Validation of the NCCN-IPI and the GELTAMO-IPI for diffuse large B-Cell lymphoma treated with R-CHOP in a large cohort of patients from a single institution.

The discriminative power of International Prognostic Index (IPI) in diffuse large B-cell lymphoma (DLBCL) decreased with the addition of rituximab to chemotherapy. The National Comprehensive Cancer Network (NCCN)-IPI and the Grupo Español de Linfomas y Trasplante Autólogo de Médula Ósea (GELTAMO)-IPI were developed to improve the risk prediction for DLBCL patients. We aim to validate the NCCN-IPI and GELTAMO-IPI in a large and homogeneous cohort of 337 DLBCL patients treated with curative intent with R-CHOP/R-CHOP-like immunochemotherapy. The IPI stratifies patients in two independent risk groups and the estimated 5-year overall survival (OS) of the high-risk (HR) group was 43%. NCCN-IPI discriminated four risk groups and GELTAMO-IPI three risk groups of patients. The predicted 5-year OS of the HR group was 38% and 29%, respectively. NCCN-IPI and GELTAMO-IPI are more accurate prognostic indices than IPI in DBLCL patients treated with immunochemotherapy. GELTAMO-IPI demonstrated enhanced discrimination than NCCN-IPI for the higher-risk population.

Clinicopathologic features and prognostic significance of CD30 expression in de novo diffuse large B-cell lymphoma (DLBCL): results in a homogeneous series from a single institution.

Introduction: The present study evaluates CD30 expression by immunohistochemistry (IHQ) in 216 patients with de novo DLBCL.Methods: CD30 expression was assessed retrospectively in all cases by IHQ. More than >0% and >20% of CD30 expression in the malignant cells were used as a cut-off for positivity. Survival was analysed in 176 patients treated with R-CHOP/R-CHOP-like regimens.Results: CD30 expression >0% was found in 66 (31%) patients, and >20% in 41 (19%). Younger patients <60 years (p = 0.03), good performance status (p = 0.04), and non-GCB subtype (p = 0.004) correlated with CD30 expression. No significant differences were found in overall survival and progression-free survival (PFS), although there was a trend towards better PFS in CD30-positive patients (p = 0.07). Among 7 patients with Epstein-Barr virus (EBV)-positive-DLBCL, CD30 was expressed in 71%, and 2-year PFS significantly inferior compared with CD30-positive EBV-negative-DLBCL patients (p = 0.01).Conclusion: CD30 is expressed in 30% of DLBCL patients, in whom targeted therapy with an anti-CD30 monoclonal antibody could be explored. CD30 is expressed more frequently younger patients, with better performance status and in the non-GCB subtype and its expression trends towards a better PFS. No significant differences regarding characteristics at diagnosis or prognosis were found between groups with different cut-off for positivity.

Long-term outcome comparing histological grades of follicular lymphoma patients treated with immunochemotherapy as first-line therapy: A retrospective analysis from two institutions.

OBJECTIVES: To clarify the impact of histological grades in follicular lymphoma. METHODS: We retrospectively analysed 250 patients diagnosed with FL treated with chemoimmunotherapy: 188 patients were grades 1-2 and 62 grade 3A. RESULTS: In our series, grade 3A FL patients were older, higher proportion of localised disease and lower bone marrow infiltration at diagnosis comparing grades 1-2 FL patients. Estimated six-year progression-free survival and time to progression showed no differences between both groups [grade 3A: 56% (95%CI: 39%-73%) and 51% (95%CI: 41%-61%) vs grades 1-2:55% (95%CI: 46%-63%) and 57% (95%CI: 49%-65%), P = .782 and P = .521, respectively]. Estimated six-year overall survival was lower, 76% (95%CI: 64%-88%) for the grade 3A group than grades 1-2 83% (95%CI: 77%-89%); P = .044. In addition to that, cumulative incidence curves of death not related to lymphoma at 10 years between groups were as follows: [0.26 (95%CI: 0.25-0.27) and 0.05 (95%CI: 0.04-0.06) for G3AFL and G1-2FL, respectively], P = .010. Grade 3A FL showed in PFS curve no relapses after 6 years. These results were absolutely reproduced in 199 patients receiving R-CHOP regimen as induction. CONCLUSIONS: Our results indicate similar long-term outcomes in terms of progression-free survival and time to progression in grades 1-2 and 3A. No relapses were observed in G3AFL group after 6 years.

Long-term safety and outcome of fludarabine, cyclophosphamide and mitoxantrone (FCM) regimen in previously untreated patients with advanced follicular lymphoma: 12 years follow-up of a phase 2 trial.

Fludarabine combinations are very affective in follicular lymphoma (FL) with high rates of complete response and prolonged survival. However, late toxicities could be a concern. The aim of the present study was to analyze the long-term impact on survival, relapse and late toxicities of a trial of treatment with fludarabine, mitoxantrone and cyclophosphamide (FCM regimen) for untreated patients with advanced stage FL. One hundred and twenty patients enrolled in a phase 2 trial of treatment with FCM regimen between 2000 and 2003 were evaluated. After a median follow-up of 12 years, 52 patients eventually relapsed/progressed with 10 year progression-free survival (PFS) of 46 %. Ten patients showed histological transformation to aggressive lymphoma with a risk of transformation of 2 and 9 % at 5 and 10 years, respectively. Three patients developed therapy-related myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML) and seven solid neoplasms with an overall risk of 3 and 8 % at 5 and 10 years, respectively. Twenty-six patients eventually died during the follow-up. Overall survival at 10 years was 83 %. In conclusion, FCM regimen allows excellent long-lasting response in previously untreated patients with FL. The incidence of late events including histological transformation and secondary neoplasia is low but not negligible.

CCR5 Δ32 homozygous cord blood allogeneic transplantation in a patient with HIV: a case report.

BACKGROUND: Allogeneic donor CCR5 Δ32 homozygous haemopoietic cell transplantation (HCT) provides the only evidence to date of long-term control of HIV infection. However, availability of conventional CCR5 Δ32 homozygous donors is insufficient to develop this as a therapeutic strategy further. METHODS: We present a 37-year-old patient with HIV-1 infection and aggressive lymphoma who had disease progression after five lines of radiochemotherapy including an autologous HCT, and in the absence of matched sibling donors, received an allogeneic HCT with four of six HLA-matched CCR5 Δ32 homozygous cord blood cells (StemCyte, Covina, CA), supported with purified CD34+ cells from a haploidentical sibling. Blood or tissue samples were obtained before and weekly after HCT to monitor transplant and HIV infection, including chimerism analysis, CCR5 genotyping and viral tropism, viral isolation and sequence, viral reservoir analysis, immune activation and proliferation, and ex-vivo cell infectivity assays. Combined antiretroviral therapy continued during the procedure. FINDINGS: The patient's HIV was CCR5-tropic by genotypic and phenotypic analyses. Baseline latent reservoir tests showed HIV DNA copies in bulk and resting CD4 T cells and in gut-associated lymphoid tissue, CD4 T-cell-associated HIV RNA, replication competent viral size of 2·1 copies per 10(7) CD4 T cells, and single copy assay of 303 copies per mL. After HCT, plasma HIV DNA load was undetectable by ultrasensitive analyses. Upon cord blood full chimerism, the patient's CCR5 Δ32 homozygous CD4 T cells responded to proliferation and activation stimuli and became resistant to infection by the patient's viral isolate and by laboratory-adapted HIV-1 strains. Death related to lymphoma progression regretfully prevented long-term monitoring of the patient's viral reservoir. INTERPRETATION: CCR5 Δ32 homozygous cord blood reconstitution can successfully eliminate HIV-1 and render the allogeneic graft recipient's T lymphocytes resistant to HIV infection. Thus, they build on the evidence available to strongly support the use of cord blood as a strategic platform for a broader application of non-functional CCR5 transplantation to other infected individuals. FUNDING: Spanish Secretariat of Research, the American Foundation for AIDS Research (amfAR).

The long term follow-up of early stage follicular lymphoma treated with radiotherapy, chemotherapy or combined modality treatment.

Local (involved-field or recently involved-site) radiotherapy is the standard therapy in limited-stage follicular lymphoma (FL). We retrospectively analyzed the value of chemotherapy in 130 patients with limited-stage FL (46 treated with radiotherapy alone [RT group], 30 with radiotherapy plus chemotherapy [COMBINED group] and 43 with chemotherapy alone [CHEMO group], 11 were managed with observation). Ninety-six percent of patients responded (RT 98%, COMBINED 100%, CHEMO 91%, p=0.179), and 37% (40/107) of patients in complete response relapsed (RT 42%, COMBINED 27%, CHEMO 41%, p=0.371). Progression-free survival (PFS) and overall survival (OS) probabilities at 10 years were similar in RT, COMBINED and CHEMO patients (PFS 41%, 61% and 39% [p=0.167], and OS 77%, 81% and 72% [p=0.821], respectively), while the COMBINED group showed a trend to better time-to-progression (TTP 43%, 72% and 47% [p=0.055]). On multivariate analysis, only a FLIPI score ≥2 showed a trend to influence PFS (HR 2.1 [95% confidence interval 0.9-4.6], p=0.067), and OS (HR 2.4 [0.9-6.5], p=0.084), while patients treated with radiotherapy plus chemotherapy (COMBINED group) showed a significantly better TTP compared with those receiving only RT (HR 0.3 [0.1-0.8], p=0.024). In our study no benefit was observed in survival with the use of systemic therapy compared with local radiotherapy.

Ictus pontocerebeloso como primera manifestación de un linfoma B difuso de células grandes intravascular de localización renal / Ictus cerebellopontine as first manifestation of an intravascular diffuse large B cell lymphoma involving at the kidney

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Serum galactomannan-based early detection of invasive aspergillosis in hematology patients receiving effective antimold prophylaxis.

BACKGROUND: There is a practical need to investigate the performance of the serum galactomannan (GM) assay in hematology patients with a potentially low pretest risk of invasive aspergillosis following effective antimold prophylaxis. METHODS: We present a 4-year study with 262 unselected consecutive high-risk episodes, prospectively managed with posaconazole primary prophylaxis and a uniform diagnostic algorithm, including biweekly serum GM quantification for early detection of invasive aspergillosis. RESULTS: A total of 2972 serum GM tests were performed (median, 11 per episode [range, 3-30]); the vast majority were negative (96.7% of tests and 83.6% of episodes). The incidence of breakthrough invasive aspergillosis was 1.9% (5/262), all with true-positive GM test results. Our study identified 30 false-positive GM evaluable episodes (85.7%; 13.8% of all evaluable episodes), validating with real-life data the low positive predictive value of the assay in this setting (12%). In 26 of these 30 episodes (86.7%), the false-positive result(s) occurred in tests performed as preemptive surveillance only. Conversely, in evaluable cases with positive GM tests and a clinical suspicion of invasive fungal disease, the performance of diagnostic-driven GM tests improved, with a positive predictive value of 89.6%. CONCLUSIONS: The low pretest risk of invasive aspergillosis in the context of effective antimold prophylaxis renders serum GM surveillance of asymptomatic patients unreliable, as all results would be either negative or false positive. The test remains useful to diagnose patients with a clinical suspicion of invasive fungal disease, calling for a more efficient copositioning of effective prophylaxis and GM testing in this clinical setting.

Frecuencia de mutaciones del gen ABL en pacientes con leucemia mieloide crónica resistentes a imatinib y resultado del cambio de tratamiento a inhibidores de tirosín-cinasa de segunda generación / Frequency of ABL gene mutations in chronic myeloid leukemia patients resistant to imatinib and results of treatment switch to second-generation tyrosine kinase inhibitors

Background and objectives: Tyrosine kinase inhibitors (TKI) have improved the management of patients with chronic myeloid leukemia (CML). However, a significant proportion of patients do not achieve the optimal response or are resistant to TKI. ABL kinase domain mutations have been extensively implicated in the pathogenesis of TKI resistance. Treatment with second-generation TKI has produced high rates of hematologic and cytogenetic responses in mutated ABL patients. The aim of this study was to determine the type and frequency of ABL mutations in patients who were resistant to imatinib or had lost the : response, and to analyze the effect of second-generation TKI on their outcome. Patients and methods: The presence of ABL mutations in 45 CML patients resistant to imatinib was evaluated by direct sequencing and was correlated with the results of the cytogenetic study (performed in 39 cases). The outcome of these patients after therapy with nilotinib or dasatinib was analyzed. Results: ABL mutations were detected in 14 out of 45 resistant patients. Patients with clonal cytogenetic evolution tended to develop mutations more frequently than those without clonal evolution. Nine out of the 15 patients with ABL mutation responded to a treatment switch to nilotinib (n = 4), dasatinib (n = 2), interferon (n = 1) or hematopoietic stem cell transplantation (n = 2). Conclusion: The frequency of ABL mutations in CML patients resistant to imatinib is high and is more frequent among those with clonal cytogenetic evolution. The change to second-generation TKI can overcome imatinib resistance in most of the mutated patients (AU)

Fundamento y objetivos: La mayoría de los pacientes con leucemia mieloide crónica (LMC) obtienen respuesta clínica bajo tratamiento con imatinib. Sin embargo, una proporción significativa de ellos no alcanza dicha respuesta o son resistentes al tratamiento, implicándose en ello mutaciones del gen ABL. El desarrollo de inhibidores de tirosín-cinasa (ITK) de segunda generación ha permitido superar la resistencia al tratamiento con imatinib en muchos casos. El objetivo de este estudio fue analizar el tipo y frecuencia de mutaciones del gen ABL en pacientes resistentes a imatinib o que han perdido la respuesta y determinar el efecto de los ITK de segunda generación, nilotinib y dasatinib. Sujetos y métodos: Se analizó la presencia de mutaciones en el gen ABL en 45 pacientes con LMC resistentes a imatinib y se correlacionó con el estudio citogenético (realizado en 39 pacientes). También se evaluó la respuesta al tratamiento con ITK de segunda generación. Resultados: Se detectó mutación del gen ABL en 14 de los 45 casos analizados, y fue más frecuente en aquellos pacientes con evolución clonal. Nueve de los 15 pacientes portadores de una mutación en el gen ABL respondieron al cambio de tratamiento con nilotinib (n = 3), dasatinib (n = 2), interferón (n = 1) o trasplante de progenitores hematopoyéticos (n = 2) (AU)

Frequency of ABL gene mutations in chronic myeloid leukemia patients resistant to imatinib and results of treatment switch to second-generation tyrosine kinase inhibitors.

BACKGROUND AND OBJECTIVES: Tyrosine kinase inhibitors (TKI) have improved the management of patients with chronic myeloid leukemia (CML). However, a significant proportion of patients do not achieve the optimal response or are resistant to TKI. ABL kinase domain mutations have been extensively implicated in the pathogenesis of TKI resistance. Treatment with second-generation TKI has produced high rates of hematologic and cytogenetic responses in mutated ABL patients. The aim of this study was to determine the type and frequency of ABL mutations in patients who were resistant to imatinib or had lost the response, and to analyze the effect of second-generation TKI on their outcome. PATIENTS AND METHODS: The presence of ABL mutations in 45 CML patients resistant to imatinib was evaluated by direct sequencing and was correlated with the results of the cytogenetic study (performed in 39 cases). The outcome of these patients after therapy with nilotinib or dasatinib was analyzed. RESULTS: ABL mutations were detected in 14 out of 45 resistant patients. Patients with clonal cytogenetic evolution tended to develop mutations more frequently than those without clonal evolution. Nine out of the 15 patients with ABL mutation responded to a treatment switch to nilotinib (n=4), dasatinib (n=2), interferon (n=1) or hematopoietic stem cell transplantation (n=2). CONCLUSION: The frequency of ABL mutations in CML patients resistant to imatinib is high and is more frequent among those with clonal cytogenetic evolution. The change to second-generation TKI can overcome imatinib resistance in most of the mutated patients.

Neoplasias hematológicas y cuidados paliativos: revisión sistemática de la literatura / Haematological malignancies and palliative care: a systematic literature review

Objetivo: Revisión sistemática de la literatura sobre la intervención de Cuidados Paliativos en el paciente con cáncer hematológico avanzado. Material y método: Realizamos una revisión sistemática sobre los artículos en PubMed y Cochrane, desde el 1 de enero de 2001 al 1 de mayo de 2009, publicados en español y en inglés, usando como palabras claves: «Haematology, Palliative Care, Dying, Death, Supporting Team, advanced Malignancies, Prognostic», así como literatura no indexada en páginas web y libros de Hematología y Cuidados Paliativos sobre temas relacionados. Se incluyeron artículos en cuyos abstracts incluyeran la información sobre la intervención de Cuidados Paliativos en el paciente con enfermedad hematológica maligna avanzada. Los artículos que solo trataban de tratamientos del tumor o de su pronóstico fueron excluidos. Resultados: Un total de 16 artículos fueron aceptados para su lectura y revisión. Se pueden diferenciar dos tipos de artículos: un grupo que hace referencia a las características clínicas de los pacientes y, un segundo grupo que hace referencia a las experiencias de profesionales, pacientes y familiares al final de la vida. Conclusiones: De la información obtenida de la revisión se constata una escasa y heterogénea información al respecto, surgiendo la necesidad de ampliar el estudio en pacientes y familiares en fases avanzadas de la enfermedad hematológica maligna (AU)

Objective: To conduct a systematic review of the literature on the palliative care intervention in the far-advanced patient with haematological malignancies. Material and method: We carried out a systematic search of articles in PubMed and Cochrane, from 1 January 2001 to 1t May 2009, published in Spanish or English, and using ‘‘Haematology, Palliative Care, Dying, Death, Supporting Team, advanced Malignancies, Prognosis’’. Websites and Palliative and Haematology journals and books were also searched. We included papers with an abstract providing information of palliative care intervention in patients with far advanced haematological malignancies. Papers dealing with tumour treatment or prognosis were excluded. Results: Sixteen papers were acceptable for full reading and assessment. Two categories of works could be differentiated; one regarding the clinical characteristics of the patients, and a second lot of papers devoted to the professional, and patient/families experiences with the disease at the end of life. Conclusions: Information provided by the review gave us little and heterogeneous information. Thus there is a great need for the patients and families living with the last stages of haematological malignancy. Further studies are needed (AU)

Influence of MBL-2 mutations in the infection risk of patients with follicular lymphoma treated with rituximab, fludarabine, and cyclophosphamide.

The employment of current treatments based on chemotherapy and immunotherapy leads to inmunosuppression. The presence of mutations or polymorphisms in genes related to immune system might involve an additional disadvantage. The aim of the present study was to analyze mannose-binding lectin (MBL-2 gene) mutations and their association with severe infections and event-free survival in patients diagnosed with follicular lymphoma, treated uniformly, in the clinical trial LNHF-03. The results of this trial showed impressive clinical efficacy but was complicated with 80 documented infectious episodes. Patients were classified into two genotypic groups, AA and AO/OO, based on their haplotypic inheritance. Neither the number of infectious episodes nor differences in event-free survival was found as a function of MBL-2 groups. Other factors, including the lymphoma malignancy and the immune alterations associated with the disease, should be considered responsible for this observation.

Multiple myeloma and hyperammonemic encephalopathy: review of 27 cases.

Hyperammonemic encephalopathy is a rarely reported complication of multiple myeloma (MM). We describe an illustrative case of hyperammonemia in the setting of an immunoglobulin (Ig) D-lambda MM, and perform a systematic review of the English-written literature. Our search yielded 26 more cases. Median age was 64 years, and 54% of patients were male. All presented with progressive impairment of their level of consciousness. Median ammonium concentration was 109 micromol/L (interquartile range, 73-149 micromol/L). Most were IgA type (10 cases), and there were 2 cases of IgD type. Most cases were aggressive or chemotherapy-resistant forms of MM. Eight patients were diagnosed with MM at the same time as the episode of hyperammonemia. Only 1 patient had signs of portal hypertension as a result of concomitant hyperdynamic heart failure. Determination of amino acid in 10 patients showed high levels of glycine, low levels of tyrosine, and a low Fischer ratio. Two patients did not receive chemotherapy and died. Twenty-two out of 25 patients who received chemotherapy against MM showed a decrease in ammonium blood concentration, and of those, 15 survived the episode (68%). Overall mortality was 44%. In conclusion, hyperammonemia is a severe complication of MM, associated with a high mortality. It should be considered in any patient with MM and a low level of consciousness. Chemotherapy directed against MM seems to be the most effective measure in order to achieve normal ammonium levels and clinical improvement.

Practice of central nervous system prophylaxis and treatment in acute leukemias in Spain. Prospective registry study.

BACKGROUND AND OBJECTIVE: Central nervous system (CNS) involvement in patients diagnosed with acute leukemias (AL) is an uncommon complication with poor prognosis. The indication and the schedules of prophylaxis and treatment of CNS involvement in AL are not homogenous among countries and within the same country. The aim of this prospective longitudinal study was to analyze and report the practice of CNS prophylaxis and treatment in patients with AL in Spain. PATIENTS AND METHOD: Prospective study conducted from June 2005 to June 2006. Adult patients (> or = 18 yr.) diagnosed with AL who received CNS prophylaxis or treatment were consecutively included through online registration. RESULTS: 265 patients from 32 hospitals were included. Mean (standard deviation) age was 44 (16) yr. and 133 (50%) were males. For acute lymphoblastic leukemia patients (n = 158), CNS therapy was given to 12 cases (10 at diagnosis and 2 at relapse) and consisted of triple intrathecal therapy (TIT, methotrexate, cytarabine and hydrocortisone) in 11 and liposomal depot cytarabine in one. CNS prophylaxis (n = 146) consisted of TIT in 135 cases, intrathecal methotrexate in 7, intrathecal cytarabine in 2 and intrathecal liposomal depot cytarabine in 2. No cranial irradiation either for prophylaxis or therapy was given in any case. In acute myeloblastic leukemia patients (n = 107), CNS therapy was administered to 17 cases (9 at diagnosis and 8 at relapse). Intrathecal therapy consisted of TIT in 11, intrathecal liposomal depot cytarabine in 5 and intrathecal cytarabine in one. One patient also received craniospinal irradiation. CNS prophylaxis (n = 90) consisted of TIT in 68 cases and intrathecal methotrexate in 22. CONCLUSIONS: In Spain, the patterns of CNS prophylaxis and therapy for AL are homogeneous. TIT was the most frequent schedule for CNS prophylaxis and therapy. The lack of use of cranial or craniospinal irradiation and the administration of new drugs (i.e.: liposomal depot cytarabine) for CNS therapy and prophylaxis is of note.

Prospective study on the practice of central nervous system prophylaxis and treatment in non-Hodgkin's lymphoma in Spain.

BACKGROUND AND OBJECTIVE: Central nervous system (CNS) involvement in patients diagnosed with non-Hodgkin's lymphoma (NHL) or other lymphoproliferative disorders is an infrequent complication with a poor prognosis. The prophylaxis and treatment of CNS involvement in these patients are not homogenous. The aim of this prospective longitudinal study was to report the current practice of CNS prophylaxis and treatment in patients with lymphoproliferative disorders in Spain. METHODS: Prospective study conducted from June 2005 to June 2006. Adult patients (> or = 18 yr) diagnosed with NHL or other lymphoproliferative disorders who received CNS prophylaxis or treatment were consecutively included through online registration. RESULTS: 228 patients from 33 hospitals were included. The mean (SD) age was 52 (16) yr and 144 (63%) were males. CNS therapy was given to 41 cases and consisted of triple intrathecal (IT) therapy (TIT, methotrexate, cytarabine and hydrocortisone) in 22, liposomal depot cytarabine in 18 and methotrexate in one. In addition, 4 patients received cranial radiotherapy. CNS prophylaxis (n = 187) consisted of TIT (166 cases), IT methotrexate (17), IT liposomal depot cytarabine (3) and IT cytarabine (1), whereas cranial or craniospinal radiotherapy was administered to 2 patients. The main reasons for CNS prophylaxis cited by the investigators included extranodal involvement (89 patients), raised serum lactate dehydrogenase level (87), IPI score > 2 (62), bulky mass (43), extranodal involvement in more than one organ (33), age over 60 yr (28) and human immunodeficiency virus infection (13). CONCLUSIONS: The results of this study point out the generalized use of TIT therapy both for CNS prophylaxis and therapy in patients with lymphoproliferative disorders in Spain. The introduction of the new formulations of drugs, especially liposomal depot cytarabine for CNS involvement, and the scarce use of radiotherapy are also of note. Similar to other studies, the absence of homogeneous criteria for CNS prophylaxis is of note.

Practice of central nervous system prophylaxis and treatment in acute leukemias in Spain. Prospective registry study

BACKGROUND AND OBJECTIVE: Central nervous system (CNS) involvement in patients diagnosed with acute leukemias(AL) is an uncommon complication with poor prognosis. The indication and the schedules of prophylaxisand treatment of CNS involvement in AL are not homogenous among countries and within the same country.The aim of this prospective longitudinal study was to analyze and report the practice of CNS prophylaxis andtreatment in patients with AL in Spain.PATIENTS AND METHOD: Prospective study conducted from June 2005 to June 2006. Adult patients ( 18 yr.)diagnosed with AL who received CNS prophylaxis or treatment were consecutively included through online registration.RESULTS: 265 patients from 32 hospitals were included. Mean (standard deviation) age was 44 (16) yr. and133 (50%) were males. For acute lymphoblastic leukemia patients (n = 158), CNS therapy was given to 12cases (10 at diagnosis and 2 at relapse) and consisted of triple intrathecal therapy (TIT, methotrexate, cytarabineand hydrocortisone) in 11 and liposomal depot cytarabine in one. CNS prophylaxis (n = 146) consistedof TIT in 135 cases, intrathecal methotrexate in 7, intrathecal cytarabine in 2 and intrathecal liposomal depotcytarabine in 2. No cranial irradiation either for prophylaxis or therapy was given in any case. In acute myeloblasticleukemia patients (n = 107), CNS therapy was administered to 17 cases (9 at diagnosis and 8 at relapse).Intrathecal therapy consisted of TIT in 11, intrathecal liposomal depot cytarabine in 5 and intrathecalcytarabine in one. One patient also received craniospinal irradiation. CNS prophylaxis (n = 90) consisted ofTIT in 68 cases and intrathecal methotrexate in 22.CONCLUSIONS: In Spain, the patterns of CNS prophylaxis and therapy for AL are homogeneous. TIT was the mostfrequent schedule for CNS prophylaxis and therapy. The lack of use of cranial or craniospinal irradiation andthe administration of new drugs (i.e.: liposomal depot cytarabine) for CNS therapy and prophylaxis is of note

FUNDAMENTO Y OBJETIVO: La infiltración del sistema nervioso central (SNC) en pacientes diagnosticados de leucemiaaguda (LA) es una complicación infrecuente que comporta un mal pronóstico. La indicación y las pautasde profilaxis y tratamiento de la infiltración neuromeníngea en la LA no son homogéneas en los diferentes países,y tampoco en los diferentes centros de un mismo país. El objetivo de este estudio longitudinal y prospectivoha sido describir la práctica real de profilaxis y tratamiento de la infiltración neuromeníngea en pacientescon LA en España.PACIENTES Y MÉTODO: Se trata de un estudio prospectivo llevado a cabo desde junio de 2005 a junio de 2006.Se incluyó, mediante registro electrónico, a los pacientes adultos (edad 18 años) diagnosticados de LA querecibieron profilaxis o tratamiento de la infiltración del SNC.RESULTADOS: Se incluyó a un total de 265 pacientes procedentes de 32 hospitales. La media (desviación estándar)de edad fue de 44 (16) años y 133 (50%) eran varones. Entre los 158 pacientes con leucemia linfoblásticaaguda, 12 (10 en el momento del diagnóstico y 2 en recaída) recibieron tratamiento del SNC por infiltraciónneuromeníngea, que consistió en tratamiento intratecal triple (TIT: metotrexato, citarabina e hidrocortisona)en 11 casos y citarabina liposómica de liberación lenta por vía intratecal en uno. La profilaxis del SNC administradaen los 146 pacientes restantes incluyó TIT en 135 casos, metotrexato intratecal en 7, citarabina intratecalen 2 y citarabina liposómica de liberación lenta por vía intratecal en 2. No se administró radioterapiacraneal ni craneoespinal a ningún paciente. Entre los 107 pacientes con leucemia mieloblástica aguda, 17tenían infiltración del SNC (9 en el momento del diagnóstico y 8 en la recaída). El tratamiento intratecal consistióen TIT en 11 casos, citarabina liposómica de liberación lenta en 5 y citarabina intratecal en uno. Unpaciente recibió además radioterapia craneoespinal. La profilaxis del SNC en los 90 pacientes restantes incluyóTIT en 68 casos y metotrexato intratecal en 22.CONCLUSIONES: En España las pautas de profilaxis y tratamiento de la infiltración neuromeníngea en pacientescon LA son homogéneas. El TIT fue el esquema usado con mayor frecuencia tanto para la profilaxis como parael tratamiento del SNC. Llama la atención la escasa utilización de la radioterapia holocraneal o craneoespinal,así como la administración de nuevos fármacos, como la citarabina liposómica de liberación lenta, en el tratamientoy la profilaxis de la meningosis leucémica

Impact of interleukin-10 polymorphisms (-1082 and -3575) on the survival of patients with lymphoid neoplasms.

BACKGROUND AND OBJECTIVES: Single-nucleotide polymorphisms (SNP) in interleukin-10 (IL-10) genes can influence immune responses, which may affect the outcome of patients with lymphoid neoplasms. The aim of this study was to explore the association between polymorphisms of IL-10-(1082A>G) and IL-10-(3575T>A) with the overall survival in patients with lymphoid neoplasms. DESIGN AND METHODS: We analyzed two IL-10 SNP (-1082 and -3575) in 472 consecutive cases with lymphoid neoplasms. Genotypes were tested for association with overall survival and classical prognostic factors by multivariate analysis. Haplotype analysis was carried out using the haplostats package implemented in R software. The implications for survival of patients with lymphoma were evaluated using multivariate analysis. RESULTS: Lymphoma patients with the IL-10-(3575T>A) genotype had a better overall survival (p= 0.002), as did the subgroup with non-Hodgkin's lymphoma (NHL) (p=0.05). Patients with the IL10(-1082GG) genotype had a better median overall survival (p=0.05). When both genotypes were included in a multivariate analysis, IL-10(-3575AA) genotype was the only independent prognostic factor for survival (HR=0.20, 95%CI 0.05-0.92). Patients with the IL-10(-1082) and (-3575) G-A/G-A diplotype had a longer overall survival (p=0.003) and this combination appeared to be an independent prognostic factor for survival (HR:0.26; 95%CI 0.08-0.83). INTERPRETATION AND CONCLUSIONS: The IL-10(-3575A/A) genotype was identified as a marker of favorable survival. Because the IL-10(-1082) and (-3575) G-A/G-A diplotype was also identified as an indicator of longer survival, we cannot exclude the potential additive role of the IL-10(-1082GG) genotype. These results need to be replicated in larger series and examined in different NHL subtypes.

The adjusted International Prognostic Index and beta-2-microglobulin predict the outcome after autologous stem cell transplantation in relapsing/refractory peripheral T-cell lymphoma.

BACKGROUND AND OBJECTIVES: Preliminary data on the use of autologous stem cell transplantation (ASCT) as a salvage therapy for peripheral T-cell lymphoma (PTCL) indicate that the results are similar to those obtained in aggressive B-cell lymphomas. The aim of our study was to analyze outcomes of a large series of patients with PTCL with a prolonged follow-up who received ASCT as salvage therapy. DESIGN AND METHODS: Between 1990 and 2004, 123 patients in this situation were registered in the GELTAMO database. The median age at transplantation was 43.5 years; in 91% of patients the disease was chemosensitive. RESULTS: Seventy-three percent of the patients achieved complete remission, 11% partial remission and the procedure failed in 16%. At a median follow-up of 61 months, the 5-year overall and progression-free survival rates were 45% and 34%, respectively. The presence of more than one factor of the adjusted International Prognostic Index (a-IPI) and a high beta2-microglobulin at transplantation were identified as adverse prognostic factors for both overall and progression-free survival and allowed the population to be stratified into three distinct risk groups. INTERPRETATION AND CONCLUSIONS: Our data show that approximately one third of patients with PTCL in the salvage setting may enjoy prolonged survival following ASCT, provided they are transplanted in a chemosensitive disease state. The a-IPI and beta2-microglobulin level predict the outcome after ASCT in relapsing/refractory PTCL.