=79), the 5q deletion had been observed by cytogenetics and was confirmed to be present in all cases by fluorescence in situ hybridization of 5q31. CONCLUSIONS: Fluorescence in situ hybridization of 5q31 detected the 5q deletion in 6% of cases without clear evidence of del(5q) by conventional banding cytogenetics. We suggest that fluorescence in situ hybridization of 5q31 should be performed in cases of a suspected '5q- syndrome' and/or if the cytogenetic study shows no metaphases or an aberrant karyotype with chromosome 5 involved (no 5q- chromosome).

Deficit of interleukin 7 in septic patients.

We recently demonstrated an overall decrease of all αß and specially γδ T cell subsets in patients with sepsis compared with healthy subjects. IL-7 is a crucial factor for development of γδ T cells and survival in sepsis but its association with sepsis severity, evolution of organ failure and death still has not been investigated. Sera from 78 patients who met criteria for sepsis were analyzed vs control group. Septic patients showed the lowest levels of IL-7. Patients with severe sepsis reached levels of IL-7 higher than those observed in the groups of uncomplicated sepsis and septic shock. The frequency of γδ T cells at admission was lower in septic patients vs control group. At the time of admission, the frequency of γδ T cells in septic patients who subsequently died was lower than the observed in the group of patients that instead survived.

Rituximab in the management of chronic immune thrombocytopenic purpura: an effective and safe therapeutic alternative in refractory patients.

Rituximab induces B-cell depletion; therefore, it has been used in the treatment of immune thrombocytopenic purpura (ITP). The aim of this retrospective study was to evaluate the effectiveness of rituximab in the treatment of 89 patients with chronic ITP refractory to several treatments. All the patients had platelet counts <30 x 10(9)/l. They had received a median of five (2-13) previous treatments, and 47 had undergone splenectomy. Rituximab was administered i.v. at 375 mg/m(2) in four weekly doses in 77 patients, and 12 patients received 1-6 doses. Forty-nine patients (55.1%) reached platelet counts >50 x 10(9)/l; 41 (46%) achieved a complete response (CR; platelets >100 x 10(9)/l), and eight (9%) obtained a partial response (platelets 50-100 x 10(9)/l). Overall, 31 patients (35%) maintained response, including 15 patients in whom splenectomy failed, with a median follow-up of 9 months (2-42), 12 for more than 1 year. The unique predictor of a maintained response was to reach a CR. Heavily treated patients (more than three different previous treatments, including any corticosteroids) and those with longer ITP duration (>10 years from diagnosis) had a worse response. Non-splenectomized patients had a better early response rate than those splenectomized. Rituximab was well tolerated, with two fever episodes following infusion and two reports of skin rash. Rituximab induced clinical responses in multi-treated refractory ITP patients with little toxicity and should be considered as an early therapeutic option in this setting, even as an alternative to splenectomy in selected patients.