Revised HLA-DP TCE-Core Permissiveness Model Better Defines Relapse Risk and Survival following Haploidentical Transplant.

The presence of an HLA-DPB1 nonpermissive mismatch (NPMM) by the TCE-3 model has been associated with improved survival following haploidentical donor transplantation (HIDT) using post-transplantation cyclophosphamide (PTCy). With the development of a revised model (TCE-Core) that further separates TCE-3 "group 3" alleles into "core" (C) and "noncore" (NC) alleles, a formerly permissive mismatch (PMM) resulting from group 3 alleles in both donor and recipient is now considered a C-NPMM if 1 or more of those alleles is NC. We aimed to study the additional effect of HLA-DPB1 C-NPMM according to the TCE-Core algorithm, as well as the directional vector of the mismatch, on outcomes following HIDT. To this end, we analyzed 242 consecutive HIDT recipients with acute leukemia or myelodysplastic syndrome who underwent transplantation between 2005 and 2021 (median age, 51 years; range, 19 to 80 years). The median follow-up was 62 months (range, 23 to 199 months). Of the 136 HIDTs classified as PMM by TCE-3, 73 were reclassified as a C-NPMM by the TCE-Core algorithm, of which 36 were in the graft-versus host (GVH) vector (37 were host-versus-graft [HVG] only). Given comparable survival between conventional NPMM and C-NPMM, GVH/bidirectional were analyzed together (nonpermissive). HVG-only C-NPMM were combined with HLA-DPB1-matched and PMM (permissive) because of similar outcomes. The presence of a TCE-Core-defined nonpermissive HLA-DP mismatch resulted in superior 5-year overall survival (OS) (66% versus 47%) and disease-free survival (DFS) (60% versus 43%). Compared to the conventional TCE-3 algorithm, TCE-Core identified a higher percentage of nonpermissive transplants (38% versus 23%) and better discriminated outcomes between nonpermissive and permissive status, with a larger difference in survival outcomes using TCE-Core compared to TCE-3 (OS Δ, 18.3% versus 12.7%; DFS Δ, 16.5% versus 8.5%). In multivariable analysis (MVA), a nonpermissive TCE-Core mismatch led to improved OS (hazard ratio [HR], .54; P = .003) and DFS (HR, .62; P = .013), largely due to decreased relapse risk (HR, .63; P = .049). In contrast, nonrelapse mortality (NRM) and graft-versus-host disease (GVHD) outcomes were not significantly impacted. In summary, the presence of nonpermissive TCE-Core HLA-DP mismatch strongly predicts survival following PTCy-based HIDT, owing to a reduction in relapse risk without a corresponding increase in GVHD or NRM. As a donor selection tool, TCE-Core appears to better discriminate HIDT outcomes while at the same time identifying a larger percentage of the potential donor pool.

How to transform urban institutional green spaces into Ancillary Botanic Gardens to expand informal botanical learning opportunities in cities.

Since many cities lack botanical gardens, we introduced the concept of Ancillary Botanic Gardens (ABG), which builds on the premise that organizations can expand informal botanical learning by adding a secondary function to their institutional green spaces. This study guides the application of the ABG concept in various spatial and functional contexts by offering practical and interpretive tools to organizations who are less used to working with nature but are interested in mitigating urban residents' detachment from nature. Online maps of 220 botanic gardens were reviewed to define types of plant collections and produce an exhaustive list of physical botanic garden elements. The collected information was developed into an ABG field checklist that was tested on three case studies in Lebanon and then used to develop guidelines for ABG establishment. The guidelines and checklist are meant to empower and guide organizations interested in establishing an ABG.

A simple prognostic system in patients with myelofibrosis undergoing allogeneic stem cell transplantation: a CIBMTR/EBMT analysis.

To develop a prognostic model for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) for myelofibrosis (MF), we examined the data of 623 patients undergoing allo-HCT between 2000 and 2016 in the United States (the Center for International Blood and Marrow Transplant Research [CIBMTR] cohort). A Cox multivariable model was used to identify factors prognostic of mortality. A weighted score using these factors was assigned to patients who received transplantation in Europe (the European Bone Marrow Transplant [EBMT] cohort; n = 623). Patient age >50 years (hazard ratio [HR], 1.39; 95% confidence interval [CI], 0.98-1.96), and HLA-matched unrelated donor (HR, 1.29; 95% CI, 0.98-1.7) were associated with an increased hazard of death and were assigned 1 point. Hemoglobin levels <100 g/L at time of transplantation (HR, 1.63; 95% CI, 1.2-2.19) and a mismatched unrelated donor (HR, 1.78; 95% CI, 1.25-2.52) were assigned 2 points. The 3-year overall survival (OS) in patients with a low (1-2 points), intermediate (3-4 points), and high score (5 points) were 69% (95% CI, 61-76), 51% (95% CI, 46-56.4), and 34% (95% CI, 21-49), respectively (P < .001). Increasing score was predictive of increased transplant-related mortality (TRM; P = .0017) but not of relapse (P = .12). The derived score was predictive of OS (P < .001) and TRM (P = .002) but not of relapse (P = .17) in the EBMT cohort as well. The proposed system was prognostic of survival in 2 large cohorts, CIBMTR and EBMT, and can easily be applied by clinicians consulting patients with MF about the transplantation outcomes.

Hematopoietic Cell Transplantation in the Management of Myelodysplastic Syndrome: An Evidence-Based Review from the American Society for Transplantation and Cellular Therapy Committee on Practice Guidelines.

The sole curative therapy for myelodysplastic syndrome (MDS) is allogeneic hematopoietic cell transplantation (HCT). Here this therapeutic modality is reviewed and critically evaluated in the context of the evidence. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the recommendations. A panel of MDS experts comprising transplantation and nontransplantation physicians developed consensus treatment recommendations. This review summarizes the standard MDS indications for HCT and addresses areas of controversy. Recent prospective trials have confirmed that allogeneic HCT confers survival benefits in patients with advanced or high-risk MDS compared with nontransplantation approaches, and the use of HCT is increasing in older patients with good performance status. However, patients with high-risk cytogenetic or molecular mutations remain at high risk for relapse. It is unknown whether administration of novel therapies before or after transplantation may decrease the risk of disease relapse in selected populations. Ongoing and future studies will investigate revised approaches to disease risk stratification, patient selection, and post-transplantation approaches to optimize allogeneic HCT outcomes for patients with MDS.

Extracorporeal photopheresis (ECP) improves overall survival in the treatment of steroid refractory acute graft-versus-host disease (SR aGvHD).

Steroid refractory acute graft-versus-host disease (SR aGvHD) is a major limitation of successful allogeneic hematopoietic stem cell transplantation (HSCT). Extracorporeal photopheresis (ECP) has been used to treat SR aGvHD effectively and with low treatment related toxicity. In this study, we retrospectively analyzed the outcomes of 103 Steroid Refractory aGvHD (SR aGvHD) patients to identify factors associated with improved outcomes including the use of ECP. A total of 79 patients received ECP as part of their SR aGVHD treatment compared to 24 patients who did not. Both groups had similar aGVHD grade and maximum organ stage at onset of aGVHD and treatment initiation. Patients in the group that received ECP had better OS (p = 0.01), DFS (p = 0.008), lower relapse (p = 0.05) and similar NRM compared to the group that did not receive ECP. Patients that received ECP treatment also had shorter hospital stays in the first 180 days after onset of SR aGvHD (20 vs. 38 days, p = 0.03). Multivariable analysis for OS indicated patient CMV status (CMV+ versus CMV-, HR 2.34, CI 1.16-4.69), regimen intensity (Myelo vs. non-Myeloablative, HR 0.39, CI 0.20-0.75), and the use of ECP (ECP vs. no ECP, HR 0.39, CI 0.20-0.75) were associated with OS. In summary, the use of ECP in the treatment of SR aGvHD results in improved overall survival secondary to lower relapse rates compared to other therapeutic modalities that do not incorporate ECP.

Lineage-Specific Relapse Prediction After Haploidentical Transplantation With Post-Transplant Cyclophosphamide Based on Recipient HLA-B-Leader Genotype and HLA-C-Group KIR Ligand.

The role of NK cell alloreactivity on outcomes after T cell-replete haploidentical donor transplantation (HIDT) remains uncertain. After transplantation, newly formed NK cells are licensed through interactions of donor inhibitory KIR (iKIR) and NKG2A receptors with their cognate ligands on recipient cells. Donor NKG2A recognizes HLA-E bound by recipient HLA class I leader peptides, a process requiring methionine (M) at position -21 of the leader sequence. An rs1050458C/T dimorphism results in approximately 40% of individuals expressing at least one copy of -21M HLA-B (M/M or M/T [M+]), allowing ligand expression. We assessed the impact of recipient HLA-B-leader genotype (M+ versus M- [T/T]) and HLA-C-group iKIR missing ligand (ML, C1C1/C2C2 versus C1C2) on relapse and disease-free survival (DFS) in recipients of post-transplantation cyclophosphamide (PTCy)-based HIDT. Based on preclinical data, we hypothesized that the relative impact of each variable may depend on disease lineage (lymphoid versus myeloid). To this end, we analyzed outcomes of 322 consecutive PTCy-based HIDT recipients with hematologic malignancy who underwent transplantation at a single institution using standardized supportive care measures with mature follow-up (median 45 months). Primary endpoints were relapse and DFS of patients based on HLA-B-leader genotype and HLA-C-group iKIR ML. Planned subgroup analysis included patient with lymphoid versus myeloid malignancy. M+ HLA-B-leader genotype and HLA-C-group iKIR ML were seen in 42% and 49% of recipients, respectively. The presence of a recipient M+ B-leader (versus M-) improved overall survival (OS) and DFS and lowered cumulative incidence of relapse (CIR), an effect primarily seen in lymphoid malignancies (80% versus 51%, 72% versus 41%, 16% versus 42%, respectively). In contrast, myeloid malignancy patients benefited most from HLA-C-group iKIR ML with better OS and DFS and lower CIR (67% versus 51%, 64% versus 44%, 25% versus 45%, respectively). Multivariate analysis confirmed the disease-specific associations of improved relapse/DFS with M+ HLA-B-leader in lymphoid malignancy (hazard ratio [HR] 0.20, P < .001/HR 0.34, P <.001) and HLA-C-group iKIR ML in myeloid malignancy (HR 0.44, P = .004/HR 0.54, P = .009). Neither HLA-B-leader nor iKIR ML was associated with the incidence of non-relapse mortality or acute or chronic graft-versus-host disease. Two distinct NK cell education pathways predict relapse and DFS after HIDT-PTCy in a disease-specific manner: the presence of recipient M+ HLA-B-leader genotype improves outcome in patients with lymphoid malignancies, whereas HLA-C-group iKIR ML improves outcome in patients with myeloid malignancies. These findings strengthen the essential role of NK cells for optimal GVL in the context of HIDT-PTCy and may suggest different approaches to improving transplant outcome depending on disease type.

Antifungal susceptibility profile of Candida clinical isolates from 22 hospitals of São Paulo State, Brazil.

This study aimed to evaluate the frequency of cryptic Candida species from candidemia cases in 22 public hospitals in São Paulo State, Brazil, and their antifungal susceptibility profiles. During 2017 and 2018, 144 isolates were molecularly identified as 14 species; C. parapsilosis (32.6%), C. albicans (27.7%), C. tropicalis (14.6%), C. glabrata (9.7%), C. krusei (2.8%), C. orthopsilosis (2.8%), C. haemulonii var. vulnera (2.1%), C. haemulonii (1.4%), C. metapsilosis (1.4%), C. dubliniensis (1.4%), C. guilliermondii (1.4%), C. duobushaemulonii (0.7%), C. kefyr (0.7%), and C. pelliculosa (0.7%). Poor susceptibility to fluconazole was identified in 6.4% of C. parapsilosis isolates (0.12 to >64 µg/mL), 50% of C. guilliermondii (64 µg/mL), 66.6% of C. haemulonii var. vulnera (16-32 µg/mL), and C. duobushaemulonii strain (MIC 64 µg/mL). Our results corroborated the emergence of C. glabrata in Brazilian cases of candidemia as previously reported. Importantly, we observed a large proportion of non-wild type C. glabrata isolates to voriconazole (28.6%; <0.015 to 4 µg/mL) all of which were also resistant to fluconazole (28.6%). Of note, C. haemulonii, a multidrug resistant species, has emerged in the Southeast region of Brazil. Our findings suggested a possible epidemiologic change in the region with an increase in fluconazole-resistant species causing candidemia. We stress the relevance of routine accurate identification to properly manage therapy and monitor epidemiologic trends.

Difference Between the Profiles Presented by Yeasts that Colonize the Vaginal Mucosa or Cause Primary or Recurrent Candidiasis.

Candida yeasts are the most frequent in the vaginal content. This yeast may be a normal microbiota but also causes candidiasis. In symptomatic cases, primary candidiasis (VVC) or recurrence (RVVC) can be considered. This study aims to compare the frequency and in vitro sensitivity profile of Candida species isolated in the vaginal content with the different stages of the presence of yeasts. A total of 258 non-pregnant patients with/without VVC were prospectively screened at a teaching Health Centre of the Faculty of Medicine, in the University of Sao Paulo. The vaginal isolates were identified by traditional and molecular methods. Yeasts were isolated in 160 women. 34% were asymptomatic, 34% with vulvovaginal candidiasis (VVC), and 32% recurrent vulvovaginal candidiasis (RVVC). C. albicans was the most frequent species with 50.1% (82/160), followed by C. parapsilosis 13.7%(22/160), C. glabrata 12.5% (20/160), and C. tropicalis (6.2%). Analysis by the group showed that, in the asymptomatic group, eight yeast species were isolated, C. albicans 44.5% (24/54), C. glabrata 20% (11/54), C. parapsilosis and Rhodotorula rubra being the most frequent. In the VVC group, 11 yeast species were identified. Most isolates were C. albicans 68.5% (37/54), C. tropicalis 7.5% (4/54), and C. parapsilosis 5.5% (3/54). In the RVVC group, ten species were identified, the most frequent being C. albicans 38.5% (20/52), C. parapsilosis 17% (9/52), C. glabrata 4% (8/52), and C. tropicalis 6% (3/52). Less frequent species, such as C. haemulonii and Trichosporon spp, were isolated in the VVC and RVVC groups, C. kefyr was isolated in the three groups studied, and Rhodotorula spp was isolated in the control and RVVC groups. Candida metapsilosis was present in two isolates from the RVVC group. Most isolates were considered sensitive to the tested antifungals. Less sensitivity was seen for caspofungin. In this study, we were able to verify that the most common species of yeasts found in vaginal secretion were isolated in the three groups studied; however, there was the diversity of species in VVC and RVVC. Cryptic species C. haemulonii and were isolated in symptomatic patients. High levels of MICs, some of the antifungals tested, in the control group, draw attention in the group of asymptomatic women. We would like to emphasize that this research aims to assist clinicians and gynecologists, as well as assist in the epidemiological studies of candidiasis, in our country, how to draw attention to the profile of sensitivity/resistance to antifungals.

A Phase II Trial of Melphalan Based Reduced-Intensity Conditioning for Transplantation of T-Replete HLA-Haploidentical Peripheral Blood Stem Cells with Posttransplant Cyclophosphamide in Patients with Hematologic Malignancies.

T-replete haploidentical donor transplants using posttransplant cyclophosphamide (haplo) have greatly expanded donor availability and are increasingly utilized. Haplo were originally performed using truly nonmyeloablative conditioning and a bone marrow graft. We have also developed myeloablative conditioning and peripheral blood stem cell (PBSC) grafts for use with haplo. However, some patients may not tolerate myeloablative conditioning but may still benefit from a more dose-intensified preparative regimen to control malignancy and diminish graft rejection. To this end, we enrolled 25 patients on a prospective phase II trial utilizing a regimen of fludarabine 30 mg/m2/day × 5 days and Melphalan 140 mg/m2 on day -1 (flu/Mel) followed by infusion of unmanipulated PBSC graft from a haploidentical donor. GVHD prophylaxis included cyclophosphamide 50 mg/kg/day on days 3 and 4, mycophenolate mofetil on day 35, and tacrolimus on day 180. Median age was 57 years (range from 35 to 68). Transplantation diagnosis included AML (n = 11), ALL (n = 4), MDS/MPD (n = 6), NHL/CLL (n = 3), and MM (n = 1). Using the refined Disease Risk Index (DRI), patients were low (n = 1), intermediate (n = 13), and high/very high (n = 11). 22 out of 25 patients engrafted with a median time to neutrophil and platelet engraftment of 18 days and 36 days, respectively. All engrafting patients achieved full peripheral blood T-lymphocyte and myeloid donor chimerism at day 30. The 180-day cumulative incidence for acute GVHD grades II-IV and III-IV was seen in 20% (95% CI 8%-37%) and 8% (95% CI 2%-22%), respectively. The 2-year cumulative incidence of chronic GVHD was 16% (95% CI 5%-33%) (moderate-severe 12% (95% CI 3%-27%)). After a median follow-up of 28.3 months, the estimated 2-year OS, DFS, NRM, and relapse were 56% (95%CI 33-74%), 44% (95%CI 23%-64%), 20% (95% CI 8%-37%), and 36% (95% CI 17%-55%), respectively. Among patients with high/very high risk DRI, 2-year OS was 53% compared to 69% for low/intermediate DRI. When compared with a contemporaneous cohort of patients at our center receiving haploidentical transplant with nonablative fludarabine, Cytoxan, and total body irradiation flu/Cy/TBI regimen, the outcomes were statistically similar to the 2-year OS at 56% vs. 63% p=0.75 and DFS at 44% vs. 46% p=0.65.

Antifungal susceptibility profile of Candida clinical isolates from 22 hospitals of São Paulo State, Brazil

This study aimed to evaluate the frequency of cryptic Candida species from candidemia cases in 22 public hospitals in São Paulo State, Brazil, and their antifungal susceptibility profiles. During 2017 and 2018, 144 isolates were molecularly identified as 14 species; C. parapsilosis (32.6%), C. albicans (27.7%), C. tropicalis (14.6%), C. glabrata (9.7%), C. krusei (2.8%), C. orthopsilosis (2.8%), C. haemulonii var. vulnera (2.1%), C. haemulonii (1.4%), C. metapsilosis (1.4%), C. dubliniensis (1.4%), C. guilliermondii (1.4%), C. duobushaemulonii (0.7%), C. kefyr (0.7%), and C. pelliculosa (0.7%). Poor susceptibility to fluconazole was identified in 6.4% of C. parapsilosis isolates (0.12 to >64 µg/mL), 50% of C. guilliermondii (64 µg/mL), 66.6% of C. haemulonii var. vulnera (16-32 µg/mL), and C. duobushaemulonii strain (MIC 64 µg/mL). Our results corroborated the emergence of C. glabrata in Brazilian cases of candidemia as previously reported. Importantly, we observed a large proportion of non-wild type C. glabrata isolates to voriconazole (28.6%; <0.015 to 4 µg/mL) all of which were also resistant to fluconazole (28.6%). Of note, C. haemulonii, a multidrug resistant species, has emerged in the Southeast region of Brazil. Our findings suggested a possible epidemiologic change in the region with an increase in fluconazole-resistant species causing candidemia. We stress the relevance of routine accurate identification to properly manage therapy and monitor epidemiologic trends.

The Transplant Evaluation Rating Scale predicts overall survival after allogeneic hematopoietic stem cell transplantation.

To evaluate the impact of psychosocial risks on post-hematopoietic stem cell transplantation (HSCT) outcomes, we prospectively conducted psychosocial assessment of 556 consecutive allogeneic HSCT patients who received their first allogeneic transplant at our center between 2003 and 2017. The Transplant Evaluation Rating Scale (TERS) score was prospectively assessed by a psychologist before transplantation, and patients were categorized as low, intermediate, or high risk based on their TERS score. Patients in the high-risk TERS group had significantly longer hospital stays during the first 180 days and 1 year post-allogeneic HSCT compared with the low-risk group (16 vs 13 and 21 vs 16 days; P = .05 and .02, respectively). The survival estimates for low-, intermediate-, and high-risk TERS groups at 3 year were as follows: overall survival (OS), 73%, 60%, and 65%; disease-free survival (DFS), 63%, 55%, and 60%; nonrelapse mortality (NRM), 11%, 20%, and 17%; and relapse, 26%, 25%, and 23%, respectively. In a multivariable analysis, intermediate- and high-risk TERS scores predicted for inferior OS, similar DFS, and higher NRM compared with low-risk TERS score. In a subset analysis of patients with low/intermediate risk per Disease Risk Index, multivariable analysis showed that high- and intermediate-risk TERS scores predicted for significantly worse OS, worse DFS, higher NRM, and similar relapse rates compared with low-risk TERS score. Our findings show that psychosocial factors as measured by TERS score are strong predictors of morbidity and mortality after HSCT among patients with low/intermediate disease risk.

Class II HLA mismatch improves outcomes following haploidentical transplantation with posttransplant cyclophosphamide.

HLA disparity is the major predictor of outcome following unrelated donor (UD) transplantation, where a single mismatch (mm) at the HLA-A, HLA-B, HLA-C, or HLA-DRB1 locus leads to increased mortality, and mismatching at multiple loci compounds this effect. In contrast, HLA disparity has not been shown to increase mortality in the context of haploidentical transplant using posttransplant cyclophosphamide (PTCy). To better define the consequences of loci-specific HLA mm, we analyzed 208 consecutive patients undergoing haploidentical transplantation for hematologic malignancy using PTCy at our institution (median age, 52 years [range, 19-75 years]; peripheral blood stem cell, 66%; reduced-intensity conditioning, 59%). Median follow-up was 65.4 months (range, 34.3-157.2 months). In univariate analysis, a single class II HLA mm at HLA-DR, HLA-DQ or a nonpermissive (np) HLA-DP mm had a protective effect on disease-free and overall survival (OS), primarily a result of reduced relapse risk. Furthermore, this survival effect was cumulative, so that patients with 3 class II mm (HLA-DR, HLA-DQ, and np HLA-DP) had the best OS. In multivariate analysis, HLA-DR mm and np HLA-DP mm were both independently associated with improved OS (hazard ratio [HR], 0.43; P =.001; and HR, 0.47; P =.011, respectively). In contrast, single or multiple mm at HLA-A, HLA-B, or HLA-C loci had no effect on acute graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse, or survival, although the presence of an HLA-A mm was associated with increased chronic GVHD incidence. The association of class II mm with lower relapse occurred without a corresponding increase in NRM or acute or chronic GVHD. These findings will require validation in larger registry studies.

Visible DNA microarray and loop-mediated isothermal amplification (LAMP) for the identification of Cryptococcus species recovered from culture medium and cerebrospinal fluid of patients with meningitis.

Cryptococcal meningitis affects normal hosts and immunocompromised patients exhibiting high mortality rates. The objective of this study was to design two molecular assays, visible microarray platforms and loop-mediated isothermal amplification (LAMP), to identify Cryptococcus spp. and the species neoformans and gattii from the cerebral spinal fluid (CSF). To identify Cryptococcus and the two species, we designed two microarrays DNA platforms based on the internal transcribed spacer (ITS) region and CAP59 gene and LAMP assays specific for Cryptococcus species. The assays were tested using CSF from patients with cryptococcal meningitis. CSF from patients with cryptococcal meningitis was cultured in Sabouraud culture medium, and the Cryptococcus spp. grown in the culture medium were also tested for LAMP and microarray platforms. The results were compared to DNA sequencing of the same genetic regions. A total of 133 CSF samples were studied. Eleven CSFs were positive for Cryptococcus (9 C. neoformans and 2 C. gattii), 15 were positive for bacteria, and 107 were negative. The CAP59 platform correctly identified 73% of the CSF samples, while the ITS platform identified 45.5%. CAP59 platform correctly identified 100% of the Cryptococcus isolates, and ITS platform identified 70%. The two sets of LAMP primers correctly identified 100% of the Cryptococcus isolates. However, for CSF samples, the amplification occurred only in 55.5% of C. neoformans. The methodologies were reliable in the identification of Cryptococcus species, mainly for isolates from culture medium, and they might be applied as adjunctive tests to identify Cryptococcus species.

Differences in Graft-versus-Host Disease Characteristics between Haploidentical Transplantation Using Post-Transplantation Cyclophosphamide and Matched Unrelated Donor Transplantation Using Calcineurin Inhibitors.

We assessed differences in presentation and response to therapy in 394 consecutive patients who developed acute or chronic graft-versus-host disease (GVHD) after receiving their first allogeneic transplantation (HSCT) from a 10/10 HLA allele-matched unrelated donor (MUD; n = 179) using calcineurin inhibitors or a T cell-replete haploidentical donor (haplo; n = 215) and post-transplantation cyclophosphamide at our center between 2005 and 2017. The median duration of follow-up for survivors was 52.5 months. The cumulative incidences for grade II-IV and grade III-IV acute GVHD at day 180 post HCT were similar, at 39% and 14%, respectively, for haplo-HSCT compared with 50% and 16% for MUD HSCT (P not significant). Haplo-HSCT recipients had a lower cumulative incidence of moderate to severe chronic GVHD, at 22% (severe, 19%), compared with 31% (severe, 29%) for MUD HSCT recipients (P = .026). The time to onset of moderate to severe chronic GVHD was faster for haplo-HSCT recipients (213 days versus 280 days; P = .011). Among patients with grade II-IV acute GVHD, there was no significant between-group difference in organ involvement, with skin the most affected (75% for haplo-HSCT versus 70% for MUD HSCT), followed by the gastrointestinal tract (71% versus 69%) and liver (14% versus 17% MUD). For chronic GVHD, haplo-HSCT recipients had less involvement of the eyes (46% versus 75% for MUD; P < .001) and of the joints/fascia (12% versus 36%; P = .001). Also for cGVHD patients, haplo-HSCT recipients and MUD HSCT recipients had similar all-cause mortality (22% versus 18%; P = .89), but the former were more likely to be off immunosuppression at 2 years post-HCT (63% versus 43%; P = .03) compared with MUD.

Impact of autologous blood transfusion after bone marrow harvest on unrelated donor's health and outcome: a CIBMTR analysis.

Pre-harvest autologous blood collection from bone marrow (BM) donors is performed to meet potential post-operative transfusion needs. This study examines the impact of autologous blood transfusion on BM donor's health and safety. The study included first-time unrelated BM donors from the United States whose BM harvest was facilitated by the National Marrow Donor Program (NMDP) centers between 2006 and 2017. Examination of 7024 BM donors revealed that 60% received at least one unit of autologous blood. The donors who received autologous blood were older, had lower hemoglobin pre-harvest, underwent longer duration of anesthesia, and higher volume BM harvest. Only donors who underwent high-volume BM harvest, defined as a BM harvest volume >27% of donor's blood volume, benefited from autologous transfusion. After a high-volume BM harvest, autologous blood transfusion was shown to decrease grade 2 to 4 collection-associated toxicities within 48 h of BM donation (p = 0.010) and shorten the time to donor-reported "complete" recovery from donation-associated symptoms (p < 0.001). Therefore, autologous transfusion could be avoided as support of marrow donation in the majority of unrelated BM donors and should be limited to cases where the planned BM harvest volume is expected to exceed 27% of donor's blood volume.

Improved Post remission survival of non- favorable risk Acute Myelogenous Leukemia (AML) patients following initial remission induction therapy with FLAG+/-Idarubicin versus 3 + 7 (Anthracycline + Cytarabine).

The fludarabine, high dose cytarabine and G-CSF with or without idarubicin combination regimen, referred to as FLAG+/-Ida, is commonly used as a salvage regimen for relapsed/refractory AML but its use as initial induction therapy has been more limited. The impact of choice of induction regimen on post remission survival remains unclear. We retrospectively analyzed 304 consecutive AML patients, with non-favorable NCCN risk who received initial treatment at our center with either 7 + 3 (n = 86) or FLAG+/-Ida (n = 218). Patients in the FLAG+/-Ida group were more likely to achieve remission after one course of induction (74 % vs 62 %, p < 0.001) and had a faster time to achieve CR (30 days vs 37.5, p < 0.001) compared to 7 + 3. The time from diagnosis to transplant was shorter among CR patients after FLAG+/-Ida compared to 7 + 3 (115 vs. 151 days, p < 0.003). The 3-year post-remission OS and DFS was significantly better for patients receiving FLAG-Ida at 54 % and 49 % compared to 39 % and 32 % for 7 + 3 respectively (P = 0.01). Factors associated with post-remission survival included age at CR1, NCCN risk, induction regimen (FLAG+/-Ida vs 3 + 7 h 0.62, p = 0.01) and receipt of HCT. Our data, with the limitations inherent to a retrospective analysis, shows that achieving CR after FLAG+/-Ida has better post remission survival than 7 + 3.

Weighty choices: selecting optimal G-CSF doses for stem cell mobilization to optimize yield.

There are limited data on the effect of donor body mass index (BMI) on peripheral blood stem cell (PBSC) mobilization response to granulocyte colony-stimulating factor (G-CSF), especially in unrelated donors. Obesity has been associated with persistent leukocytosis, elevated circulating progenitor cells, and enhanced stem cell mobilization. Therefore, we hypothesized that adequate collection of CD34+ cells may be achieved with lower doses (per kilogram of body weight) of G-CSF in donors with higher BMI compared with donors with lower BMI. Using the Center for International Blood and Marrow Transplant Research database, we evaluated the impact of donor BMI on G-CSF-mobilized PBSC yield in healthy unrelated donors. We examined 20 884 PBSC donations collected at National Marrow Donor Program centers between 2006 and 2016. We found significantly higher collection yields in obese and severely obese donors compared with normal and overweight donors. An increase in average daily G-CSF dose was associated with an increase in stem cell yield in donors with normal or overweight BMI. In contrast, an increase in average daily G-CSF dose beyond 780 µg per day in obese and 900 µg per day in severely obese donors did not increase cell yield. Pain and toxicities were assessed at baseline, during G-CSF administration, and postcollection. Obesity was associated with higher levels of self-reported donation-related pain and toxicities in the pericollection and early postdonation recovery periods. This study suggests a maximum effective G-CSF dose for PBSC mobilization in obese and severely obese donors, beyond which higher doses of G-CSF add no increased yield.

Visible DNA microarray and loop-mediated isothermal amplification (LAMP) for the identification of Cryptococcus species recovered from culture medium and cerebrospinal fluid of patients with meningitis

Cryptococcal meningitis affects normal hosts and immunocompromised patients exhibiting high mortality rates. The objective of this study was to design two molecular assays, visible microarray platforms and loop-mediated isothermal amplification (LAMP), to identify Cryptococcus spp. and the species neoformans and gattii from the cerebral spinal fluid (CSF). To identify Cryptococcus and the two species, we designed two microarrays DNA platforms based on the internal transcribed spacer (ITS) region and CAP59 gene and LAMP assays specific for Cryptococcus species. The assays were tested using CSF from patients with cryptococcal meningitis. CSF from patients with cryptococcal meningitis was cultured in Sabouraud culture medium, and the Cryptococcus spp. grown in the culture medium were also tested for LAMP and microarray platforms. The results were compared to DNA sequencing of the same genetic regions. A total of 133 CSF samples were studied. Eleven CSFs were positive for Cryptococcus (9 C. neoformans and 2 C. gattii), 15 were positive for bacteria, and 107 were negative. The CAP59 platform correctly identified 73% of the CSF samples, while the ITS platform identified 45.5%. CAP59 platform correctly identified 100% of the Cryptococcus isolates, and ITS platform identified 70%. The two sets of LAMP primers correctly identified 100% of the Cryptococcus isolates. However, for CSF samples, the amplification occurred only in 55.5% of C. neoformans. The methodologies were reliable in the identification of Cryptococcus species, mainly for isolates from culture medium, and they might be applied as adjunctive tests to identify Cryptococcus species.