Early Fever in Allogeneic Stem Cell Transplantation: Are Presepsin and YKL-40 Valuable Diagnostic Tools?

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a lifesaving treatment but carries a high infection risk. Diagnosing infections remains challenging due to the limited accuracy of standard biomarkers. Methods: This single-center study aimed to evaluate presepsin (PSP) and YKL-40 as infection biomarkers in febrile patients during the allo-HSCT pre-engraftment phase. Biomarker levels were prospectively measured in 61 febrile episodes from 54 allo-HSCT patients at admission, representing baseline levels, and then at Day 1, 3, 5, and 7 following fever onset. The diagnostic value was compared to that of procalcitonin (PCT). Results: PSP showed fair diagnostic value on Day 1 (AUC 0.656; 95% CI: 0.510-0.802) and Day 3 (AUC 0.698; 95% CI: 0.559-0.837). YKL-40 did not provide any significant diagnostic value across measured time points. PCT outperformed PSP and YKL-40, particularly on Day 3 (AUC 0.712; 95% CI: 0.572-0.852). When combining biomarkers, the best model for predicting infection used PSP > 3.144 ng/mL and PCT > 0.28 µg/L on Day 3, resulting in R2 of about 31% (p < 0.001). Conclusions: Neither test showed sufficient discriminative power for early infection to recommend their use as individual diagnostic tools in clinical practice.

Specific antigen-based stratification of membranous nephropathy in patients after haematopoietic stem cell allotransplantation - a case series and literature review.

BACKGROUND: Nephrotic syndrome (NS) is a rare complication that can occur after haematopoietic stem cell transplantation (HSCT). In patients with membranous nephropathy (MN) who have undergone allogeneic HSCT, a new antigen called protocadherin FAT1 has been identified. Our objective is to present a case series of MN patients after HSCT with a novel antigen-based stratification. CASE PRESENTATIONS: Patients who developed full-blown NS due to MN after an HSCT were enrolled in the University Hospital Centre Zagreb study. The first two patients were treated with an HSCT for acute myeloid leukaemia, and both developed NS after cessation of graft versus host disease (GVHD) prophylaxis. The first patient had reduced kidney function, while the second had completely preserved function. Kidney biopsy showed MN with only subepithelial deposits. A thorough examination revealed that there was no secondary cause of the disease. The patients achieved complete remission after undergoing immunosuppression treatment. The third patient underwent HSCT for acute lymphoblastic leukaemia. He developed both acute and chronic GVHD and also experienced avascular hip necrosis. After sixteen years, the patient developed NS with preserved kidney function. The kidney specimen showed membranous nephropathy (MN) with mesangial and subepithelial deposits. Extensive research was conducted, but no secondary cause for the MN was detected. All three cases tested negative for anti-PLA2R antibodies. Biopsy tissue samples were analysed using laser microdissection and tandem mass spectrometry of glomeruli for the detection of different specific antigens. Patients one and two tested positive for FAT1, whereas patient three tested positive for PCSK6. CONCLUSIONS: MN can develop at various time intervals after HSCT. Specific antigen testing can help establish the relationship between MN and HSCT. In the future, serum testing for anti-FAT1 antibodies in HSCT patients could be significant in diagnosing FAT1-associated MN, similar to how anti-PLA2R antibodies are significant in diagnosing PLA2R-associated MN.

Alternative donor strategy in unrelated hematopoietic stem cell transplantation - outcome with mismatched donors.

PURPOSE: This study retrospectively investigated the association between the level of human leukocyte antigen (HLA) mismatches (MMs), direction of disparities and differences at particular HLA locus on clinical outcomes of hematopoietic stem cell transplantation (HSCT). Investigated outcomes were overall survival (OS) and disease-free survival (DFS), graft-versus-host disease (GvHD), relapse and non-relapse mortality (NRM). PATIENTS AND METHODS: Study cohort included 108 adult patients transplanted between 2011 and 2021 and their 9/10 mismatched unrelated donors (MMUD). All individuals were typed for HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 loci using Polymerase Chain Reaction-Sequence Specific Primers, PCR-Sequence Based Typing and Next-Generation Sequencing. All statistical analyses were done in the MedCalc software, version 19.2.6. RESULTS: Patients with MMs at HLA-B locus demonstrated worse OS (P â€‹= â€‹0.0440, HR â€‹= â€‹2.00, n â€‹= â€‹20). Absence of HLA-DRB5 was associated with a higher incidence of GvHD (P â€‹= â€‹0.0112, HR â€‹= â€‹1.93, n â€‹= â€‹67). A lower incidence of GvHD was observed in patients with HLA class II MMs compared to patients with HLA class I MMs (P â€‹= â€‹0.0166, HR â€‹= â€‹1.94, n â€‹= â€‹29). Finally, analysis of PIRCHE score (PS) impact revealed that patients with HLA class II PS â€‹> â€‹10 in GvH direction showed higher incidence of GvHD compared to patients with HLA class II PS â€‹< â€‹10 (P â€‹= â€‹0.0073, HR â€‹= â€‹2.01, n â€‹= â€‹55). CONCLUSION: Obtained results undisputedly indicate the necessity to further investigate this matter on a larger patient group, with focus on specific HLA alleles to define precisely priority criteria for selecting the best donor for all patients, thus improving the outcome of HSCT with an MMUD.

Non-Myelofibrosis Chronic Myeloproliferative Neoplasm Patients Show Better Seroconversion Rates after SARS-CoV-2 Vaccination Compared to Other Hematologic Diseases: A Multicentric Prospective Study of KroHem.

Disease- and treatment-mediated immunodeficiency might render SARS-CoV-2 vaccines less effective in patients with hematologic diseases. We performed a prospective non-interventional study to evaluate humoral response after one and two doses of mRNA-1273, BNT162b2, or ChAdOx1 nCoV-19 vaccine in 118 patients with different malignant or non-malignant hematologic diseases from three Croatian treatment centers. An electrochemiluminescent assay was used to measure total anti-SARS-CoV-2 S-RBD antibody titers. After one vaccine dose, 20/66 (33%) achieved seropositivity with a median antibody titer of 6.1 U/mL. The response rate (58/90, 64.4%) and median antibody titer (>250 U/mL) were higher after two doses. Seropositivity varied with diagnosis (overall p < 0.001), with the lowest rates in lymphoma (34.6%) and chronic lymphocytic leukemia (52.5%). The overall response rate in chronic myeloproliferative neoplasms (CMPN) was 81.3% but reached 100% in chronic myeloid leukemia and other non-myelofibrosis CMPN. At univariable analysis, age > 67 years, non-Hodgkin's lymphoma, active treatment, and anti-CD20 monoclonal antibody therapy increased the likelihood of no vaccine response, while hematopoietic stem cell recipients were more likely to respond. Age and anti-CD20 monoclonal antibody therapy remained associated with no response in a multivariable model. Patients with the hematologic disease have attenuated responses to SARS-CoV-2 vaccines, and significant variations in different disease subgroups warrant an individualized approach.

Various approaches for accessing the influence of human leukocyte antigens disparity in haploidentical stem cell transplantation.

INTRODUCTION: We investigated the association of HLA on clinical outcomes in our cohort of patients in the haplo-HSCT program using the HLAMatchmaker (EM) and PIRCHE score (PS) algorithms. METHODS: The group comprised 64 patients (male = 35-54.7%, female 29-45.3%; median age 43 years) and their related haplo-HSCT donors (male = 30-46.9%, female 34-53.1%). HLA-A/B/C/DRB1/DQB1/DPB1 loci were analyzed. RESULTS: Multivariate analysis of the association between different HLA or patient/donor-related parameters and clinical outcome revealed the following associations with statistical significance: GvHD and HLA class I PS in the GvH direction (p = .0420) and relapse with diagnosis (p = .0163). For OS, the only variable showing a tendency of association was the source of HSCT (p = .0965). CONCLUSION: Combined results of univariate and multivariate analysis suggest that the patients awaiting the selection of the best haplo-HSCT donor could benefit the most from the combination of all three approaches, in cases when a suitable donor can be chosen from a number of potential donors.

B regulatory cells and monocyte subpopulations in patients with chronic graft-vs-host disease.

AIM: To assess the correlations of B regulatory cells (Bregs) and monocyte subsets in peripheral blood with the National Institutes of Health (NIH)-consensus-defined clinical manifestations of chronic graft-vs-host disease (cGvHD), in an attempt to establish their role as cellular biomarkers. METHODS: This multidisciplinary prospective study enrolled adult cGVHD patients treated in the University Hospital Center Zagreb and University of Zagreb School of Medicine. Immunophenotypic subpopulations of CD24highCD38high Bregs (CD27-, CD27+, and total) and monocyte (classical, intermediate, and non-classical) counts were correlated with demographic, transplant, and cGVHD-related data. Bivariate correlation analysis was performed to evaluate the correlations between Bregs and monocytes subsets and cGVHD organ involvement, as well as cGVHD severity and immunosuppression intensity. RESULTS: Twenty-two adult patients (54.5% female) with cGVHD were enrolled. The median (range) age was 44.5 years (24-65). All patients were transplanted for hematologic malignancies and 40.9% had severe NIH cGVHD global score. The median time from cGVHD diagnosis to the analysis was 16.6 months (0-176). The organ most frequently affected with cGVHD were the eyes (68.2%), skin (45.5%), lungs (45.5%), and liver (40.9%). Lower total and CD27-Bregs counts were correlated with worse cGVHD severity, higher immunosuppression intensity, and lung cGVHD, in terms of cell count, but also with skin cGVHD, in terms of percentages. Patients with liver and joint/fascia cGVHD had a lower percentage of non-classical monocytes and patients with more severe global NIH score had a higher classical monocytes count. CONCLUSION: Different organs affected by cGVHD are differently associated with different subpopulations of Bregs and monocytes.

Circulating YKL-40 in Philadelphia-negative myeloproliferative neoplasms.

Objectives: Philadelphia-negative chronic myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF), are characterized by clonal myeloproliferation and a strong inflammatory atmosphere. YKL-40, expressed in granulocytes, macrophages, megakaryocytes and malignant cells, is an acute phase reactant with an important role in tissue remodeling and atherosclerotic inflammation. The aim of this study was to investigate serum YKL-40 levels in MPNs and to assess its clinical correlations. Methods: ELISA test was used to measure serum YKL-40 levels in 111 MPN patients and in 32 healthy controls. Results: Serum YKL-40 levels were higher in ET, post-ET MF, PV, post-PV MF and primary MF patients, when compared to healthy controls (p < 0.001). Higher serum YKL-40 levels were associated with parameters indicative of the increased inflammatory state (higher C-reactive protein, poor performance status, presence of constitutional symptoms and cardiovascular risk factors). Additionally, higher serum YKL-40 levels in MF patients were associated with blast phase disease, lower hemoglobin and higher Dynamic International Prognostic Scoring System score. In the multivariate Cox regression models, higher serum YKL-40 levels in ET and PV patients were independently associated with an increased risk of thrombosis (HR 4.64, p = 0.031) and impaired survival in MF patients (HR 4.31, p = 0.038). Conclusion: These results indicate that higher circulating YKL-40 levels in MPNs might have a pathophysiological role in disease progression and thrombosis development. Assessing circulating YKL-40 could help in identification of ET and PV patients at a high risk of future cardiovascular events and has a good potential for improving prognostication of MF patients.

Serum procalcitonin in Philadelphia-negative myeloproliferative neoplasms.

Philadelphia-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are rare clonal hematopoietic stem cell disorders accompanied by a strong inflammatory milieu, which is directly responsible for constitutional symptoms associated with the disease, such as fever, weight loss or night sweats. Non-hematologists sometimes (and often wrongly) consider the fever in MPN patients to be a symptom of an underlying disease, which may have devastating consequences. Serum procalcitonin (PCT) is a circulating biomarker commonly used to improve the diagnostic accuracy of bacterial infections and to guide antibiotic therapy. The aim of this study was to test whether PCT could aid the clinician in the early diagnosis of bacterial infections in MPNs. This study investigated PCT in 41 ambulatory MPN patients (13 ET, 13 PV and 15 MF) who had no signs of infection and compared it to 10 MPN patients with microbiologically and/or serologically documented bacterial infections. Median PCT in MPN patients was 0.02 ng/mL (range 0.01-0.09 ng/mL). No difference in PCT was found between ET, PV and MF patients (p = 0.993), whereas MPN patients with documented bacterial infections had significantly higher PCT (median PCT 2.45, range 0.90-5.40 ng/mL) when compared to MPN patients with (median PCT 0.03 ng/mL) or without constitutional symptoms (median PCT 0.02 ng/mL; p < 0.001 for both analyses). These results clearly show that PCT should not be considered as a disease biomarker in MPNs and careful clinical assessment for the signs of infection is needed when MPN patients present with fever and high PCT.

Sarcopenia among patients after allogeneic hematopoietic stem cell transplantation and the impact of chronic graft-versus-host disease.

PURPOSE: This study investigated the frequency and characteristics of sarcopenia among patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a specific focus on the chronic graft-versus-host disease (cGVHD) population and its association with malnutrition, vitamin D and clinical characteristics. METHODS: We assessed sarcopenia, vitamin D levels, and nutritional status in 73 patients who underwent allo-HSCT, of which 45 were diagnosed with cGVHD. Sarcopenia was diagnosed according to the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. RESULTS: Sarcopenia was diagnosed in 19.2% of patients after allo-HSCT with statistically no significant difference between cGVHD and non-cGVHD patients. The risk factor for sarcopenia was the male gender. Sarcopenia in allo-HSCT patients correlated strongly with malnutrition and with current corticosteroid treatment (p < 0.005). Among cGVHD patients sarcopenia additionally correlated strongly with the number of prior systemic immunosuppressive therapy lines (p < 0.005) and moderately with the intensity of immunosuppression, cGVHD severity global rating assessed by both the health care provider and the patient and joint and fascia cGVHD involvement (p < 0.05). Vitamin D deficiency was found in more than 54.8% of patients, but the correlation to sarcopenia was not found. CONCLUSION: Sarcopenia was found to be common in long term survivors of allo-HSCT independently of the cGVHD diagnosis. Prospective longitudinal studies are needed for a better understanding of factors affecting the development of sarcopenia after allo-HSCT.

Ibrutinib as a salvage therapy after allogeneic HCT for chronic lymphocytic leukemia.

The purpose of our study is to provide information on safety and efficacy of ibrutinib as salvage treatment after allo-HSCT for CLL. A total of 56 patients were included, 36 (64%) males; median age at transplantation was 48 years (range: 35-64) and the median number of treatment lines prior to transplantation was 3 (1-10). The median time between allo-HSCT and Ibrutinib was 30 months (range: 1-140). Overall, 40 (71%) patients responded to Ibrutinib; 23 (41%) PR, and 17 (30%) CR. At time of ibrutinib initiation, ten patients had active chronic GVHD that resolved under Ibrutinib, whilst a single patient developed limited de novo chronic GVHD on Ibrutinib. Fourteen patients discontinued ibrutinib, four because of toxicity and ten because of disease progression. Overall, 14 patients progressed (median PFS = 24 months) among them 10 died. Two-year OS and PFS probabilities were 72% (95% CI: 52-84) and 50% (95% CI: 32-66), respectively. Patients with late relapse after allo-HSCT (≥24 months) had a better PFS after ibrutinib. Our study shows that ibrutinib can be safely administered for CLL relapse after allo-HSCT, with comparable efficacy to non-transplanted patients with high-risk disease.

The MHC gamma block matching: Impact on unrelated hematopoietic stem cell transplantation outcome.

Matching for HLA-A, -B, -C, -DRB1, -DQB1 alleles is the gold standard in hematopoietic stem cell transplantation (HSCT). However, this is often not enough to prevent postransplantational complications. The HLA mismatches (MM) have been associated with higher risk of acute graft versus host disease (GvHD). Gamma block (GB) is located in central HLA region, between HLA-B/C and HLA-DRB/DQB blocks and contains many inflammatory and immune regulatory genes. Single nucleotide polymorphisms (SNPs) within that block can be considered as markers for MHC haplotype matching. Aim of the research was to test whether MM in GB impact the outcome of HSCT in 51 patients transplanted with HLA 10/10 matched unrelated donor. The recipient-donor pairs were typed using PCR SSP kit that detects 25 SNPs within GB. Fifteen out of 51 (29.41%) pairs were GT matched (GT-M) while 36 out of 51 pairs (70.59%) were mismatched (GT-MM). In a univariate analysis, GT-MM was a significant risk factor associated with aGvHD (P = 0.041), although this association was not seen in multivariate analysis. No significant difference in overall survival and relapse occurrence was seen. These results were obtained on a small sample, and it is necessary to further test the possible role of GT matching in unrelated HSCT.

Quantitative polymerase chain reaction technology in chimerism monitoring after hematopoietic stem cell transplantation: One center experience.

Chimerism status evaluation is a routine test performed in post-hematopoietic stem cell transplantation (HSCT) period. The aim of the study was to evaluate a quantitative polymerase chain reaction (qPCR) method (GenDx, Utrecht, the Netherlands) applicability for this purpose. The study included 74 recipient/donor pairs tested for informative markers: median of four and six informative markers was found for patients (related and unrelated donor, respectively). Higher sensitivity of qPCR method was confirmed by analysis of recipient post-HSCT samples (N = 800) among which microchimerism (0.1%-1% recipient DNA) was detected in 21.8% of cases. The ability to detect less than 1% of minor population, as opposed to the short tandem repeat (STR) method for which 1% is the limit, translated into earlier identification of a disease relapse for four patients in our study sample.

Ibrutinib for bridging to allogeneic hematopoietic cell transplantation in patients with chronic lymphocytic leukemia or mantle cell lymphoma: a study by the EBMT Chronic Malignancies and Lymphoma Working Parties.

The aim of this retrospective study was to investigate the safety and efficacy of allogeneic hematopoietic cell transplantation (alloHCT) in patients pre-treated with ibrutinib. Eligible were patients aged >18 years allotransplanted for chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) after prior exposure to ibrutinib who were registered with the EBMT registry. Seventy patients (CLL 48, MCL 22) were included. At the time of alloHCT, 73% of the patients were ibrutinib responsive. All patients except one engrafted, and acute GVHD grade 2-4 (3-4) was observed in 49% (12%) of 68 evaluable patients. The cumulative incidence of chronic GVHD was 54% 1 year after transplant. In the CLL group, 12-month non-relapse mortality, relapse incidence (RI), progression-free survival (PFS), and overall survival (OS) were 10, 30, 60, and 72%, respectively, and in the MCL group 5, 19, 76, and 86%, respectively. Pre-transplant ibrutinib failure and poor performance status predicted inferior RI, PFS and OS in the CLL group. In conclusion, ibrutinib does not affect the safety of a subsequent alloHCT. While the relatively high post-transplant relapse risk in ibrutinib-exposed patients with CLL deserves further study, in patients with MCL consolidating disease responses to ibrutinib with alloHCT seems to be a promising option.

Influence of Blood Count, Cardiovascular Risks, Inherited Thrombophilia, and JAK2 V617F Burden Allele on Type of Thrombosis in Patients With Philadelphia Chromosome Negative Myeloproliferative Neoplasms.

INTRODUCTION: Thrombosis is the most common complication in Philadelphia chromosome negative (Ph-) myeloproliferative neoplasms patients. PATIENTS AND METHODS: In a cohort of 258 Ph- myeloproliferative neoplasm patients, the difference between patients with and without thrombosis was analyzed according to genetic thrombophilia factors, JAK2 V617F status and burden allele, blood count, cardiovascular risk factors and age. Patients were also divided in polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) subgroups as well as by the type of thrombosis. RESULTS: Analysis of cardiovascular risk factors regarding arterial thrombosis showed that PV patients with thrombosis had higher incidence of diabetes (P = .030), ET patients more often had hypertension (P = .003) and hyperlipidemia (P = .005), while PMF patients had hyperlipidemia (P = .046) and at least one cardiovascular risk factor (P = .044). Moreover, leukocytes > 18 × 109/L and V617F burden allele > 25.7% were statistically significantly different in PV patients (P = .019 and borderline significant at P = .055, respectively), while in ET patients leukocytes > 9.2 × 109/L (P < .001) and age at diagnosis of > 55 years were statistically significantly different (P = .002). PMF patients with V617F burden allele ≤ 34.8% were more prone to thrombosis (P = .032). When comparing patients with and without venous thrombosis, cutoff value of V617F burden allele > 90.4% was significant for PV patients with thrombosis (P = .036), as was > 56.7% for PMF patients with thrombosis (P = .046). Platelets ≤ 536 × 109/L and age at diagnosis > 54 years showed statistically significant difference for ET patients with thrombosis (P = .015 and P = .041, respectively). CONCLUSION: On the basis of our results, a new scoring system for thrombosis risk in PV could be made, while PMF prognostic model may be expanded for better recognition of potential thrombotic risk factors.

Serum chitotriosidase: a circulating biomarker in polycythemia vera.

OBJECTIVES: Serum chitotriosidase activity (CHIT1) is a biomarker of macrophage activation with an important role in inflammation-induced tissue remodeling and fibrosis. Macrophages have been described to play a crucial role in regulating pathological erythropoiesis in polycythemia vera (PV). The aim of this study was to evaluate CHIT1 in patients diagnosed with Philadelphia-negative myeloproliferative neoplasms (MPNs). METHODS: Using fluorometric assay, we measured CHIT1 in 28 PV, 27 essential thrombocythemia (ET), 17 primary myelofibrosis (PMF), 19 patients with secondary myelofibrosis and in 25 healthy controls. RESULTS: CHIT1 was significantly higher in PV (p < .001) and post-PV myelofibrosis (MF) transformation (post-PV MF) (p = .020), but not in ET (p = .080), post-ET MF transformation (p = .086), and PMF patients (p = .287), when compared to healthy controls. CHIT1 in PV was positively correlated with hemoglobin (p = .026), hematocrit (p = .012), absolute basophil count (p = .030) and the presence of reticulin fibrosis in the bone marrow (p = .023). DISCUSSION: A positive correlation between CHIT1 and these distinct laboratory PV features might imply macrophages closely related to clonal erythropoiesis as cells of CHIT1 origin. In addition, a positive association between CHIT1 and reticulin fibrosis might indicate its potential role in PV progression. CONCLUSION: CHIT1 might be considered as a circulating biomarker in PV. Additional studies are needed to clarify the role of CHIT1 in promoting disease progression and bone marrow fibrosis in PV.

Early human cytomegalovirus reactivation is associated with lower incidence of relapse of myeloproliferative disorders after allogeneic hematopoietic stem cell transplantation.

Conflicting results have been reported regarding the association between early cytomegalovirus (CMV) reactivation and relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This prompted us to evaluate the impact of CMV reactivation on outcomes of 155 consecutive adult patients transplanted in our institution. In our study, CMV reactivation did not affect cumulative incidence (CI) of relapse in patients with lymphoproliferative disorders. However, the CI of relapse in patients with myeloproliferative disorders (AML and MPN) was 37% (95% CI, 21-53) in patients without CMV reactivation as opposed to 17% (95% CI, 9-28) in patients with CMV reactivation (p = 0.03). An important correlation between CMV reactivation and relapse was found in patients with MPN; the CI of relapse was 50% (95% CI, 12-80) in patients without CMV reactivation as opposed to only 7% (95% CI, 0-27) in patients with CMV reactivation (p = 0.02). A substantial reduction of relapse in myeloproliferative disorders associated with CMV reactivation was confirmed by multivariate analysis (HR 2.73; 95% CI, 1.09-6.82, p = 0.03) using time-dependent covariates for high-risk disease, older age, RIC conditioning, ATG, grade II-IV acute, and chronic GVHD. To our knowledge, we are the first to show an association of CMV reactivation with relapse reduction in MPN patients. This putative virus vs myeloproliferation effect warrants further research.

High incidence of aseptic hip necrosis in Hodgkin lymphoma patients treated with escalated BEACOPP receiving methylprednisolone.

BACKGROUND: Escalated BEACOPP (eBEACOPP) is an effective but fairly toxic regimen for the treatment of Hodgkin lymphoma (HL). Avascular necrosis (AVN) of femoral head was previously reported to increase in patients treated with eBEACOPP, but so far, no systematic analysis of its frequency has been published. AIMS: To analyse the frequency and identify possible risk factors for AVN development in patients treated with eBEACOPP. METHODS: We identified 26 patients treated with eBEACOPP for newly diagnosed high-risk advanced-stage HL, 25 of whom were alive at the time of study. All patients were invited to participate in a cross-sectional study; 17 patients responded and were evaluated by magnetic resonance imaging and orthopaedic examination. RESULTS: Six patients (35.3%) were diagnosed with AVN after receiving eBEACOPP treatment. AVN was not correlated with age, gender, number of received eBEACOPP cycles, irradiation therapy or cumulative dose of steroids administered. There were significantly more cases of AVN in patients receiving methylprednisolone than prednisone (P = 0.01). CONCLUSION: The use of methylprednisolone was shown to be a risk factor for the development of AVN in patients treated with eBEACOPP and should not be the corticosteroid of choice in the treatment of patients with HL.