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Donor lymphocyte infusion has been used in the management of relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation. It can eradicate minimal residual disease or be used to rescue a hematologic relapse, being able to induce durable remissions in a subset of patients. With the increased use of haploidentical hematopoietic cell transplantation, there is renewed interest in the use of donor lymphocytes to either treat or prevent disease relapse post transplant. Published retrospective and small prospective studies have shown encouraging results with therapeutic donor lymphocyte infusion in different haploidentical transplantation platforms. In this consensus paper, finalized on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we summarize the available evidence on the use of donor lymphocyte infusion from haploidentical donor, and provide recommendations on its therapeutic, pre-emptive and prophylactic use in clinical practice.

A 33-year-old man in Madrid, Spain, with chronic myeloid leukemia in lymphoid blastic phase underwent allogeneic stem cell transplantation (SCT) from a matched unrelated donor in 2011. Four years later, [...]

Accurate estimates of tree diameter, height, volume, and biomass are important for numerous economic and ecological applications. In this study, we report exponential equations to predict tree DBH (cm), stem volume over bark (VOB, m3), and total above-stump biomass (TASB, kg) using three varying levels of input data for Pinus radiata D. Don, Eucalyptus globulus Labill., and Eucalyptus nitens (H.Deane & Maiden) Maiden planted trees. The three sets of input data included: (1) tree height (HT, m), (2) tree HT and ground projected living crown area (CA, m2), and (3) tree HT, CA, and additional stand parameters. The analysis was performed using a large dataset covering the range of distribution of the species in central Chile and included stands of varying ages and planting densities. The first set of equations using only HT were satisfactory with Adj-R2 values ranging from 0.78 to 0.98 across all species and variables. For all three species, estimation of DBH, VOB, and TASB as a function of HT improved when CA was added as an additional independent variable, increasing Adj-R2 and reducing RMSE. The inclusion of stand variables, such as age and stand density, also resulted in further improvement in model performance. The models reported in this study are a robust alternative for DBH, VOB, and TASB estimations on planted stands across a wide range of ages and densities, when height and CA are known, especially when input data are derived from remote sensing techniques. [ABSTRACT FROM AUTHOR]

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has shown favorable results in the treatment of hematological malignancies. Despite the use of post-transplant cyclophosphamide (PTCy), graft versus host disease (GVHD) remains as one of the main complications in this setting. Since the skin appears affected in up to 80% of cases of acute GVHD (aGVHD), its prognosis and diagnosis are essential for the correct management of these patients. Plasma concentration of elafin, an elastase inhibitor produced by keratinocytes, has been described elevated at the diagnosis of skin GVHD, correlated with the grade of GVHD, and associated with an increased risk of death. In this study we explored elafin plasma levels in the largest series reported of T cell–replete haplo-HSCT with PTCy. Plasma samples drawn from 87 patients at days +15 and +30 were analyzed ("discovery cohort"). Elafin levels at days +15 were no associated with chronic GVHD, non-relapse mortality, relapse, therapy-resistant GVHD, or overall survival. In our series, elafin levels at day +30 were not associated with post-transplant complications. On the other hand, elafin plasma levels at day +15 were higher in patients with severe skin aGVHD (21,313 vs. 14,974 pg/ml; p = 0.01). Of note, patients with higher elafin plasma levels at day +15 presented a higher incidence of stage III-IV skin aGVHD (HR = 18.9; p < 0.001). These results were confirmed (HR = 20.6; p < 0.001) in an independent group of patients (n = 62), i.e. the "validation cohort." These data suggest that measurement of elafin in patients undergoing haplo-HSCT with PTCy might be useful for an early identification of those patients who are at higher risk of suffering severe skin aGVHD and thus, improve their treatment and prognosis. [ABSTRACT FROM AUTHOR]

Estimating carbon stocks in wooded systems is crucial to quantify national greenhouse gas balance estimates. However, inaccurate estimates are likely due to the divergent architecture of many species. The monkey puzzle tree Araucaria araucana, with its umbrella-like architecture is a vivid example. This species, often found in monodominant stands at high elevations, is the greatest carbon reservoir in the landscape, hence estimating its carbon storage is crucial. To provide the necessary basis for these estimations, we documented the variation in basic density and moisture content along the stem profile, identified the most suitable biomass estimation models, and quantified biomass allocation for three age ranges. We measured, felled, weighed, and separated trees into three categories: stem wood, stem bark, and foliage (branches + scaly leaves). The log-linear form of the simple allometric equation Y = aXb, based on diameter at breast height as the explanatory variable, covered a large part of the variation and showed good cross-validation performance (>0.96). Models using more covariates achieved lower absolute errors, but the estimation of the additional model parameters was associated with greater uncertainty. A multi-objective model comparison revealed that the best additional covariate to further improve biomass estimation was total tree height. The mean absolute percentage error was 9.8% for the total aboveground biomass, 8% for stem wood, 12% for stem bark and 24% for foliage. Changes in biomass distribution among tree components were related to age. For older trees, there was a relative increase in stem wood, a decreased proportion of foliage, but no change in stem bark. The proportion of stem bark biomass is similar to that of Araucaria angustifolia, but higher than in other conifers and most trees in general. Our results provide key properties for A. araucana and general guidance for the selection of easily-measurable variables allowing for excellent predictive power for local biomass estimation. [ABSTRACT FROM AUTHOR]

Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a curative procedure for several hematological malignancies. Haploidentical HSCT (haplo-HSCT) using high-dose post-transplantation cyclophosphamide (PTCy) makes transplantation possible for patients with no HLA-matched sibling donor. However, this treatment can cause complications, mainly infection, graft-vs.-host disease (GVHD), and conditioning-related toxicity. In recent years, different biomarkers in the form of tissue-specific proteins have been investigated; these may help us to predict complications of allo-HSCT. In this study we explored two such biomarkers, suppression of tumorigenicity 2 (ST2) and regenerating islet-derived 3α (REG3α), in the largest series reported of T cell–replete haplo-HSCT with PTCy. Plasma samples drawn from 87 patients at days +15 and +30 were analyzed. ST2 and REG3α levels at day +15 were not associated with post-transplant complications. ST2 levels at day +30 were higher in patients with grade II-IV acute GVHD, mainly those who received reduced intensity conditioning (RIC; median 2,503 vs. 1,830 ng/ml; p = 0.04). Of note, patients with higher plasma ST2 levels at day +30 also presented a higher incidence of non-relapse mortality (HR, 7.9; p = 0.004) and lower 2-year overall survival (25 vs. 44 months; p = 0.02) than patients with lower levels. Patients with REG3α levels higher than 1,989 pg/ml at day +30 presented a higher incidence of acute gastrointestinal GVHD in the whole cohort (HR, 8.37; p = 0.003) and in the RIC cohort (HR 6.59; p = 0.01). These data suggest that measurement of ST2 and REG3α might be useful for the prognosis and prediction of complications in patients undergoing haplo-HSCT with PTCy. [ABSTRACT FROM AUTHOR]

Background: Poor mobilization results are unexpected after G‐CSF‐induced peripheral blood stem cell collection in healthy donors. However, 2%‐5% of the donors are poor mobilizers. Factors predicting CD34+‐cell yield after mobilization in related alternative donors are still poorly known. Patients and methods: Baseline characteristics and efficacy results of G‐CSF induced mobilization of 159 adult healthy donors in our institution from 2008 to 2016 were retrospectively analyzed. All donors received 10 μg/kg of G‐CSF once a day subcutaneously for 4 days. Leukapheresis started on the 5th day of G‐CSF treatment. Donors were classified as poor mobilizers if they had less than 20 000 CD34 + cell/mL peripheral blood count in the 5th day of G‐CSF treatment or if they needed three or more leukapheresis for graft collection. Results: Age, weight, and platelet count before and after mobilization were significantly different between poor and good mobilizers. Poor mobilizers (n = 16) were older (50.6 vs 41.7 years, P = 0.002), weight lower (64 vs 75 kg, P = 0.00) and showed a lower platelet count before (199.5 vs 219.0 × 109/L, P = 0.03) and after (192.5 vs 206 × 109/L, P = 0.019) mobilization. In the multivariate analysis only the 30% of the variability of mobilization was explained by the model (sensitivity 80%, specificity 70%). Conclusion: In this cohort of healthy donors in a single institution, older age, less weight, and lower platelet count was associated with poorer mobilization. With clinical and analytic factors it is not possible to predict more than 30% of the variability. Further studies are needed to investigate new variables. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal photopheresis (ECP) is an efficient and established therapy to treat acute and chronic graft vs host disease (GVHD). Using an "off‐line" method, the first step (mononuclear cell [MNC] collection) is decisive, as long as a high MNC yield and purity in the collected product is desirable. Two "off‐line" devices were compared: the COBE Spectra and the Spectra Optia (Terumo BCT), using both continuous and intermittent protocols. Patients and methods: Twelve patients with GvHD (7 acute/5 chronic) were enrolled between June 2014 and May 2015 and were alternatively assigned for each procedure to either the COBE Spectra or the Spectra Optia cell separator. Patients characteristics and procedure/product parameters were analyzed. Results: Two hundred procedures (100 per device) were included. The Spectra Optia system showed higher total nucleated cells and MNC collection efficiencies (18.6(10.2‐29.7) vs 7.9(4.1‐14.8)% and 43.6(20.3‐59.5) vs 23.3(11.4‐37.1)%, P < .001) and monocyte and lymphocyte collection efficiencies (55.2(17.7‐83.2) vs 22.8(9‐38.9)% and 38.3(26.7‐53.4) vs 22.2(9‐38.9)%, respectively, P < .001). Absolute platelet loss (PL) and PL per liter of blood processed were significantly lower in the Spectra Optia group (22.9(18.3‐28.1) vs 33.6(26.5‐41.1)%, P < .001 and 3.7(3.1‐4.5) vs 4.3(3.5‐4.2)%, P = .01, respectively). However, granulocyte contamination was higher (4.5(1.3‐36) vs 1.2(0.4‐5.7)%, P < .001) and a higher product haematocrit was obtained with the Spectra Optia (1(0.5‐1.6) vs 0.3(0.2‐0.5)%, P < .001), without an impact on irradiation time. Conclusions: In our study, Spectra Optia proved to be safe and effective in collecting MNC with high yield and purity for ECP in GvHD. [ABSTRACT FROM AUTHOR]

Summary: We conducted a phase 2 trial to evaluate the safety and efficacy of bendamustine instead of BCNU (carmustine) in the BEAM (BCNU, etoposide, cytarabine and melphalan) regimen (BendaEAM) as conditioning for autologous stem‐cell transplantation (ASCT) in patients with aggressive lymphomas. The primary endpoint was 3‐year progression‐free survival (PFS). Sixty patients (median age 55 [28–71] years) were included. All patients (except one who died early) engrafted after a median of 11 (9–72) and 14 (4–53) days to achieve neutrophil and platelet counts of >0.5 × 109/l and >20 × 109/l, respectively. Non‐relapse mortality at 100 days and 1 year were 3.3% and 6.7%, respectively. With a median follow‐up of 67 (40–77) months, the estimated 3‐year PFS and overall survival (OS) were 58% and 75%, respectively. Patients in partial response at study entry had significantly worse PFS and OS than patients who underwent ASCT in complete metabolic remission, and this was the only prognostic factor associated with both PFS (Relative risk [RR], 0.27 [95% confidence interval {CI} [0.12–0.56]) and OS (RR, 0.40 [95% CI 0.17–0.97]) in the multivariate analysis. BendaEAM conditioning is therefore a feasible and effective regimen in patients with aggressive lymphomas. However, patients not in complete metabolic remission at the time of transplant had poorer survival and so should be considered for alternative treatment strategies. [ABSTRACT FROM AUTHOR]

Abstract: Background: High‐risk acute leukemia (AL) and myelodysplastic syndrome (MDS) remain a therapeutic challenge. Unmanipulated haploidentical‐related donor transplantation based on a myeloablative conditioning regimen (HAPLO‐MAC) and post‐transplant cyclophosphamide (PT‐Cy) as prophylaxis against graft vs host disease (GvHD) is now a promising rescue strategy that could become universally available. Objective: To evaluate the results of HAPLO‐MAC with PT‐Cy in patients with AL and MDS reported to the Haploidentical Transplantation Subcommittee of the Spanish Group for Hematopoietic Transplantation (GETH). Patients and methods: We report our multicenter experience using an IV busulfan‐based HAPLO‐MAC regimen and PT‐Cy for treatment of 65 adults with high‐risk AL and MDS. Results: Engraftment was recorded in 64 patients (98.5%), with a median time to neutrophil and platelet recovery of 16 and 27 days, respectively. The cumulative incidence of grade II‐IV acute GvHD and chronic GvHD was 28.6% and 27.5%, respectively. After a median follow‐up of 31 months for survivors, the cumulative incidence of non‐relapse mortality and relapse at 2 years was 18.8% and 25%, respectively. Estimated 30‐month event‐free survival and overall survival were 56% and 54.5%, respectively. Conclusion: HAPLO‐MAC comprising an IV busulfan‐based conditioning regimen enabled long‐term disease control with acceptable toxicity in high‐risk AL and MDS. [ABSTRACT FROM AUTHOR]

Background: Development of de novo alloantibodies against recipient's red blood cell (RBC) antigens by engrafted donor's lymphocytes is a known phenomenon in the setting of allogeneic hematopoietic stem cell transplantation (HSCT). This situation is usually clinically insignificant. We report a case of early clinically relevant hemolytic anemia in a blood group A1 D+ patient, due to a limited production of anti-D and anti-A1 produced by nonpreviously sensitized newly engrafted donor's immune system.Case Report: A 31-year-old Caucasian woman, blood group A1 , D+, with Hodgkin's lymphoma, received an unmanipulated haploidentical allogeneic peripheral blood HSCT after a nonmyeloablative conditioning regimen. Donor blood group was A2 B, D-. The patient had an uneventful course until Day +34, when she developed clinically significant hemolytic anemia with a positive direct antiglobulin test. Anti-D and anti-A1 produced by the donor-engrafted lymphocytes were detected both in serum and in eluate. The hemolysis produced an accelerated group change, turning the patient's ABO group into A2 B 2 weeks after the detection of the alloantibodies. As the residual patient's RBCs progressively disappeared, anti-D and anti-A1 production decreased and were not detected in serum by Day +41.Conclusion: This case illustrates that de novo alloantibody production against ABO and D antigens by the newly engrafted donor's lymphocytes can occasionally cause clinically significant anemia. To our knowledge, this is the first case reported of clinically significant hemolytic anemia due to a transient anti-D anti-A1 alloimmunization after T-cell-repleted haploidentical HSCT. [ABSTRACT FROM AUTHOR]

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Acute lymphoblastic leukemia (ALL) following solid organ or hematologic malignancy (secondary ALL, s-ALL) is not well characterized. We analyzed the characteristics and outcome of patients with s-ALL and compared them with those of patients with de novo- ALL. Of 448 patients, 24 (5%) had previous neoplasia. Sixteen patients had received previous cytotoxic therapy (therapy-associated ALL, t-ALL), and eight had not (antecedent-malignancy ALL, am-ALL). Except for more advanced age in patients with s-ALL, no statistically significant differences were observed in WBC count, CNS involvement, immunophenotype or cytogenetics between the groups, nor in complete remission (t-ALL: 94%; am-ALL: 75%; de novo-ALL: 85%), 3-year remission duration (58%; 50%; 72%), overall survival (71%; 38%; 60%) or event-free survival (53%, 38%; 53%). Our study did not show poor clinical or cytogenetic features or inferior outcome in ALL patients with antecedent neoplastic disease, irrespective of the type of treatment received for the neoplasia. [ABSTRACT FROM AUTHOR]

The FOXP3 gene encodes for a protein (Foxp3) involved in the development and functional activity of regulatory T cells (CD4+/CD25+/Foxp3+), which exert regulatory and suppressive roles over the immune system. After allogeneic stem cell transplantation, regulatory T cells are known to mitigate graft versus host disease while probably maintaining a graft versus leukemia effect. Short alleles (≤(GT)15) for the (GT)n polymorphism in the promoter/enhancer of FOXP3 are associated with a higher expression of FOXP3, and hypothetically with an increase of regulatory T cell activity. This polymorphism has been related to the development of auto- or alloimmune conditions including type 1 diabetes or graft rejection in renal transplant recipients. However, its impact in the allo-transplant setting has not been analyzed. In the present study, which includes 252 myeloablative HLA-identical allo-transplants, multivariate analysis revealed a lower incidence of grade III-IV acute graft versus host disease (GVHD) in patients transplanted from donors harboring short alleles (OR = 0.26, CI 0.08–0.82, p = 0.021); without affecting chronic GVHD or graft versus leukemia effect, since cumulative incidence of relapse, event free survival and overall survival rates are similar in both groups of patients. [ABSTRACT FROM AUTHOR]