Benet Nomdedeu

Importance of Radiotherapy in the Outcome of Patients With Primary CNS Lymphoma: An Analysis of the CHOD/BVAM Regimen Followed by Two Different Radiotherapy Treatments

PURPOSE To assess the effect of a reduced dose of radiotherapy (RT) in patients with primary CNS lymphoma (PCNSL) responding to the cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD)/carmustine, vincristine, methotrexate, and cytarabine (BVAM) regimen. PATIENTS AND METHODS Patients received one cycle of CHOD and two of BVAM. In the first trial, all 31 patients received 45-Gy whole-brain RT (CHOD/BVAM I). In the second, with 26 patients, RT dose was reduced to 30.6 Gy if there was a complete response (CR) after chemotherapy (CHOD/BVAM II). RESULTS Age, performance status, and chemotherapy received were similar in both protocols. CR rate at the end of all treatment was 68% for CHOD/BVAM I and 77% and for CHOD/BVAM II. Treatment modality was the only predictor of relapse, with 3-year relapse risks of 29% and 70% for CHOD/BVAM I and II, respectively. This was specifically important in the 25 patients less than 60 years old (3-year relapse risk, 25% v 83%; P =.01). The 5-year overall survival (OS) was 36%. Age (< 60 v > or = 60 years) was the only predictor for OS in the multivariate analysis (relative risk, 2.1; 95% confidence interval, 1.4 to 2.8). RT dose was the only predictor of OS in patients younger than 60 years old who achieved CR at the end of all treatment (3-year OS, 92% v 60% for patients receiving 45 or 30.6 Gy, respectively; P =.04). CONCLUSION Reduction of the RT dose from 45 Gy to 30.6 Gy in patients younger than 60 years old with PCNSL who achieved CR resulted in an increased risk of relapse and lower OS.

Cytogenetic risk stratification in chronic myelomonocytic leukemia

Background The prognostic value of cytogenetic findings in chronic myelomonocytic leukemia is unclear. Our purpose was to evaluate the independent prognostic impact of cytogenetic abnormalities in a large series of patients with chronic myelomonocytic leukemia included in the database of the Spanish Registry of Myelodysplastic Syndromes. Design and Methods We studied 414 patients with chronic myelomonocytic leukemia according to WHO criteria and with a successful conventional cytogenetic analysis at diagnosis. Different patient and disease characteristics were examined by univariate and multivariate methods to establish their relationship with overall survival and evolution to acute myeloid leukemia. Results Patients with abnormal karyotype (110 patients, 27%) had poorer overall survival (P=0.001) and higher risk of acute myeloid leukemia evolution (P=0.010). Based on outcome analysis, three cytogenetic risk categories were identified: low risk (normal karyotype or loss of Y chromosome as a single anomaly), high risk (presence of trisomy 8 or abnormalities of chromosome 7, or complex karyotype), and intermediate risk (all other abnormalities). Overall survival at five years for patients in the low, intermediate, and high risk cytogenetic categories was 35%, 26%, and 4%, respectively (P<0.001). Multivariate analysis confirmed that this new CMML-specific cytogenetic risk stratification was an independent prognostic variable for overall survival (P=0.001). Additionally, patients belonging to the high-risk cytogenetic category also had a higher risk of acute myeloid leukemia evolution on univariate (P=0.001) but not multivariate analysis. Conclusions Cytogenetic findings have a strong prognostic impact in patients with chronic myelomonocytic leukemia.

Development and validation of a prognostic scoring system for patients with chronic myelomonocytic leukemia

The natural course of chronic myelomonocytic leukemia (CMML) is highly variable but a widely accepted prognostic scoring system for patients with CMML is not available. The main aim of this study was to develop a new CMML-specific prognostic scoring system (CPSS) in a large series of 558 patients with CMML (training cohort, Spanish Group of Myelodysplastic Syndromes) and to validate it in an independent series of 274 patients (validation cohort, Heinrich Heine University Hospital, Düsseldorf, Germany, and San Matteo Hospital, Pavia, Italy). The most relevant variables for overall survival (OS) and evolution to acute myeloblastic leukemia (AML) were FAB and WHO CMML subtypes, CMML-specific cytogenetic risk classification, and red blood cell (RBC) transfusion dependency. CPSS was able to segregate patients into 4 clearly different risk groups for OS (P < .001) and risk of AML evolution (P < .001) and its predictive capability was confirmed in the validation cohort. An alternative CPSS with hemoglobin instead of RBC transfusion dependency offered almost identical prognostic capability. This study confirms the prognostic impact of FAB and WHO subtypes, recognizes the importance of RBC transfusion dependency and cytogenetics, and offers a simple and powerful CPSS for accurately assessing prognosis and planning therapy in patients with CMML.

Salvage treatment with etoposide (VP-16), ifosfamide and cytarabine (Ara-C) for patients with recurrent primary central nervous system lymphoma.

Abstract:  Background: Survival of patients with primary central nervous system lymphoma (PCNSL) has improved with methotrexate‐based combination regimens and radiotherapy (RT). However, the prognosis of patients who fail or relapse after initial response is poor. Very little data is available on salvage treatment at recurrence.

Hematopoiesis-related microRNA expression in myelodysplastic syndromes

MicroRNAs (miRNAs) are negative regulators of expression of genes involved in hematopoiesis. The present study sought to link hematopoiesis-relevant miRNAs with myelodysplastic syndromes (MDS) and MDS progression to acute myeloid leukemia (AML). We assessed 25 mature miRNAs in total RNA from bone marrow (BM) and peripheral blood (PB) of 25 newly diagnosed patients with MDS and 12 controls. Twelve miRNAs in BM and six in PB were differentially expressed between patients with MDS and controls. Three of these miRNAs, belonging to the cluster 17–92, were overexpressed in both BM and PB. miR-15a in BM ( p = 0.034) and miR-16 in PB ( p = 0.005) were differentially expressed between low-risk and high-risk groups. miR-222 ( p = 0.0023) and miR-181a ( p = 0.014) expression was higher in AML than in MDS in both BM and PB. This study adds further evidence to the role of miRNAs in the pathogenesis of MDS and their transformation into AML.

Complex, Not Monosomal, Karyotype Is the Cytogenetic Marker of Poorest Prognosis in Patients With Primary Myelodysplastic Syndrome

PURPOSE Complex karyotype (CK) is the poorest risk factor in patients with myelodysplastic syndrome (MDS). It has recently been reported that monosomal karyotype (MK) worsens the prognosis of patients with CK. PATIENTS AND METHODS; We analyzed 1,054 adult patients with MDS with an abnormal karyotype from the Spanish Registry of MDS. The aim of the study was to describe the incidence, characteristics, and prognosis of MK; the main end points were overall survival (OS) and leukemia-free survival. RESULTS MK was identified in 172 patients (16%), most of whom (88%) presented with CK. Variables significantly associated with OS were age (hazard ratio [HR], 1.90; P < .001), bone marrow (BM) blast percentage (HR, 1.05; P < .001), hemoglobin level (HR, 1.71; P < .001), platelet count (HR, 1.41; P < .001), karyotype complexity (CK [three abnormalities]: HR, 1.81; P = .003; very CK [> three abnormalities]: HR, 2; P < .001), and abnormalities of chromosome 5 and/or 7 (HR, 1.89; P < .001). Variables significantly related to the risk of transformation to acute myeloid leukemia (AML) were higher BM blast percentage (HR, 1.12; P < .001) and karyotype complexity (CK: HR, 2.53; P = .002; very CK: HR, 2.77; P < .001). CONCLUSION After accounting for karyotype complexity, MK was not associated with OS or evolution to AML. In conclusion, these results demonstrate that the prognostic value of MK in MDS is not independent and is mainly the result of its strong association with number of chromosomal abnormalities.

Red blood cell alloimmunization in transfused patients with myelodysplastic syndrome or chronic myelomonocytic leukemia

BACKGROUND: Red blood cell (RBC) alloimmunization is a major problem in chronically transfused patients because of the risk of hemolytic reactions and limited availability of compatible blood. This study was aimed at determining the characteristics of RBC alloimmunization in transfusion‐dependent patients with myelodysplastic syndrome or chronic myelomonocytic leukemia (MDS/CMML).

Prognostic impact of severe thrombocytopenia in low-risk myelodysplastic syndrome.

Thrombocytopenia is very common in myelodysplastic syndrome (MDS); however, its clinical impact in low‐risk patients remains controversial.

Darbepoetin α for the treatment of anemia in patients with myelodysplastic syndromes

Anemia occurs as a comorbidity in from 80% to 85% of patients with myelodysplastic syndromes (MDS): It causes fatigue, increases transfusion needs, and reduces quality of life. Darbepoetin α (DA) is an erythropoiesis‐stimulating protein (ESP) that is more highly glycosylated and has a longer half‐life relative to recombinant human erythropoietin (rHuEPO), thus, allowing less frequent administration, increased convenience, and better compliance.

Effectiveness of azacitidine in unselected high-risk myelodysplastic syndromes: results from the Spanish registry

The benefit of azacitidine treatment in survival of high-risk myelodysplastic syndromes (MDS) patients compared with conventional care treatment (CCT) has not been established outside clinical trials. To assess its effectiveness, we compared overall survival (OS) between azacitidine and conventional treatment (CCT) in high-risk MDS patients, excluding those undergoing stem cell transplantation, submitted to the Spanish MDS registry from 2000 to 2013. Several Cox regression and competing risk models, considering azacitidine as a time-dependent covariate, were used to assess survival and acute myeloblastic leukemia (AML) progression. Among 821 patients included, 251 received azacitidine. Median survival was 13.4 (11.8–16) months for azacitidine-treated patients and 12.2 (11–14.1) for patients under CCT (P=0.41). In a multivariate model, age, International prognostic scoring system and lactate dehydrogenase were predictors of OS whereas azacitidine was not (adjusted odds ratio 1.08, 95% confidence interval 0.86–1.35, P=0.49). However, in patients with chromosome 7 abnormalities, a trend toward a better survival was observed in azacitidine-treated patients (median survival 13.3 (11–18) months) compared with CCT (median survival 8.6 (5–10.4) months, P=0.08). In conclusion, our data show that, in spite of a widespread use of azacitidine, there is a lack of improvement in survival over the years. Identification of predicting factors of response and survival is mandatory.