Scleral lenses for severe chronic GvHD-related keratoconjunctivitis sicca: a retrospective study by the SFGM-TC.

Chronic GvHD-related keratoconjunctivitis sicca (cGvHD-related KCS) can significantly alter the quality of life of patients after allogeneic hematopoietic stem cell transplantation. The aim of this work was to assess the efficacy and tolerability of scleral lenses to treat severe cGvHD-related KCS. In this retrospective, multicenter study, we included 60 consecutive patients diagnosed with cGvHD-related KCS and fitted with scleral lenses. Patients were evaluated at baseline and at 2 months with the following tests: the Ocular Surface Disease Index (OSDI) to assess quality of life, the Oxford score to grade corneal damage and the logarithm of minimal angle of resolution (Log MAR) scale to determine visual acuity. We observed improvement in quality of life in 58 patients (97%). All parameters improved at 2 months. We observed significant differences at 2 months compared with baseline for the mean OSDI (86 versus 30, respectively, P<0.001), the mean Oxford score (3.2 versus 1.3, respectively, P<0.001) as well as visual acuity (Log MAR of 0.33 versus 0.10, respectively, P<0.001). Treatment with scleral lenses was discontinued in only 5 patients (8%) with a median follow-up of 20.5 months (range: 2-125 months). Scleral lenses were very efficient and well tolerated in patients with severe cGvHD-related KCS.

Pre-transplant donor CD4- invariant NKT cell expansion capacity predicts the occurrence of acute graft-versus-host disease.

Clinically useful pre-transplant predictive factors of acute graft-versus-host-disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT) are lacking. We prospectively analyzed HSC graft content in CD34+, NK, conventional T, regulatory T and invariant natural killer T (iNKT) cells in 117 adult patients before allo-SCT. Results were correlated with occurrence of aGVHD and relapse. In univariate analysis, iNKT cells were the only graft cell populations associated with occurrence of aGVHD. In multivariate analysis, CD4- iNKT/T cell frequency could predict grade II-IV aGVHD in bone marrow and peripheral blood stem cell (PBSC) grafts, while CD4- iNKT expansion capacity was predictive in PBSC grafts. Receiver operating characteristic analyses determined the CD4- iNKT expansion factor as the best predictive factor of aGVHD. Incidence of grade II-IV aGVHD was reduced in patients receiving a graft with an expansion factor above versus below 6.83 (9.7 vs 80%, P<0.0001), while relapse incidence at two years was similar (P=0.5).The test reached 94% sensitivity and 100% specificity in the subgroup of patients transplanted with human leukocyte antigen 10/10 PBSCs without active disease. Analysis of this CD4- iNKT expansion capacity test may represent the first diagnostic tool allowing selection of the best donor to avoid severe aGVHD with preserved graft-versus-leukemia effect after peripheral blood allo-SCT.

Incidence and risk factors for hemorrhagic cystitis in unmanipulated haploidentical transplant recipients.

BACKGROUND: Hemorrhagic cystitis (HC) is a common complication after hematopoietic allogeneic stem cell transplantation (HSCT) associated with intensity of the conditioning regimen, cyclophosphamide (Cy) therapy, and BK polyomavirus (BKPyV) infection. METHODS: We analyzed 33 consecutive haploidentical (haplo) HSCT recipients transplanted for hematologic diseases. Eleven patients had a previous transplant. Median follow-up was 11 months. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine + mycophenolate mofetil and post-HSCT Cy. RESULTS: Thirty-two of 33 patients achieved neutrophil recovery. Cumulative incidence (CI) of platelet recovery was 65%. CI grade II-IV acute GVHD was 44%. Twenty patients developed HC in a median time of 38 days. CI of HC at day 180 was 62%. BKPyV was positive in blood and urine of 91% of patients at HC onset. HC resolved in 18/20 patients. Factors associated with HC were previous transplant (P = 0.01) and occurrence of cytomegalovirus reactivation before HC (P = 0.05). Grade II-IV acute GVHD was not associated with HC (P = 0.62). CI of day 180 viral infections was 73%. Two-year overall survival (OS) was 50%; HC did not impact OS (P = 0.29). CONCLUSION: The incidence of HC after haplo with post-HSCT Cy is high and is associated with morbidity, especially in high-risk patients such as those with a previous transplant history and with impaired immune reconstitution.

HLA-matched allogeneic stem cell transplantation improves outcome of higher risk myelodysplastic syndrome A prospective study on behalf of SFGM-TC and GFM.

Allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only a curative treatment in patients with higher risk myelodysplastic syndrome (MDS), although demethylating agents (DMA) have been reported to improve survival. The advantage of HSCT over other treatment comes from retrospective studies and the aim of the current study was to prospectively test this hypothesis, analyzing in particular patients from the pre-transplant period to avoid the selection bias of performing transplantation. This study was conducted to compare overall survival in MDS patients candidates to transplantation according to donor availability. The majority of patients (76%) received a treatment with DMA after registration, 69% had a human leukocyte antigen (HLA)-identical donor, 70% of whom were transplanted. Baseline patient and disease characteristics were similar according to donor availability. Four-year overall survival was significantly better in patients with an HLA matched donor (37%) compared to patients without donor (15%). There was also evidence that this overall survival advantage was because of transplantation. Mortality risk was decreased after transplantation but it became significant only after the second year post transplant, because of early transplant-related mortality. Our results appear to justify, in higher risk MDS, a transplantation approach in all potential candidates who have an HLA identical donor.

[Allogeneic stem cell transplantation from an HLA-haploidentical related donor: SFGM-TC recommendations (Part 1)]. / Greffes de cellules souches hématopoïétiques à partir d'un donneur haplo-identique : recommandations de la SFGM-TC (première partie).

Haploidentical allogeneic stem cell transplantation (CST) has globally taken off in the past decade. It appears to be a valid alternative to other sources of stem cells; however, further research is necessary to validate the use of this approach in standard patient care. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. This is part one of the recommendations regarding allogeneic stem cell transplantation from an HLA-haploidentical related donor.

[Allogeneic stem cell transplantation from an HLA-haploidentical related donor: SFGM-TC recommendations (part 2)]. / Greffes de cellules souches hématopoïétiques à partir d'un donneur haploidentique : recommandations de la SFGM-TC (deuxième partie).

Haploidentical allogeneic stem cell transplantation (CST) has globally taken off in the past decade. It appears to be a valid alternative to other sources of stem cells; however, further research is necessary to validate the use of this approach in standard patient care. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. This is part two of the recommendations regarding allogeneic stem cell transplantation from an HLA-haploidentical related donor.

Skin ulcers related to chronic graft-versus-host disease: clinical findings and associated morbidity.

BACKGROUND: According to the National Institutes of Health classification of chronic graft-versus-host disease (cGVHD), skin ulcers after allogeneic haematopoietic stem-cell transplantation (HSCT) are recorded as having the maximal severity score but published data are scarce. OBJECTIVES: To describe skin ulcers related to cGVHD with an emphasis on clinical findings, associated morbidity, management and evolution. PATIENTS AND METHODS: A multicentre retrospective analysis was carried out of patients with a diagnosis of cGVHD skin ulcers. RESULTS: All 25 patients included in the study had sclerotic skin cGVHD and 21 had lichenoid skin lesions associated with the sclerotic skin lesions. Thirteen patients had severe cGVHD without considering the skin, because of the involvement of an extracutaneous organ by cGVHD. The median time from HSCT to the onset of ulcers was 44 months. In addition to scleroderma, initial skin lesions at the site of ulcers were bullous erosive lichen in 21 patients and bullous erosive morphoea in four patients. Fifteen patients had an inaugural oedema. Ulcers were mostly bilateral with a predilection for the lower limbs. They were frequently colonized but few infections occurred. Four patients died during a median follow-up period of 55 months. CONCLUSIONS: Chronic graft-versus-host disease skin ulcers occur in patients with sclerodermatous skin cGVHD, are associated with severe cGVHD, often start with bullous lichenoid lesions or bullous morphoea and seem to cause more morbidity than mortality, given the low rate of mortality observed in our series of patients.

[Vaccination post hematopoietic stem cell transplantation: which vaccines and when and, how to vaccinate? An SFGM-TC report]. / Vaccinations post-allogreffe de cellules souches hématopoïétiques: lesquels? Quand? Comment?

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding vaccination post Hematopoietic Stem Cell Transplantation with practical focus on which vaccines to use and when and how to vaccinate?

Enteropathy-associated T-cell lymphoma: a review on clinical presentation, diagnosis, therapeutic strategies and perspectives.

INTRODUCTION: Enteropathy-associated T-cell lymphoma (EATL) is a rare complication of celiac disease (<1% of lymphomas) and has a poor prognosis. METHODS: International literature review with PubMed search (up to January 2009) of pathophysiological, clinical and therapeutic data. RESULTS: EATL is found in patients with a mean age of 59 years, often with a complication that signals its diagnosis. Refractory celiac disease (RCD), equivalent to low-grade intraepithelial T-cell lymphoma, could be an intermediary between celiac disease and high-grade invasive T-cell lymphoma. The median survival is 7 months, with no significant difference between stages; the cumulative 5-year survival is less than 20%. The poor prognosis is determined by disease that has often spread before it is diagnosed (50%), multifocal involvement of the small bowel (50%), poor general health status and undernutrition, and recurrence of complications (infections, perforations, gastrointestinal haemorrhages, occlusions), thus delaying the chemotherapy and contributing to frequent chemotherapy resistance. There is currently no effective and consensual treatment: preventive surgery for complications is controversial, and the results of chemotherapy are disappointing. The classic CHOP protocol (combination of doxorubicin-cyclophosphamide-vincristine-prednisone) does not have satisfactory results and survival remains poor, especially in patients with underlying RCD. High-dose chemotherapy with autotransplantion seems to only improve the prognosis in localised forms. Allogeneic bone marrow transplantation was not evaluated. In all, 1/3 of patients, being unfit for treatment, die before 3 months and half of treated patients stop chemotherapy prematurely due to inefficacy, intolerance and/or complications. CONCLUSION: Improvement of the prognosis requires collaboration in order to compose a national cohort, to evaluate new diagnostic and therapeutic strategies and to define prognostic factors.

Enfermedad de Kawasaki: diagnóstico y tratamiento / Kawasaki disease: Diagnosis and treatment

Introducción: La enfermedad de Kawasaki es la principal causa de cardiopatía adquirida en niños en los países desarrollados. A pesar de un tratamiento eficaz, la dificultad en el diagnóstico precoz de la enfermedad, así como la existencia de pacientes no respondedores siguen haciendo de esta enfermedad una causa de enfermedad coronaria importante en nuestro medio. Objetivos: Analizar las características clínicas y epidemiológicas de los pacientes diagnosticados de enfermedad de Kawasaki, los tratamientos empleados y las alteraciones coronarias secundarias. Métodos: Se revisaron de forma retrospectiva las historias clínicas de los niños diagnosticados de enfermedad de Kawasaki desde enero de 2002 hasta diciembre de 2008 en un hospital de tercer nivel del área sur de Madrid. Se consideró diagnóstico de enfermedad la presencia de los criterios clínicos propuestos por la Academia Americana de Pediatría en 2004.ResultadosVeintitrés pacientes fueron diagnosticados de enfermedad de Kawasaki durante el periodo estudiado. La mediana de edad fue de 26 meses (rango: 2 meses–10 años). Diecinueve pacientes (82%) eran menores de 5 años. Todos los pacientes presentaron fiebre y afectación bucofaríngea. Veintiún pacientes (91%) fueron tratados con inmunoglobulina intravenosa (IGIV), todos antes del 10° día de enfermedad [mediana 5,5 días, (rango 2–8 días)]. Diecisiete de estos pacientes (81%) recibieron el tratamiento a partir del 5° día de fiebre. En un solo caso (4,7%) se administró más de una dosis de IGIV por persistencia de la fiebre. Tres varones [13,0%, (IC 95%: 1–26%)], uno de ellos de 4 meses de edad, desarrollaron aneurismas coronarios. Conclusiones: En nuestro estudio se confirma que la enfermedad de Kawasaki afecta predominantemente a niños menores de 5 años. El porcentaje de anomalías coronarias sigue siendo elevado a pesar de un tratamiento precoz y adecuado (AU)

Introduction: Kawasaki disease is the leading cause of acquired heart disease in children. In spite of the efficacy of intravenous immunoglobulin (IGIV), the absence of a specific diagnostic test and due to there being IGIV-refractory patients, Kawasaki disease is a major cause of coronary artery abnormalities (CAA). Objectives: To analyze the clinical and epidemiological characteristics of cases of Kawasaki disease, to evaluate the efficacy of treatments used and the CAA observed. Methods: We retrospectively reviewed the medical records of children diagnosed with Kawasaki disease between January 2002 and December 2008 in a tertiary public Hospital in the South of Madrid. The diagnosis of Kawasaki disease was based on the clinical criteria proposed by the American Academy of Pediatrics in 2004.ResultsTwenty three children were identified. Median age was 26 months (range: 2 months–10 years). Nineteen children (82%) were younger than 5 years old. Fever and changes in the lips and oral cavity were present in all cases. Twenty-one patients (91%) received IGIV, all of them before the 10th day of disease. One child (4.7%) required the administration of more than one dose of IGIV, because persistence of fever. CAA was recorded in three patients [13.0%, (95% CI: 1–26%)], including a four month-old boy. All patients with CAA were treated with the recommended dose of IGIV, 2g/kg, between the 5th and 8th day of disease. Conclusions: Kawasaki disease was more common in children less than five years old. We observed a high rate of CAA in children with Kawasaki disease in spite of appropriate and timely treatment (AU)

[High risk of cardiac dysfunction after treatment of secondary acute myeloid leukemia following chemotherapy and radiotherapy for breast cancer]. / Risque élevé de dysfonction cardiaque des leucémies aiguës myéloïdes secondaires à un cancer du sein.

Secondary acute myeloid leukaemia (AML) occurring after breast cancer is a rare long-term complication of the chemo- and/or radiation therapy required to treat breast cancer. The usually recognized curative option of these secondary AML includes courses of anthracycline-based chemotherapy followed by haematopoietic stem cell transplantation (HSCT). Cardiac dysfunction during AML treatment of these patients previously treated with anthracyclines for breast cancer has not been reported to date. We evaluated the evolution of cardiac function in seven patients treated with anthracyclines and/or autologous or allogeneic bone marrow transplantation for secondary AML occurring after breast cancer. All of the patients who received a cumulative anthracycline dose above the cardiac toxicity threshold developed cardiac symptoms during AML chemotherapy courses. Moreover, four of the five transplanted patients developed severe heart failure among which two were fatal. Thus, the risk of severe cardiac dysfunction after treatment of secondary AML following breast cancer must be taken in account as part of the therapeutic strategy of those patients. As discussed here, an accurate evaluation of risk factors, the use of sensitive detection tests and of cardioprotective drugs as well as that of non-cardiotoxic chemotherapy might decrease the occurrence and severity of this life-threatening complication.

Prediction of relapse by day 100 BCR-ABL quantification after allogeneic stem cell transplantation for chronic myeloid leukemia.

Chronic myeloid leukemia (CML) relapse after allogeneic stem cell transplantation (SCT) is a relatively frequent situation, which is correlated to disease status, time from diagnosis to transplant and T-cell depletion. We evaluated the potential for early minimal residual disease (MRD) BCR-ABL quantification to predict relapse of CML patients receiving allogeneic SCT. Minimal residual disease was analyzed by real-time quantitative reverse transcriptase-polymerase chain reaction (RQ-PCR) at day 100 (d100) in 38 patients with >1 year follow-up after conventional non-T-cell-depleted SCT. Normal ABL control values from 1724 follow-up blood samples were used to define an RQ-PCR amplifiability index and the limits of reliable use of BCR-ABL ratios. We then compared the 14 patients with a high-level d100 BCR-ABL/ABL ratio (> or = 10(-4)) to that of the 24 patients with a negative/low-level ratio (<10(-4)). Despite being comparable for all classical parameters, the incidence of relapse was significantly higher in the high MRD group (11/14 (79%)) compared to that of the low/negative MRD group (7/24 (29%)) (P = 0.009), with d100 MRD values representing an independent risk factor of relapse and disease-free survival, but not of overall survival, in multivariate analysis. These data should facilitate risk-adapted post-transplant immunosuppression and/or tyrosine kinase inhibitor therapy based on an early evaluation of MRD.

Evolución en las características epidemiológicas de la tuberculosis en Navarra (1994-2003) / Evolution of the epidemiological characteristics of tuberculosis in Navarra (1994-2003)

Objetivo. Describir los cambios en la incidencia y en el perfil epidemiológico de la tuberculosis en Navarra. Métodos. Se analizaron los casos de tuberculosis del período 1994-2003 según el sistema de enfermedades de declaración obligatoria, completado con los diagnósticos microbiológicos y con los casos captados por otros registros sanitarios.Resultados. La incidencia de tuberculosis disminuyó desde 21 por 100.000 habitantes en el quinquenio 1994-1998 hasta 16 por 100.000 en 1999-2003. En ambos períodos los casos en hombres duplicaron a los de mujeres, y la máxima incidencia se produjo en los grupos de 25 a 44 y mayores de 65 años. Los diagnósticos de tuberculosis en personas con infección por el VIH disminuyeron del 15,1 al 6,6% y los realizados en personas inmigrantes aumentaron del 2,2 al 21,3%. Algo más del 3% de los casos había recibido tratamiento antituberculoso previo y en torno al 6% presentaban resistencia a algún fármaco, sin diferencias significativas entre periodos. La proporción de tuberculosis potencialmente transmisibles (73%) no experimentó cambios significativos, ni la de aquellas con baciloscopia de esputo positiva (53%). El número de brotes (agrupaciones de dos o más casos) pasó de 18 a 26 y el porcentaje de casos secundarios a otro reciente aumentó desde 3,6 a 10,1% (p<0,001). En el período 1999-2003, la localización pulmonar se presentó de forma aislada en el 67,7% y combinada con otras localizaciones en otro 5,1%. La forma pleural aislada apareció en el 9,9% y la meníngea en el 1,5% de los pacientes.Conclusión. Se ha avanzado en el control de la tuberculosis aunque todavía la incidencia es alta respecto a otros países europeos. El control de los casos importados es uno de los retos para los próximos años, sin descuidar las medidas de control en la población autóctona

Aim. To describe the changes in the incidence and the epidemiological profile of tuberculosis in Navarra. Methods. The cases of tuberculosis in the 1994-2003 period were analysed. Cases reported to the system of obligatory notifiable diseases, completed with the microbiological diagnoses and the cases collected in other health registers. Results. The incidence of tuberculosis fell from 21 per 100,000 inhabitants in the five-year period 1994-1998 to 16 per 100,000 in 1999-2003. In both periods the number of cases in men doubled that in women, and the maximum incidence occurred in the age groups from 25 to 44 and over 65 years of age. The diagnoses of tuberculosis in persons with HIV infection fell from 15.1% to 6.6% and those in immigrants rose from 2.2% to 21.3%. Somewhat over 3% of the cases had received prior anti-tuberculosis treatment and about 6% showed resistance to some medicine, without significant differences between periods. The proportion of potentially transmissible tuberculosis (73%) underwent no significant changes, nor did that of those with positive sputum bacilloscopy. The number of outbreaks (groupings of two or more cases) rose from 18 to 26 and the percentage of cases secondary to another recent case rose from 3.6% to 10.1% (p<0,001). In the 1999-2003 period, pulmonary localisation occurred in isolated form in 67.7% of the patients, and in combination with other localisations in another 5.1%. The isolated pleural form appeared in 9.9% and the meningeal form in 1.5%. Conclusion. There has been an advance in the control of tuberculosis although its incidence is still high with respect to other European countries. Control of imported cases is one of the challenges to be faced in coming years, without neglecting control measures in the autochthonous population

Captación gástrica de Galio67 en la infección por virus de la inmunodeficiencia humana / Gastric uptake of Gallium67 in the human immunodeficiency virus infection

Actualmente la infección por el virus de la inmunodeficiencia humana (VIH) es una enfermedad crónica en que son frecuentes presentaciones clínicas con fiebre, adenopatías y pérdida de peso, cuya etiología es preciso determinar, para indicar un tratamiento específico. El paciente con inmunodeficiencia adquirida puede presentar infecciones oportunistas gastrointestinales o procesos linfomatosos o sarcomatosos gástricos, que pueden acumular citrato de Galio67. Presentamos 2 casos con captación gástrica de Ga67 en los que se practicó endoscopia con biopsia. En el primero de ellos, que había recibido tratamiento previo con omeprazol y almalgato por reflujo gastroesofágico, no se demostró patología y en el segundo se diagnosticó infección por Helicobacter pylori. Creemos que en los casos con VIH la captación gástrica de Ga67 debe indicar al clínico la necesidad de descartar patologías asociadas (AU)

Mielodisplasia con deleción del cromosoma 7 asociada a tuberculosis y hepatitis C: ¿un modelo de sinergismo inmunodepresor? / Myelodysplasia with cromosome 7 delection associated to tuberculosis and virus C hepatitis: a pattern of immunodepressor synergyism?

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Hemorragia cerebral fatal en un cuadro de trombocitopenia severa asociada a infección por Brucella

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