Host space, not energy or symbiont size, constrains feather mite abundance across passerine bird species.

Comprehending symbiont abundance among host species is a major ecological endeavour, and the metabolic theory of ecology has been proposed to understand what constrains symbiont populations. We parameterized metabolic theory equations to investigate how bird species' body size and the body size of their feather mites relate to mite abundance according to four potential energy (uropygial gland size) and space constraints (wing area, total length of barbs and number of feather barbs). Predictions were compared with the empirical scaling of feather mite abundance across 106 passerine bird species (26,604 individual birds sampled), using phylogenetic modelling and quantile regression. Feather mite abundance was strongly constrained by host space (number of feather barbs) but not by energy. Moreover, feather mite species' body size was unrelated to the body size of their host species. We discuss the implications of our results for our understanding of the bird-feather mite system and for symbiont abundance in general.

Influence of physical fitness and weight status on autonomic cardiac modulation in children.

BACKGROUND: This study provides reference values for cardiovascular modulation at rest, during maximal exercise test and recovery after exercise in Caucasian children according to weight status and cardiorespiratory fitness (CRF) level. Additionally, the current study analyzed several correlations between autonomic cardiovascular modulation, cardiorespiratory performance and cardiometabolic risk. The principal goal of this study was to analyze cardiac function at rest, during maximum exercise, and during the recovery phase in children grouped according to weight status and CRF level. METHODS: One hundred and fifty-two healthy children (78 girls) 10-16 years of age were divided into three groups: soccer and basketball players (SBG), endurance group (EG), and sedentary people with overweight and obesity (OOG). A cardiac RR interval monitor recorded the cardiac data and specific software analyzed the cardiac autonomic response through heart rate (HR) and HR variability. The study analyzed resting HR (RHR), HRpeak, and HR recovery (HRR). RESULTS: OOG showed significant poorer performance in the Léger test lower V̇O2 max and higher values of blood pressure at rest and post-exercise than sport groups. The EG presented the best results in CRF and cardiometabolic risk (CMR) in relation to SBG and OOG. The OOG showed higher percentage of HR values, compatible with an unhealthy cardiovascular autonomic modulation than the sport groups, with significant differences in bradycardia, HR reserve, and HRR 5 min. CONCLUSIONS: Aerobic performance, vagal activity, blood pressure, chronotropic competence, and HRR have significant associations with CMR parameters. IMPACT: The current study presents reference values of autonomic cardiac function in Caucasian children according to weight status and cardiorespiratory fitness level. Aerobic performance, vagal activity, blood pressure, chronotropic competence, and heart rate during the recovery period after exercise have significant associations with cardiometabolic risk parameters. Children with overweight and obesity show signs of autonomic dysfunction reflected as low cardiac vagal activity and poor chronotropic competence.

Removal of NO at low concentrations from polluted air in semi-closed environments by activated biochars from renewables feedstocks.

Efficient measures are urgently required in large cities for nitric oxide (NO) elimination from air in urban semi-closed environments (parking lots and tunnels), characterized by low NO concentrations (<10 ppmv) and temperatures. One of the most promising abatement alternatives is the NO oxidation to NO2, which can be further easily captured in an alkali solution or over a porous solid. However, most of the research devoted to this topic is focused on the elimination of NO from fuel exhaust gases, with high NO concentrations (400-2000 ppmv). In this work, sustainable and low-cost activated biochars of different origin and having very different ash contents were employed in NO removal at very low concentrations. Thus, low ash content forestry (oak woodchips, OAK) and high ash content from agriculture (oilseed rape straw, OSR) biochars were subjected to physical activation with CO2 at 900 °C (OAK550-A900CO2 and OSR700-A900CO2, respectively). The NO removal performance tests of such activated carbons were carried out at different experimental conditions: i.e., temperature, relative humidity (0-50 vol% RH), NO-containing gas (N2 or air), amount of activated carbon, and NO concentration, to assess how the activated biochar properties influence their NO removal capacity. The sample OSR700-A900CO2 contained a higher population of oxygen surface functionalities, which might play an important role in the NO removal efficiency in dry conditions since they could assist NO oxidation on carbon active sites when used above room temperature (50-75 °C). However, at room temperature (25 °C), the presence of narrow micropore size distribution at 6 Å became a more relevant property, since it facilitates an intimate contact between NO and O2. Accordingly, the activated biochar from OAK was much more efficient, achieving complete removal of NO from air flow (dry or with 50 vol% RH) at 25 °C during 400 min of testing, making it an ideal candidate as biofilter for purifying air streams of semi-closed spaces contaminated with low concentrations of NO.

Removal of NO at low concentration from air in urban built environments by activated miscanthus biochar.

This work presents an innovative and sustainable approach to remove NO emissions from urban ambient air in confined areas (underground parking areas or tunnels) using low-cost activated carbons obtained from Miscanthus biochar (MSP700) by physical activation (with CO2 or steam) at temperatures ranging from 800 to 900 °C. The NO removal capacity of the activated biochars was evaluated under different conditions (temperature, humidity and oxygen concentration) and compared against a commercial activated carbon. This last material showed a clear dependence on oxygen concentration and temperature, exhibiting a maximum capacity of 72.6% in air at 20 °C, whilst, its capacity notably decreased at higher temperatures, revealing that physical NO adsorption is the limiting step for the commercial sample that presents limited oxygen surface functionalities. In contrast, MSP700-activated biochars reached nearly complete NO removal (99.9%) at all tested temperatures in air ambient. Those MSP700-derived carbons only required low oxygen concentration (4 vol%) in the gas stream to achieve the full NO removal at 20 °C. Moreover, they also showed an excellent performance in the presence of H2O, reaching NO removal higher than 96%. This remarkable activity results from the abundance of basic oxygenated surface groups, which act as active sites for NO/O2 adsorption, along with the presence of a homogeneous microporosity of 6 Å, which enables intimate contact between NO and O2. These features promote the oxidation of NO to NO2, which is further retained over the carbon surface. Therefore, the activated biochars studied here could be considered promising materials for the efficient removal of NO at low concentrations from air at moderate temperatures, thus closely approaching real-life conditions in confined spaces.

Monitoring detailed mangrove hurricane damage and early recovery using multisource remote sensing data.

Due to their location in tropical latitudes, mangrove forests are susceptible to the impact of hurricanes and can be vastly damaged by their high-speed winds. Given the logistic difficulties regarding field surveys in mangroves, remote sensing approaches have been considered a reliable alternative. We quantified trends in damage and early signs of canopy recovery in a fringe Rhizophora mangle area of Marismas Nacionales, Mexico, following the landfall of Hurricane Willa in October 2018. We monitored (2016-2021) broad canopy defoliation using 21 vegetation indices (VI) from the Google Earth Engine tool (GEE). We also mapped a detailed canopy fragmentation and developed digital surface models (DSM) during five study periods (2018-2021) with a consumer-grade unmanned aerial vehicle (UAV) over an area of 100 ha. Based on optical data from the GEE time series, results indicated an abrupt decline in the overall mangrove canopy. The VARI index was the most reliable VI for the mangrove canopy classification from a standard RGB sensor. The impact of the hurricane caused an overall canopy defoliation of 79%. The series of UAV orthomosaics indicate a gradual recovery in the mangrove canopy, while the linear model predicts at least 8.5 years to reach pre-impact mangrove cover conditions. However, the sequence of DSM estimates that the vertical canopy configuration will require a longer time to achieve its original structure.

Quantitative Interspecific Approach to the Stylosphere: Patterns of Bacteria and Fungi Abundance on Passerine Bird Feathers.

Feathers are the habitat of a myriad of organisms, from fungi and bacteria to lice and mites. Although most studies focus on specific taxa and their interaction with the bird host, anecdotal data glimpse feathers as holders of a system with its own ecology, what we call here the stylosphere. A major gap in our knowledge of the stylosphere is the ecology of the total abundance of microorganisms, being also rare to find studies that analyze abundance of more than one group of microorganisms at the bird interspecific level. Here, we quantified bacterial and fungi abundances through qPCR on the wing feathers of 144 birds from 24 passerine and one non-passerine bird species from three localities in Southern Spain. Bacteria and fungi abundances spanned three orders of magnitude among individual birds, but were consistent when comparing the right and the left wing feathers of individuals. Sampling locality explained ca. 14% of the variation in both bacteria and fungi abundances. Even when statistically controlling for sampling locality, microbial abundances consistently differed between birds from different species, but these differences were not explained by bird phylogeny. Finally, bird individuals and species having more bacteria also tended to held larger abundances of fungi. Our results suggest a quite complex explanation for stylosphere microorganisms' abundance, being shaped by bird individual and species traits, as well as environmental factors, and likely bacteria-fungi interactions.

An investigation of the utility of plasma Cytomegalovirus (CMV) microRNA detection to predict CMV DNAemia in allogeneic hematopoietic stem cell transplant recipients.

Precise identification of patients at highest risk for developing Cytomegalovirus (CMV) DNAemia may improve CMV infection management in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) setting. Here, we studied the potential use of detecting free CMV micro(mi)RNAs circulating in plasma for predicting CMV DNAemia in this clinical scenario. A total of 62 adult allo-HSCT recipients were included in this prospective observational multicenter study. Plasma CMV DNA load was monitored using the CMV RealTime CMV PCR (Abbott Molecular, Des Plaines, IL, USA). Detection of mature CMV miRNAs in plasma drawn by days + 7, + 14 and + 30 after allo-HSCT was performed using the miScript PCR System (Qiagen, Hilden, Germany). Assays could be optimized for five out of the seven targeted CMV miRNAs: UL36-5p, US33-5p, UL148D, UL22A-5p and UL112-3p. Of the 62 patients included in the study, 42 developed a first episode of CMV DNAemia at a median of 35 days after allo-HSCT. All targeted CMV miRNA were detected early after transplantation, with CMV miRNA US33-5p and UL112-3p the most commonly found species at any time point; nevertheless, neither the detection rate of CMV miRNAs nor their abundance allowed discrimination between patients with subsequent CMV DNAemia and those with no CMV DNAemia. The data presented herein do not support any predictive utility of these CMV miRNAs for first episodes of CMV DNAemia in a cohort consisting primarily of allo-HSCT patients receiving haploidentical allografts.

Incidence, features, and outcomes of cytomegalovirus DNAemia in unmanipulated haploidentical allogeneic hematopoietic stem cell transplantation with post-transplantation cyclophosphamide.

BACKGROUND: Conflicting data have been published as to the risk of cytomegalovirus (CMV) DNAemia and CMV disease in patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplantation cyclophosphamide. METHODS: We conducted a multicenter retrospective study including 118 patients subjected to unmanipulated haplo-HSCT to further clarify this issue. An historic cohort comprising 165 patients undergoing other transplant modalities (HLA-matched related, matched unrelated or mismatched) was built for comparison purposes. Plasma CMV DNA monitoring was performed using two highly sensitive real-time PCR assays. RESULTS: Overall, the cumulative incidence of CMV DNAemia, recurrent CMV DNAemia, and CMV DNAemia requiring preemptive antiviral therapy in patients undergoing haplo-HSCT was 63.9%, 34.9%, and 50.1%, respectively. These figures were rather comparable for other transplant modalities (P = .22, P = .13 and P = .72, respectively). A trend toward longer duration of episodes and shorter CMV DNA doubling times was observed in haplo-HSCT patients in comparison with other transplant modalities. Furthermore, median CMV DNA peak load was significantly higher in haplo-HSCTs (P = .008), yet overall mortality by day 180 and 365 was the same across comparison groups. There were five cases of CMV disease, and all occurred in haplo-HSCT patients. This latter observation is worrying and merits further investigation. CONCLUSIONS: The incidence of initial and recurrent episodes of CMV DNAemia either requiring or not antiviral therapy in unmanipulated haplo-HSCT was comparable to other transplant modalities in our cohort.

A Unique Homeostatic Signaling Pathway Links Synaptic Inactivity to Postsynaptic mTORC1.

mTORC1-dependent translational control plays a key role in several enduring forms of synaptic plasticity such as long term potentiation (LTP) and mGluR-dependent long term depression. Recent evidence demonstrates an additional role in regulating synaptic homeostasis in response to inactivity, where dendritic mTORC1 serves to modulate presynaptic function via retrograde signaling. Presently, it is unclear whether LTP and homeostatic plasticity use a common route to mTORC1-dependent signaling or whether each engage mTORC1 through distinct pathways. Here, we report a unique signaling pathway that specifically couples homeostatic signaling to postsynaptic mTORC1 after loss of excitatory synaptic input. We find that AMPAR blockade, but not LTP-inducing stimulation, induces phospholipase D (PLD)-dependent synthesis of the lipid second messenger phosphatidic acid (PA) in rat cultured hippocampal neurons of either sex. Pharmacological blockade of PLD1/2 or pharmacogenetic disruption of PA interactions with mTOR eliminates mTORC1 signaling and presynaptic compensation driven by AMPAR blockade, but does not alter mTORC1 activation or functional changes during chemical LTP (cLTP). Overexpression of PLD1, but not PLD2, recapitulates both functional synaptic changes as well as signature cellular adaptations associated with homeostatic plasticity. Finally, transient application of exogenous PA is sufficient to drive rapid presynaptic compensation requiring mTORC1-dependent translation of BDNF in the postsynaptic compartment. These results thus define a unique homeostatic signaling pathway coupling mTORC1 activation to changes in excitatory synaptic drive. Our results further imply that more than one canonical mTORC1 activation pathway may be relevant for the design of novel therapeutic approaches against neurodevelopmental disorders associated with mTORC1 dysregulation.SIGNIFICANCE STATEMENT Homeostatic and Hebbian forms of synaptic plasticity are thought to play complementary roles in regulating neural circuit function, but we know little about how these forms of plasticity are distinguished at the single neuron level. Here, we define a signaling pathway that uniquely links mTORC1 with homeostatic signaling in neurons.

Unexpected bird-feather mite associations revealed by DNA metabarcoding uncovers a dynamic ecoevolutionary scenario.

The high relevance of host-switching for the diversification of highly host-specific symbionts (i.e., those commonly inhabiting a single host species) demands a better understanding of host-switching dynamics at an ecological scale. Here, we used DNA metabarcoding to study feather mites on passerine birds in Spain, sequencing mtDNA (COI) for 25,540 individual mites (representing 64 species) from 1,130 birds (representing 71 species). Surprisingly, 1,228 (4.8%) mites from 84 (7.4%) birds were found on host species that were not the expected to be a host according to a recent bird-feather mite associations catalog. Unexpected associations were widespread across studied mite (40.6%) and bird (43.7%) species and showed smaller average infrapopulation sizes than typical associations. Unexpected mite species colonized hosts being distantly related to the set of their usual hosts, but with similar body size. The network of bird-mite associations was modular (i.e., some groups of bird and mite species tended to be more associated with each other than with the others), with 75.9% of the unexpected associations appearing within the module of the typical hosts of the mite species. Lastly, 68.4% of mite species found on unexpected hosts showed signatures of genetic differentiation, and we found evidence for reproduction or the potential for it in many of the unexpected associations. Results show host colonization as a common phenomenon even for these putatively highly host-specific symbionts. Thus, host-switching by feather mites, rather than a rare phenomenon, appears as a relatively frequent phenomenon shaped by ecological filters such as host morphology and is revealed as a fundamental component for a dynamic coevolutionary and codiversification scenario.

Feather mites play a role in cleaning host feathers: New insights from DNA metabarcoding and microscopy.

Parasites and other symbionts are crucial components of ecosystems, regulating host populations and supporting food webs. However, most symbiont systems, especially those involving commensals and mutualists, are relatively poorly understood. In this study, we have investigated the nature of the symbiotic relationship between birds and their most abundant and diverse ectosymbionts: the vane-dwelling feather mites. For this purpose, we studied the diet of feather mites using two complementary methods. First, we used light microscopy to examine the gut contents of 1,300 individual feather mites representing 100 mite genera (18 families) from 190 bird species belonging to 72 families and 19 orders. Second, we used high-throughput sequencing (HTS) and DNA metabarcoding to determine gut contents from 1,833 individual mites of 18 species inhabiting 18 bird species. Results showed fungi and potentially bacteria as the main food resources for feather mites (apart from potential bird uropygial gland oil). Diatoms and plant matter appeared as rare food resources for feather mites. Importantly, we did not find any evidence of feather mites feeding upon bird resources (e.g., blood, skin) other than potentially uropygial gland oil. In addition, we found a high prevalence of both keratinophilic and pathogenic fungal taxa in the feather mite species examined. Altogether, our results shed light on the long-standing question of the nature of the relationship between birds and their vane-dwelling feather mites, supporting previous evidence for a commensalistic-mutualistic role of feather mites, which are revealed as likely fungivore-microbivore-detritivore symbionts of bird feathers.

Successful Treatment of Severe Aspergillosis with Isavuconazole Therapy after Allogeneic Stem Cell Transplantation.

Invasive fungal infections are one of the main infectious complications in allogeneic stem cell transplantation (SCT). Triazoles (voriconazole, posaconazole) are the main prophylactic and therapeutic options for the treatment of invasive aspergillosis. However, pharmacological interactions and hepatotoxicity limit its use. Isavuconazole (ISV) is a recently approved azole with a promising interaction and safety profile. We present a case with invasive aspergillosis in the post-allogeneic SCT setting in a critically ill patient with severe multiorgan failure due to veno-occlusive disease. The patient was treated with ISV and B amphotericin during severe kidney and liver failure and multiple immunosuppressants, without significant drug-related toxicity and with favorable outcome. The interaction and safety profile of ISV is discussed along the reported experience. ISV can be an effective salvage therapy even in complex clinical situations with multiple potential interactions.

Factors predicting peripheral blood progenitor cell mobilization in healthy donors in the era of related alternative donors: Experience from a single center.

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.

Mononuclear cell collection for extracorporeal photopheresis by using the "off-line" system: A comparative study between COBE Spectra and Spectra Optia devices.

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.

Underwater Acoustic Impulsive Noise Monitoring in Port Facilities: Case Study of the Port of Cartagena.

Recording underwater impulsive noise data is an important aspect of mitigating its environmental impact and improving maritime environmental management systems. This paper describes the method used and results of the spatial monitoring of both the baseline noise level and the impulsive noise sources in the Port of Cartagena. An autonomous vessel was equipped with a smart digital hydrophone with a working frequency range between 10 and 200 kHz and a received voltage response (RVR) of, approximately, -170 dB re 1V/µPa. A GIS map was drawn up with the spatiotemporal distribution of the basal sound pressure levels by coupling the acoustic data with the vessel's GPS positions to identify the sources of the impulsive noise of interest and their temporal characteristics. The loading of cargo containers was identified as the main source of impulse noise. This study is the first of a series designed to obtain accurate information on underwater noise pollution and its potential impact on biodiversity in the Port of Cartagena.

Inonotosis in Patient with Hematologic Malignancy.

We report a lung-invasive fungal disease with possible cutaneous needle tract seeding in a patient with a febrile neutropenia caused by the Basidiomycetes mold Inonotus spp. Although rare, Inonotus spp. should be added to the list of microorganisms causing invasive fungal disease in neutropenic patients with hematologic malignancies.

Donor Cell-Derived Hematologic Neoplasms after Hematopoietic Stem Cell Transplantation: A Systematic Review.

Development of de novo hematologic malignancies in donor cells after allogeneic stem cell transplantation (allo-SCT) provides a useful in vivo model to study the process of leukemogenesis. A systematic analysis of the cases reported in the literature was performed to identify risk factors and mechanisms involved in the pathogenesis of donor cell-derived hematologic neoplasms (DCHN) and leukemogenic transformation. Relevant data were extracted from 137 cases. Cases of DCHN show a wide heterogeneity with regard to recipient/donor age, sex mismatch, and conditioning regimen. Some characteristics, such as the type of primary disease, the type of hematologic malignancy of the DCHN, and the stem cell source used in the transplant procedure, differ from those expected. Mechanisms involved in the pathogenesis of DCHN are complex, and several hypotheses have been proposed, such as pre-existing hematologic neoplasms or premalignant clones in the donor, decreased immune surveillance, and damage to bone marrow microenvironment in the recipient. Most likely several if not all these mechanisms play a role in DCHN development. Novel approaches, such as next-generation sequencing to study consecutive samples after allo-SCT in these patients, appear to be promising to decipher the mechanisms of leukemogenesis.

Sex-Dependent Expression and Fitness Consequences of Sunlight-Derived Color Phenotypes.

To understand whether early phenotypes are adaptive, knowledge of the environmental factors involved in their variation and the derived benefits from their expression is needed. Temperature and sunlight are considered two major selective forces influencing phenotypic coloration of birds at a global scale. However, within-population color adaptations in response to sunlight temperature variation have been scarcely investigated, and their acclimatization capacity is currently unknown. In addition, the sexes differ in their sensitivity to environmental factors during growth. This study evaluates how melanin plumage coloration varies in relation to sex and sunlight exposure in developing griffon vultures Gyps fulvus and how this correlates with survival. The results show that individuals grown in nests more exposed to sunlight developed paler plumages, as predicted by the thermal melanism hypothesis. In addition, paler males-but not females-have lower survival probability. Finally, a significant sexual dichromatism in fledgling plumage was observed, with females being paler than males. These results reveal within-population color variation related to sunlight temperature conditions, probably as a capacity for local acclimatization through color plasticity, and also provide evidence of sex differences in fitness optima for this trait under ecological pressures.

Busulfan-based myeloablative conditioning regimens for haploidentical transplantation in high-risk acute leukemias and myelodysplastic syndromes.

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.