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El objetivo de nuestro trabajo es analizar diferentes objetos científicos y estudiar posibles estrategias didácticas vehiculizadas por el dispositivo de atelier. Utilizaremos como metodología el relevamiento de experiencias educativas, y de conceptos científicos adecuados para las etapas de infancia, que cruzaremos con algunas definiciones clave utilizadas por distintos artistas y movimientos. Nos centraremos en aquellas estrategias que la práctica artística contribuye a vincular con las prácticas pedagógicas, a fin de plantear algunas metodologías de innovación didáctica. Proponemos que la educación pueda tomar la metodología activa y de experimentación del arte, de cuestionamiento y reflexión que están en el centro de las prácticas artísticas contemporáneas, con fines pedagógicos que apunten a la mejor comprensión de algunos conceptos y fenómenos científicos relevantes.

A partir da Licenciatura em Educação Inicial e da Licenciatura em Artes Visuais da Universidade Católica do Uruguai, foi implementado um projeto que busca nutrir professores com elementos para se aventurar no espaço do atelier, seu design e as ferramentas que ele oferece, para a inovação didática. Na América Latina há pouca formação específica na adaptação de novas pedagogias que envolvem recursos artísticos, orientadas para o desenvolvimento de habilidades relacionadas à empatia, comunicação, compreensão de seu contexto e respeito ao meio ambiente. Para esta proposta pedagógica, incluímos algumas das técnicas e postulados da cultura de ateliê que foi desenvolvida nas Escolas de Educação Infantil no início dos anos 1960, no município italiano de Reggio Emilia. São escolas inspiradas na abordagem socioconstrutivista do conhecimento e na valorização de uma multiplicidade de linguagens expressivas de Loris Malaguzzi (Cavallini et al., 2017). O ateliêconfigura-se como um espaço que cristaliza a aprendizagem. Nas palavras de Vecchi: “a percepção sensorial, o gosto da sedução, o que Malaguzzi chamou de vibração estética, podem atuar como catalisadores do aprendizado, e como podem sustentar e alimentar um conhecimento que não se nutre apenas de informações”. Para essa proposta, temos três objetivos específicos: 1) Sensibilizar os participantes na desconstrução da aparente neutralidade dos objetos cotidianos, compreender as formas de percepção do sujeito; 2) Refletir sobre o postulado fazer é pensar, definido pelo filósofo Richard Sennet como a convicçãode que todas as habilidades, mesmo as mais abstratas como pensar, deduzir, etc., começam como práticas corporais (2013); 3) Exercer um papel docente posicionado como guia e facilitador de experiências.

From the Education área and the Visual Arts área, of the Catholic University of Uruguay, we create a course to nurture teachers with elements to venture into the space of the atelier, its design, and the tools it provides, for the didactic innovation. In Latin America there is little specific training in the adaptation of new pedagogies that involve artistic resources, oriented towards the development of skills related to empathy, communication, understanding of their context and respect for the environment. For this pedagogical proposal, we include some of the techniques and postulates from the Early Childhood Schools in the early 1960s, in the Italian municipality of Reggio Emilia. They are schools inspired by the socio-constructivist theory, and the valorization of a multiplicity of expressive languages of Loris Malaguzzi (Cavallini et al., 2017). The atelier is configured as a space that crystallizes learning. In Vecchi's words: “sensory perception, the taste of seduction, what Malaguzzi called the aesthetic vibration, can act as catalysts for learning, and how they can support and feed a knowledge that is not nourished only by information”. Our specific objectives was: 1) To sensitize the participants in the deconstruction of the apparent neutrality of everyday objects; 2) To reflect on the postulate to do is to think, from Richard Sennet (2013) and 3) to change the teaching role positioned as a guide and facilitator of experiences. A partir da Licenciatura em Educação Inicial e da Licenciatura em Artes Visuais da Universidade Católica do Uruguai, foi implementado um projeto que busca nutrir professores com elementos para se aventurar no espaço do atelier, seu design e as ferramentas que ele oferece, para a inovação didática. Na América Latina há pouca formação específica na adaptação de novas pedagogias que envolvem recursos artísticos, orientadas para o desenvolvimento de habilidades relacionadas à empatia, comunicação, compreensão de seu contexto e respeito ao meio ambiente. Para esta proposta pedagógica, incluímos algumas das técnicas e postulados da cultura de ateliê que foi desenvolvida nas Escolas de Educação Infantil no início dos anos 1960, no município italiano de Reggio Emilia. São escolas inspiradas na abordagem socioconstrutivista do conhecimento e na valorização de uma multiplicidade de linguagens expressivas de Loris Malaguzzi (Cavallini et al., 2017). O ateliêconfigura-se como um espaço que cristaliza a aprendizagem. Nas palavras de Vecchi: “a percepção sensorial, o gosto da sedução, o que Malaguzzi chamou de vibração estética, podem atuar como catalisadores do aprendizado, e como podem sustentar e alimentar um conhecimento que não se nutre apenas de informações”. Para essa proposta, temos três objetivos específicos: 1) Sensibilizar os participantes na desconstrução da aparente neutralidade dos objetos cotidianos, compreender as formas de percepção do sujeito; 2) Refletir sobre o postulado fazer é pensar, definido pelo filósofo Richard Sennet como a convicçãode que todas as habilidades, mesmo as mais abstratas como pensar, deduzir, etc., começam como práticas corporais (2013); 3) Exercer um papel docente posicionado como guia e facilitador de experiências. Desde la Licenciatura en Educación Inicial y la Licenciatura en Artes Visuales de la Universidad Católica del Uruguay, se ha implementado un proyecto que busca nutrir a los docentes de elementos incursionar en el espacio del atelier, su diseño, y las herramientas que proporciona, para la innovación didáctica. En América Latina son escasas las formaciones específicas en la adaptación de nuevas pedagogías que involucren recursos artísticos, orientadas hacia el desarrollo de competencias relacionadas con la empatía, la comunicación, la comprensión de su contexto y el respeto por el medio ambiente. Para esta propuesta pedagógica incluimos algunas de las técncias y postulados de la cultura del atelier que se gesta en las Escuelas de Infancia en los inicios de los años 60, en el municipio italiano Reggio Emilia. Son escuelas inspiradas en el enfoque socio-constructivista del conocimiento y la valorización de una multiplicidad de lenguajes expresivos de Loris Malaguzzi (Cavallini et al., 2017). El atelier se configura como un espacio que cristaliza los aprendizajes. En palabras de Vecchi: “la percepción sensorial, el gusto de la seducción, lo que Malaguzzi llamaba la vibración estética, pueden ejercer de catalizadores de un aprendizaje, y cómo pueden apoyar y alimentar un conocimiento que no se nutre solo de información”. Para esta propuesta, nos planteamos tres objetivos específicos: 1) Sensibilizar a los participantes en la deconstrucción de la neutralidad aparente de los objetos cotidianos, para comprender las formas de percepción del sujeto; 2) Reflexionar acerca del postulado hacer es pensar, definido por el filósofo Richard Sennet como la convicción de que todas las habilidades incluso las más abstractas como pensar, deducir, etc., comienzan como prácticas corporales (2013); 3) Ejercitar un rol docente posicionado como guía y facilitador de experiencias.

Objective: To verify the safety and potential effect on ALS progression of a low-intensity immunosuppressive regimen followed by autologous hematopoietic stem cell transplantation (aHSCT) in amyotrophic lateral sclerosis (ALS) patients. Methods: ALS eligible patients underwent a set of clinical and laboratory evaluations at T-4 (screening), T-1 (pre-treatment visit), and for the 12 consecutive months after treatment (T3, T6, T9, T12). We evaluated the tolerability of the procedure, its efficacy on clinical course and quality of life (QoL). Results: Eight of the 11 ALS patients enrolled received the established immunoablative protocol. The procedure was well tolerated and side effects were those expected. One patient died 4 months after the conditioning regimen and another patient underwent tracheotomy just before T3 for a sudden respiratory failure, but he is still alive 4 years after the procedure without being ventilated any more. A third patient died 10 months after conditioning. In the other cases, there was no statistical difference in all functional measures and QoL pre- and post-treatment; however, a transitory slopes’ reduction of ALSFRS-R and seated SVC% after the conditioning procedures was reported. Moreover, although not statistically significant, trends of reduction of CD4 + and increment of CD8 + were found. Conclusions: aHSCT was overall well tolerated, but it was not followed by any significant modification in disease progression. Considering the negative results of this small trial, further studies aimed to evaluate the possible efficacy of the aHSCT using a higher-intensity regimen should be carefully and with caution evaluated.

BACKGROUND Extracorporeal photopheresis (ECP) is a recognized second-line treatment for steroid-refractory chronic graft-versus-host disease (cGVHD). Treatment course is usually long, expensive, and demanding for patients, so predictors for response are needed. We carried out a retrospective study on cGVHD patients treated at our institution with the aim to identify a possible correlation between apheretic yields composition and probability of response. STUDY DESIGN Patients treated for at least 6 months were eligible for the study. Flow cytometry data, including absolute counts of lymphocytes and their subpopulations in ECP products from cGVHD patients, were collected. For each cell population 1) the median dose per procedure harvested during the first 3 months of treatment and 2) the cumulative dose collected in the same period were compared with clinical response. RESULTS A total of 726 ECP procedures were performed in 15 patients. Overall response, defined as either a complete response (CR) or a partial response according to National Institutes of Health criteria, was obtained in 10 of 15 patients (66.7%), and CR, in eight of 15 (53.3%). According to Cox regression analysis, the probability of achieving an overall response is significantly correlated with the median number of CD3+, CD3+CD4+, and CD3+CD8+ lymphocytes collected during the early treatment phase (first 3 months). CONCLUSION Our data suggest that CD3+ cell evaluation in ECP during the early phase of treatment course could predict response and help identify patients who deserve further treatment.

The clinical outcome of primary refractory (PRF) AML patients is poor and only a minor proportion of patients is rescued by allogenic hematopoietic stem cell transplantation (HSCT). The identification of pre-HSCT variables may help to determine PRF AML patients who can most likely benefit from HSCT. We analyzed PRF AML patients transplanted between 1999 and 2012 from a sibling, unrelated donor or a cord blood unit. Overall, 227 patients from 26 Gruppo Italiano Trapianto di Midollo Osseo e Terapia cellulare centers were included in the analysis. At 3 years, the overall survival was 14%. By multivariate analysis, the number of chemotherapy cycles, (hazard ratio (HR): 1.87; 95% confidence interval (CI): 1.24-2.85; P=0.0028), the percentage of bone marrow or peripheral blood blasts (HR: 1.75; 95% CI: 1.16-2.64; P=0.0078), the adverse cytogenetic (HR: 1.44; 95% CI: 1.00-2.07; P=0.0508) and the age of patients (HR: 1.77; 95% CI: 1.08-2.88; P=0.0223) remained significantly associated with survival. Thus, we set up a new score predicting at 3 years after transplantation, an overall survival probability of 32% for patients with score 0 (no or 1 prognostic factor), 10% for patients with score 1 (2 prognostic factors) and 3% for patients with score 2 (3 or 4 prognostic factors).

BACKGROUND Extracorporeal photopheresis (ECP) is a recognized second-line treatment for steroid-refractory chronic graft-versus-host disease (cGVHD). Treatment course is usually long, expensive, and demanding for patients, so predictors for response are needed. We carried out a retrospective study on cGVHD patients treated at our institution with the aim to identify a possible correlation between apheretic yields composition and probability of response. STUDY DESIGN Patients treated for at least 6 months were eligible for the study. Flow cytometry data, including absolute counts of lymphocytes and their subpopulations in ECP products from cGVHD patients, were collected. For each cell population 1) the median dose per procedure harvested during the first 3 months of treatment and 2) the cumulative dose collected in the same period were compared with clinical response. RESULTS A total of 726 ECP procedures were performed in 15 patients. Overall response, defined as either a complete response (CR) or a partial response according to National Institutes of Health criteria, was obtained in 10 of 15 patients (66.7%), and CR, in eight of 15 (53.3%). According to Cox regression analysis, the probability of achieving an overall response is significantly correlated with the median number of CD3+, CD3+CD4+, and CD3+CD8+ lymphocytes collected during the early treatment phase (first 3 months). CONCLUSION Our data suggest that CD3+ cell evaluation in ECP during the early phase of treatment course could predict response and help identify patients who deserve further treatment.

Purpose The genetic basis of myelodysplastic syndromes (MDS) is heterogeneous, and various combinations of somatic mutations are associated with different clinical phenotypes and outcomes. Whether the genetic basis of MDS influences the outcome of allogeneic hematopoietic stem-cell transplantation (HSCT) is unclear. Patients and Methods We studied 401 patients with MDS or acute myeloid leukemia (AML) evolving from MDS (MDS/AML). We used massively parallel sequencing to examine tumor samples collected before HSCT for somatic mutations in 34 recurrently mutated genes in myeloid neoplasms. We then analyzed the impact of mutations on the outcome of HSCT. Results Overall, 87% of patients carried one or more oncogenic mutations. Somatic mutations of ASXL1, RUNX1, and TP53 were independent predictors of relapse and overall survival after HSCT in both patients with MDS and patients with MDS/AML (P values ranging from .003 to .035). In patients with MDS/AML, gene ontology (ie, secondary-type AML carrying mutations in genes of RNA splicing machinery, TP53-mutated AML, or de novo AML) was an independent predictor of posttransplantation outcome (P = .013). The impact of ASXL1, RUNX1, and TP53 mutations on posttransplantation survival was independent of the revised International Prognostic Scoring System (IPSS-R). Combining somatic mutations and IPSS-R risk improved the ability to stratify patients by capturing more prognostic information at an individual level. Accounting for various combinations of IPSS-R risk and somatic mutations, the 5-year probability of survival after HSCT ranged from 0% to 73%. Conclusion Somatic mutation in ASXL1, RUNX1, or TP53 is independently associated with unfavorable outcomes and shorter survival after allogeneic HSCT for patients with MDS and MDS/AML. Accounting for these genetic lesions may improve the prognostication precision in clinical practice and in designing clinical trials.

Approximately one-third of patients with myelodysplastic syndrome (MDS) receiving allogeneic hematopoietic stem cell transplantation (HSCT) are cured by this treatment. Treatment failure may be due to transplant complications or relapse. To identify predictive factors for transplantation outcome, we studied 519 patients with MDS or oligoblastic acute myeloid leukemia (AML

The CIBMTR score predicts survival of AML patients undergoing allogeneic transplantation with active disease after a myeloablative or reduced intensity conditioning: a retrospective analysis of the Gruppo Italiano Trapianto Di Midollo Osseo

The genetic basis of myelodysplastic syndromes (MDS) is heterogeneous, and various somatic mutations are associated with different phenotypes and clinical outcomes. The only curative treatment for MDS patients is allogeneic hematopoietic stem cell transplantation (HSCT) which is considered as a therapeutic option until the age of 65-70 in eligible patients. Whether the genetic basis influences the outcome of HSCT is currently unclear. Recently, we observed that mutations on ASXL1, RUNX1 and TP53 genes are independent predictors of relapse and overall survival in MDS patients after HSCT, and that the integration of these mutations into currently available predictive models increases the capability to capture prognostic information at individual patient level (Della Porta MG et al. J Clin Oncol, 2016 in press). In this study, we explored the possibility of developing a clinical/molecular predictive model to specifically estimate the outcome after HSCT in patients with MDS or acute myeloid leukemia evolving from MDS (MDS/AML). We studied 401 patients undergoing allogeneic HSCT for primary MDS or MDS/AML between 1997 and 2013 and reported to the GITMO registry. We used massively parallel sequencing to examine tumor samples collected before HSCT for somatic mutations in 34 recurrently mutated genes in myeloid neoplasms. In multivariable analysis with probability of relapse as endpoint the following factors showed independent prognostic value: percentage of marrow blasts (>10% vs. ≤10%, HR 1.43, P=0.04), cytogenetic risk according to IPSSR (poor/very poor vs. very low/low/intermediate risk, HR 1.85, P=.002), disease status at transplant (refractoriness to induction chemotherapy vs. complete remission, HR 2.4, P40 vs. ≤40 years, HR 1.68, P=.001), comorbidity risk according to HCT-CI (high vs. low/intermediate risk 2.10, P Based on regression coefficients, we developed a clinical/molecular model predictive for the risk of relapse after transplantation in MDS and MDS/AML. Accordingly, a score value of 1 was assigned for each of the following risk factors: marrow blasts >10%, poor/very poor cytogenetic risk according to IPSSR, refractoriness to induction chemotherapy, and driver mutations in ASLX1/RUNX1/TP53 genes. A relapse risk index was calculated as the sum of these weighted scores, and was then categorized into 4 risk groups: low (score=0), intermediate (score=1-2), high (score=3), and very high (score=4). The cumulative incidence of relapse was estimated by a competing risks approach with TRM. In patients receiving standard conditioning, 5-year probability of survival after allogeneic HSCT was 61%, 43%, 39% and 19% for low, intermediate, high and very high risk (P This model serves as a proof of concept that the integration of somatic mutations significantly increase the capability to capture prognostic information in MDS and MDS/AML patients receiving allogeneic HSCT, and may provide a basis for improving clinical decision-making. Possible interventions in patients with high risk of disease relapse after HSCT according to genotype may include the anticipation of the transplant procedure in early disease phase, the use of innovative conditioning regimens to increase the probability to eradicate MDS clone, and prophylaxis of disease recurrence after transplantation by donor leukocyte infusions and targeted/novel therapies Disclosures Ciceri: MolMed SpA: Consultancy.

Abstract 2009 To evaluate the role of allografting from unrelated donors in the treatment of myeloma we conducted a retrospective study through the Italian Bone Marrow Transplantation Donor Registry. Overall, from 2000 through 2009, 196 myeloma patients, median age 51 years (32–67), for a total of 199 allografts, were transplanted from an unrelated donor at 34 Centers in Italy. Fifty-two (28.1%%), 69 (37.3%), and 64 (34.6%) patients were prepared for transplant with a myeloablative, a reduced-intensity and a non-myeloablative conditioning respectively. Patient characteristics of the 3 cohorts are reported in Table 1.ConditioningMyeloablativeReduced-intensityNon-myeloablativePatient number (%)52/185 (28)69/185 (37)64/185 (35)Median Age455355Previous therapy lines < 2 (%)23 (27)33 (38)30 (35)Previous therapy lines ≥ 2 (%)29 (29)36 (37)34 (34)Stem Cell Source BM (%)24 (57)18 (43)0 (0)Stem Cell Source PBSC (%)28 (19)51 (36)64 (45) Cumulative incidence of acute grade II-IV graft-versus-host-disease (GVHD) was 46.4% whereas chronic GVHD was 45.1%. There was no difference in GVHD incidence among the 3 cohorts defined by type of conditioning. Complete and partial remissions in patients who survived at least 3 months post-transplant were 27% and 28% for an overall response rate of 55%. At a median follow up of 32 (0–118) months post-transplant, in the entire study population, median OS from diagnosis was 70.6 months while OS and EFS from the allograft were 18.9 and 14.9 months. Overall, the cumulative incidence of transplant related mortality (TRM) was 29.6% at 1 year and 32.4% at 5 years post-transplant. OS from diagnosis and EFS from transplant were 70.6 and 28.2 months; 66.8 and 9.1 months; and 111.9 and 22.4 months in patients who respectively underwent a myeloablative, a reduced-intensity and a non-myeloablative transplant. One-year and 5-year TRM was 33.3% and 35.7%, 32.2% and 34.4%, and 22.1% and 26.5% respectively. Univariate and multivariate analyses, assessed by multivariate Cox proportional hazards models, were performed for the following variables: number of previous chemotherapy lines (1,2 vs. ≥3), disease status at transplant, HLA- matched antigens (10/10 vs. 9/10 vs. ≤8/10), recipient/donor gender combinations, hematopoietic cell source (peripheral blood vs. bone marrow), conditioning (myeloablative vs. reduced-intensity vs. non-myeloablative), use of anti-thymoglobulin in the conditioning, acute GVHD, chronic GVHD, best response post-transplant, year of transplant (2000–02 vs. 2003–05vs. 2006–09). By univariate analysis, lower number of chemotherapy lines before the allograft, disease status at transplant, a fully HLA-identical donor, the use of peripheral hematopoietic cells rather than bone marrow were statistically significant variables for better OS whereas disease status at transplant, a fully HLA-identical donor, chronic GVHD (either limited or extensive) were statistically significant for better EFS. However, by multivariate analysis, only the development of chronic GVHD (HR 0.50; p Disclosures: Patriarca: Roche: Honoraria; Celgene: Honoraria; Schering-Plough: Honoraria; Janssen: Honoraria. Boccadoro:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Background Transfusion-dependency affects the natural history of myelodysplastic syndromes. Secondary iron overload may concur to this effect. The relative impact of these factors on the outcome of patients with myelodysplastic syndrome receiving allogeneic stem-cell transplantation remains to be clarified. Design and Methods We retrospectively evaluated the prognostic effect of transfusion history and iron overload on the post-transplantation outcome of 357 patients with myelodysplastic syndrome reported to the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) registry between 1997 and 2007. Results Transfusion-dependency was independently associated with reduced overall survival (hazard ratio=1.48, P =0.017) and increased non-relapse mortality (hazard ratio=1.68, P =0.024). The impact of transfusion-dependency was noted only in patients receiving myeloablative conditioning (overall survival: hazard ratio=1.76, P =0.003; non-relapse mortality: hazard ratio=1.70, P =0.02). There was an inverse relationship between transfusion burden and overall survival after transplantation ( P =0.022); the outcome was significantly worse in subjects receiving more than 20 red cell units. In multivariate analysis, transfusion-dependency was found to be a risk factor for acute graft- versus -host disease ( P =0.04). Among transfusion-dependent patients undergoing myeloablative allogeneic stem cell transplantation, pre-transplantation serum ferritin level had a significant effect on overall survival ( P =0.01) and non-relapse mortality ( P =0.03). This effect was maintained after adjusting for transfusion burden and duration, suggesting that the negative effect of transfusion history on outcome might be determined at least in part by iron overload. Conclusions Pre-transplantation transfusion history and serum ferritin have significant prognostic value in patients with myelodysplastic syndrome undergoing myeloablative allogeneic stem cell transplantation, inducing a significant increase of non-relapse mortality. These results indicate that transfusion history should be considered in transplantation decision-making in patients with myelodysplastic syndrome.

Antifungal therapy may be unable to eradicate invasive mycosis in leukemia patients. The presence of persisting pulmonary nodules owing to mycosis seems to increase the risk of fungal relapse after chemotherapy and transplant procedures. Between 1997 and 2004, 10 acute leukemia patients underwent pulmonary surgery for invasive mycosis. The median time from diagnosis of mycosis to surgery was 135 days (range 21-147). Three patients underwent emergency surgery, owing to hemoptysis. In the other seven patients with nodule/cavitation remaining after antifungal treatment, surgery (three wedge resections, four lobectomies) was scheduled before transplant. Pathologic examination confirmed two aspergillosis and three zygomycosis. The only side effect was pneumothorax in one case. Nine patients were considered cured. Six patients underwent bone marrow transplantation (three allogeneic, three autologous) with antifungal prophylaxis without relapse during the transplant procedure. In selected patients scheduled for bone marrow transplantation, surgical resection of localized pulmonary fungus nodules combined with antifungal prophylaxis seem to be an effective treatment for preventing mycotic relapse.

We report a high incidence of neutropenia in patients treated with rituximab prior to and following autologous stem cell transplantation (ASCT). Fourteen patients with follicular or mantle-cell lymphoma were treated with high dose (HD) therapy followed by an in vivo-purged autologous graft. Ten of these patients received two additional courses of rituximab after the transplant. Seven experienced severe neutropenia after the second administration. Our data suggest that early administration of rituximab following a transplant may favor the onset of neutropenia.

Mucormycosis infections, caused by fungi of the families Rhizopus, Mucor or Absidia, are typically rapidly progressive and often fatal. We report a 27-year-old male with acute myeloid leukemia (AML) developing an invasive pulmonary-CNS mucormycosis during the neutropenic period after salvage induction chemotherapy; the infection was successfully controlled with surgery and antifungal therapy. The patient received two courses of consolidation chemotherapy and underwent autologous stem cells transplantation (ASCT) while receiving secondary antifungal systemic prophylaxis with liposomal Amphotericin B (L-AMB, Ambisome). There was no clinical, radiological or microbiological evidence of mycotic reactivation during the bone marrow transplantation (BMT) procedure.

Molecular remission and reconstitution of a full chimera with arsenic trioxide in a patient with acute promyelocytic leukemia relapsed after allogeneic bone marrow transplantation

Background The outcome of primary refractory (PRF) acute myeloid leukemia (AML) patients is poor with a minor proportion rescued by allogeneic hematopoietic stem cell transplantation (HSCT). The identification of pre-HSCT variables may help to identify PRF AML most likely to benefit from HSCT. The EBMT group reported factors predicting the outcome of 168 patients with PRF AML receiving an unrelated donor stem cell transplantation; 5-years OS was 22% and factors associated to an improved survival were the numbers of chemotherapy cycles (< 3), bone marrow blast infiltration Patients and study design We analyzed the clinical outcome of 242 patients transplanted in 26 GITMO centers. Patients disease status at HCST included PRF AML defined as failure to achieve a complete response (CR) after one or more chemotherapy cycles containing active drugs on AML. The cytogenetic and molecular risk was defined according to the European LeukemiaNet. The main clinical and outcome follow up data were retrieved from the GITMO database. The main end-points of the study were overall survival (OS) and leukemia-free survival (LFS). Results The median age at HSCT was 49 years (18-72) and 55% of patients were male. Before HSCT, 58% received ≤ 2 chemotherapy cycles. Median time from diagnosis to HSCT was 6 months (1-19) and in 85% was ≥ 3 months. An intermediate-II/adverse karyotype was detected in 58% of patients, > 25% marrow blast infiltration or any level of peripheral blood (PB) blasts was found in 60% and a pre-HSCT Karnofsky score < 90 was present in 43%. Donors were HLA identical sibling in 48% and matched unrelated in 19%, related mismatched in 19%, unrelated mismatched in 3% and cord blood in 11%. Anti-CMV antibodies were present in 87% of patients and in 65% of the donors. Conditioning regimen intensity was myeloablative or reduced in 69% and 31%, respectively; 49% of patients received T cell depletion (92% in vivo and 8% ex vivo). Neutrophils and platelets engraftment was achieved in 87% of patients after a median of 17 (9-52) and 17 (3-150) days, respectively. In all, 35 (14%) patients died within 30 days from HSCT. Of 207 patients evaluable for response, 138 (66%) achieved CR after a median time of 32 days (range 16-130) from HSCT and 69 did not (33%). Median survival of patient who achieved CR was 10 months while it was 2 months for those who did not. Seventy patients (51%) relapsed after a median time of 3 months (1-31), 64 died of disease, 6 survived and 2 of these latter reachieved CR. Sixty-eight patients (49%) maintained CR, 34(50%) died and 34 survived. A t the last follow up 42 patients were alive, 36 in CR and 6 with disease with a median follow up of 27 months (range 1,8-14). The median OS of the whole patient cohort was 5,7 months. At 3-years, the OS and LFS was 15% and 23% respectively. AGvHD was registered in 39% of patients (grade > 2 in 30% of cases) while cGVHD occurred in 29% (extended in 44% of cases). The 3-years cumulative incidence of NRM was 17%. By univariate analysis, the number of chemotherapy cycles to achieve CR (≤ 2), the time to HSCT (< 3 months), the cytogenetics risk favorable/intermediate I, the number of marrow blasts < 25% or the absence of blasts in the peripheral blood, the PS ≥ 90 and the lack of any form of T cell depletion, were all associated to a better survival. By multivariate analysis, the number of chemotherapy cycles, (Hazard Ratio (HR): 1.51; 95% confidence interval (CI): 1.04–2.19; P=0.029), the lack of T cell depletion (HR: 1.66; 95% CI: 1.15–2.40; P=0.007), the degree of BM or PB blast infiltration (HR: 1.59; 95% CI: 1.01–2.25; P=0.043), and the PS (HR: 1.46; 95% CI: 1.00–2.14; P=0.048) remained significantly associated with survival. On the basis of this multivariate analysis, we set up a new score predicting a different 3 years OS: score 0 (0 or 1 adverse prognostic factor, with 28% survival), score 1 (2 adverse prognostic factor, 17% survival); score 2 (2 or 3 adverse prognostic factors, 10% survival) (Figure 1) Conclusion The clinical outcome of PRF AML remains poor. The new simple clinical GITMO score helps indentifying patients most likely will benefit or not from the HSCT. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Myelodysplastic syndromes (MDS) are heterogeneous myeloid neoplasms that range from indolent conditions to forms very close to acute leukemia (AML). The International Prognostic Scoring System (IPSS) is the benchmark for clinical decision-making. Recently, the International Working Group for Prognosis in MDS (IWG-PM) defined 5 new cytogenetic risk groups on a large cohort of patients representing the basis for the revised IPSS (IPSS-R) together with refined categories for marrow blasts and cytopenias (Blood. 2012;120:2454-65). IPSS-R categorization enables more accurate definition of the prognosis of MDS patients, in particular those in low or intermediate-1 IPSS risk groups. Despite recent progress, the only curative treatment for MDS remains allogeneic stem cell transplantation (allo-SCT), which however involves a non-negligible risk of mortality/morbidity. Allo-SCT is not considered in patients with very low IPSS-R risk, whose median survival is 9 years. Conversely, eligible patients with high or very high IPSS-R risk, whose survival is 1–2 years, should be offered immediate transplantation. Uncertainty exists about the optimal timing of allo-SCT in the low and intermediate IPSS-R risk groups, and to address this issue we performed an ad hoc decision analysis. We analyzed two cohorts of MDS patients (age 18-70 years): i) 477 patients diagnosed with MDS at the Policlinico S. Matteo, Pavia, Italy between 2000–2010, who mostly received best supportive care; ii) 488 patients who received allo-SCT in the same period reported to the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) registry. We adopted a continuous time multi-state Markov approach to model the natural history of the disease. Each IPSS-R risk group is represented by a state, and transition is allowed to the next state (to AML from very high risk) or to death. A transition intensity (i.e., instantaneous risk of moving to another state) is then estimated for each possible transition. Allo-SCT is modeled as a time-dependent covariate with 3 levels: i) no allo-SCT; ii) transplantation done no more than 3 months before; iii) transplantation done more than 3 months before. The effect of allo-SCT on survival was estimated by hazard ratios (HR) with respect to the no allo-SCT level. We examined two different policies: policy A) perform allo-SCT after t months since entering the low IPSS-R risk state or immediately in case of disease progression before the planned delay time t; policy B) perform allo-SCT after t months since entering the intermediate IPSS-R risk state or immediately in case of disease progression before the planned delay time t. For each policy, the expected survival of patients with different age at diagnosis was calculated. According to the model, a patient with a low IPSS-R risk is expected to spend 2.13 years in this risk group, and 2.39 years in the intermediate one. The cumulative incidence of progression from low to a higher IPSS-R risk was 27% at 3 years, while that of progression from intermediate to a higher risk was 39% at 3 years. Overall, expected survival times from diagnosis were higher under policy B vs policy A. Expected survival times were up to three years greater under policy B with respect to policy A for younger patients. When the waiting time before transplantation was progressively increased from 0 to 60 months, there was an increase in expected survival under policy A (in younger patients this increases by about two further years if transplant is delayed until 60 months in low IPSS-R risk state). Conversely, under policy B, delaying transplant further reduces expected survival, by up to about three years with a delay of 60 months after entering intermediate risk state or further progression to high risk state. In summary, this study suggests that a delayed transplantation strategy is advisable for patients with early disease, i.e. very low and low IPSS-R risk, whereas no further delay is advised for patients belonging to intermediate or higher risk categories. When indicated, setting the timing of intervention immediately after disease progression makes such a strategy easy to implement in the clinical practice. These results provide clinicians with a base of evidence to maximize the effectiveness of allo-SCT in MDS patients. Disclosures No relevant conflicts of interest to declare.

The aim of our study was to evaluate the impact of an early intensification programme including chemotherapy (CHT), autologous stem cell transplantation (ASCT) and radiation therapy (RT) in patients with primary mediastinal large B cell lymphoma (MLCL) with sclerosis presenting with adverse prognostic factors. Between 1993 and 1999, 19 patients with MLCL were referred to our institution. Four patients were classified as low risk according to the age-adjusted International Prognostic Index (AA-IPI). Fifteen (79%) were categorised in the high–intermediate or high risk group and were considered eligible for ASCT. Induction therapy consisted of VACOP-B (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin) for 12 weeks. After induction therapy the four low risk patients achieved a complete remission (CR) and did not undergo ASCT. Of the 15 poor risk patients, five achieved CR, seven partial remission (PR), and three showed refractory disease (RD). All these patients received mobilising therapy consisting of high-dose cyclophosphamide. After peripheral stem cell (PSC) collection, to obtain a greater tumor mass reduction before transplantation, the seven patients in PR underwent further treatment with high-dose etoposide and those with RD received two cycles of DHAP (dexamethasone, cytarabine and cisplatin). At the time of ASCT, seven patients were in CR, six in PR and two had RD. After transplantation using BEAM as preparative regimen, all patients but one achieved a CR. Seven patients with minimal (

Background The only curative treatment for patients with myelodysplastic syndrome (MDS) is allogeneic stem cell transplantation (allo-SCT). Decision to transplant is currently based on the International Prognostic Scoring System (IPSS), which has limitations. Recently, a revised IPSS (IPSS-R) has been developed (Blood. 2012;120:2454-2465). Aim To identify predictive factors for transplantation outcome, we studied 519 patients with MDS or acute myeloid leukemia (AML) evolving from MDS who received allo-SCT and were reported to the GITMO registry between 2000 and 2010. Results 1 Posttransplantation outcome according to cytogenetics. Cytogenetic abnormalities were classified according to MDS Cytogenetic Scoring System (MCSS) criteria. Four groups of patients with different overall survival (5-year OS ranging from 48% to 15%, P=.003) and probability of relapse (P=.001) after transplantation were identified. In a multivariate model, MCSS significantly affected OS (HR 1.29, P=.001) and probability of relapse (HR 1.40, P Results 2 Posttransplantation outcome according to degree of peripheral blood cytopenia and percentage of marrow blasts. No significant effect of neutrophil and platelet count on posttransplantation outcome was noticed. The 5-year OS was 51%, 40% and 33% in patients with hemoglobin >10g/dl, between 8-10 g/dl and Results Posttransplantation outcome of patients stratified according to IPSS-R. Patients were then classified according to IPSS-R criteria: 59 patients had a low risk (11%), 89 patients (17%) an intermediate risk, 207 (40%) a high risk, and 164 (32%) a very high risk. Five-year OS was 71%, 58%, 39% and 23%, respectively (Figure 1, P=.001). 5-year cumulative incidence of relapse was 4%, 12%, 23% and 39%, respectively (P= We analyzed the prognostic effect of IPSS-R score by a multivariate model. The IPSS-R score significantly affected OS (HR 1.41, P Recipient age (≥50 years) and presence of comorbidity (high risk according to HCT-CI score) were significant risk factors for increased NRM (HR 1.79, P=.02 and HR 1.83 P=.017, respectively), while MK and lack of complete remission after induction chemotherapy showed an independent effect on relapse risk (HR 2.23, P=.001 and HR 1.94, P=.001, respectively). According to the presence of these additional risk factors, the cumulative incidence of NRM among different IPSS-R categories ranged from 13% to 52% in patients receiving standard conditioning (P Conclusions This study clearly shows that IPSS-R allows a reliable prediction of posttransplantation outcome in MDS patients. Allo-SCT offers optimal survival benefits when the procedure is performed before MDS patients progress to advanced disease stages. Disclosures: Rambaldi: Novartis: Honoraria; Sanofi: Honoraria; Italfarmaco: Honoraria.

Abstract 2005 Background and Aim The dismal prognosis of AML patients undergoing allogeneic stem cell transplantation not in complete remission at time of conditioning poses challenging clinical decisions. In these patients, a recent, large retrospective analysis conducted by the CIBMTR showed that a myeloablative HCST can induce an overall 19% long term survival. Based on five adverse pretransplantation variables (first CR duration less than 6 months, circulating blasts, donor other than HLA-identical sibling, Karnofsky or Lansky score less than 90, and poor-risk cytogenetics) this analysis allowed to set up a pre-HSCT score (from 0 to ≥3) able to identify four risk groups defining a 3-years overall survival (OS) probability ranging from 6% up to 42% (Duval M, JCO 2010). However, this CIBMTR analysis was limited to patients with the following characteristics: a) de novo AML or secondary AML to a previous MDS b) patients receiving a TBI or busulfan based myeloablative conditioning regimens (MAC) and a BM or PB derived stem cell graft. Here we report data obtained in Italy in a similar cohort of AML patients that also included those receiving a reduced-intensity conditioning (RIC) regimen and those grafted with a cord blood unit. Study design, patients and transplants characteristics We retrospectively analyzed data reported to the GITMO registry by 20 Italian centers on 523 AML patients who underwent a first HSCT being not in complete remission (CR) at time of conditioning, between 1999 and 2010. The median age at HSCT was 47,6 years (18–72), the male/female ratio 50%. At diagnosis 71,5% were de novo AML, 23% were secondary to a previous MDS/CMML, while in 5,5% the AML was therapy related or secondary to a previous CMN. Before HSCT conditioning, patients were primary refractory (PIF) in 34%, in first or subsequent untreated relapse in 45% and 16%, respectively or an untreated MDS to AML evolution in 5%. Before HSCT, 79% of PIF received ≥2 chemotherapy cycles and for relapsed patients the duration of the first CR was < 6 months in 50%. An intermediate-II or adverse karyotype was detected in 43% of patients, a greater than 25% marrow blast infiltration or any level of peripheral blood (PB) blasts was found in 53% and a pre-HSCT Karnofsky score less than 90 was present in 38%. The stem cell source was the PB in 65%, the bone marrow in 28% and the cord blood in 6%. Donors were HLA identical sibling or matched unrelated donor in 69%, a family or unrelated mismatched in 25% and a cord blood unit in 6%. Anti-CMV antibodies were present in 87% of patients and in 66% of the donors, while donor-recipient pair were sex-matched in 50% of the cases. More than 60% patients received a MAC and 37% a RIC program. Results After HSCT, a myeloid and platelets engraftment was achieved in 87% of patients after a median of 17 (9–63) and 18 (2–117) days, respectively. Acute GVHD (grade ≥2 60%) was registered in 46% while chronic GVHD developed in 31%. The median follow up of the whole patients cohort was 5,36 months (0.09–133) while that of survivors was 26 months (1–133) with 96 patients alive and 77 leukemia-free. A multivariate analysis identified 7 pre-HSCT adverse variables that significantly influenced survival: an AML secondary to a previous chronic myeloproliferative neoplasm or a therapy related AML (HR 1,83, 95%CI 1,14–2,96, p 0,013), a relapsed AML with a first CR duration < 6 months (HR 1,39, 95%CI 1,06–1,82, p 0,018), an AML with a PIF after ≥2 chemotherapy cycles pre-HSCT (HR 1,74, 95%CI 1,11–2,74, p 0,016), an intermediate II/adverse cytogenetics (HR1,71, 95%CI 1,11–2,62, p 0,015), BM blasts ≥25% or any level of PB at HSCT (HR 1,65, 95%CI, 1,31–2,07, p 0.000) and a mismatched related/unrelated donor (HR 1,56, 95%CI, 1,23–1,98, p 0.000). At 3-years, the OS and LFS of our patients was 16% and 21%. Interestingly, when applied to our results, the CIBMTR score was fully validated in our patients with a 3-year survival rate decreased from 40% (score 0, HR1) to 26% (score 1, HR 1,39; 95%CI 0.88–2,12, p 0,142), to 18% (score 2, HR 1,58; 95%CI 1–2,43, p 0,04) to 5% (score 3, HR 2,83; 95%CI 1,71–4,16, p 0,000) (Figure 1). Conclusions Our results confirm that a) HSCT is a potentially curative option for a significant proportion of AML patients undergoing transplant not in remission, b) these patients may benefit from either a MAC or a RIC conditioning regimens and c) the CIBMTR score applied to this poor prognosis AML cohort is a useful tool for patient counseling and for planning the HSCT activity. Disclosures: No relevant conflicts of interest to declare.

Abstract 116 Myelodysplastic syndromes (MDS) are heterogeneous myeloid neoplasms that range from indolent conditions with a near normal life expectancy to forms very close to acute myeloid leukemia (AML). The WHO classification-based Prognostic Scoring System (WPSS) is able to classify MDS patients into five risk groups (very low, low, intermediate, high, and very high) with different median survival (from more than 10 to about 1 yr). Despite recent progress, the only curative treatment for MDS remains allogeneic stem cell transplantation (allo-SCT), which however involves a non-negligible risk of mortality and morbidity. Allo-SCT is not considered in patients with low WPSS risk, whose median survival is >10 yr. Conversely, eligible patients with high or very high WPSS risk, whose median survival is 1–2 yr, should be offered immediate transplantation. Uncertainty exists about the optimal timing of allo-SCT in the low and intermediate WPSS-risk groups, and to address this issue we performed an ad hoc decision analysis. We analyzed two cohorts of MDS patients: i) 615 patients diagnosed with MDS at the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, between 1992–2007, who were followed regularly and mostly received best supportive care; ii) 405 patients who received allo-SCT between 1997–2007, reported to the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) registry. In this latter cohort, variables were analyzed at the time of transplantation in patients undergoing allo-SCT upfront, and at the time of remission-induction chemotherapy in those receiving treatment before allo-SCT. We adopted a continuous time multi-state Markov approach to model the natural history of the disease. In this model, each WPSS risk group is represented by a state, and transition is allowed to the next state (to AML from very high risk) or to death. A transition intensity (i.e., instantaneous risk of moving to another state) is then estimated for each possible transition. Allo-SCT is modeled as a time-dependent covariate with 3 levels: i) no allo-SCT; ii) transplantation done no more than 3 months before; iii) transplantation done more than 3 months before. The effect of allo-SCT on survival was estimated by hazard ratios (HR) with respect to the no allo-SCT level. We examined two different policies: policy A) to perform allo-SCT after t months since entering the low-risk state or at the time of progression to intermediate risk; policy B) to perform allo-SCT after t months since entering the intermediate-risk state or at the time of progression to high risk. For each policy, the expected survival of patients with different age at diagnosis was calculated. According to the model, a patient with a low WPSS risk is expected to spend 6.2 years (95% CI, 5.5–7.0) in this risk group, and, in case of progression, 3.5 years (95% CI, 3.1–4.0) in the intermediate one. The cumulative incidence of progression from low to a higher WPSS risk was 9%, 31% and 41% at 1, 3 and 5 years, respectively, while that of progression from intermediate to a higher risk was 18%, 40% and 53% at 1, 3 and 5 years, respectively. Overall, expected survival times from diagnosis were higher under policy A vs policy B. Expected survival decreased with increasing age (from 30 to 65 yr) under policy A, while there was little effect of age under policy B. For younger patients, expected survival times were up to four years greater under policy A, while there was no estimated benefit for patients closer to age 65. When the waiting time before transplantation was progressively increased from 0 to 60 months, there was a small decrease in expected survival under policy A for younger patients. Conversely, varying the time of transplantation between 0–60 months did not substantially influence expected survival under policy B. These findings suggest that in eligible patients with low or intermediate WPSS-risk MDS there is no clear benefit in adopting a delayed transplantation strategy, as the risk of progression abolishes the expected gain in survival resulting from postponing the procedure. In particular, younger patients appear to benefit from early transplantation in the low risk state. This is at variance with a previous decision analysis based on the International Prognostic Scoring System (IPSS) (Blood. 2004;104:579–85), which concluded that for low and intermediate-1 IPSS-risk MDS, delayed allo-SCT was associated with maximal life expectancy. This paper is on behalf of GITMO investigators. Disclosures: No relevant conflicts of interest to declare.

WHO classification and WPSS score (JCO2007;25:3503) have been recently proved to have prognostic significance in myelodysplastic syndromes (MDS), but their impact on the outcome of patients (pts) receiving allogeneic stem-cell transplantation (allo-SCT) is still to be clarified. We retrospectively evaluated the prognostic value of WHO classification and WPSS at the time of transplant in 406 MDS pts who underwent allo-SCT between 1990 and 2006. Patients were reclassified according to the WHO criteria: 30 had refractory anemia (RA/RARS), 54 refractory cytopenia (RCMD/RS), 51 RA with excess blasts (RAEB), type 1 and 95 RAEB type 2. One hundred twenty-seven pts were classified as acute myeloid leukemia (AML). The median recipient age was 48 years (range 17–67). There were 281 HLA-matched sibling and 125 unrelated donor SCT. One hundred forty-three pts (35%) received a reduced intensity regimen (RIC). Considering WHO categories, the probability of OS at 5-years was 0.8 in RA/RARS, 0.52 in RCMD/RS, 0.48 in RAEB-1, 0.26 in RAEB-2 and 0.29 in AML, while the probability of RFS at 5-years was 0.92, 0.78, 0.74, 0.47 and 0.44 respectively. The cumulative probability of TRM was 0.43. We performed a Cox analysis with WHO category, cytogenetics, transfusion dependency, recipient age, disease status, type of donor and type of conditioning as covariates. WHO classification had a significant effect on both OS (P=0.017), and RFS (P=0.01). Cytogenetic risk significantly affected RFS (P=0.04), while had a borderline effect on OS (P=0.09). A regular transfusion dependency before SCT was associated with a reduced OS (P=0.01) and increased TRM (P=0.037), while no significant effect on RFS was noticed. Age and stage of the disease at transplant showed a significant effect on OS (P=0.02 and P=0.04, respectively). RIC and active disease at transplant were associated to a reduced probability of RFS (P=0.02 and P=0.017 respectively). Age and use of myeloablative conditioning were significant risk factors for TRM (P=0.018 and P=0.032 respectively). The WPSS score, based on MDS-WHO category, cytogenetics and transfusion dependency at the time of SCT, was calculated for 171 pts. WPSS showed a prognostic significance on both OS and RFS in a Cox analysis with age of recipient, disease status, type of donor and type of conditioning as covariates (P=0.02 and P=0.01). Focusing the analysis on 84 MDS pts without excess blasts, multilineage dysplasia and regular transfusion-dependency significantly affected post-transplant OS (P=0.005 and P=0.009, respectively), and were associated to an increased TRM. In this clinical setting, WPSS allowed to identify 2 major groups of pts (very-low/low vs. intermediate risk) with significant different OS and TRM (P=0.013 and P=0.039). In conclusion, these data show that WHO classification and WPSS have a relevant prognostic value for the post-transplantation outcome of MDS pts and should be taken into account in transplantation decision-making, especially in subjects with less advanced disease. The independent negative effect of transfusion dependency strengthens the rationale to examine the consequences of iron overload and the potential benefit of chelation therapy in MDS transplant setting.

Α and β tryptase genes cluster on the short arm of human chromosome 16 and encode lineage-associated serine proteases that are abundantly expressed in mast cells and, in trace amounts, in basophils. Under physiologic conditions no other myeloid cells express tryptases. However, in several myeloid leukemia cell lines and in AML blasts, the level of tryptase is elevated. In vitro, AML blasts are capable to produce and release the α-protryptase constitutively. Recently, elevated levels of serum tryptase have been detected in certain FAB subtypes of AML, particularly in AML-M4eo. In an attempt at correlating the levels of tryptase with FAB classification and cytogenetics, we have analyzed serum samples collected at diagnosis, from 103 AML and 57 ALL patients referred to our Institution. The total serum concentration was determined by UniCAP 100 and UniCAP Tryptase Fluorenzyme Immunoassay Kit (Pharmacia-Upjohn, Uppsala, Sweden). The median value of tryptase level in the control group (50 healthy people; mean age 35 y, range 20–50; M/F= 26/24) amounted to less than 5 ng/ml. We found elevated tryptase levels (more than 15 ng/ml) in 46 out of 103 AML-patients (44.6%) and in 1 out of 57 ALL-patients (1.75%) (p = 89.3 ng/ml) (p = 0.0001), in comparison with other cytogenetic groups (diploid, n= 43; t(15;17), n=10; other, n=29). Our data suggest that elevated serum tryptase levels at diagnosis may play a role as a marker for CBF AML subtypes.

The efficacy of ASCT in pts with CLL may be compromised by the reinfusion of neoplastic cells with the autograft leading to relapse. For this reason in our Institution pts eligible for an ASCT receive Campath-1H before peripheral blood stem cell (PBSC) mobilization to perform a purging in vivo in order to minimise the contamination of the collection. We evaluate the safety and feasibility of APBSCT in fourteen CLL patients pretreated with Fludarabine (FAMP) containing regimens and subsequent Campath-1H subcutaneusly (10 mg x 3/w for 6 weeks). A FAMP containing regimen had been administered as first line treatment in 12 cases and as second line in 2 cases; median number of FAMP cycles administered was 6 (range 4–8). In all but one pts PBSC were mobilized with Ara-C (800mg/m2/12h x 3 d) followed by G-CSF while the last pt received only G-CSF. Median age at transplant was 57.5 y (range 45–63); all pts were in CR, 9 pts showing a polyclonal rearrangement of the IgH at PCR by consensus primer. Conditioning regimen consisted of 12 Gy TBI plus cyclophosphamide 120 mg/kg in 9 pts aged < 60 y, Melphalan 180 mg/sqm in the 5 pts aged > than 60 y. Median number of CD34+ cells reinfused was 17.1 x106/kg (range3.4–30.4), the reinfused product was polyclonal for the IgH in 9 cases. The median time for PMN (> 500/μl) and PLT (> 20000/μl) recovery was 9 (range 8–10) and 11 (range 9–13) days respectively. During marrow aplasia nine pts experienced an episode of fever > 38°C with a median duration of 2 days (1–8); in three pts the cause of fever remained of unknown origin while in the remaining 6 cases a sepsis due to Staphilococcus Aureus was recorded. Intravenous antibiotics were administered in 7 cases; none of the pts required intravenous antifungal therapy. No grade 3–4 extrahematological toxicity and no treatment related deaths were observed. During the 3 months post transplant period two pts required hospitalisation for fever in one case and for acute polineuropathy in the other case; in both cases no pathogens have been isolated. In none of the pts a CMV reactivation was recorded even in the 6 cases showing a reactivation during Campath-1H treatment. An Herpes Zooster infection was observed in 2 pts after 5 and 10 months from transplant. The recovery of CD4+ and CD8+ cells is illustrated in the followig table. CD4 and CD8 reconstitution after ASCT pre ASCT month +3 month +6 month +12 * * 6 pts CD4/ μl 57 91 86 174 CD8/ μl 171 310 377 540 After a median follow-up of 10 months (3–30) from transplant all pts are in CR. At the three months post-transplant evaluation, performed in 13 cases, all but one pts showed polyclonal IgH rearrangement. ASCT after sequential treatment with FAMP and Campath-1H is feasible with any evidence of increased number of major infections; a substantial number of pts achieved after transplant a polyclonal IgH rearrangement.

Thrombotic microangiopathy (TMA) usually occurs during the first weeks following transplantation in the setting of systemic infections or graft-versus-host reaction. However, some cases without any evidence of other complications or after autologous transplantation have been reported. Transplant-associated TMA (BMT-TMA) incidence ranges from 0% to 74%, possibly due to different diagnostic criteria. The GITMO Group provided the opportunity to retrospectively study 4334 consecutive Italian patients who received bone marrow transplants (1759 allogeneic and 2575 autologous BMT), during the 1985-1995 period. The present report focuses on patients with severe TMA requiring specific treatment. We identified nine cases of TMA as a complication of allogeneic BMT (0.51%), whereas three patients developed the syndrome after ABMT (0.13%); four of the 12 patients were not receiving CsA at the time of TMA onset. Finally, it is noteworthy that TMA occurred in seven patients as a late complication (up to 90 days after BMT). Despite intensive treatment, five of the seven patients with thrombotic thrombocytopenic purpura died. One death was observed among the five cases with hemolytic uremic syndrome.