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The present research focuses on a continuum description of stratified metamaterials achieved through the superposition of layers with alternating chirality. Each layer is constructed as a periodic assembly of centre-symmetric periodic cells, formed by a recurring arrangement of rigid circular discs connected by elastic ligaments. The layers are interconnected through elastic pins passing through the centres of aligned discs, allowing for either restrained or free relative rotation. A micropolar continuum model is used to describe each individual layer. The overall response of the metamaterials to in-plane forces is derived using a multi-field non-local model, expressed in terms of the average and difference of displacement and rotational fields. The overall micropolar and standard (Cauchy) constitutive tensors have been determined in closed form. The validity of the equivalent generalized micropolar model has been confirmed through comparison with discrete Lagrangian solutions of representative examples. In addition, a detailed analysis of a pseudo-indentation test has been carried out. This article is part of the theme issue 'Current developments in elastic and acoustic metamaterials science (Part 2)'.

This article focuses on characterizing a class of quasi-periodic metamaterials created through the repeated arrangement of an elementary cell in a fixed direction. The elementary cell consists of two building blocks made of elastic materials and arranged according to the generalized Fibonacci sequence, giving rise to a quasi-periodic finite microstructure, also called Fibonacci generation. By exploiting the transfer matrix method, the frequency band structure of selected periodic approximants associated with the Fibonacci superlattice, i.e. the layered quasi-periodic metamaterial, is determined. The self-similarity of the frequency band structure is analysed by means of the invariants of the symplectic transfer matrix as well as the transmission coefficients of the finite clusters of Fibonacci generations. A high-frequency continualization scheme is then proposed to identify integral-type or gradient-type non-local continua. The frequency band structures obtained from the continualization scheme are compared with those derived from the Floquet-Bloch theory to validate the proposed scheme. This article is part of the theme issue 'Current developments in elastic and acoustic metamaterials science (Part 1).'

We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125) and the combination of busulfan and fludarabine (BuFlu, n = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40-65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, p = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, p = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches., (© 2024. The Author(s).)

Background: Pure red cell aplasia (PRCA) is a possible complication after allogeneic hematopoietic stem cell transplantation (HSCT) with major ABO incompatibility. Patients experience delayed engraftment of the erythroid series, with prolonged transfusion-dependent anemia and iron overload., Methods: We performed a revision of the most recent literature about post-HSCT PRCA treatment procedures. Moreover, we conducted a retrospective study, over the last 13-years, which included all consecutive major ABO mismatched HSCT performed in our unit, with the aim to assess PRCA incidence, risk factors, and response to different treatments. Overall, 194 patients received a major ABO mismatched transplant from 2010 to 2022. For each patient, data about demographic and transplant characteristics, engraftment, blood transfusion, and possible treatment received were collected., Results: The literature review returned 23 eligible papers on PRCA treatment, with high success rate using plasma-exchange (PEX) and immunoadsorption procedures, daratumumab, and eltrombopag. Our study identified a total of 24 cases of PRCA. Among risk factors for PRCA development, we have found older recipient age (p=0.01), high pre-HSCT IgG and IgM IHA titer (p<0.0001), major rather than bidirectional ABO incompatibility (p=0.02), low T CD8 lymphocyte count in the graft (p=0.006), relative donor (p=0.02) and bone marrow as stem cell source (p=0.002). However, multivariate analysis confirmed only pre-HSCT IgG IHA titer as the unique risk factor for PRCA occurrence. The optimal cut-off value of pre-HSCT IgG IHA for PRCA development, resulted to be 1/64, with a 100% sensitivity and 68.8% specificity (p<0.0001). All patients with PRCA had received rhEPO and transfusion support and 20 patients received additional treatments like PEX, rituximab, and more recently daratumumab. Comprehensively, PEX and rituximab obtained a response in half of the cases, at a variable time, while the few cases of patients we treated with daratumumab suggest promising results. The overall response rate in our cohort was 75%, with significantly better survival (94.4% vs. 16.7%) and lower transplant-related mortality (6.3% vs. 80%) for PRCA responders., Conclusions: Standardized guidelines on when and how to treat PRCA are necessary because the current treatment is controversial among centers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Metafuni, Busnego Barreto, Valentini, Giammarco, Limongiello, Sorà, Bianchi, Massini, Piccirillo, Putzulu, Frioni, Bacigalupo, Teofili, Chiusolo and Sica.)

Despite emergence of novel therapies to treat hematologic malignancies, allogeneic hematopoietic cell transplantation (allo-HCT) remains an essential treatment modality capable of curing these diseases. Allo-HCT has been also shown to be curative in benign hematologic disorders such as aplastic anemia, sickle cell disease, and thalassemia, among others. Recently, the American Society for Transplantation and Cellular Therapy (ASTCT) published standardized definitions for hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism. To attempt broader international consensus, a panel of adult and pediatric physician transplant experts was assembled from European Society for Blood and Marrow Transplantation (EBMT), ASTCT, the Center for International Blood and Marrow Transplant Research (CIBMTR), and Asia-Pacific Blood and Marrow Transplantation (APBMT). Consensus was defined as ≥70% of voting members strongly agreeing or somewhat agreeing with a definition. With few exceptions, there was a consensus to endorse the prior ASTCT definitions. Importantly, we revised existing EBMT and CIBMTR data collection forms to align with these harmonized definitions that will facilitate research and international collaboration among transplant researchers and across transplant registries., (© 2024. The Author(s).)

Background: Allogeneic hemopoietic stem cell transplantation (HSCT) currently remains the only curative treatment for patients with myelofibrosis (MF). Transplant related mortality (TRM) and relapse, remain two significant complications which need to be addressed., Aims: The aim of this manuscript is to review current available reports on changes which have recently occurred, to improve the outcome of MF patients undergoing an allogeneic HSCT., Methods: Published papers were used to analyze different aspects of allogeneic HSCT., Results: Changes and updates are provided on selection of patients, prognostic systems, managing splenomegaly, conditioning regimens, predicting transplant outcome, stem cell sources, stem cell donors, graft versus host disease (GvHD) prophylaxis, patients with blast phase, hematopoietic reconstitution, disease markers, donor chimerism, and treatment of relapse., Conclusions: The review outlines new transplant platforms which are now available for patients with myelofibrosis, together with persisting problems, among which, older age combined with marrow fibrosis and an inflammatory disease. Relapse also requires aggressive monitoring of drivers mutations, and early cellular therapy., (© 2024 Wiley Periodicals LLC.)

Hemorrhagic cystitis (HC) is a highly impacting complication in allogeneic hematopoietic stem cell transplantation (HSCT), occurring in 12%-37% of patients. The impact of transplant- and patient-specific variables has been described, with a possible role for JCV and BKV, which may be cooperating with cytomegalovirus (CMV). Here, we analyze 134 letermovir-exposed, CMV-free patients, treated with the same cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, describing risk factors for HC. The overall incidence of HC was 23%. Patients with HLA mismatched transplant, higher comorbidity score, and receiving three alkylating agents with TBF (thiotepa, busulfan, and fludarabine) conditioning regimen had a higher risk of HC in multivariate analysis (OR: 4.48, 6.32, and 1.32, respectively). A HC-score including male gender, TBF conditioning, and HLA-mismatch stratifies the risk of HC in the first 100 days after HSCT. The role of BKV and JCV was not highly impacting in those patients, suggesting a possible synergistic effect between CMV and JCV in causing HC. HC can be interpreted as the combination of patient-related factors, chemotherapy-related toxicities-especially due to alkylating agents-and immunological elements., (© 2024 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Autologous peripheral blood stem cell transplantation (aPBSCT) provides optimal outcomes in POEMS syndrome but the definition of the best treatment before aPBSCT remains to be defined because of the rarity of the disease and the heterogeneity of published case series. We collected clinical and laboratory data of patients with POEMS syndrome undergoing aPBSCT from 1998 to 2020 in ten Italian centers. The primary endpoint of the study was to evaluate the impact of prior therapies and mobilization regimen on outcome. We divided the patients into three groups: patients who did not receive any treatment before transplant (15 patients, group A: front-line), patients pre-treated with other agents (14 patients, group B) and patients treated with cyclophosphamide as their mobilizing regimen (16 patients, group C). The three groups did not show differences in terms of demographic and clinical characteristics. All 45 patients underwent aPBSCT after a high-dose melphalan conditioning regimen, with a median follow-up of 77 months (range, 37-169 months). The responses were not statistically different between the three groups (P=0.38). Progression-free and overall survival rates at 6 years were: 70% (95% confidence interval: 55-85%) and 91% (95% confidence interval: 82-99) 65%, respectively, and did not differ between the three groups. The cumulative incidence of transplant-related mortality and relapse was 4% and 36%, respectively. In conclusion, in a relatively large number of patients with POEMS syndrome, undergoing an autologous transplant, pre-treatment and disease status at transplant did not appear to have an impact on major transplant outcomes.

We studied the incidence of acute graft versus host disease (GvHD) and its outcome in three consecutive time frames (year <2000; 2000-2010; >2010), in 3,120 patients allografted in two transplant Centers between 1976 and 2020. The median age increased over the three periods from 32 to 42 to 54 years ( p  < 0.00001). The median day of onset of GvHD in the three periods was day +14, day +16, and day +30, respectively ( p  < 0.0001). The cumulative incidence (CI) of GvHD grades II-IV in the three periods was 47, 24, and 16%, respectively ( p  < 0.00001). The CI of GvHD grades III-IV was 13, 5, and 4% ( p  < 0.001). In multivariate analysis, significant predictive factors for GvHD II-IV, on top of year of transplant, were anti-thymocyte globulin (ATG) (RR 0.67, p  > 0.001); post-transplant cyclophosphamide (PTCY) (RR 0.41, p  < 0.001), a family mismatched donor (RR 1.31, p  = 0.03) a matched unrelated donor (RR 2.1, p < 0.001), an unrelated mismatched donor (RR1.8, p  = 0.001), donor age above 40 years (RR 1.27, p  < 0.001), hematological malignancy-as compared to aplastic anemia (RR 2.3, p  < 0.001). When selecting only GvHD grade II, in a multivariate analysis, there was a significant reduction of transplant-related mortality (TRM) for patients grafted in 2001-2010 (RR 0.62, p  < 0.0001) and for patients grafted in 2011-2020 (RR 0.35, p  < 0.0001) as compared to grafts before the year 2000. A similar reduction in time was seen for patients with GvHD grades III-IV. The overall TRM in the three periods was 30, 22, and 16% ( p  < 0.0001) and survival was 47, 51, and 58% ( p  < 0.0001). Relapse risk was unchanged. In conclusion, we showed improved prevention of acute GvHD with time, together with a significant delay in the onset of the disease. Treatment of GvHD has also improved over time, as suggested by both reduced TRM and improved survival in more recent transplant periods., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Di Francesco, Raiola, Dominietto, Di Grazia, Gualandi, Van Lint, Bregante, Chiusolo, Laurenti, Sora, Giammarco, Metafuni, Fresa, Sica, Angelucci and Bacigalupo.)

New options for medical therapy and risk scoring systems containing molecular data are leading to increased complexity in the management of patients with myelofibrosis. To inform patients' optimal care, we updated the 2015 guidelines on indications for and management of allogeneic haematopoietic stem-cell transplantation (HSCT) with the support of the European Society for Blood and Marrow Transplantation (EBMT) and European LeukemiaNet (ELN). New recommendations were produced using a consensus-building methodology after a comprehensive review of articles released from January, 2015 to December, 2022. Seven domains and 18 key questions were selected through a series of questionnaires using a Delphi process. Key recommendations in this update include: patients with primary myelofibrosis and an intermediate-2 or high-risk Dynamic International Prognostic Scoring System score, or a high-risk Mutation-Enhanced International Prognostic Score Systems (MIPSS70 or MIPSS70-plus) score, or a low-risk or intermediate-risk Myelofibrosis Transplant Scoring System score should be considered candidates for allogeneic HSCT. All patients who are candidates for allogeneic HSCT with splenomegaly greater than 5 cm below the left costal margin or splenomegaly-related symptoms should receive a spleen-directed treatment, ideally with a JAK-inhibitor; HLA-matched sibling donors remain the preferred donor source to date. Reduced intensity conditioning and myeloablative conditioning are both valid options for patients with myelofibrosis. Regular post-transplantation driver mutation monitoring is recommended to detect and treat early relapse with donor lymphocyte infusion. In a disease where evidence-based guidance is scarce, these recommendations might help clinicians and patients in shared decision making., Competing Interests: Declaration of interests NK has received honoraria for lectures and advisory boards from Kite, Jazz, Merck Sharp & Dohme, Neovii Biotech, Alexion, Takeda, Novartis, Riemser, Pfizer, and Bristol Myers Squibb. NK has also received research support from Neovii, Riemser, Novartis, and Deutsche Knochenmarkspender Datei, and research grants from Neovii, Jazz, Celgene, and Novartis. AMV has received honoraria for lectures from Novartis, Incyte, AbbVie, GlaxoSmithKline, Bristol Myers Squibb, and AOP Orphan Pharmaceutical GmbH. CH has received honoraria for lectures from AbbVie, AOP Orphan Pharmaceutical GmbH, Bristol Myers Squibb, CTIBioPharma, Imago Biosciences, Incyte, Novartis, Galacteo, Geron, Gilead, GlaxoSmithKline, Janssen, Keros, Promedior, Roche, Shire, and Sierra. SK has received grants or contracts from AOP Orphan Pharmaceutical GmbH, Janssen, Geron, and Novartis. SK has received consulting fees from Novartis, Bristol Myers Squibb, Incyte, AOP Orphan Pharmaceutical GmbH, Baxalta, CTI Biopharma, Pfizer, Sanofi, Celgene, Shire, Janssen, Geron, Karthos, Sierra Oncology, GlaxoSmithKline, Imago Biosciences, AbbVie, and iOMEDICO. SK has received honoraria for lectures from Novartis, Bristol Myers Squibb, Pfizer, Incyte, Ariad, Shire, Roche, AOP Orphan Pharmaceutical GmbH, Janssen, Geron, Celgene, Karthos, Abbvie, iOMEDICO, and GlaxoSmithKline. SK has received payment for expert testimony from Novartis and GlaxoSmithKline. SK has received funding for travel from Alexion, Novartis, Bristol Myers Squibb, Celgene, Incyte, Ariad, AOP Orphan Pharmaceutical GmbH, CTI Biopharma, Pfizer, Sanofi, Janssen, Geron, Imago Biosciences, GlaxoSmithKline, PharmaEssentia, Sierra Oncology, AbbVie, and iOMEDICO. SK has a patent for bromodomain and extra-terminal motif inhibitors related to RWTH Aachen University (Aachen, Germany). SK has received honoraria for participation on data safety monitoring boards and advisory boards from Pfizer, Incyte, Novartis, AOP Orphan Pharmaceutical GmbH, Bristol Myers Squibb, Celgene, Geron, Janssen, CTI Biopharma, Roche, Baxalta, Sanofi, Myeloproliferative Neoplasm Hub, Sierra Oncology, GlaxoSmith Kline, AbbVie, and PharmaEssentia. SK is chairman of the Hemostasis Working Party of the German Society of Hematology and Medical Oncology, speaker of the German Study Group of the Myeloproliferative Neoplasm Hub, member of the Guidelines Committee of European Haematology Association, and an associate editor for the Hemasphere journal. DPM has received honoraria for lectures from GlaxoSmithKline, Bristol Myers Squibb, Novartis, and AbbVie. TJ has received grants from CTI Biopharma, Kartos Therapeutics, and Incyte. TJ has received honoraria for participation on advisory boards from Care Dx, Bristol Myers Squibb, Incyte, Abbvie, CTI Biopharma, Kite, Cogent Biosciences, Blueprint Medicine, Telios Pharma, and Protagonist Therapeutics. NH has received honoraria for lectures from Novartis. AR has received honoraria for lectures from Novartis, Bristol Myers Squibb, Sanofi, Abbvie, Amgen, Pfizer, Kite-Gilead, Jazz, Astellas, Incyte, and Omeros. MG has received honoraria for lectures from AOP Orphan Pharmaceutical GmbH, Novartis, Bristol Myers Squibb, AbbVie, Pfizer, Janssen, Gilead, AstraZeneca, Lilly, and GlaxoSmithKline. VG has received grants from Novartis and Incyte. VG has received consulting fees from Novartis, Incyte, Bristol Myers Squibb, Celgene, GlaxoSmithKline, CTI Biopharma, Morphosys, AbbVie, and Pfizer. VG has received honoraria for lectures from GlaxoSmithKline. VG has received funding for travel and registration fees from GlaxoSmithKline. VG is a member of the Executive Committee of the Canadian Myeloproliferative Neoplasm Group. NP has received honoraria for lectures from Novartis, Bristol-Myers Squibb, and Abbvie. NP has received funding for travel and registrations fees from Abbvie and Novartis. NP has received honoraria for participation on advisory boards from Novartis and Abbvie. JM has received grants from Incyte, Novartis, Roche, CTI Biopharma, Geron, Kartos, Karyopharm, PharmaEssentia, AbbVie, and Bristol Myers Squibb. JM has received consulting fees from Incyte, Novartis, CTI Biopharma, Geron, Kartos, Karyopharm, Bristol Myers Squibb, AbbVie, PharmaEssentia, Galecto, Imago, Merck, Pfizer, GlaxoSmithKline, and MorphoSys. MD has received honoraria for lectures from Pfizer, Merck Sharp & Dohme, and Novartis. MD has received funding for travel and registration fees from Biotest. FP has received honoraria for lectures from Novartis, Bristol Myers Squibb, Abbvie, AOP Orphan Pharmaceutical GmbH, and Janssen. FP has received honoraria for participation on advisory boards from Novartis, Bristol Myers Squibb, GlaxoSmithKline, Abbvie, AOP Orphan Pharmaceutical GmbH, Janssen, Karyiopharma, Kyowa Kirin and MEI, Sumitomo, and Kartos. TB has received honoraria for lectures from AOP Orphan Pharmaceutical GmbH, Novartis, and Pharma Essentia. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

We report 634 patients who underwent unmanipulated haploidentical (HAPLO) bone marrow transplantation (BMT) in two Centers. The diagnosis was acute myeloid leukemia (AML) (n = 251), acute lymphoblastic leukemia (ALL)(n = 107), myelodysplastic syndrome and myelofibrosis (MDS + MF) (n = 125) and chronic lymphoproliferative disorders (n = 151). Median age was 52 years (16-74). Graft versus host disease (GvHD) prophylaxis was intravenous cyclosporin (CSA) starting on day 0, oral mycophenolate on day +1, and post-transplant cyclophosphamide (PTCY) on days +3 + 5. Primary graft failure was seen in 23 patients (3,6%); 17 /23 (74%) were rescued with second HAPLO graft, and were alive at one year. The cumulative incidence of acute GvHD grade II-IV was 29% and 3% for grade III-IV; the cumulative incidence of moderate severe chronic GvHD was 23%: older donor and patients age were significant predictors of both acute and chronic GvHD. The overall non relapse mortality (NRM) at 2 years was 19%: 8%, 21% and 30% in patients aged <40, 41-60 > 60 years. Disease free survival (DFS) at 5 years was 64% for acute leukemia in first remission, 51% for acute leukemia CR2, 25% for acute leukemia advanced disease and 49% for MDS/MPN. We confirm, on a relatively large number of patients, that unmanipulated HAPLO BMT with PTCY on days +3 + 5, mostly after a myeloablative conditioning regimen, is followed by a low incidence of graft failure and grade III-IV GvHD; moderate severe chronic GvHD is 23% and NRM at 2 years 19%; 5 year DFS is influenced by remission status of the underlying disease., Competing Interests: Declaration of Competing Interest No conflicts to disclosure., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Post-transplant cyclophosphamide (PTCy) allows safe and effective partially matched donor allogeneic blood or marrow transplantation (alloBMT), so that almost everyone in need of the procedure now has a donor. Moreover, PTCy and other recent advances have lowered alloBMT mortality rates to less than half of that seen before the turn of the century, at costs that are substantially less than most newly approved anticancer agents. These advances also make tailoring BMT based on patients' unique diseases and characteristics now feasible for further improving outcomes. Personalizing every aspect of alloBMT, including conditioning, donor, graft type, and post-transplant maintenance is now possible. For example, alloBMT's antitumor activity historically was restricted to the allogeneic graft-versus-tumor effect directed against histocompatibility antigens. However, replacing exhausted immune systems with healthy non-exhausted, non-tolerant ones likely can enhance the activity of novel targeted therapies. The impressive results seen with tyrosine kinase inhibitors after alloBMT for patients with both Ph+ acute lymphoblastic leukemia and FLT/ITD+ acute myeloid leukemia herald the potential of precision BMT., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

High dose Post transplant cyclophosphamide (PTCy) is now regarded as a very effective way of preventing acute and chronic GvHD, and it's use has rapidly expanded world-wide., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The current COVID-19 pandemic has placed unprecedented stress on the healthcare system, including HSCT. Several international organizations have created guidelines for managing different aspects of HSCT in the context of the pandemic. Comparing 2019 and 2020, our transplant center performed the same number of transplants. In both periods, transplants were mainly for patients with acute leukemia; thus, the urgency criteria was respected in light of pandemic restraints. Transplants by sibling donors and cord blood units remained the same, while transplants by unrelated donors were increased, in particular from European registries, and transplants by haploidentical donors were decreased. This change was made in light of the necessity of cryopreserving all apheresis products. We decided against cryopreserving bone marrow products due to the greater risk of drastic reduction in CD34 + cell count during the process. For urgent cases with only a haploidentical donor available, we opted for the use of PBSC following stimulation with G-CSF. GvHD prophylaxis was performed with PTCY on days + 3 + 5, cyclosporine with tapering from day + 100, and mycophenolic acid until day + 90 post-HSCT. Post-transplant outcomes such as graft failure, sepsis, and GVHD were not affected by the changes implemented. As a result of logistic difficulties, we halted our Car-T program from the start of the lockdown in March 2020 until September 2020. In accord with international guidelines, we were able to continue our HSCT program in the order to ensure a lifesaving treatment for patients with hematologic diseases for whom this procedure cannot be postponed., (Copyright © 2023. Published by Elsevier Ltd.)

Allogeneic peripheral blood stem cells mobilization is now the basis of most stem cell transplants. In a very limited number of cases, mobilization is suboptimal leading to further collection procedures, to suboptimal cell doses infusion with delayed engraftment time, increased risks of transplant procedure and of related costs. To date we have no recognized and shared criteria for early estimating the probability of poor mobilization in healthy donors. We then analyzed allogeneic peripheral blood stem cell donations performed at the Fondazione Policlinico Universitario A.Gemelli IRCCS Hospital from January 2013 to December 2021 in order to identify premobilization factors associated with successful mobilization. The following data were collected: age, gender, weight, complete blood cell count at baseline, G-CSF dose, number of collection procedures, CD34+ cell count in peripheral blood on the first day of collection, CD34+ cell dose per kg body weight of recipient. Mobilization efficacy was defined according to the number of CD34+ cells in peripheral blood on day +5 of G-CSF administration. We classified donors as sub-optimal mobilizers or good mobilizers according to the achievement of the 50 CD34+ cell/μL threshold. We observed 30 suboptimal mobilizations in 158 allogeneic peripheral blood stem cell donations. Age and baseline white blood cell count were factors significantly associated with negative or positive impact on mobilization, respectively. We did not find significant differences in mobilization based on gender or G-CSF dose. Using cut-off values of 43 years and 5.5×10 9 /L WBC count, we built a suboptimal mobilization score: donors who reach 2, 1 or 0 points have a 46%, 16% or 4% probability of suboptimal mobilization, respectively. Our model explains 26% of the variability of mobilization confirming that most of the mobilization magnitude depends on genetically determined factors; however, suboptimal mobilization score is a simple tool providing an early assessment of mobilization efficacy before G-CSF administration begins in order to support allogeneic stem cells selection, mobilization and collection. Through a systematic review, we looked for confirmation of our findings. According to the published articles, all the variables we included in our model are confirmed to be strongly related to the success of mobilization. We believe that score system approach could be applied in clinical practice to assess the risk of mobilization failure at baseline allowing for a priori intervention., Competing Interests: Declaration of Competing Interest The authors declare no competing interests related to this manuscript., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cytokine release syndrome (CRS) and consumptive coagulopathy can complicate the treatment with chimeric antigen receptor T (CAR-T) cells. The modified version of the Endothelial Activation and Stress Index (mEASIX), a score derived from haematopoietic stem cell transplantation, combines platelets, C-reactive protein (CRP), and lactate dehydrogenase (LDH) and has been correlated with CRS and endothelial biomarkers. In 38 consecutive patients with aggressive lymphoproliferative disease we measured a coagulative laboratory panel at baseline and early after infusion of anti-CD19 CAR-T. The panel was investigated also in the presence of CRS graded 2 or higher, or immune effector cell-associated neurotoxicity syndrome (ICANS). Moreover, we examined the relationship between mEASIX, coagulation biomarkers, and toxicities of CAR-T cells. During CRS grade 2 or higher, we found increased prothrombin time (PT) and activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, factor VIII (FVIII), and von Willebrand factor (vWF) antigen levels, and decreased platelet count and antithrombin levels. The occurrence of immune effector cell-associated neurotoxicity syndrome was associated with higher PT values, D-dimer, FVIII, and vWF levels, and decreased fibrinogen levels and platelet count. A higher mEASIX score correlated with increased aPTT values, fibrinogen, D-dimer, FVIII and vWF levels, and decreased antithrombin levels. Baseline mEASIX was predictive for consumptive coagulopathy and CRS graded 2 or higher, and for progression-free survival and overall survival., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Competing Interests: Competing interests: The authors declare no conflict of Interest.

Purpose: Depressive disorders are the most common manifestation of psychological distress in allogenic hematopoietic stem cell transplantation. Few studies have yet investigated the relationship between therapeutic educational interventions and outcomes in these patients with specific attention to those related to mental health. Aim of this study was to understand how much educational intervention can represent a protective factor in preventing psycho-emotional distress-related issues in this setting., Design: A prospective observational study of a multicenter cohort was conducted., Participants: Adult patients undergoing allogeneic hematopoietic stem cell transplantation., Methods: A pre-transplant therapeutic educational programme was offered to a cohort of adult patients undergoing allo-HSCT recruited in ten transplant centers of the GITMO network between May 2018 and January 2019. Depression, Anxiety and Stress scale was used to collect data on psycho-emotional distress at admission (T0), at the day of transplant (T1) and at discharge (T2). Descriptive data were collected and reported, and comparative analyses were done among patients who were compliant with the pre-transplant educational intervention and those who did not (for any reason)., Findings: A cohort of 133 allo-HSCT patients was observed. In patients who did not receive pre-transplant educational intervention, higher levels of depression at admission (p = 0.01) and at the day of transplant (p = 0.03), higher levels of anxiety (p = 0.01 and p = 0.01 respectively) as well as higher levels of stress (p < 0.01 and p = 0.01) were observed. Problem solving and "face to face" interview were the best methods to provide education to patients. Those who received pre-transplant education through "face-to-face" interview reported significant low levels of depression during the whole hospital stay period (p < 0.01; p = 0.01; p = 0.01) and less anxiety and stress at admission (p < 0.05 and p = 0.01 respectively). Depression was more represented in female than male participants at T0 (16.5% vs 9.0%; p = 0.01), while among T0 and T2 the males had a significant higher increasing of depression than females (p = 0.03)., Conclusion: Our study demonstrated that pretreatment therapeutic educational programs with specific learning modalities can be effective in limiting the potential risk of developing moderate-to-severe anxiety-depressive states and stress symptoms related to allo-HSCT., Implications for Psychosocial Providers: Further studies are needed to confirm our results and to understand whether containing psycho-emotional distress can have any relationship with medium- and long-term post-transplant complications.

Haploidentical stem cell transplantation is a viable strategy in the absence of an HLA-identical donor, but in myelofibrosis (MF), concerns may rise due to the risk of graft failure. Considering that engraftment is a major issue in MF, we sought to highlight its impact on survival outcomes. In addition, we explored the impact of pretransplantation ruxolitinib administration as an independent variable on outcomes. Here we report the results of a retrospective, monocentric experience with T cell-replete haploidentical bone marrow transplantation with post-transplantation cyclophosphamide as graft-versus-host disease (GVHD) prophylaxis in 51 consecutive MF-affected patients. The median duration of follow-up was 47 months. All 51 patients received a double-alkylating conditioning regimen, and 21 patients (41%) received pretransplantation ruxolitinib. Thirty-seven of 49 evaluable patients (76%) achieved full donor chimerism with neutrophil engraftment, 8 of 49 (16%) experienced graft rejection, and 4 of 49 (8%) had primary poor graft function. Splenectomy was more frequent among patients who engrafted (P = .06). Graft rejection was the sole factor negatively impacting overall survival (hazard ratio [HR], 4.19; 95% confidence interval [CI], 1.37 to 12.80; P = .01) and the major determinant for nonrelapse mortality (HR, 10.31; 95% CI, 2.54 to 41.82; P = .001). The 24-month incidence of relapse was 19% and was negatively impacted by splenectomy (HR, 5.84; 95% CI, 1.28 to 26.72; P = .02). The cumulative incidence of grade II-IV acute GVHD was 27% (95% CI, 20% to 33%), and that of grade III-IV acute GVHD was 8% (95% CI, 4% to 12%). The 24-month cumulative incidence of all-grade chronic GVHD was 28% (95% CI, 21% to 35%). Our data show that T cell-replete haploidentical bone marrow transplantation following double-alkylating conditioning in patients with MF is associated with favorable rates of GVHD and an acceptable relapse risk; nevertheless, rejection is not negligible and is associated with significant mortality. Splenectomy, which favors engraftment, is predictive of a higher risk of relapse., Competing Interests: Conflict of interest statement: There are no conflicts of interest to report Authorship statement: M.G. and S.B. contributed equally to this work., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: In the last decade, many steps forward have been made in acute myeloid leukemia prognostic stratification, adding next-generation sequencing techniques to the conventional molecular assays. This resulted in the revision of the current risk classification and the introduction of new target therapies., Aims and Methods: We wanted to evaluate the prognostic impact of acute myeloid leukemia (AML) mutational pattern on relapse occurrence and survival after allogeneic stem cell transplantation. A specific next-generation sequencing (NGS) panel containing 26 genes was designed for the study. Ninety-six patients studied with NGS at diagnosis were included and retrospectively studied for post-transplant outcomes., Results: Only eight patients did not show any mutations. Multivariate Cox regression revealed FLT3 (HR, 3.36; p=0.02), NRAS (HR, 4.78; p=0.01), TP53 (HR, 4.34; p=0.03), and WT1 (HR 5.97; p=0.005) mutations as predictive variables for relapse occurrence after transplantation. Other independent variables for relapse recurrence were donor age (HR, 0.97; p=0.04), the presence of an adverse cytogenetic risk at diagnosis (HR, 3.03; p=0.04), and the obtainment of complete remission of the disease before transplantation (HR, 0.23; p=0.001). Overall survival appeared to be affected only by grade 2-4 acute GvHD occurrence (HR, 2.29; p=0.05) and relapse occurrence (HR, 4.33; p=0.0001) in multivariate analysis., Conclusions: The small number of patients and the retrospective design of the study might affect the resonance of our data. Although results on TP53, FLT3, and WT1 were comparable to previous reports, the interesting data on NRAS deserve attention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Metafuni, Amato, Giammarco, Bellesi, Rossi, Minnella, Frioni, Limongiello, Pagano, Bacigalupo, Sica and Chiusolo.)

Donor selection may contribute to improve clinical outcomes of T cell-replete haploidentical stem cell transplantation (Haplo-SCT) with post-transplant cyclophosphamide (PT-Cy). Impact of second-degree related donor (SRD) was not fully elucidated in this platform. We retrospectively compared the outcome of patients receiving Haplo-SCT either from a SRD (n = 31) or a first-degree related donor (FRD, n = 957). Median time to neutrophil and platelet recovery did not differ between a SRD and a FRD transplant (p = 0.599 and 0.587). Cumulative incidence of grade II-IV acute graft-versus host disease (GVHD) and moderate-severe chronic GVHD was 13% and 19% after SRD vs 24% (p = 0.126) and 13% (p = 0.395) after FRD transplant. One-year cumulative incidence of non-relapse mortality (NRM) was 19% for SRD and 20% for FRD (p = 0.435) cohort. The 3-year probability of overall survival (OS) and progression-free survival (PFS) was 42% vs 55% (p = 0.273) and 49% vs 35% (p = 0.280) after SRD and FRD transplant, respectively. After propensity score adjustment or matched pair analysis, the outcome of patients receiving Haplo-SCT from a SRD or a FRD did not differ in terms of NRM, OS, PFS, acute and chronic GVHD. Our results suggest that a SRD is a viable option for Haplo-SCT with PT-Cy when a FRD is not available., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

This paper formalizes smooth curve coloring (i.e., curve identification) in the presence of curve intersections as an optimization problem, and investigates theoretically properties of its optimal solution. Moreover, it presents a novel automatic technique for solving such a problem. Formally, the proposed algorithm aims at minimizing the summation of the total variations over a given interval of the first derivatives of all the labeled curves, written as functions of a scalar parameter. The algorithm is based on a first-order finite difference approximation of the curves and a sequence of prediction/correction steps. At each step, the predicted points are attributed to the subsequently observed points of the curves by solving an Euclidean bipartite matching subproblem. A comparison with a more computationally expensive dynamic programming technique is presented. The proposed algorithm is applied with success to elastic periodic metamaterials for the realization of high-performance mechanical metafilters. Its output is shown to be in excellent agreement with desirable smoothness and periodicity properties of the metafilter dispersion curves. Possible developments, including those based on machine-learning techniques, are pointed out., (© 2022. The Author(s).)

The aim of this study was to evaluate the role of WT1 expression after allogeneic stem cell transplantation (alloHSCT) in patients with acute myeloid leukemia (AML). We studied WT1 expression in bone marrow cells from 50 patients in complete remission on day +60 after transplant. WT1 was assessed on unfractionated bone marrow mononuclear cells (MNC) and on CD34+ selected cells (CD34+). A ROC curve analysis identified 800 WT1 copies on CD34+ selected cells, as the best cut-off predicting relapse (AUC 0.842, p=0.0006, 85.7% sensitivity and 81.6% specificity) and 100 copies in MNC (AUC 0.819, p=0.007, 83.3% sensitivity and 88.2% specificity). Using the 800 WT1 copy cut off in CD34+ cells, the 2 year cumulative incidence of relapse was 12% vs 38% (p=0.005), and 2 year survival 88% vs 55% (p=0.02). Using the 100 WT1 copy cut off in unfractionated MNC, the 2 year cumulative incidence of relapse 13% vs 44% (p=0.01) and the 2 year survival 88% vs 55% (p=0.08). In a multivariate Cox analysis WT1 expression in CD34 cells proved to highly predictive of relapse (p=0.004); also WT1 expression on unfractionated cells predicted relapse (p=0.03). In conclusion, day-60 WT1 expression after allogeneic HSCT is a significant predictor of relapse, particularly when tested on CD34+ selected bone marrow cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chiusolo, Metafuni, Minnella, Giammarco, Bellesi, Rossi, Sorà, Limongiello, Frioni, Piccirillo, Bianchi, Valentini, Teofili, Sica and Bacigalupo.)

Although the effects of malnutrition on morbidity and mortality in adult patients undergoing allogeneic hematopoietic stem cell transplantation are clear, the relationship with quality of life (QOL) is less clear. The purpose of this study was to assess the relationship between malnutrition and QOL. A prospective observational study was conducted in 36 adult patients undergoing allogeneic hematopoietic stem cell transplantation. Adapted criteria of the Global Leadership Initiative on malnutrition have been used for the diagnosis of malnutrition in clinical settings. A cancer linear analog scale was used to assess QOL. Overall QOL at 14 days after allogeneic hematopoietic stem cell transplantation was 37.1 (95% CI 2.9-45.39) in patients without severe malnutrition, versus 16.0 (95% CI - 6.6 to 38.6) in patients with severe malnutrition (p = 0.05). At discharge, it was 48.0 (95% CI 38.4-57.6) versus 34.0 (95% CI 4.1-63.9) (p = 0.27). The results of our study suggest that patients with severe malnutrition at discharge tend to have worse QOL. A larger cohort of patients is required to confirm this hypothesis., (© 2022. The Author(s).)

Purpose: Hemorrhagic cystitis (HC) is a frequent complication of allogeneic hematopoietic stem-cell transplantation (HSCT). HC worsens transplant outcomes and patient wellbeing in terms of pain, hospitalization, and need for supportive care. A deeper understanding of the risk factors of HC may lead to more intensive prevention in high-risk patients., Methods: In this report, we analyzed 237 consecutive patients who received HSCT with the aim of identifying possible risk factors for HC and their consequences, with a particular focus on transplant- and gender-related risk factors., Results: HC occurred in 17% of patients, with a higher incidence in males (21% vs 11%, p = 0.03). Risk factors identified for HC included age over 55 years, male recipient, HLA mismatch, reduced intensity conditioning, and cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis. Increased HC was seen in patients with grade II-IV acute GVHD and detectable BKV and JCV viruria. In a multivariate model, increased age remained significant (p = 0.013). Patients with HC had longer hospitalizations and increased non-relapse mortality (NRM). Among male recipients, independent risk factors for HC included age (p = 0.016) and prostate volume (p = 0.016). Prostatic hyperplasia (volume more than 40 cm 3 ) occurred in 33% of male patients, of which 32% developed HC (compared with 16% of patients without prostatic hyperplasia; p = 0.032)., Conclusions: Age is the most important risk factor for HC. Additional potential risk factors include cyclophosphamide-based GVHD prophylaxis and HLA mismatch. Among male recipients, prostatic hyperplasia is an additional independent risk factor. As HC is common and associated with prolonged hospitalization, more intensive prophylactic strategies should be considered in high-risk patients., (© 2022. The Author(s).)

The goal of therapy for patients with essential thrombocythemia (ET) and polycythemia vera (PV) is to reduce thrombotic events by normalizing blood counts. Hydroxyurea (HU) and interferon-α (IFN-α) are the most frequently used cytoreductive options for patients with ET and PV at high risk for vascular complications. Myeloproliferative Disorders Research Consortium 112 was an investigator-initiated, phase 3 trial comparing HU to pegylated IFN-α (PEG) in treatment-naïve, high-risk patients with ET/PV. The primary endpoint was complete response (CR) rate at 12 months. A total of 168 patients were treated for a median of 81.0 weeks. CR for HU was 37% and 35% for PEG (P = .80) at 12 months. At 24 to 36 months, CR was 20% to 17% for HU and 29% to 33% for PEG. PEG led to a greater reduction in JAK2V617F at 24 months, but histopathologic responses were more frequent with HU. Thrombotic events and disease progression were infrequent in both arms, whereas grade 3/4 adverse events were more frequent with PEG (46% vs 28%). At 12 months of treatment, there was no significant difference in CR rates between HU and PEG. This study indicates that PEG and HU are both effective treatments for PV and ET. With longer treatment, PEG was more effective in normalizing blood counts and reducing driver mutation burden, whereas HU produced more histopathologic responses. Despite these differences, both agents did not differ in limiting thrombotic events and disease progression in high-risk patients with ET/PV. This trial was registered at www.clinicaltrials.gov as #NCT01259856., (© 2022 by The American Society of Hematology.)

The aim of this study was to develop a predictive score for moderate-severe chronic graft-versus-host disease (cGVHD) on day +100 after allogeneic stem cell transplantation (HSCT). We studied 1292 patients allografted between 1990 and 2016, alive on day +100 after transplant, without cGVHD, and with full biochemistry laboratory values available. Patients were randomly assigned to a training and a validation cohort (ratio 1:1). In the training cohort, a multivariate analysis identified 4 independent predictors of moderate-severe cGVHD: gamma-glutamyl transferase ≥75 UI/l, creatinine ≥1 mg/dl, cholinesterase ≤4576 UI/l, and albumin ≤4 g/dl. A score of 1 was assigned to each variable, producing a low (0 to 1), intermediate (2 to 3), and high (4) score. The cumulative incidence of moderate-severe cGVHD was 12%, 20%, and 52% (P < .0001) in the training cohort, and 13%, 24%, and 33% (P = .002) in the validation cohort, respectively. The 5-year cumulative incidence of transplant-related mortality (TRM) was 5%, 14%, 27% (P < .0001) and 5%, 16%, 31% (P < .0001), respectively. The 5-year survival was 64%, 57%, 54% (P = .009) and 70%, 59%, 42% (P = .0008) in the 2 cohorts, respectively. In conclusion, Day100 score predicts cGVHD, TRM, and survival and, if validated in a separate group of patients, could be considered for trials of preemptive therapy., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

We report a retrospective analysis of 198 allogeneic hematopoietic stem cell transplant (HSCT) recipients with post-transplant cyclophosphamide (PTCY), cyclosporine and mycophenolate mophetil as graft-versus-host-disease (GVHD) prophylaxis: the donors were HLA-matched (n = 78), or haploidentical relatives (HAPLO) (n = 120). The two groups were comparable except for older age in the HAPLO group. The main diagnosis were acute leukemia (57%) and myelofibrosis (21%). In the HLA-matched and HAPLO group the outcomes were as follows: aGVHD grade II-IV, 10% vs 27% (p = 0.005); moderate-severe cGVHD, 4% vs 19% (p = 0.004); transplant related mortality (TRM) at 1 year 10% vs 21% (p = 0.04); relapse at 1 year 24% vs 10% (p = 0.051) respectively. Disease free survival (DFS) at 1 year was 65% for matched and 68% for HAPLOs (p = 0.85). DFS and OS were independently predicted by age over 60 and higher DRI, whether the only independent predictive variable for GVHD and relapse free survival (GRFS) was age over 60. In conclusion: given the same PTCY based, GVHD prophylaxis, HLA-mismatched grafts are exposed to a higher risk of acute and chronic GVHD. This translates in increased TRM. DFS is comparable for HLA matched and HAPLO grafts., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Abstract: In allogeneic hematopoietic stem cell transplantation (AHSCT), falls can lead to immediate and late consequences and in some cases to death. We analyzed risks and causes of falls with root cause analysis (RCA) based on which improvement interventions were implemented.A retrospective observational study was conducted to analyze with RCA data of incidence reports and medical records of patients admitted; an expert panel identified actions to prevent falls, which were collected in a checklist.Between December 2017 and November 2019, 214 patients were admitted to ordinary hospital stays for AHSCT or AHSCTrelated complications. In this period, 15 falls, involving 11 patients, occurred resulting in a 2.32 d/patient incidence. In 66.67% of cases minor head trauma occurred. Diuretic drugs (93.33%), induced hyper-diuresis in nonbladder catheter patients (93.33%) and antihypertensive drugs (93.33%) were reported as most common cause in our incident reports. The most frequent fall time slot was between 10 PM and 7 AM (60%). We determined with RCA diuretics and consequent induced hyper-diuresis (80%), self-insufficiency (40%), antihypertensive (33.3%) and noncompliance (33.3%) as the most common cause of falls. Finally, 16 actions, collected in a "safe comfort" checklist, were identified to prevent falls.Diuretic drugs inducing hyper-diuresis, self-insufficiency, poor patient compliance, orthostatic hypotension, fever, night-time and obstacles within inpatient units are the most common contributing factors. Therefore, administration of diuretic and antihypertensive drugs should be rescheduled and a multidimensional risk assessment scale integrated with a preventive action plan, such as the safe comfort checklist, should be implemented to reduce falls., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Idiopathic aplastic anemia is a rare and life-threatening disorder, and hematopoietic stem cell transplantation (HSCT) from a matched sibling donor (MSD) is the standard treatment strategy for young patients. Alternative donor transplantation (ADT) from a matched unrelated donor or an HLA haploidentical donor is not commonly used in the frontline setting. This systematic review/meta-analysis was conducted to compare ADT as an upfront, rather than delayed, treatment strategy in the absence of an MSD to immunosuppressive therapy (IST) in severe aplastic anemia (SAA). We searched PubMed/MEDLINE and Embase (1998 to 2019) for studies that compared the outcomes of ADT with IST as upfront therapy in patients with SAA. We included studies with 5 patients or more in each arm. Studies that included patients with inherited forms of bone marrow failure syndromes were excluded. The primary outcome was the 5-year overall survival (OS) rate. Five studies met the inclusion criteria and were included in this meta-analysis. The pooled 5-year odds ratio (OR) for OS was statistically significant at 0.44 (95% confidence interval [CI], 0.23 to 0.85) in favor of upfront ADT. In addition, survival was compared between upfront ADT versus salvage ADT in 6 studies. The pooled 5-year OR for OS was statistically significant at 0.31 (95% CI, 0.15 to 0.64) in favor of upfront ADT. Although this analysis has some limitations, including the retrospective nature of the included studies, the lack of ethnic diversity, the predominantly pediatric population, and the relatively suboptimal IST regimen used in some of the studies, it indicates that upfront ADT is a potential alternative treatment option in young and pediatric SAA patients who lack an HLA identical sibling donor, particularly when optimal IST is not available. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Classification of myeloproliferative neoplasms is based on hematologic, histopathologic, and molecular characteristics, including the BCR-ABL1 and JAK2 V617F or MPL and CALR. Although the different gene mutations ought to be mutually exclusive, several cases with co-occurring BCR-ABL1 and JAK2 V617F or CALR have been identified with a frequency of 0.2-2.5% in the European population. The tyrosine kinase abnormalities appeared to affect independent subclones because imatinib mesylate (IM) treatment induced Ph+-CML remission, whereas the JAK2V617F clone either persisted or clinically expanded after a major response of Ph+-clone. Allogeneic stem cell transplantation is at present the only potentially curative therapy for these patients after therapy with ruxolitinib and TKI inhibitor. We describe the case of 3 young people treated in our institution for the coexistence of BCR/ABL chronic myeloid leukemia and another Philadelphia chromosome-negative (Ph-) Chronic myeloproliferative disease. They received ruxolitinib, imatinib/nilotinib, and allogeneic transplantation with safe and efficient results., Competing Interests: Competing interests: The authors declare no conflict of Interest.

The number of patients with myelofibrosis (MF) undergoing an allogeneic hemopoietic stem cell transplantation (HSCT) is increasing: in the analysis of the European Group for Blood and Marrow Transplantation (EBMT) the number of MF has increased from 515 in 2014 to 748 in 2018 . This reflects the fact that HSCT is currently the only curative treatment, capable of inducing prolonged disease-free survival. Nevertheless, several problems prevent more patients from undergoing an allogeneic HSCT: we will be discussing indications for HSCT, comorbidities, splenomegaly, older age and disease phase. Donor type and stem cell source are less of a problem. Several transplant platforms exist, including different strategies for graft versus host disease (GvHD) prophylaxis, Age tailored conditioning regimens need to be implemented, to allow older and fragile patients to undergo an allogeneic HSCT., (© 2021 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

We studied pretransplant minimal residual disease (MRD) in 224 patients (median age 44 years; range 17-65) with acute myeloid leukemia (AML) undergoing allogeneic stem cell transplant (HSCT) in complete remission. MRD was evaluated on marrow samples using multicolor flow cytometry and assessment of WT1 gene expression. Both methods showed a strong prognostic value and their combination allowed the identification of three groups of patients with different risk of relapse. In multivariate analysis, combined MRD was the only predictor of cumulative incidence of relapse, regardless of donor type, conditioning regimen, first or second CR at HSCT, HSCT year, and ELN risk group. Multivariate regression model showed that only negative combined MRD status (P < .001) and myeloablative conditioning (P = .004) were independently associated with better OS. Among MRD-positive patients, a reduced incidence of relapse was observed in patients receiving haplo transplant (P < .05) and in patients who showed grade II-IV aGVHD (P < .03). In patients with negative combined MRD, the intensity of conditioning regimen did not affect the overall favorable outcome. We suggest that pretransplant MRD evaluation combined with transplant-related factors can identify AML patients at higher risk for relapse and might help in defining the overall transplant strategy., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aplastic anemia is a relatively rare but potentially fatal disorder, with a reported higher incidence in developing countries in comparison to the West. There are significant variations in epidemiological as well as etiological factors of bone marrow failure syndromes in the developing countries in comparison to the developed world. Furthermore, the management of bone marrow failure syndromes in resource constraint settings has significant challenges including delayed diagnosis and referral, limited accessibility to healthcare facilities, treatment modalities as well as limitations related to patients who require allogeneic stem cell transplantation. Here we will provide a review of the available evidence related to specific issues of aplastic anemia in the developing countries and we summarize suggested recommendations from the Eastern Mediterranean blood and bone marrow transplantation (EMBMT) group and the severe aplastic anemia working party of the European Society of blood and marrow transplantation (SAAWP of EBMT) related to the diagnosis and therapeutic options in countries with restricted resources., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Competing Interests: Competing interests: The authors declare no conflict of Interest.

This retrospective study assessed the effectiveness of eltrombopag (EPAG), a thrombopoietin receptor agonist, in the treatment of poor graft function (PGF) following an allogeneic haemopoietic stem cell transplantation (HSCT). Complete response was defined as normalization of blood counts, whereas partial response was defined as transfusion independence. A total of 48 patients with full donor chimerism after HSCT, received EPAG for a median of 120 days (range 10-591). Patients with uni- bi- or tri-lineage cytopenia started treatment at a median of 95 days (range 17-877) after HSCT. The overall response rate was 75%: 24 patients had a complete response and 12 had a partial response. Positive predictors of response were an HLA-matched donor, a CD34 + dose at transplant > 4 × 10 6 /kg, and starting EPAG treatment at least 90 days after HSCT. Patients with more than one positive predictor had a response rate of 92% for the overall patient cohort and 94% for patients with tri-lineage cytopenia. One-year survival was 89% for complete responders, 60% for partial responders and 20% for non-responders (p = 0.0004). EPAG improves peripheral blood counts in patients with poor graft function following HSCT. Response to EPAG can be predicted and has a significant impact on survival., (© 2021. Japanese Society of Hematology.)