Treatment of steroid-refractory chronic graft-versus-host disease with imatinib: Real-life experience of the Spanish group of hematopoietic transplantation (GETH).

Treatment of steroid-refractory chronic graft-versus-host disease (cGVHD) is a challenge. Here, we describe a retrospective analysis of 66 patients with steroid-refractory cGVHD treated with imatinib (starting dose of 100 mg in 70% of patients; maximum dose of 100-200 mg in 74%). Most patients had multi-organ involvement (≥2 organs, 83%), with the most affected being skin (85%), oral mucosa (55%), eyes (42%), and lungs (33%). The overall response rate was 41% (21 partial and three complete responses). The organ with the best response rate was the skin (46%), followed by gastrointestinal tract (43%), liver (41%), the oral mucosa (36%), eyes (29%), and lungs (18%). Imatinib led to steroid tapering in 17/38 patients. Twenty-five (38%) patients experienced imatinib-related adverse events, comprising extra-hematologic toxicity (n = 24, 36%) and hematologic toxicity (n = 6, 9%). No cases of grade 4-5 toxicity were reported. The main causes of imatinib discontinuation were treatment failure (52%) and toxicity (9%). After a median follow-up of 41 months, the 3-year overall survival was 81%, with no difference between imatinib responders and non-responders. These real-life results show that imatinib is safe and has moderate efficacy in patients with heavily pre-treated cutaneous sclerotic cGVHD; however, activity against lung cGVHD is very limited.

Eritroaféresis terapéutica: experiencia en pacientes con policitemia vera y eritrocitosis secundaria / Therapeutic erythroapheresis: Experience in patients with polycythemia vera and secondary erythrocytosis

La eritrocitaféresis terapéutica (ET) es una estrategia más eficiente que la flebotomía en la reducción del hematocrito en las eritrocitosis primarias y secundarias. Objetivo: Analizar la tasa de respuesta y seguridad de la ET en policitemia vera (PV) y eritrocitosis secundaria (ES). Pacientes y método: Revisión retrospectiva de los pacientes con PV o ES tratados con ET, ante el fracaso a flebotomías o con comorbilidades que impedían cambios importantes de volemia. Resultados: Se realizaron 127 sesiones de ET (48 PV y 79 ES) en 20 pacientes (12 ES y 8 PV). La respuesta se obtuvo en el 87,5% de PV y en el 50% de ES. La tasa de complicaciones fue del 7,08%. Conclusiones: A pesar del tamaño de nuestra muestra y la heterogeneidad clínica de nuestra serie, podemos postular que la ET reduce de manera segura los valores de hematocrito en menor tiempo que la flebotomía, especialmente en pacientes con PV y en casos seleccionados de ES en quienes se prevé intolerancia hemodinámica a la flebotomía o en quienes falla este método

Therapeutic erythrocytapheresis (TE) is a more efficient strategy compared to phlebotomy to deplete levels of haematocrit in primary and secondary erythrocytosis. Objective: To analyse response rate and safety profile of TE in polycythemia vera (PV) and secondary erythrocytosis (SE). Patients and method: Retrospective review of all patients with PV or SE treated with TE, due to phlebotomy failure, or comorbidities that prevented changes of blood volumen. Results: 217 TE sessions (48 PV and 79 SE) corresponding to 20 patients (12 ES and 8 PV). Response were achieved in 87.5% of PV patients and in 50% of SE patients. Adverse effects related to TE performance occurred in 7.08%. Conclusion: Despite our small sample size and the heterogeneous nature of the patients included, we can postulate that TE is a secure strategy that can achieve haematocrit depletion in a shorter time than phlebotomy, specifically in PV patients and in selected cases of SE with expected haemodynamic intolerance to phlebotomies or in patients who fail to respond to phlebotomies

Therapeutic erythroapheresis: Experience in patients with polycythemia vera and secondary erythrocytosis. / Eritroaféresis terapéutica: experiencia en pacientes con policitemia vera y eritrocitosis secundaria.

Therapeutic erythrocytapheresis (TE) is a more efficient strategy compared to phlebotomy to deplete levels of haematocrit in primary and secondary erythrocytosis. OBJECTIVE: To analyse response rate and safety profile of TE in polycythemia vera (PV) and secondary erythrocytosis (SE). PATIENTS AND METHOD: Retrospective review of all patients with PV or SE treated with TE, due to phlebotomy failure, or comorbidities that prevented changes of blood volumen. RESULTS: 217 TE sessions (48 PV and 79 SE) corresponding to 20 patients (12 ES and 8 PV). Response were achieved in 87.5% of PV patients and in 50% of SE patients. Adverse effects related to TE performance occurred in 7.08%. CONCLUSION: Despite our small sample size and the heterogeneous nature of the patients included, we can postulate that TE is a secure strategy that can achieve haematocrit depletion in a shorter time than phlebotomy, specifically in PV patients and in selected cases of SE with expected haemodynamic intolerance to phlebotomies or in patients who fail to respond to phlebotomies.

Ruxolitinib in refractory acute and chronic graft-versus-host disease: a multicenter survey study.

Graft-versus-host disease is the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. First-line treatment is based on the use of high doses of corticosteroids. Unfortunately, second-line treatment for both acute and chronic graft-versus-host disease, remains a challenge. Ruxolitinib has been shown as an effective and safe treatment option for these patients. Seventy-nine patients received ruxolitinib and were evaluated in this retrospective and multicenter study. Twenty-three patients received ruxolitinib for refractory acute graft-versus-host disease after a median of 3 (range 1-5) previous lines of therapy. Overall response rate was 69.5% (16/23) which was obtained after a median of 2 weeks of treatment, and 21.7% (5/23) reached complete remission. Fifty-six patients were evaluated for refractory chronic graft-versus-host disease. The median number of previous lines of therapy was 3 (range 1-10). Overall response rate was 57.1% (32/56) with 3.5% (2/56) obtaining complete remission after a median of 4 weeks. Tapering of corticosteroids was possible in both acute (17/23, 73%) and chronic graft-versus-host disease (32/56, 57.1%) groups. Overall survival was 47% (CI: 23-67%) at 6 months for patients with aGVHD (62 vs 28% in responders vs non-responders) and 81% (CI: 63-89%) at 1 year for patients with cGVHD (83 vs 76% in responders vs non-responders). Ruxolitinib in the real life setting is an effective and safe treatment option for GVHD, with an ORR of 69.5% and 57.1% for refractory acute and chronic graft-versus-host disease, respectively, in heavily pretreated patients.

Seguridad de los recambios plasmáticos terapéuticos en la lesión renal aguda secundaria a vasculitis / Safe of plasma exchange in acute renal failure secondary to vasculitis

No disponible

Combination of a triple alpha-globin gene with beta-thalassemia in a gypsy family: importance of the genetic testing in the diagnosis and search for a donor for bone marrow transplantation for one of their children.

BACKGROUND: The simultaneous presence of a heterozygous ß-thalassemia with α-gene triplication may cause anything from a thalassemia trait to thalassemia intermedia of mild to moderate severity. CASE PRESENTATION: An 8-month-old ethnic Gypsy male infant with failure to thrive from birth, mild jaundice and splenomegaly. Clinical signs were compatible with severe microcytic anemia requiring bi-monthly blood transfusions. The ß-thalassemia gene analysis found homozygous mutation IVS-I-110 (G>A) (c.93-21G>A) in intron 1 of the hemoglobin beta globin gene and a non-pathogenic sequence variant (single nucleotide polimorfism (SNP) Rs1609812). In addition, the patient had α gene triplication (ααα(anti 3.7)/αα) caused by double heterozygosity for a 3.7 kb fragment that contained only the hemoglobin alpha globin gene-2 gene. This finding led to screening and follow up in first-degree relatives, twin brothers and a sister and parents to provide them with appropriate genetic counseling. Nowadays, new horizons could open a new therapeutic management until definitive cure of these diseases through gene therapy or mutation-specific genome editing. CONCLUSIONS: Genetic testing can provide an early diagnosis and facilitates the search for a suitable donor for transplantation.

Therapeutic leukapheresis: 9-year experience in a University Hospital.

BACKGROUND: Hyperleucocytosis is associated with higher morbidity and mortality related to possible development of leucostasis, tumour lysis syndrome and/or disseminated intravascular coagulation. There is insufficient evidence of the need for leukocytapheresis during early treatment of hyperleucocytosis, and its efficiency remains controversial, although leucoreduction is a measure that can prevent adverse events and death. The aim of this study was to analyse the safety and effectiveness of therapeutic leukocytapheresis and its influence on early mortality in our case series, adjusted to independent mortality risk factors described in the literature. MATERIALS AND METHODS: This was a retrospective review (June 2003-June 2012) of procedures carried out for the treatment of hyperleucocytosis at the Haematology and Haemotherapy Service of Miguel Servet University Hospital. The patients' data and technical information were prospectively registered for each leukocytapheresis session. RESULTS: Thirteen patients underwent a total of 27 leukocytapheresis procedures. After an average of two sessions, a statistically significant drop in the initial leucocyte counts was observed (p<0.01), as well as a relevant drop in lactate dehydrogenase levels. The only analytical value statistically related to early mortality in univariate analysis was initial creatinine level greater than 1.2 mg/dL (p=0.012, OR=2.5). DISCUSSION: Despite the small size and limited homogeneity of our case series, we can conclude that leukocytapheresis is a safe and effective therapeutic measure for leucoreduction in haematological pathologies of any lineage, particularly in patients without acute myeloid leukaemia. Patients with acute myeloid leukaemia had worse outcomes within 6 months of having finished leukocytapheresis sessions, as well as in terms of mean global survival and mean time of mortality. However, global mortality rates were similar in patients with or without acute myeloid leukaemia.

Factores predictores de respuesta a las eritroaféresis terapéuticas en pacientes con sobrecarga férrica bioquímica con hemocromatosis hereditaria tipo 1 y sin ella / Predictive factors of response to erytrhocytapheresis in patients with biochemical iron overload with or without hereditary hemochromatosis type 1

Fundamento y objetivo: El aumento progresivo de los depósitos de hierro favorece el desarrollo de diversas entidades, algunas de ellas irreversibles. La piedra angular terapéutica en la sobrecarga férrica ha sido, hasta ahora, la flebotomía. Sin embargo, la eritroaféresis extrae más del doble de hematíes y hierro en cada sesión que una flebotomía convencional, permitiendo alcanzar la depleción férrica en menor tiempo. Los objetivos de este estudio fueron describir las características clínicas y parámetros analíticos de pacientes con sobrecarga férrica tratados mediante eritroaféresis, analizar los resultados globales y por subgrupos, y postular factores predictores de respuesta, así como valorar la seguridad de la técnica. Pacientes y método: Estudio descriptivo, longitudinal y prospectivo de 663 sesiones de eritroaféresis correspondientes a 35 pacientes (entre diciembre de 2002 y octubre de 2011). La respuesta se definió como una cifra de ferritina sérica menor a 50 ng/ml durante dos meses. Para el análisis estadístico se empleó el programa SPSS® versión 17.0 y el nivel mínimo de significación estadística se estableció en un valor de p < 0,05. Resultados: Alcanzaron la respuesta el 77% de los pacientes, con una mediana de 11 (intervalo intercuartílico 1-42) sesiones de eritroaféresis y al cabo de una mediana de 11 (1-108) meses. El 87,5% de los pacientes que no lograron la respuesta redujeron sus valores de ferritina en más del 50%. El descenso en todos los parámetros del metabolismo del hierro fue estadísticamente significativo en el global de pacientes. Fueron factores predictores de respuesta a las eritroaféresis con significación estadística: edad < 60 años, casos de hemocromatosis hereditaria y pacientes con flebotomías previas al inicio de las eritroaféresis. Conclusiones: La eritroaféresis es una técnica efectiva y segura para la depleción férrica en pacientes con sobrecarga de hierro, especialmente en los casos de hemocromatosis hereditaria de alto riesgo que no responden a las flebotomías (AU)

Background and objective: Progressive increase of iron stores leads to the development of varied diseases, some of them irreversible. Until now, phlebotomy has been the cornerstone in the treatment of iron overload. Nevertheless, each erytrhocytapheresis procedure removes more than twice the volume of red cells and iron than phlebotomy, allowing to achieve iron depletion in shorter time. Our aim was to describe clinical features and analytical tests parameters of patients with iron overload, to analyze global and subsets results, to suggest predictive factors of response and to evaluate security of the procedure. Patients and method: Descriptive, longitudinal and prospective study of 663 procedures corresponding to 35 patients (December 2002 to October 2011). Response was defined as a serum ferritine value lower than 50 ng/mL during two months. Statistical analysis was done with SPSS® v 17.0 and the minimum level of statistical significance was defined as p-value < 0,05. Results: Seventy-seven percent of patients reached response with 11 (interquartile range 1-42) erytrhocytapheresis procedures and at 11 (1-108) months. Eighty-seven point five percent of patients who did not achieve response had their ferritine values reduced in more than 50%. The decrease of all iron metabolism parameters was statistically significant. Statistically significant predictive factors of response to erytrhocytapheresis were: patients younger than 60 years-old, hereditary hemochromatosis cases, and patients who had received treatment with phlebotomies prior to erytrhocytapheresis. Conclusions: Erytrhocytapheresis is a secure and effective procedure for iron depletion in patients with iron overload, especially in high risk hereditary hemochromatosis cases that do not respond to phlebotomies (AU)

[Predictive factors of response to erytrhocytapheresis in patients with biochemical iron overload with or without hereditary hemochromatosis type 1]. / Factores predictores de respuesta a las eritroaféresis terapéuticas en pacientes con sobrecarga férrica bioquímica con hemocromatosis hereditaria tipo 1 y sin ella.

BACKGROUND AND OBJECTIVE: Progressive increase of iron stores leads to the development of varied diseases, some of them irreversible. Until now, phlebotomy has been the cornerstone in the treatment of iron overload. Nevertheless, each erytrhocytapheresis procedure removes more than twice the volume of red cells and iron than phlebotomy, allowing to achieve iron depletion in shorter time. Our aim was to describe clinical features and analytical tests parameters of patients with iron overload, to analyze global and subsets results, to suggest predictive factors of response and to evaluate security of the procedure. PATIENTS AND METHOD: Descriptive, longitudinal and prospective study of 663 procedures corresponding to 35 patients (December 2002 to October 2011). Response was defined as a serum ferritine value lower than 50 ng/mL during two months. Statistical analysis was done with SPSS(®) v 17.0 and the minimum level of statistical significance was defined as p-value < 0,05. RESULTS: Seventy-seven percent of patients reached response with 11 (interquartile range 1-42) erytrhocytapheresis procedures and at 11 (1-108) months. Eighty-seven point five percent of patients who did not achieve response had their ferritine values reduced in more than 50%. The decrease of all iron metabolism parameters was statistically significant. Statistically significant predictive factors of response to erytrhocytapheresis were: patients younger than 60 years-old, hereditary hemochromatosis cases, and patients who had received treatment with phlebotomies prior to erytrhocytapheresis. CONCLUSIONS: Erytrhocytapheresis is a secure and effective procedure for iron depletion in patients with iron overload, especially in high risk hereditary hemochromatosis cases that do not respond to phlebotomies.