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Outcome of early treatment of COVID-19 with antivirals or anti-spike monoclonal antibodies (MABs) in patients with haematological malignancies (HM) is unknown. A retrospective study of HM patients treated for mild/moderate COVID-19 between March 2021 and July 2022 was performed. The main composite end-point was treatment failure (severe COVID-19 or COVID-19-related death). We included 328 consecutive patients who received MABs (n = 120, 37%; sotrovimab, n = 73) or antivirals (n = 208, 63%; nirmatrelvir/ritonavir, n = 116) over a median of two days after symptoms started; 111 (33.8%) had non-Hodgkin lymphoma (NHL); 89 (27%) were transplant/CAR-T (chimaeric antigen receptor T-cell therapy) recipients. Most infections (n = 309, 94%) occurred during the Omicron period. Failure developed in 31 patients (9.5%). Its independent predictors were older age, fewer vaccine doses, and treatment with MABs. Rate of failure was lower in the Omicron versus the pre-Omicron period (7.8% versus 36.8%, p < 0.001). During the Omicron period, predictors of failure were age, fewer vaccine doses and diagnosis of acute myeloid leukaemia/myelodysplastic syndrome (AML/MDS). Independent predictors of longer viral shedding were age, comorbidities, hospital admission at diagnosis, NHL/CLL, treatment with MABs. COVID-19-associated mortality was 3.4% (n = 11). The mortality in those who developed severe COVID-19 after early treatment was 26% in the Omicron period. Patients with HM had a significant risk of failure of early treatment, even during the Omicron period, with high mortality rate., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

The aim of this retrospective study was to assess the rate of full donor chimerism (F-DC) in patients with myelofibrosis, prepared for an allogeneic stem cell transplant, with one or two alkylating agents. We analyzed 120 patients with myelofibrosis, for whom chimerism data were available on day +30. There were two groups: 42 patients were conditioned with one alkylating agent (ONE-ALK), either thiotepa or busulfan or melphalan, in combination with fludarabine, whereas 78 patients were prepared with two alkylating agents, thiotepa busulfan and fludarabine (TBF). Patients receiving TBF were older (57 vs 52 years), were less frequently splenectomized pre-HSCT (31% vs 59%), had more frequently intermediate-2/high DIPSS scores (90% vs 74%), were grafted more frequently from alternative donors (83% vs 33%) and received more frequently ruxolitinib pre-HSCT (26% vs 7%). The proportion of patients with F-DC on day +30, in the TBF vs the ONE-ALK group, was respectively 87% vs 45% (P < .001). The 5-year cumulative incidence of relapse was 9% in the TBF group, vs 43% for the ONE-ALK group (P < .001). The 5-year actuarial disease-free survival was 63% for TBF and 38% for the ONE-ALK group (P = .004). In conclusion, early full donor chimerism is a prerequisite for long term control of disease in patients with myelofibrosis, undergoing an allogeneic HSCT. The combination of two alkylating agents in the conditioning regimen, provides a higher chance of achieving full donor chimerism on day+30, and thus a higher chance of long term disease free survival., (© 2020 Wiley Periodicals LLC.)

About 105 consecutive acute myeloid leukemia (AML) patients treated with the same induction-consolidation program between 2004 and 2013 were retrospectively analyzed. Median age was 47 years. The first induction course included fludarabine (Flu) and high-dose cytarabine (Ara-C) plus idarubicin (Ida), with or without gemtuzumab-ozogamicin (GO) 3 mg/m(2) (FLAI-5). Patients achieving complete remission (CR) received a second course without fludarabine but with higher dose of idarubicin. Patients not achieving CR received an intensified second course. Patients not scheduled for early allogeneic bone marrow transplantation (HSCT) where planned to receive at least two courses of consolidation therapy with Ara-C. Our double induction strategy significantly differs from described fludarabine-containing regimens, as patients achieving CR receive a second course without fludarabine, to avoid excess toxicity, and Ara-C consolidation is administrated at the reduced cumulative dose of 8 g/m(2) per cycle. Toxicity is a major concern in fludarabine containing induction, including the recent Medical Research Council AML15 fludarabine, cytarabine, idaraubicin and G-CSF (FLAG-Ida) arm, and, despite higher anti-leukemic efficacy, only a minority of patients is able to complete the full planned program. In this article, we show that our therapeutic program is generally well tolerated, as most patients were able to receive subsequent therapy at full dose and in a timely manner, with a 30-day mortality of 4.8%. The omission of fludarabine in the second course did not reduce efficacy, as a CR rate of 83% was achieved and 3-year disease-free survival and overall survival (OS) were 49.6% and 50.9%, respectively. Our experience shows that FLAI-5/Ara-C + Ida double induction followed by risk-oriented consolidation therapy can result in good overall outcome with acceptable toxicity. Am. J. Hematol. 91:755-762, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

We assessed WT1 expression (expressed as messenger copies/10(4) ABL1) from marrow cells of 122 patients with acute myeloid leukaemia (AML), before and after an unmanipulated allogeneic haemopoietic stem cell transplant (HSCT). The median age was 44 years (15-69), 59% were in first remission, 74% received a myeloablative conditioning regimen and the median follow up was 865 d (34-2833). Relapse was higher in 67 patients with WT1 expression, at any time post-HSCT, exceeding 100 copies (54%), as compared to 16%, for 55 patients with post-HSCT WT1 expression <100 copies (P < 0·0001). Similarly, actuarial 5-year survival (OS) was 40% vs. 63%, respectively (P = 0·03). In multivariate Cox analysis, WT1 expression post-HSCT was the strongest predictor of relapse (Hazard Ratio [HR] 4·5, P = 0·0001), independent of disease phase (HR 2·3, P = 0·002). Donor lymphocyte infusions (DLI) were given to 17 patients because of increasing WT1 levels: their OS was 44%, vs. 14% for 21 patients with increasing WT1 expression who did not receive DLI (P = 0·004). In conclusion, WT1 expression post-HSCT is a strong predictor of leukaemia relapse and survival in AML; WT1 may be used as a marker for early interventional therapy., (© 2013 Blackwell Publishing Ltd.)

Objective: Radiographs are an integral part of detecting proximal caries. The aim of this study was to evaluate the effect of contrast, brightness, noise, sharpness, and γ adjustment of digital intraoral radiographs on the diagnosis of proximal caries. Materials and methods: In this in vitro study, 40 extracted teeth including 20 premolars and 20 molars with enamel lesions (white spot or dentin discoloration seen through the enamel) were mounted together in groups of eight inside the skull. Bitewing radiographic images of each dental group were obtained by a photostimulable phosphor plate sensor with exposure conditions of 8 mA, 70 kV, and 0.2 s. The images were reconstructed by the built‐in software and examined by two oral and maxillofacial radiologists in various settings of contrast, brightness, sharpness, noise, and γ. The teeth were then cut mesiodistally and the presence or absence of caries was confirmed by an oral and maxillofacial pathologist using a stereomicroscope. The data were then analyzed using the κ agreement coefficient, sensitivity, specificity, and accuracy (α =.05). Results: Adjustment of brightness and contrast led to higher diagnostic performance with an accuracy of 82.5% and 83.8 (for observers 1 and 2, respectively) and 82.5% (for both observers), respectively. Noise adjustment was the least helpful approach for diagnosis of proximal dental caries among other adjustments, with an accuracy of 78.8% and 77.5% for observers 1 and 2, respectively. Conclusion: Brightness and contrast setting was more efficient in improving the diagnostic potential of bitewing radiographs compared to other adjustments. [ABSTRACT FROM AUTHOR]

Objectives: Allogeneic hematopoietic stem‐cell transplantation (HCT) is the only curative option for most hematologic malignancies. However, HSCT can cause early menopause and various complications in premenopausal women. Therefore, we aimed to investigate risk factors predicting early menopause and its clinical implications among survivors post HCT. Methods: We retrospectively analyzed 30 adult women who had received HCT at premenopausal status between 2015 and 2018. We excluded patients who had received autologous stem cell transplantation, had relapsed, or died of any cause within 2 years of HCT. Results: The median age at HCT was 41.6 years (range, 22–53). Post‐HCT menopause was identified in 90% of myeloablative conditioning (MAC) HCT and 55% of reduced‐intensity conditioning (RIC) HCT (p =.101). In the multivariate analysis, the post‐HCT menopausal risk was 21 times higher in a MAC regimen containing 4 days of busulfan (p =.016) and 9.3 times higher in RIC regimens containing 2–3 days of busulfan (p =.033) than that of non‐busulfan‐based conditioning regimens. Conclusions: Higher busulfan dose in conditioning regimens is the most significant risk factor affecting post‐HCT early menopause. Considering our data, we need to decide on conditioning regimens and individualized fertility counseling before HCT for premenopausal women. [ABSTRACT FROM AUTHOR]

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.)

Summary: Haematopoietic stem cell reinjection may be a curative option for poor graft function after haematopoietic stem cell transplantation; however, literature supporting its use remains limited. We conducted a multicentre retrospective study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy, including 55 patients. We demonstrated response rates of nearly 40% and two‐year survival of more than 60% in the context of an otherwise deadly complication and we observed that the timing of injection and the degree of cytopenia are strongly associated with outcomes. This study shows the feasibility of the procedure informing on its epidemiology, outcomes and prognostic factors, setting the stage for future guidelines. [ABSTRACT FROM AUTHOR]

In vitro combination of echinocandins and isavuconazole against the emerging species Candida auris is mainly synergistic. However, this combination has not been evaluated in clinical settings. A pharmacokinetic/pharmacodynamic modeling and simulation approach based on in vitro data may be helpful to further study the therapeutic potential of these combinations. Therefore, the aims of this study were to characterize the time course of growth and killing of C. auris in response to the combination of the three approved echinocandins and isavuconazole using a semimechanistic model and to perform model‐based simulations in order to predict the in vivo response to combination therapy. In vitro static time‐kill curve data for isavuconazole and echinocandins combinations against six blood isolates of C. auris were best modeled considering the total killing of the fungal population as dependent on the additive effects of both drugs. Once assessed, the predictive performance of the model using simulations of different dosing and fungal susceptibility scenarios were conducted. Model‐based simulations revealed that none of the combinations at standard or higher dosages would be effective against the studied isolates of C. auris and it was predicted that the combinations of isavuconazole with anidulafungin or caspofungin would be effective for minimum inhibitory concentrations up to 0.03 and 0.06 mg/L respectively, whereas the combination with micafungin would lead to treatment failure. The current approach highlights the importance of bridging the in vitro results to the clinic. [ABSTRACT FROM AUTHOR]

Summary: In a prospective, explorative study, the donor‐source difference of haploidentical family (HF), matched sibling (MS), and unrelated donors (UD) was evaluated for the outcome of haematopoietic cell transplantations (HCT) in 101 patients with acute myeloid leukaemia (AML) in complete remission (CR). To eliminate compounding effects, a uniform conditioning regimen containing antithymocyte globulin (ATG) was used. After transplantation, there was a significantly higher cumulative incidence of acute graft‐versus‐host disease (GVHD) in HF‐HCT patients (49%, 7%, and 16% for HF‐, MS‐ and UD‐HCT respectively; p < 0.001). A quarter of acute GVHD cases observed in HF‐HCT patients occurred within three days of engraftment and were characterized by diffuse skin rash, fever, weight gain, and hypoalbuminaemia. This peri‐engraftment acute GVHD was not observed in MS‐HCT or UD‐HCT patients. Additionally, a significantly higher proportion of HF‐HCT patients achieved complete donor chimaerism in the peripheral mononuclear cells at one month (88%, 46%, and 69% for HF‐, MS‐ and UD‐HCT respectively; p = 0.001). There was no significant difference in engraftment, chronic GVHD, leukaemia recurrence, non‐relapse mortality, and patient survival. In patients with AML in CR who received HCT using ATG‐containing conditioning, stronger donor–patient alloreactivity was observed in HF‐HCT, in terms of increased acute GVHD and higher likelihood of complete donor chimaerism. [ABSTRACT FROM AUTHOR]

Objectives: Patients with high‐risk hematologic diseases require intensive modalities, including high‐dose chemotherapy and allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Haploidentical T‐cell–replete transplantation is a logical choice because of the limited availability of matched sibling donors and the prolonged time needed to identify matched unrelated donors in Thailand. Methods: The clinical outcomes data of 43 patients undergoing allo‐HSCT were reviewed. All patients had high‐risk hematologic malignancies, were younger than 20 years, and were in complete cytological remission at the time of allo‐HSCT. We used two different conditioning regimens: total body irradiation (TBI) combined with cyclophosphamide, fludarabine, and melphalan (n = 23) and thiotepa combined with fludarabine and busulfan (n = 20). All patients received a graft‐versus‐host disease prophylaxis regimen consisting of cyclophosphamide, mycophenolate mofetil, and a calcineurin inhibitor or sirolimus. Results: There was no difference in engraftment between patients receiving either of the regimens. After a median follow‐up of 35.8 (range, 0.6–106.2) months, the overall survival (OS) and event‐free survival (EFS) rates were 62.4% and 54.7%, respectively. OS and EFS were comparable between the respective regimens. Conclusions: We conclude that thiotepa‐based conditioning has similar efficacy and tolerability as TBI‐based conditioning for haploidentical HSCT with post‐transplant cyclophosphamide. [ABSTRACT FROM AUTHOR]

Data from 200 children with high-risk acute myeloid leukaemia who underwent their first haploidentical haematopoietic stem cell transplantation (haplo-HSCT) between 2015 and 2021 at our institution were analysed. The 4-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 71.9%, 62.3% and 32.4% respectively. The 100-day cumulative incidences of grade II-IV and III-IV acute graft-versus-host disease (aGVHD) were 41.1% and 9.5% respectively. The 4-year cumulative incidence of chronic GVHD (cGVHD) was 56.1%, and that of moderate-to-severe cGVHD was 27.3%. Minimal residual disease (MRD)-positive (MRD+) status pre-HSCT was significantly associated with lower survival and a higher risk of relapse. The 4-year OS, EFS and CIR differed significantly between patients with MRD+ pre-HSCT (n = 97; 63.4%, 51.4% and 41.0% respectively) and those with MRD-negative (MRD-) pre-HSCT (n = 103; 80.5%, 73.3% and 23.8% respectively). Multivariate analysis also revealed that acute megakaryoblastic leukaemia without Down syndrome (non-DS-AMKL) was associated with extremely poor outcomes (hazard ratios and 95% CIs for OS, EFS and CIR: 3.110 (1.430-6.763), 3.145 (1.628-6.074) and 3.250 (1.529-6.910) respectively; p-values were 0.004, 0.001 and 0.002 respectively). Thus, haplo-HSCT can be a therapy option for these patients, and MRD status pre-HSCT significantly affects the outcomes. As patients with non-DS-AMKL have extremely poor outcomes, even with haplo-HSCT, a combination of novel therapies is urgently needed., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Background: The broad‐spectrum triazole isavuconazole is used for the treatment of invasive aspergillosis and mucormycosis. Data regarding human plasma concentrations in clinical routine of the drug are rare. Objectives: Plasma concentrations of isavuconazole were determined in critically ill ICU patients while considering different patients' characteristics. Methods: Retrospective analysis of isavuconazole plasma concentrations were obtained as part of routine therapeutic drug monitoring (TDM) of ICU patients with invasive aspergillosis or other fungal infections treated with isavuconazole. Plasma levels 0–4 h after last dosing were defined as peak levels (Cmax), those 20–28 h after last dosing as trough levels (Cmin). Results: Overall, 223 isavuconazole levels of 41 patients were analysed, divided into 141 peak levels and 82 trough levels. The overall median Cmax was 2.36 μg/ml (mean 2.43 μg/ml, range 0.41–7.79 μg/ml) and the overall median Cmin was 1.74 μg/ml (mean 1.77 μg/ml, range 0.24–4.96 μg/ml). In total, 31.7% of the Cmin values of the total cohort were below the plasma target concentrations of 1 μg/ml, defined as EUCAST antifungal clinical breakpoint for Aspergillus fumigatus. Both peak and trough plasma levels of isavuconazole were significantly lower among patients with a body mass index (BMI) ≥25. In addition, a significant correlation was observed between isavuconazole trough levels and sepsis‐related organ failure assessment (SOFA) score. Conclusions: This study shows that isavuconazole plasma concentrations vary in critical ill ICU patients. Significantly lower isavuconazole levels were associated with elevated BMI and higher SOFA score indicating a need of isavuconazole TDM in this specific patient population. [ABSTRACT FROM AUTHOR]

The objective of this guideline is to provide healthcare professionals with clear, up-to-date and practical guidance on the management of thrombotic thrombocytopenic purpura (TTP) and related thrombotic microangiopathies (TMAs), including complement-mediated haemolytic uraemic syndrome (CM HUS); these are defined by thrombocytopenia, microangiopathic haemolytic anaemia (MAHA) and small vessel thrombosis. Within England, all TTP cases should be managed within designated regional centres as per NHSE commissioning for highly specialised services., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Antifungal agents can have complex dosing and the potential for drug interaction, both of which can lead to subtherapeutic antifungal drug concentrations and poorer clinical outcomes for patients with haematological malignancy and haemopoietic stem cell transplant recipients. Antifungal agents can also be associated with significant toxicities when drug concentrations are too high. Suboptimal dosing can be minimised by clinical assessment, laboratory monitoring, avoidance of interacting drugs, and dose modification. Therapeutic drug monitoring (TDM) plays an increasingly important role in antifungal therapy, particularly for antifungal agents that have an established exposure‐response relationship with either a narrow therapeutic window, large dose‐exposure variability, cytochrome P450 gene polymorphism affecting drug metabolism, the presence of antifungal drug interactions or unexpected toxicity, and/or concerns for non‐compliance or inadequate absorption of oral antifungals. These guidelines provide recommendations on antifungal drug monitoring and TDM‐guided dosing adjustment for selected antifungal agents, and include suggested resources for identifying and analysing antifungal drug interactions. Recommended competencies for optimal interpretation of antifungal TDM and dose recommendations are also provided. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Reduction in incidence of non-COVID-19 respiratory virus infection amongst haematology inpatients following UK social distancing measures It is predicted that there may be a rebound in RSV incidence once social distancing measures are relaxed,15 due to increased RSV susceptibility following reduced transmission during COVID-19-related restrictions. Keywords: BioFire polymerase chain reaction; bone marrow transplantation; influenza; respiratory syncytial virus; SARS-CoV-2 EN BioFire polymerase chain reaction bone marrow transplantation influenza respiratory syncytial virus SARS-CoV-2 194 197 4 10/12/21 20211015 NES 211015 Since the SARS-CoV-2 pandemic began, countries across the globe have seen repeated periods of government-enforced social distancing to restrict transmission in response to rises in COVID-19 incidence.1 Social distancing in the UK was first introduced in March 2020, and for six of the following 12 months the population was under strict national restrictions. BioFire polymerase chain reaction, bone marrow transplantation, influenza, respiratory syncytial virus, SARS-CoV-2. [Extracted from the article]

Objective: As peripheral blood (PB) Wilm'sTumor 1 (WT1)‐mRNA expression is established as MRD‐marker during conventional AML chemotherapy, impact of pretransplant WT1 expression remains unclear. Therefore, we aimed to assess prognostic impact of pretransplant WT1 expression on post‐transplant outcome in patients with AML/MDS. Methods: In 64 AML/MDS patients, pretransplant WT1 expression was retrospectively analyzed using a standardized assay offering high sensitivity, specificity, and a validated cut‐off. Patients were divided into three groups determined by pretransplant remission and WT1 expression. Post‐transplant outcome of these groups was compared regarding cumulative incidence of relapse (CIR), relapse‐free (RFS), and overall survival (OS). Results: Pretransplant forty‐six patients (72%) showed hematologic remission, including 21 (46%) MRD‐negative and 25 (54%) MRD‐positive patients indicated by WT1 expression, while 18 refractory patients (28%) showed active disease. Two‐year estimates of post‐transplant CIR, RFS, and OS were similar in MRD‐positive (61%, 37%, 54%) and refractory patients (70%, 26%, 56%), but significantly inferior compared with MRD‐negative patients (10%, 89%, 90%). After multivariable adjustment, pretransplant MRD negativity measured by WT1 expression retained its prognostic impact on CIR (P =.008), RFS (P =.005), and OS (P =.049). Conclusions: PB WT1 expression represents a useful method to estimate pretransplant MRD, which is highly predictable for post‐transplant outcome and may help improving peri‐transplant management in AML/MDS patients. [ABSTRACT FROM AUTHOR]

Summary: Community respiratory viral infections (CRVIs) are associated with pulmonary function impairment, alloimmune lung syndromes and inferior survival in human leucocyte antigen (HLA)‐matched allogeneic haematopoietic stem cell transplant (HCT) recipients. Although the incidence of viral infections in HLA‐haploidentical HCT recipients who receive post‐transplant cyclophosphamide (PTCy)‐based graft‐versus‐host disease (GVHD) prophylaxis is reportedly increased, there are insufficient data describing the incidence of CRVIs and the impact of donor source and PTCy on transplant outcomes. Analysing patients receiving their first HCT between 2012 and 2017 for acute myeloid leukaemia, acute lymphoblastic leukaemia and myelodysplastic syndromes, we describe comparative outcomes between matched sibling transplants receiving either calcineurin‐based GVHD prophylaxis (SibCNI, N = 1605) or PTCy (SibCy, N = 403), and related haploidentical transplants receiving PTCy (HaploCy, N = 757). The incidence of CRVIs was higher for patients receiving PTCy, regardless of donor type. Patients in the HaploCy cohort who developed a CRVI by day +180 had both a higher risk of treatment‐related mortality [hazard ratio (HR) 2⋅14, 99% confidence interval (CI) 1⋅13–4⋅07; P = 0⋅002] and inferior 2‐year overall survival (HR 1⋅65, 99% CI 1⋅11–2⋅43; P = 0⋅001) compared to SibCNI with no CRVI. This finding justifies further research into long‐term antiviral immune recovery, as well as development of preventive and treatment strategies to improve long‐term outcomes in such patients. [ABSTRACT FROM AUTHOR]

Background: Azacitidine (AZA) is the standard treatment for myelodysplastic syndromes (MDS); however, many patients prematurely stop therapy and have a dismal outcome.Methods: The authors analyzed outcomes after AZA treatment for 402 MDS patients consecutively enrolled in the Italian MDS Registry of the Fondazione Italiana Sindromi Mielodisplastiche, and they evaluated the North American MDS Consortium scoring system in a clinical practice setting.Results: At treatment discontinuation, 20.3% of the patients were still responding to AZA, 35.4% of the cases had primary resistance, and 44.3% developed adaptive resistance. Overall survival (OS) was better for patients who discontinued treatment while in response because of planned allogeneic hematopoietic stem cell transplantation (HSCT; median OS, not reached) in comparison with patients with primary resistance (median OS, 4 months) or adaptive resistance (median OS, 5 months) or patients responsive but noncompliant/intolerant to AZA (median OS, 4 months; P = .004). After AZA discontinuation, 309 patients (77%) received best supportive care (BSC), 60 (15%) received active treatments, and 33 (8%) received HSCT. HSCT was associated with a significant survival advantage, regardless of the response to AZA. The North American MDS Consortium scoring system was evaluable in 278 of the 402 cases: patients at high risk had worse OS than patients at low risk (3 and 7 months, respectively; P < .001). The score was predictive of survival both in patients receiving BSC (median OS, 2 months for high-risk patients vs 5 months for low-risk patients) and in patients being actively treated (median OS, 8 months for high-risk patients vs 16 months for low-risk patients; P < .001), including transplant patients.Conclusions: Real-life data confirm that this prognostic scoring system for MDS patients failing a hypomethylating agent seems to be a useful tool for optimal prognostic stratification and for choosing a second-line treatment after AZA discontinuation. [ABSTRACT FROM AUTHOR]

The presence of donor‐specific anti‐human leukocyte antigen (HLA) antibodies (DSAs) has been recognized as a major risk factor for graft failure (GF) after haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide (haplo‐PTCy). However, the role of DSAs in salvage haplo‐PTCy for rescuing patients with nonmalignant disorders (NMDs) has not yet been reported. The present study retrospectively analyzed 22 patients with NMDs who underwent salvage haplo‐PTCy from January 2008 to December 2017. The median age at the time of the rescue haplo‐PTCy was 9 years (range, 1–26 years). Median time from the first transplant to second haplo‐PTCy was 56 days (range, 37–591 days). Among all patients, six (27.3%) had DSAs, with a median DSA strength (mean fluorescence intensity [MFI]) of 5201 (range, 1412–11,543) in the first DSA testing. In addition, the median DSA MFI was 2672 (range, 832–10,498) before the bone marrow infusion. Overall, GF occurred in 5 (25%) of the 20 assessable patients. Three of four (75%) patients with DSAs experienced GF versus 2 of 16 (12.5%) DSA‐negative patients (P = 0.032). The median DSA MFI for patients with GF was 6437 (range, 1412–10,498) versus 1845 (range, 832–2672) for those who engrafted or had early death (P = 0.030). One‐year event‐free survival was significantly lower in DSA‐positive patients than in those without DSAs (16.7% vs. 62.5%, P = 0.002). DSA‐negative patients had an acceptable 1‐year survival of 62.5%. In conclusion, this study suggests that DSAs may be associated with deleterious outcomes after salvage haplo‐PTCy in patients with NMDs. [ABSTRACT FROM AUTHOR]

Summary: In recent years there have been major advances in the use of molecular diagnostic and monitoring techniques for patients with acute myeloid leukaemia (AML). Coupled with the simultaneous explosion of new therapeutic agents, this has sown the seeds for significant improvements to treatment algorithms. Here we show, using a selection of real‐life examples, how molecular monitoring can be used to refine clinical decision‐making and to personalise treatment in patients with AML with nucleophosmin (NPM1) mutations, core binding factor translocations and other fusion genes. For each case we review the established evidence base and provide practical recommendations where evidence is lacking or conflicting. Finally, we review important technical considerations that clinicians should be aware of in order to safely exploit these technologies as they undergo widespread implementation. [ABSTRACT FROM AUTHOR]

Background: Invasive fungal disease (IFD) is a serious complication among the immunocompromised population. Isavuconazole is a newer broad‐spectrum antifungal agent with promising efficacy and safety. However, there remains limited data to favor its use over current first‐line agents. Objectives: We aimed to evaluate isavuconazole use and describe rates of associated breakthrough invasive fungal disease (bIFD). Methods: A single‐center, retrospective study was conducted to evaluate patients receiving isavuconazole for prophylaxis or treatment of IFD between July 1, 2017 and December 31, 2018. Patient‐related and outcomes data were extracted from electronic medical records. Descriptive statistics were used to analyze our findings. Results: A total of 54 patients received 61 isavuconazole courses. Isavuconazole was most commonly prescribed for primary prophylaxis in the acute myeloid leukemia (AML) and allogeneic hematopoietic stem cell transplant (HSCT) population along with treatment for possible invasive fungal disease. The primary reasons for choosing isavuconazole included QTc shortening effects, decreased risk of acute kidney injury, broader spectrum of activity, and concern for breakthrough invasive fungal disease on a different prophylactic agent. We found a breakthrough rate of 8.5% for patients and 7.8% for courses. Conclusions: Isavuconazole appears to be a promising alternative for prophylaxis and treatment of invasive fungal disease. We observed similar bIFD rates and improved tolerability when compared to historical data for posaconazole and voriconazole. [ABSTRACT FROM AUTHOR]

Alternate donor HSCT for thalassemia major from a matched unrelated donor or haploidentical family donor is a feasible therapeutic option in children with no matched family donor. Aggressive pretransplant immunosuppression, reduced toxicity conditioning, and PTCY result in excellent thalassemia‐free survival. We describe here our experience in this cohort. We performed a retrospective analysis of the data on children who underwent a haploidentical HSCT for thalassemia major with PTCY at our center from August 2017 to August 2019. All children received pretransplant immune suppression for 6 weeks with fludarabine and dexamethasone, hypertransfusion and chelation with intravenous desferrioxamine. Conditioning included thiotepa, fludarabine, rabbit ATG, and cyclophosphamide, and GvHD prophylaxis included PTCY with tacrolimus. Twenty children were included and nineteen children engrafted. Acute hypertension occurred in five children, bacterial infection in eight children and viral respiratory infection in three children. Three children suffered from graft rejection. Reactivation of viruses namely CMV, adenovirus, and BK virus was seen in 60% of children. Grades 1‐2 acute GvHD of the skin in four children (20%) and limited chronic GvHD of the skin in four children (20%). Immune cytopenia was documented in three children (15%). Haploidentical HSCT offers a therapeutic option for children with thalassemia major with no suitably matched family or unrelated donors. Our reduced toxicity regimen with PTCY offers a DFS of 75% and OS of 95% with low transplant‐related mortality of 5%. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders and is rare in children. Allogeneic hematopoietic stem cell transplantation (HSCT) is commonly used in children with MDS with excess blasts and in patients with refractory cytopenia of childhood (RCC) associated with monosomy 7, complex karyotype, severe neutropenia, or transfusion dependence. We recruited 27 children with MDS who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT). At transplantation, 10 patients had RCC, 12 patients had advanced MDS (RAEB and RAEB-T), and 5 patients had myelodysplasia-related acute myeloid leukemia (MDRAML). All patients received granulocyte colony-stimulating factor (G-CSF)-mobilized bone marrow cells and peripheral blood stem cells. At a median follow-up of 24.1 months (range: 2.0-74.5 months) after HSCT, the estimated probabilities of 3-year disease-free survival (DFS) and overall survival (OS) were both 81.9% (95% CI, 66.8-100.0%). The estimated 3-year incidences of relapse (CIR) and non-relapse mortality (NRM) were both 7.4% (95% CI, 1.2%-21.4%). The 100-day cumulative incidence of grade II-IV aGVHD was 52.6% (95% CI, 42.9-62.3%), while that of grade III-IV aGVHD was 11.1% (95% CI, 5.1-17.1%). The 3-year cumulative incidences of overall and extensive cGVHD were 42.3% (95% CI, 19.8%-57.5%) and 21.1% (95% CI, 2.5%-63.2%), respectively. Univariate analysis showed that chronic GVHD significantly affected OS and DFS. Haploidentical HSCT may be an effective treatment option with easier donor availability for pediatric patients with MDS. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare ventral mesh rectopexy (VMR) and pelvic organ prolapse suspension surgery (POPS) in management of patients presenting with rectal prolapse. Methods: Our study was a prospective cohort trial in which 120 female patients with complete rectal prolapse were included, 60 patients had had VMR and the other 60 had had POPS as a surgical management for complete rectal prolapse. Results had been compared 6 months postoperatively regarding operative time, postoperative pain, hospital stay, complications of surgery including recurrence of the rectal prolapse, the efficacy of each operation in treatment of rectal prolapse and associated symptoms. Results: The patients were assessed 6 months postoperatively. There was no significant statistical difference regarding hospital stay and postoperative pain. Operative time was significantly shorter in POPS in comparison with VMR (P value < 0.05). VMR showed slight improvement regarding constipation and continence scores; however, this was statistically significant. VMR showed less complications compared to POPS. Complications with rectopexy happened only with 4 patients compared to 24 patients in POPS groups, 2 cases of recurrence in rectopexy group compared to 6 cases of recurrence in POPS. Conclusion: POPS is comparable to VMR in management of rectal prolapse and in improving the ODS symptoms. Thus, POPS can be used as easier, faster option to treat rectal prolapse in selected patients. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic cell transplantation (HCT) remains the only curable option for adult patients with hematologic malignancies. According to guidelines published by the American Society for Transplantation and Cellular Therapy, allogeneic HCT should be offered to all intermediate‐ and high‐risk patients with acute leukemia. While matched‐related donor (MRD) grafts continue to be the preferred stem cell source for allogeneic HCT, studies comparing MRD grafts to matched‐unrelated donor (MUD) grafts showed comparable outcomes in patients with acute leukemia. Unfortunately, for those without a suitable matched‐related graft, the probability of finding a suitable matched‐unrelated donor varies significantly depending on racial and ethnic background. With allogeneic HCT procedures increasing year after year due to the increased availability of suitable donors, each of these alternative donor sources merits special clinical considerations, specifically with regard to infections. Infections remain a significant cause of morbidity and mortality after allogeneic transplant, especially in those receiving alternative donor grafts. Due to the high‐risk nature associated with these donor grafts, it is important to understand the true risk of developing infectious complications. While there are a multitude of infections that have been described in patients post‐allogeneic HCT, this review seeks to focus on the incidence of cytomegalovirus (CMV) and invasive fungal infections (IFI) in adult patients receiving alternative donor source transplantation for hematologic malignancies. [ABSTRACT FROM AUTHOR]

Summary: Background: Invasive fungal diseases remain a major cause of morbidity and mortality in cancer patients undergoing intensive cytotoxic therapy. The choice of the most appropriate antifungal treatment (AFT) depends on the fungal species suspected or identified, the patient's risk factors (eg length and depth of granulocytopenia) and the expected side effects. Objectives: Since the last edition of recommendations for 'Treatment of invasive fungal infections in cancer patients' of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) in 2013, treatment strategies were gradually moving away from solely empirical therapy of presumed or possible invasive fungal diseases (IFDs) towards pre‐emptive therapy of probable IFD. Methods: The guideline was prepared by German clinical experts for infections in cancer patients in a stepwise consensus process. MEDLINE was systematically searched for English‐language publications from January 1975 up to September 2019 using the key terms such as 'invasive fungal infection' and/or 'invasive fungal disease' and at least one of the following: antifungal agents, cancer, haematological malignancy, antifungal therapy, neutropenia, granulocytopenia, mycoses, aspergillosis, candidosis and mucormycosis. Results: AFT of IFDs in cancer patients may include not only antifungal agents but also non‐pharmacologic treatment. In addition, the armamentarium of antifungals for treatment of IFDs has been broadened (eg licensing of isavuconazole). Additional antifungals are currently under investigation or in clinical trials. Conclusions: Here, updated recommendations for the treatment of proven or probable IFDs are given. All recommendations including the levels of evidence are summarised in tables to give the reader rapid access to key information. [ABSTRACT FROM AUTHOR]

Human leukocyte antigen (HLA)‐haploidentical hematopoietic stem cell transplantation (haplo‐HSCT) is an effective alternative to HLA‐matched transplantation. However, Epstein‐Barr virus (EBV) infection causes morbidity and mortality in patients undergoing haplo‐HSCT. Here, we retrospectively evaluated the incidence and risk factors of EBV‐DNAemia and EBV‐associated diseases in 131 patients who underwent haplo‐HSCT. Patients were classified into the no EBV infection groups, EBV‐DNAemia group and EBV‐associated disease group. Cumulative incidences of acute graft‐vs‐host disease, EBV infections, overall survival (OS), and relapse were analyzed. The cumulative incidences of EBV‐DNAemia and EBV‐associated disease were 26.9% and 33.3%, respectively. In multivariate analysis, cytomegalovirus (CMV)‐DNAemia was confirmed as an independent risk factor associated with EBV‐DNAemia and EBV‐associated disease. Patients with EBV‐associated disease had higher transplant‐related mortality (TRM) rates and lower OS rates, but similar relapse rates. Overall, these findings demonstrated the cumulative incidences of EBV‐DNAemia and EBV‐associated disease and identified correlations of EBV infection with TRM, relapse, and OS. Additionally, CMV‐DNAemia was a risk factor for EBV‐DNAemia and EBV‐associated disease. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) infection is a worldwide concern with a broad distribution. In immunosuppressed populations, such as solid organ and hematopoietic stem cell transplant (HSCT) recipients, it can reactivate leading to acute hepatic failure. Different risk factors are known for higher rates of reactivation, and entecavir, tenofovir, and lamivudine are often used for prophylaxis and treatment. However, data regarding the impact of antiviral drugs in neutrophil and platelet engraftment are still unknown and concern the management of viral hepatitis post‐HSCT. Methods: We performed a single‐center, retrospective, observational study reviewing medical records of patients referred for hematopoietic stem cell transplant from 2010 to 2017, which were also HBV infected, aiming to describe outcomes related to antiviral treatment and also the impact on platelet and neutrophil recovery after transplant. A secondary goal consisted of analyzing the impact of HBV infection in early and late mortality post‐HSCT. The study included patients with positive blood bank screening for hepatitis B infection (HBsAg, Anti‐HBc or HBV‐NAT), confirmed later on by a laboratory routine serology. Results: A total of 1132 hematopoietic stem cell recipients were assessed between 2010 and 2017. Eighty‐six patients were confirmed to have HBV infection, of which six were HBsAg‐positive, 20 were isolated anti‐HBc‐positive, and 60 had resolved infection (anti‐HBc‐positive and anti‐HBs‐positive). With regard to prophylaxis, 19 patients underwent HSCT on HBV antiviral therapy or prophylaxis: two were HBeAg‐positive, three were HBeAg‐negative and HBV‐DNA was only detectable in three of them. Moreover, one patient had an occult HBV infection. Regarding therapy, 9 patients were on entecavir, 6 patients on lamivudine, two on tenofovir, and two of them on a combination of tenofovir + lamivudine due to HIV co‐infection. Reverse seroconversion was not identified in any patients receiving antiviral therapy or prophylaxis, but it was detected in one patient with occult hepatitis B and another with resolved infection. No severe side effects led to therapy discontinuation in the treated group, which also did not have any significant delay in neutrophil or platelet engraftment when compared to patients without antiviral therapy. In addition, the only factors associated with increased mortality were transplant onset after 50 years, allogeneic transplant and myeloablative conditioning regimens. Interestingly, the presence of HBsAg or detectable HBV‐DNA was not related to worse outcomes, neither the use of rituximab. In multivariate analysis, the use of antiviral therapy, the occurrence of graft‐versus‐host disease or CMV reactivation also was not linked to increased mortality. Conclusions: To sum up, HBV serology, ALT, and HBV‐DNA monitoring are essential to detect hepatic flares earlier, even in populations with chronic inactive hepatitis, due to the possibility of later seroconversion. HBV infection was not related to increased 2‐year mortality post‐transplant. Antiviral prophylaxis did not cause any important clinical or laboratory side effects that could demand discontinuation, and its use was not associated with later neutrophil and platelet engraftments. [ABSTRACT FROM AUTHOR]

Summary: Donor selection for older leukaemia patients undergoing haematopoietic cell transplant (HCT) is not well defined: outcomes might be improved with a younger offspring donor rather than an older human leukocyte antigen (HLA)‐matched sibling donor (MSD). We extended our multicentre dataset. A total of 185 acute leukaemia patients (≥ 50 years) transplanted in first complete remission who received HCT from offspring (n = 62) or MSD (n = 123) were included. A 1:1 ratio matched‐pair analysis was performed. We were able to match 54 offspring with 54 MSD patients. Outcomes were compared between the two matched‐pair groups. The cumulative incidence of grade II/IV acute graft‐versus‐host disease (GVHD) (26% vs. 35%; P = 0·23) and chronic GVHD (37% vs. 24%; P = 0·19) was comparable between groups (MSD vs. offspring). The lower three‐year transplant‐related mortality (9% vs. 26%; P = 0·023) and relapse incidence (6% vs. 17%; P = 0·066) resulted in higher overall survival (85% vs. 58%; P = 0·003) and leukaemia‐free survival (LFS) (85% vs. 56%; P = 0·001) in offspring HCT compared with that in MSD HCT. These data might favour a young offspring over an older MSD in patients >50 years. The current analyses confirm that non‐HLA donor characteristics, such as kinship and donor age, rather than HLA disparity, predominantly influence survival in older acute leukaemia patients. [ABSTRACT FROM AUTHOR]

Background: The volume of haploidentical hematopoietic stem cell transplant (haplo-HSCT) has increased dramatically in recent years. However, the associated higher risk of delayed engraftment may increase patient transfusion requirements.Study Design and Methods: The post-HSCT RBC and platelet transfusions of 195 haplo-HSCT recipients were evaluated. Patient and transplant-related factors potentially impacting the number of products transfused and time to transfusion independence were assessed.Results: Nearly all (98.4%) patients were transfused in the first 30 days, and 59.2% were transfused between days 31 and 100. Among the transfused patients, medians of 5 units (interquartile range [IQR] = 3-8) of RBCs and 11 units (6-20) platelets were given in the first 30 days, and medians of 3 units (IQR = 1-7) of RBCs and 6 units (2-18) of platelets were transfused between days 31 and 100. Median times for achieving RBC and platelet transfusion independence were 34 (95% CI: 28-40) and 25 (95% CI: 23-27) days, respectively. Multivariable analyses showed that RBC transfusions in the 10 days before HSCT were associated with significantly increased and sustained RBC and platelet transfusion requirements. Major ABO incompatibility led to increased RBC transfusions. Advanced disease was associated with increased transfusions during the first 30 days, whereas GVHD increased platelet transfusions between days 31 and 100. Effects of age, sex, CD34+ cell dose, stem cell source, and conditioning regimen were limited or insignificant.Conclusions: This study for the first time provided quantitative transfusion data on a large cohort of haplo-HSCT recipients and identified factors predictive of increased transfusions. [ABSTRACT FROM AUTHOR]

GLO:1XW/01nov19:bjh16189-fig-0001.jpg PHOTO (COLOR): Cumulative incidence of infection-related mortality (A); bacterial infections (B); CMV reactivation (C), EBV reactivation (D), BK virus cystitis (E) and fungal infection (F). Eight patients were admitted to the intensive care unit (ICU) because of a serious and life-threatening bacterial infection, which was lethal in five patients (Data S1). Furthermore, only one of our patients developed CMV disease (CMV retinitis) compared to the 15% incidence of CMV organ disease after PBSC Haplo-HCT with PT-Cy reported by Slade et al ([6]). Overall, although the CI of viral reactivation was relatively high, none of the viral infections required admission to the ICU and only one patient died from viral infection (severe BK virus cystitis). [Extracted from the article]

Objectives: Umbilical cord blood transplantation (UCBT) and haploidentical hematopoietic stem cell transplantation (haplo‐HSCT) modalities have been developed to offset the lack of matched donors. In this study, we compare the transfusion requirements of patients undergoing UCBT and haplo‐HSCT in a single institution with the aim of providing additional information for clinicians to choose the most adequate alternative graft for HSCT. Methods: The study reviewed 67 and 46 patients undergoing UCBT and haplo‐HSCT, respectively. Results: There were no significant differences for RBC and PLT requirements according to the transplantation modality. Median time to RBC transfusion independence was 35 and 25.5 days in patients who received an UCBT and haplo‐HSCT, respectively (P = 0.38), while median time to platelet transfusion independence was 31 days for UCBT patients and 23 for haplo‐HSCT patients (P < 0.001). Days until neutrophils > 0.5 × 109/L were the only variable that significantly influenced RBC and PLT requirements for both transplantation modalities. Cumulative incidence of RBC and PLT transfusion independence at 90 days after transplantation was similar for both UCBT and haplo‐HSCT. Conclusions: Both transplantation platforms require prolonged and intensive supportive RBC and PLT transfusion therapy. Both transplantation platforms require prolonged and intensive supportive RBC and PLT transfusion therapy. [ABSTRACT FROM AUTHOR]

Summary: Reactivation of hepatitis B virus (HBV) by reverse seroconversion (HBV‐RS) after allogeneic haematopoietic stem cell transplantation (allo‐HSCT) can occur in patients with resolved HBV infection (rHBV, defined as negative HBV surface antigen [HBsAg] and positive HBV core antibody), and may cause fatal hepatitis. To explore the risk factors, we retrospectively identified 817 consecutive patients who underwent allo‐HSCT from 2005 to 2016 in this largest single centre cohort from National Taiwan Univerisity Hospital. Transplants using donors or recipients positive for HBsAg or HBV DNA were excluded, leaving 445 rHBV patients for analysis. The 3‐ and 5‐year cumulative incidence of HBV‐RS after allo‐HSCT was 8·7% and 10·5%, respectively, at a median 16 months after allo‐HSCT. All had concurrent HBV reactivation. HBV flares developed in 19% of HBV‐RS cases, but none experienced hepatic failure. Neither did it impact non‐relapse mortality or overall survival. Multivariate analysis revealed that patients with donor lacking hepatitis B surface antibody and extensive chronic graft‐versus‐host disease (cGVHD) have the highest risk for HBV‐RS, with 5‐year incidence of 24·2%. In conclusion, adoptive immunity transfer from the donor seems to have protective effects against HBV‐RS, which may alter future donor selection algorithms, and combined with extensive cGVHD provides a good target for risk‐adaptive HBV prophylaxis. [ABSTRACT FROM AUTHOR]

The article focuses on the survival and relapse rate associated with immunotherapy donor lymphocyte infusion (DLI) which is used for allogeneic haematopoietic stem cell transplantation (Allo-HSCT). It talks about the Allo-HSCT being used for treatment in patients with haematological malignancies. It tells about the non-relapse mortality (NRM) rate being low for Allo-HSCT.

Summary: Assessment of minimal residual disease (MRD) is being routinely used to assess response in patients with acute myeloid leukaemia (AML). While it is well established that pre‐transplant positive MRD studies predict for relapse in patients transplanted either from matched sibling donors or matched unrelated donors, it is currently unknown whether MRD has comparable prognostic value in haploidentical stem cell transplantation (haplo‐SCT). To this end we performed a retrospective analysis using the Acute Leukaemia Working Party/European Society of Blood and Marrow Transplantation multicentre registry. All adult AML patients with known MRD status at transplant who underwent a first T‐cell replete haplo‐SCT while in remission between 2006 and 2016 were included. Two hundred and sixty‐five MRD‐negative and 128 MRD‐positive patients were assessed. In multivariate analysis, MRD‐negative patients experienced lower relapse incidence and better leukaemia‐free survival (LFS) compared to MRD‐positive patients. Subset analysis for MRD‐positive patients revealed that patients with donors positive for cytomegalovirus experienced decreased relapse rates as well as increased survival. A 6‐month landmark analysis suggests that the clinical benefit of pre‐transplant MRD negativity in terms of relapse, overall survival and LFS is realized at this time point. Pre‐transplant MRD status is potentially a pivotal prognosticator of outcome in AML patients undergoing T‐cell replete haplo‐SCT. [ABSTRACT FROM AUTHOR]

Summary: Poor graft function (PGF) is a severe complication of allogeneic haematopoietic stem cell transplantation (allo‐HSCT). Murine studies have demonstrated that effective haematopoiesis depends on the specific bone marrow (BM) microenvironment. Increasing evidence shows that BM macrophages (MФs), which constitute an important component of BM immune microenvironment, are indispensable for the regulation of haematopoietic stem cells (HSCs) in the BM. However, little is known about the number and function of BM MФs or whether they directly interact with HSCs in PGF patients. In the current prospective case‐control study, PGF patients showed a significant increase in classically activated inflammatory MФs (M1; 2·18 ± 0·11% vs. 0·82 ± 0·06%, P < 0·0001), a striking reduction in alternatively activated anti‐inflammatory MФs (M2; 3·02 ± 0·31% vs. 21·89 ± 0·90%, P < 0·0001), resulting in a markedly increased M1/M2 ratio (0·82 ± 0·06 vs. 0·06 ± 0·002; P < 0·0001) in the BM compared with good graft function patients. Meanwhile, standard monocyte subsets were altered in PGF patients. Dysfunctional BM MФs, which were characterized by reduced proliferation, migration and phagocytosis, were evident in PGF patients. Furthermore, BM MФs from PGF patients with high tumour necrosis factor‐α and interleukin 12 levels and low transforming growth factor‐β levels, led to impaired BM CD34+ cell function. In summary, our data indicate that an unbalanced BM M1/M2 ratio and dysfunctional MФs may contribute to the occurrence of PGF following allo‐HSCT. [ABSTRACT FROM AUTHOR]