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La aplasia pura de células rojas (APCR) es una anemia aislada secundaria a la insuficiencia de eritropoyesis de patogénesis desconocida. Es un trastorno raro sin preferencia por edad o sexo. Se presenta un caso de APCR secundario al timoma; un tipo de aplasia adquirida que debe sospecharse en casos de anemia normocítica normocrómica con reticulocitopenia. El diagnóstico se confirma por la ausencia de eritroblastos en la médula ósea. El tratamiento consiste en timectomía, y a veces tratamiento corticoide o inmunosupresor. El diagnóstico diferencial de la APCR como complicación hematológica de algunas enfermedades autoinmunitarias incluye a estas.

Mesenchymal stromal cells (MSC) may exert their functions by the release of extracellular vesicles (EV). Our aim was to analyze changes induced in CD34+ cells after the incorporation of MSC‐EV. MSC‐EV were characterized by flow cytometry (FC), Western blot, electron microscopy, and nanoparticle tracking analysis. EV incorporation into CD34+ cells was confirmed by FC and confocal microscopy, and then reverse transcription polymerase chain reaction and arrays were performed in modified CD34+ cells. Apoptosis and cell cycle were also evaluated by FC, phosphorylation of signal activator of transcription 5 (STAT5) by WES Simple, and clonal growth by clonogenic assays. Human engraftment was analyzed 4 weeks after CD34+ cell transplantation in nonobese diabetic/severe combined immunodeficient mice. Our results showed that MSC‐EV incorporation induced a downregulation of proapoptotic genes, an overexpression of genes involved in colony formation, and an activation of the Janus kinase (JAK)‐STAT pathway in CD34+ cells. A significant decrease in apoptosis and an increased CD44 expression were confirmed by FC, and increased levels of phospho‐STAT5 were confirmed by WES Simple in CD34+ cells with MSC‐EV. In addition, these cells displayed a higher colony‐forming unit granulocyte/macrophage clonogenic potential. Finally, the in vivo bone marrow lodging ability of human CD34+ cells with MSC‐EV was significantly increased in the injected femurs. In summary, the incorporation of MSC‐EV induces genomic and functional changes in CD34+ cells, increasing their clonogenic capacity and their bone marrow lodging ability. stem cells 2019;37:1357–1368, Schematic representation of the experiments carried out in this work. CD34+ cells isolated from leukapheresis (for in vitro experiments) or from cord blood (for in vivo experiments) were cocultured with mesenchymal stromal cell‐extracellular vesicles (MSC‐EV) for 24 hours. After that, gene expression profile, viability, proliferation capacity, and colony‐forming capacity of CD34+ cells were assessed in both CD34+ cocultivated alone or with MSC‐EV. Finally, their engraftment ability was analyzed in nonobese diabetic/severe combined immunodeficient mice.

The use of immunochemotherapy has improved the outcome of follicular lymphoma (FL). Recently, complete response at 30 months (CR30) has been suggested as a surrogate for progression-free survival. This study aimed to analyse the life expectancy of FL patients according to their status at 30 months from the start of treatment in comparison with the sex and age-matched Spanish general population (relative survival; RS). The training series comprised 263 patients consecutively diagnosed with FL in a 10-year period who needed therapy and were treated with rituximab-containing regimens. An independent cohort of 693 FL patients from the Grupo Español de Linfomas y Trasplante Autólogo de Médula Ósea (GELTAMO) group was used for validation. In the training cohort, 188 patients were in CR30, with a 10-year overall survival (OS) of 53% and 87% for non-CR30 and CR30 patients, respectively. Ten-year RS was 73% and 100%, showing no decrease in life expectancy for CR30 patients. Multivariate analysis indicated that the FL International Prognostic Index was the most important variable predicting OS in the CR30 group. The impact of CR30 status on RS was validated in the independent GELTAMO series. In conclusion, FL patients treated with immunochemotherapy who were in CR at 30 months showed similar survival to a sex- and age-matched Spanish general population.

Background: The use of immunochemotherapy has substantially increased the outcome of patients with follicular lymphoma (FL). Nowadays, life expectancy for those reaching a durable response is excellent. Recently, complete response at 30 months (CR30) has been suggested as a surrogate for progression-free survival. The aim of this study was to analyze the life expectancy of FL patients according to their status at 30 months from the start of treatment in comparison with the sex and age-matched Spanish general population (relative survival; RS). Methods: 263 patients consecutively diagnosed with FL in a 10-year period, needing therapy and treated with rituximab-containing regimens, constituted the training series. An independent cohort of 693 FL patients from the GELTAMO group was used for validation. Findings: In the training cohort, 188 patients (71%) were in complete response at 30 months, with a 10-year overall survival of 53% and 87% for non-CR30 and CR30 patients, respectively. Ten-year RS was 73% and 100%, showing no decrease in life expectancy for CR30 patients. Follicular Lymphoma International Prognostic Index (FLIPI), beta2-microglobulin and response to induction, but not maintenance therapy or PET/CT assessment after induction, predicted RS in the CR30 patients group. FLIPI was the most important variable predicting overall survival in the CR30 group in the multivariate analysis. The impact of CR30 status on RS was validated in the independent GELTAMO series. Interpretation: Follicular lymphoma patients treated with immunochemotherapy who were in complete remission at 30 months showed similar survival to that of the sex- and age-matched Spanish general population. Funding: Instituto de Salud Carlos III, Ministerio de Salud, Espana, Ministerio de Economia y Competitividad, Espana, CIBERONC, the program "Fellowship de Gilead Sciences", Spanish Group of Lymphoma and Bone Marrow Transplantation (GELTAMO). Declaration of Interest: The authors declare no conflicts of interest. Ethical Approval: All the patients gave informed consent to participate in the study according to the declaration of Helsinki and the ethical standards of the Ethic Committee of the Hospital Clinic de Barcelona and in each participating centre in accordance with institutional standards.

Summary The diagnostic criteria for follicular lymphoma (FL) transformation vary among the largest series, which commonly exclude histologically-documented transformation (HT) mandatorily. The aims of this retrospective observational multicentre study by the Spanish Grupo Espanol de Linfoma y Transplante Autologo de Medula Osea, which recruited 1734 patients (800 males/934 females; median age 59 years), diagnosed with FL grades 1–3A, were, (i) the cumulative incidence of HT (CI-HT); (ii) risk factors associated with HT; and (iii) the role of treatment and response on survival following transformation (SFT). With a median follow-up of 6·2 years, 106 patients developed HT. Ten-year CI-HT was 8%. Considering these 106 patients who developed HT, median time to transformation was 2·5 years. High-risk FL International Prognostic Index [Hazard ratio (HR) 2·6, 95% confidence interval (CI): 1·5–4·5] and non-response to first-line therapy (HR 2·9, 95% CI: 1·3–6·8) were associated with HT. Seventy out of the 106 patients died (5-year SFT, 26%). Response to HT first-line therapy (HR 5·3, 95% CI: 2·4–12·0), autologous stem cell transplantation (HR 3·9, 95% CI: 1·5–10·1), and revised International Prognostic Index (HR 2·2, 95% CI: 1·1–4·2) were significantly associated with SFT. Response to treatment and HT were the variables most significantly associated with survival in the rituximab era. Better therapies are needed to improve response. Inclusion of HT in clinical trials with new agents is mandatory.

Background Non-Hodgkin lymphoma patients have a 25% increased risk of secondary primary neoplasms (SPNs). Regarding the controversy about the increased risk of SPN in patients exposed to radioimmunotherapy (RIT), we have analyzed this issue in a cohort of follicular lymphoma (FL) patients treated with/without RIT. Patients and Methods A retrospective study including all consecutive FL patients diagnosed since 2001 was performed. Demographic, clinical data including the incidence of any kind of neoplasm (excluding basocellular skin carcinoma) were recorded. Results A total of 242 patients were registered, male/female: 103/139, mean age: 59.9 yr (15–86), stage IV (57.8%), and Follicular Lymphoma Prognostic Index (FLIPI) low-risk (62.15%) predominance. Ninety-six patients (39.7%) were treated with 90Y-IT. The median follow-up for patients treated or not with 90Y-IT was 61 (8–273) and 38 (1–171) months. With respect to SPN incidence, 38 (15.6%) patients have at least two cancers, in 17 (44.7%), FL was the SPN; for the rest (226), the global incidence of SPNs was 9.3% (21), but there were no differences related to the exposition or not to 90Y-IT (P = 0.26). In seven patients, more than two (2–6) different therapies were registered; four were exposed to fludarabine-based therapy, three to radiotherapy and two to autologous stem-cell transplantation, and in the RIT cohort, two patients developed myelodysplastic syndrome. Conclusion This is one of the largest single institution reports assessing the risk of SPN in FL patients treated (96) or not (146) with 90Y-IT. It seems that 90Y-IT does not increase significantly the risk of SPN but avoiding its use after fludarabine and other intense cytotoxic schemes is recommended.

Introduction: Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma accounting for around 22% of them. Their natural history is characterized by multiple relapses and progressively shorter response durations after every new line of therapy for this is desirable to offer the best first-line approach to each patient. However, still now this aspect remains unclear. In the current guidelines several first line options are included: immunotherapy (Rituximab (R) x4 or Lenalidomide+/- R), immunochemotherapy (CHOP, RCVP, Bendamustine + R), radioimmunotherapy for elderly patients. Moving forward, the consolidation with radioimmunotherapy or extended dose immunotherapy (R every 8 weeks for 4 or 12 doses) still appears as an optional part of the therapy (NCCN V3.2016). Radioimmunotherapy with 90Yttrium-ibritumomab tiuxetan (90Y-IT) is available in our institution since 2006 and more than 100 patients have been treated with RIT since then. Here an institutional analysis focus in their use as consolidation is presented. Aim: To analyze the experience with 90Y-IT as a consolidation therapy in patients in CR after first-line therapy. Patients & methods: A retrospective analysis was performed including all the patients that have received RIT with 90Y-IT. Inclusion criteria were: patients 18 years or older with a grade 1-2a follicular lymphoma, RIT was received as a consolidation therapy in complete response (CR) after a first-line therapy. Demographic and follow-up data were included. International working group (IWG) criteria of response was used. Progression free survival (PFS) was calculated from the date of RIT to the date of a confirmed relapse according IWG criteria, overall survival (OS) was calculated from the FL diagnosis to the last contact. Results: A total of 31 FL patients have received 90Y-IT been in CR after a first-line of therapy and were included for the study. Mean age at diagnosis was 61.2 (29-86) years with a female predominance (19, 61.3% vs. 12, 38.7%). 80.6% (26) with ECOG 0-1 and 19.4 ECOG 2. A third of them (10, 32.3%) were diagnosed with low tumor burden (stage I-II), 2 (9.7) of them presented extra nodal infiltration (subcutaneous and gut) and 12 (38.7%) showed bone marrow infiltration demonstrated by flow cytometer or biopsy. There were no patients with bulky disease. Stages: I: 7 (22.6%), II: 3 (9.7%), III: 9 (29.1%), IV: 12 (38.7%). As first-line therapy the patients received: Rx4: 11 (35.5%) cases, R-Cyclophosphamide vincristine prednisone (R-COPx6): 3 (9.7%) cases and 17 (54.8) R-cyclophosphamide doxorubicin, vincristine and prednisone (R-CHOP21x4-6). The median follow-up was 58.0 (10-107) months. During this time only 5 (16.1%) of patients have relapsed and need another therapy. None of the patients that have received R-CHOP+90Y-IT have relapsed; the relapsed patients received Rx4 (4) and R-COP (1). The median PFS after 90Y-IT has not reached, the mean was 83.3 (71.7-94.98) months, see Fig 1. Four (12.9%) patients have died, none of them were relapsed and the mortality was due to other causes. The median OS was not reached, the mean was 95.8 (85.6-106.1) months. As long-term events one 82 years old patient developed a colon cancer after 67 months of RIT, one 72 years old female a breast cancer after 17 months of RIT and one 71 years patients a MGUS after 24 months of RIT, none of them related with mortality events. Conclusions: The use of immunotherapy with rituximab or combined schedules with immunochemotherapy (R-COP and R-CHOP) followed by consolidation with 90Y-IT remains as a valid option for follicular lymphoma patients. After ~5 years of follow-up: 63.6% (Rx4+RIT), 66.7% (R-COP+RIT) and 100% (R-CHOP+RIT) of patients continue with complete response and off of therapy. Disclosures No relevant conflicts of interest to declare.