This open label clinical study provides updated evaluation of the strategy of single unit cord blood transplants (CBTs) with co-infusion of third-party donor (TPD) mobilized hematopoietic stem cells (MHSC). Fifty-five adults with high-risk hematological malignancies, median age 34 years (16-60 years) and weight 70 kg (43-95 kg), received CBTs (median 2.39 Â 10 7 total nucleated cell (TNC) per kg and 0.11 Â 10 6 CD34 þ per kg) and TPD-MHSC (median 2.4 Â 106 CD34 þ per kg and 3.2 Â 10 3 CD3 þ per kg). Median time to ANC and to CB-ANC 40.5 Â 10 9 /l as well as to full CB-chimerism was 10, 21 and 44 days, with maximum cumulative incidences (MCI) of 0.96, 0.95 and 0.91. Median time to unsupported platelets 420 Â 10 9 /l was 32 days (MCI 0.78). MCI for grades I-IV and III-IV acute GVHD (aGVHD) were 0.62 and 0.11; 12 of 41 patients (29%) who are at risk developed chronic GVHD, becoming severely extensive in three patients. Relapses occurred in seven patients (MCI ¼ 0.17). The main causes of morbi-mortality were post-engraftment infections. CMV reactivations were the most frequent, their incidence declining after the fourth month. Five-year overall survival and disease-free survival (Kaplan-Meier) were 56 % and 47% (63% and 54% for patients p40 years). In conclusion, CBT with single units of relatively low cell content and 0-3 HLA mismatches is feasible as a first choice option for adult patients who lack a readily available adequate adult donor.

EU-FP7-HEALTH-2009, REBORNE Project (GA: 241876).

Rituximab-induced B cell depletion has been proven to be a useful therapy for autoimmune hemolytic anemia (AIHA). The aim of this retrospective study was to evaluate the effectiveness of rituximab in the treatment of 36 patients with AIHA refractory to several treatments. These patients had received a median of four (1-8) previous treatments, and 13 patients had undergone splenectomy. Rituximab was administered by intravenous infusion at a dose of 375 mg/m2 once weekly for 4 doses in 29 patients, and 7 patients received 1-6 doses. Overall, 28 of 36 patients (77%) achieved response. Twenty-two patients (61%) reached a complete response (CR), and 6 patients (16%) obtained a partial response (PR). All patients that reached CR (61%) were able to maintain the response during more than 6 months with a median follow-up of 14 months (1-86 months). Sixteen patients maintained response (Maintained Response; MR) for more than 1 year. The predictors of MR were achievement of CR and negative Coombs test result. Splenectomized patients showed a better response rate than those non-splenectomized. Rituximab was well tolerated, and only one patient presented a transitory rash during infusion. Rituximab induced clinical responses in multi-treated severe refractory both warm and cold AIHA patients with little toxicity and consequently, this therapy should be considered as an early therapeutic option in this setting.Response to Reviewers: In order to read the response to reviewers see attachment. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 AbstractRituximab-induced B cell depletion has been proven to be a useful therapy for autoimmune hemolytic anemia (AIHA). The aim of this retrospective study was to evaluate the effectiveness of rituximab in the treatment of 36 patients with AIHA refractory to several treatments. These patients had received a median of four (1-8) previous treatments, and 13 patients had undergone splenectomy.Rituximab was administered by intravenous infusion at a dose of 375 mg/m 2 once weekly for 4 doses in 29 patients, and 7 patients received 1-6 doses.Overall, 28 of 36 patients (77%) achieved response. Twenty-two patients (61%) reached a complete response (CR), and 6 patients (16%) obtained a partial response (PR). All patients that reached CR (61%) were able to maintain the response during more than 6 months with a median follow-up of 14 months (1-86 months). Sixteen patients maintained response (Maintained Response; MR) for more than 1 year. The predictors of MR were achievement of CR and negative Coombs test result. Splenectomized patients showed a better response rate than those non-splenectomized. Rituximab was well tolerated, and only one patient presented a transitory rash during infusion. Rituximab induced clinical responses in multi-treated severe refractory both warm and cold AIHA pati...

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BACKGROUND Extracorporeal photopheresis (ECP) is an effective treatment. However, protocols differ widely, and some questions, such as the number of cells to be collected or the number of ECP treatment days per treatment cycle, are still unsolved. The aim of this study was to compare a multistep (offline) (Spectra Optia and Macogenic G2) against an integrated (inline) ECP system (Therakos Cellex system) with respect to mononuclear cell (MNC) collection. STUDY DESIGN AND METHODS The number and quality parameters of the MNC products collected were evaluated together with some machine parameters, such as collection time. Comparisons were made through paired sample analysis with the t test. RESULTS Fourteen patients underwent 15 double‐paired procedures using both ECP protocols. The average MNC collected in the multistep procedure was 77.4 × 108, four times more than in the integrated procedure (18.5 × 108). MNC purity (84.4% vs. 63.8%) and enrichment (27.9 vs. 5.9) in the product collected were also higher in the multistep procedure. The whole ECP time was higher in the multistep than in the integrated procedure (272 vs. 106 min), but the calculated time to collect 25 × 108 MNCs in the multistep was shorter compared with the one‐step procedure (77.8 vs. 172 min). All these differences between the two protocols were statistically significant. CONCLUSIONS These two ECP protocols are different with respect to MNC collection and length of procedure. Some unresolved questions, such as the better MNC dose to inactivate or the number of consecutive days that ECP should be performed for optimal clinical efficacy, require further review.

Rituximab induces B-cell depletion; therefore, it has been used in the treatment of immune thrombocytopenic purpura (ITP). The aim of this retrospective study was to evaluate the effectiveness of rituximab in the treatment of 89 patients with chronic ITP refractory to several treatments. All the patients had platelet counts <30 x 10(9)/l. They had received a median of five (2-13) previous treatments, and 47 had undergone splenectomy. Rituximab was administered i.v. at 375 mg/m(2) in four weekly doses in 77 patients, and 12 patients received 1-6 doses. Forty-nine patients (55.1%) reached platelet counts >50 x 10(9)/l; 41 (46%) achieved a complete response (CR; platelets >100 x 10(9)/l), and eight (9%) obtained a partial response (platelets 50-100 x 10(9)/l). Overall, 31 patients (35%) maintained response, including 15 patients in whom splenectomy failed, with a median follow-up of 9 months (2-42), 12 for more than 1 year. The unique predictor of a maintained response was to reach a CR. Heavily treated patients (more than three different previous treatments, including any corticosteroids) and those with longer ITP duration (>10 years from diagnosis) had a worse response. Non-splenectomized patients had a better early response rate than those splenectomized. Rituximab was well tolerated, with two fever episodes following infusion and two reports of skin rash. Rituximab induced clinical responses in multi-treated refractory ITP patients with little toxicity and should be considered as an early therapeutic option in this setting, even as an alternative to splenectomy in selected patients.

Background and study aim: Advanced therapy medicinal products (ATMP) frequently lack of clinical data on efficacy to substantiate a future clinical use. This study aims to evaluate the efficacy to heal long bone delayed unions and non-unions, as secondary objective of the EudraCT 2011-005441-13 clinical trial, through clinical and radiological bone consolidation at 3, 6 and 12 months of follow-up, with subgroup analysis of affected bone, gender, tobacco use, and time since the original fracture. Patients and methods: Twenty-eight patients were recruited and surgically treated with autologous bone marrow derived mesenchymal stromal cells expanded under Good Manufacturing Practices, combined to bioceramics in the surgical room before implantation. Mean age was 39 ± 13 years, 57% were males, and mean Body Mass Index 27 ± 7. Thirteen (46%) were active smokers. There were 11 femoral, 4 humeral, and 13 tibial non-unions. Initial fracture occurred at a mean ± SD of 27.9 ± 31.2 months before recruitment. Efficacy results were expressed by clinical consolidation (no or mild pain if values under 30 in R This paper is part of a Supplement supported by The Orthopaedic Surgery and Traumatology Spanish Society (SECOT).

Recent research suggests that growth differentiation factor 11 (GDF11) could reverse age-related diseases and that its blood concentration decreases with age. This poses plasma from young donors as a therapeutic GDF11 source to treat age-related diseases. In addition, the tissue source of circulating GDF11 remains unknown. We analysed GDF11 levels in paired samples of serum, plasma and platelet lysate (PL) from 23 volunteers. Plasma and PL were collected by plateletpheresis. Here, we show that GDF11 is highly concentrated in platelets and that the circulating levels reported in previous studies could be biased as a result of serum sample manipulation.