Introduction:Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare plasma cell dyscrasia. Growth differentiation factor-15 (GDF-15) is related with renal function, but few studies have focused on it in renal impairment of POEMS syndrome. Objective:To evaluate the potential of circulating GDF-15 concentration as a biomarker for renal function in POEMS syndrome. Methods:150 Chinese patients, diagnosed with POMES syndrome, were enrolled and divided into three subgroups according to their chemotherapy stage. All the patients' medical records were retrospectively analyzed and plasma VEGF and GDF-15 were measured using ELISA kits. Treatment-naïve patients were followed up for 13±6 months. Results:Plasma GDF-15 concentration positively correlated with serum creatinine (r=0.4048; P<0.0001), blood urea nitrogen (r=0.3302; P<0.0001), risk stratification (r=0.3949; P<0.0001), while negatively correlating with eGFR (r=-0.5057; P<0.0001) and albumin (r=-0.3800; P=0.0014). GDF-15>547.8 pg/mL provided an AUC of 0.8541 in diagnosing renal impairment (eGFR<60mL/min/1.73m2) in POEMS syndrome. With a prevalence of renal impairment of 16.7%, GDF-15>547.8 pg/mL showed a prominent NPV (94.9%) for the diagnosis of renal impairment in POEMS syndrome. Moreover, treatment-naïve patients with serous effusion had higher plasma GDF-15 concentration (P=0.0004) and lower eGFR (P=0.0001) than those without serous effusion. Noteworthy, baseline GDF-15 was positively correlated with ΔeGFR (r=0.4694, P=0.0044). Conclusion:Circulating GDF-15 concentration is associated with serous effusion, renal function and risk stratification, while a plasma GDF-15 < 547.8 pg /mL can help rule out renal impairment in POEMS syndrome. Baseline plasma GDF-15 is associated with renal remission after chemotherapy.

Plasma cell disorders (PCDs) are marked by the clonal proliferation of abnormal plasma cells and bone marrow plasma cells (BMPCs), causing various clinical complications. These PCDs include subtypes with distinct clinical features. Multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are more common and relatively well-studied. In contrast, primary light-chain amyloidosis (AL) and POEMS syndrome (POEMS) are rare and remain less understood. To investigate the role of clonal hematopoietic (CH) mutations and potential interconnections in these diseases, we sequenced CH mutations in lymphoid and myeloid lineages, as well as myeloma driver gene mutations, in BMPCs from affected patients. Recurrent lymphoid CH mutations (in FAT1, KMT2D, MGA, and SYNE1) and myeloma driver gene mutations (in ZFHX3 and DIS3) were found in the dominant clonal and subclonal plasma cell populations. These moderately aging-associated lymphoid CH mutations had a higher burden in MM than in AL or POEMS. Binary matrix factorization of these mutations revealed the subgroups associated with progression-free survival (PFS) (observed in MM, AL, and POEMS), age at diagnosis (in AL and POEMS), serum differential free light chain (dFLC) levels, plasma cell burden (in AL), and serum vascular endothelial growth factor (VEGF) levels (in POEMS). Moreover, the poor PFS associated with MGA or SYNE1 mutations was confirmed across MM, AL, and POEMS. CH mutations partially explained the shared pathogenesis of MM, AL, POEMS, and MGUS, and helped identify patient subgroups with specific clinical features.

The global toll of mental illness is broad and far-reaching, affecting individuals, families, communities and society as a whole. The World Health Organization (WHO) estimates that approximately one in four people worldwide will be affected by a mental health problem in their lifetime. Some diagnoses do not have long-term stability. Considering the possibility of multiple co-existing psychiatric disorders when confronting a patient, it can therefore be assumed that the change in the patient’s diagnosis is not a change in the disease, but rather a change in one of the features of the assessed disorder. A high value of this feature will manifest as a certain disease, and a low value will manifest as another disease. There has been a great deal of academic research showing a strong link between personality traits and mental illnesses, specifically in terms of how different mental illnesses are characterized by different personality types. The change in diagnosis can lead to changes in treatment. However, it would be helpful if personality traits could be mapped to the possible traits of the mental illness at the outset, to identify possible trends in the patient’s condition and to provide more individualized and precise treatment. So the aim of this paper is to expound the possibilities and reasons for the occurrence of changes in psychodiagnostics findings in order to set the basis for discussion, and to point out the continuity and relevance of personality traits and mental disorders by means of several psychological models.

Waldenström macroglobulinemia (WM), a rare incurable low-grade B-cell lymphoma, exhibits heterogeneous survival outcomes. We evaluated the prognostic performance of a novel modified staging system of WM (MSS-WM) through comparison with existing models in a single-center cohort of 294 symptomatic WM patients. MSS-WM demonstrated significant stratification capacity (p < 0.0001), with 5-year overall survival rates of 89% (low-risk), 84% (low-intermediate), and 52% (intermediate/high-risk). All MSS-WM factors, including age, serum albumin, and LDH demonstrated independent prognostic impact. In addition, high beta-2 microglobulin level also showed negative prognostic impacts (p = 0.0002). While high concordance of MSS-WM and the revised IPSS (rIPSS-WM) was confirmed, the rIPSS-WM exhibited better predictive accuracy. However, MSS-WM's simplified structure enhances clinical utility, enabling rapid risk stratification: 89% 5-year survival in low-risk vs 52% in high-risk groups. This practical staging system requires no complex calculations, making it preferable for routine clinical implementation while maintaining comparable prognostic discrimination.

The majority of multicentric Castleman disease (MCD) patients in China are idiopathic MCD (iMCD) with systemic manifestations. The evaluation of symptomatic treatment response in iMCD currently relies on clinicians' assessments of patients' symptoms rather than patient-reported outcomes (PROs), which may be influenced by subjective judgments from physicians. PRO results in iMCD patients are rarely mentioned in current treatment response evaluations. This study aims to comprehensively describe changes in symptom burden, quality of life, psychological status, and social function in iMCD patients before and after treatment using PROs, and analyze their relationship with treatment responses. Patients with iMCD diagnosed and treated at Peking Union Medical College Hospital were included. PRO survey results (MCD-SS, SF-36, PHQ-9, and WPAI:GH) were collected from patients before and after treatment, along with clinical data, symptom, biochemical, and lymph node evaluation results. Paired analysis was used to observe changes in PRO results before and after treatment, which were then compared with treatment responses (biochemcial and symptomatic responses) evaluated according to Castleman Disease Collaborative Network (CDCN) criteria. A total of 19 iMCD patients were included. At the baseline, the MCD-SS reported a median of 11 MCD-related clinical symptoms, with a baseline median total score of 3.30 and a median fatigue dimension score of 5.50. After treatment, both the total MCD-SS score and fatigue score decreased significantly (P: 0.022~0.049). In terms of overall health status, the median “vitality” dimension score of the SF-36 increased significantly 8~12 months after treatment (55.0 vs. 75.0, P = 0.0055), and 78.9% of patients self-reported their health status as “slightly better” or “much better” compared to baseline. The PHQ-9 survey indicated a median baseline score of 8.0, with 13 patients (68.4%) exhibiting depressive symptoms and 7 patients (36.8%) potentially having moderate-to-severe depression. After treatment, the proportion of moderate/severe depressive symptoms decreased to 15.8%. Regarding social function, the WPAI:GH survey showed that 47.7% of iMCD patients were unemployed before treatment, decreasing to 31.6% 4~6 months after treatment. PRO results were consistent with symptomatic and biochemical responses evaluated with CDCN criteria. For iMCD patients with clinical fatigue grades of G0, G1, and G2, the median MCD - SS fatigue scores were 2.0, 5.5, and 7.5 points respectively (P < 0.005). In patients who achieved complete symptomatic or biochemical remission, the depression - related scores, fatigue scores, and overall symptom scores decreased significantly (P: 0.0083~0.035). Our study concluded that PROs, as measurable indicators of patient self-report, demonstrate similarity to objective treatment response evaluations and can serve as a supplementary component in response assessment.

AbstractThe majority of multicentric Castleman disease (MCD) patients in China are of the idiopathic subtype (iMCD) with systemic manifestations. However, the impact of iMCD on life quality, mental and psychological status, social function, and caregiving burden is poorly understood. To address this gap, a cross-sectional web-based survey was conducted with 178 iMCD patients and 82 caregivers, including 42 patient-caregiver dyads. Patient-reported outcome measurements were performed using four self-administered questionnaires (MCD-SS, SF-36, PHQ-9, and WPAI:GH). Caregiver-reported outcome measurements were performed using three questionnaires (SF-36, Zarit-22, CRA) to assess the caregiving burden. Correlation analysis was performed in patient-caregiver dyads. Patients reported a median of nine symptoms by MCD-SS, with a high mean score of 4.34 for the Fatigue domain. Their SF-36 scores indicated significant declines in physical and mental health compared to the Chinese general population (p < 0.001). Based on PHQ-9, around 65% of patients exhibited depressive symptoms, with 28.6% of them experiencing mild to severe major depression. Only 47.2% (84/178) of the patients were employed, and 28.5% experienced impaired work time. Caregivers also reported lower SF-36 scores than the general population (p < 0.05) and expressed feeling of self-criticism, lack of family support and financial problems. Correlations were observed between patients’ symptom burden, mental health impairment and caregiving burden (correlation coefficient: 0.31 ~ 0.55). Our study concluded that fatigue and depressive symptoms significantly impact the life quality and social well-being of iMCD patients. The disease also affect the physical and mental health of caregivers, leading to feelings of guilt and a lack of family support.

Waldenström macroglobulinemia (WM) has been recognized as a rare subtype of low-grade B-cell lymphoma. Although WM mostly has an indolent course and the prognosis has improved during the last decades, WM remains incurable and perpetually relapse and most patients succumb to disease progression. Prognostic parameters of WM have been reexamined and a modified staging system of WM (MSS-WM) has been formulated recently. However, the derivation and validation cohorts included predominantly patients from the USA and Europe Our aim was to provide evidence of MSS-WM for 294 symptomatic WM patients in Asia. We identified 294 active WM patients diagnosed between January 2000 and December 2023 from the Department of Hematology, Peking Union Medical College Hospital, Beijing, China. All diagnoses were reviewed based on the 2003 diagnostic criteria in the Second International Workshop on WM. Prognosis stratification was analyzed based on the MSS-WM, and compared with the 2009 prognostic scoring system for WM (IPSS-WM) and the 2019 revised international prognostic scoring system (rIPSS-WM). Overall survival (OS) was defined as the duration from diagnosis to death. The final follow-up date was May 31, 2024. The median age was 64 years old, and the majority (71.4%) were male (Table S1). The median follow-up period was 48 months (0.3-241 months). Eighty-three patients died during the follow-up, with an estimated 5-year OS rate of 74.2%. On univariate analysis, all MSS-WM factors revealed independent prognostic impact with hazard ratios 2.44 for age 66-75 years old (P = 0.0003), 3.83 for age older than 75 years old (P < 0.0001), 2.21 for albumin lower than 35g/L (P = 0.0017), 2.06 for lactate dehydrogenase higher than upper limit of normal (P = 0.0345) (Table 1). In the multivariate analysis of 236 patients, hazard ratios were 2.34 (P = 0.002) for age 66-76 years old, 2.7 (P = 0.0126) for age older than 75 years old, 1.94 (P = 0.0636) for albumin, 2.16 (P = 0.0636) for lactate dehydrogenase. Additionally, our results showed independent prognostic impact of beta-2 microglobulin higher than 4mg/L with hazard ratio 3.07 (P = 0.0002) and hemoglobin level with hazard ratio 2.10 (P = 0.0225), which is similar to the prognostic impact of beta-2 microglobulin in rIPSS-WM and hemoglobin in IPSS-WM, respectively. According to MSS-WM in all 294 patients, 58 (19.7%) patients were classified as low risk (MSS-LR), 129 (43.9%) were low-intermediate risk (MSS-LIR), 76 (25.8%) were intermediate risk (MSS-IR), and 31 (10.5%) were high risk (MSS-HR). The 5-year OS rates were 89%, 84%, 52%, 52%, respectively (P < 0.0001). The hazard ratios were 1.49 (95% CI, 0.71-3.53, P = 0.3205) for MSS-LIR versus MSS-LR, 3.99 (95% CI, 2.36-6.84, P < 0.0001) for MSS-IR versus MSS-LIR, and 1.03 (95% CI, 0.54-1.87, P = 0.9182) for MSS-HR versus MSS-IR. In 233 patients available of IPSS-WM scores, 43 (18.5%) patients were classified as low risk, 102 (43.8%) were intermediate risk, and 88 (37.8%) were high risk. The 5-year OS rates were 88%, 84%, respectively (P = 0.0001). The rIPSS-WM scores were available in 236 patients. Among them, 30 (12.7%) patients were classified as very-low risk, 73 (30.9%) were low risk, 69 (29.2%) were intermediate risk, 46 (19.5%) were high risk, and 18 (7.6%) were very-high risk. The 5-year OS rates were 97%, 85%, 75%, 56%, and 40%, respectively (P < 0.0001). The majority of patients had comparable performance between MSS-WM and IPSS-WM or rIPSS-WM. Based on IPSS-WM, a proportion of high risk patients (11/88, 12.5%) were down-staged in MSS-WM, and a few patients in low risk (2/43, 4.6%) and in intermediate risk group (3/102, 2.9%) were up-staged in MSS-WM. Based on rIPSS, a small fraction of rIPSS low risk patients (5/73, 6.8%) were up-staged as MSS-WM IR. Our study provide evidence for the applicability of MSS-WM in a WM patient cohort in Aisa, and compared it with rIPSS-WM and IPSS-WM. MSS-WM, as a simplified model, demonstrated strong discrimination between patients with good and dismal prognosis, potentially facilitating its clinical use.

Waldenström macroglobulinemia (WM) is a type of B-cell lymphoma that produces IgM. Our study aimed to investigate the role of CXCL13, a chemokine essential for B lymphocytes, in the evaluation of treatment response and prognosis in WM. We collected serum samples and clinical data from 72 WM patients, with 69 patients receiving systemic therapy and 3 patients opting not to receive treatment. Serum CXCL13 levels at baseline and after six months of treatments were measured by enzyme-linked immunosorbent assay. The median serum level of CXCL13 was 1 539.2 pg/ml (range 10.0–21 389.9) at baseline and significantly decreased to 123.1 pg/ml (range 0.0–6 741.5) after 6 months of treatments. At baseline, higher CXCL13 levels were associated with lower hemoglobin levels ( p = 0.001), higher β2-microglobulin levels ( p = 0.001), lower albumin levels ( p = 0.046), and higher IPSS-WM scores ( p = 0.013). After 6 months of treatment, patients who achieved PR/VGPR had significantly lower CXCL13 levels compared to those with SD (70.2 pg/ml vs 798.6 pg/ml, p = 0.002). The median follow-up period was 40 months (range 4.2–188). Eight patients died during the follow-up period. Overall survival differed based on CXCL13 levels. When grouped by baseline CXCL13 levels, the median OS was 60.0 months in patients with serum CXCL13 > 2 000 pg/ml, while it was not reached in patients with low CXCL13 levels ( p < 0.001). Based on CXCL13 levels after the treatments, the median OS was 74.0 months in patients with serum CXCL13 > 200 pg/ml, while it was not reached in patients with CXCL13 ≤ 200 pg/ml. In a subgroup of 28 patients with a series of serum samples, the increase of serum CXCL13 level was associated with disease progression or the start of next-line therapy ( p < 0.001). Our study concludes that serum CXCL13 levels decrease in WM patients treated with various regimens and correlate with treatment response. Detecting serum CXCL13 at baseline or after treatment help in predicting prognosis.

Background: Langerhans cell histiocytosis (LCH) is a rare highly heterogeneous histiocytosis, which can be divided into single system(SS) and multiple system(MS) according to clinical site of involvement. There are few studies related to single-system unifocal adult LCH currently. Aims: Objective of this single-center retrospective study is to describe the clinical features, affected organs, gene mutations, treatment and prognosis of adult single-system unifocal LCH patients. Methods: This retrospective study included patients ≥14 years old, and diagnosed with single-system unifocal LCH in Peking Union Medical College Hospital (Beijing, China) from September 2001 to December 2022. Results: Overall 109 patients were enrolled in this study, with a 2.03:1 male to female ratio. Median age at diagnosis was 33 years (14-69). The most common clinical manifestations were bone pain, accounting for 30.3%, followed by cough (11.0%) and diabetes insipidus (11.0%). The most common organs involved were bone (53.2%), followed by lung (18.3%), pituitary (10.1%), lymph nodes (5.5%), skin (2.8%), liver (2.8%) and thyroid (0.9%). Among the 20 patients with lung involvement, 17 patients had smoking history. The frequency of BRAFV600E mutation, MAP2K1 mutation and BRAFindel mutation were 24.3%, 10.8% and 2.7% respectively. BRAFV600Emutations and MAP2K1 mutations were independent of the type of organ involved and were not associated with OS and PFS. As for first-line treatment, 48 had surgery, 15 had radiotherapy, 16 were suggested observation, 9 had chemotherapy. All of the 20 patients with lung involvement were suggested to quit smoking. After a median follow-up time of 43.2 months (0.2-246.6), 3 patients died of respiratory failure, and the estimated 3-year overall survival (OS) was 98.7%. 24 patients developed disease progression, of which 5 had local recurrence, 4 progressed to single system multiple lesions (SS-M) and 15 progressed to MS, and the estimated 3-year progression-free survival (PFS) was 79.0%. Progression rate of pituitary involvement was the highest, 45.5% (5/11), followed by lymph node 33.3% (2/6), lung 20.0% (4/20) and bone 19.0% (11/58) (Figure 1). Univariate analysis showed that patients whose age at diagnosis ≤30 years had significant shorter PFS than those older than 30 years (the estimated 3-year PFS 89.1% vs 66.9%, p =0.039). Summary/Conclusion: In this study, we report a large series of single-system unifocal adult LCH patients. Bone is the most commonly involved organ. The overall survival of single-system unifocal adult LCH is good，and more than 30 years at diagnosis indicate good PFS.Figure1: Progression pattern of each affected organ（N=106） Keywords: Adult, Langerhans Cell Histiocytosis

Background Langerhans cell histiocytosis (LCH) is a rare highly heterogeneous histiocytosis, which can be divided into single system and multiple system disease according to site of involvement. There is a paucity of studies examining unifocal LCH in adults in the molecular era. Results We retrospectively analysed records from 70 patients with unifocal LCH. The median age at diagnosis was 36 years (18–69). The most common organ involved was the bone (70.0%), followed by pituitary gland (7.1%). Target gene sequencing of lesion tissues was performed on 32 of the 70 patients. MAPK/PI3K pathway alterations were observed in 78.1% of the patients; the most common mutations included BRAF V600E (28.1%), MAP2K1 (18.8%) and PIK3CA (9.4%). After a median follow-up time of 39.4 months (0.7–211.8), 10 (14.3%) patients developed disease progression, of whom 4 had local recurrence, 2 progressed to single-system multifocal and 4 progressed to multiple system LCH. The 3-year progression-free survival (PFS) was 81.9%. Univariate analysis showed that age < 30 years at diagnosis was associated with worse 3-year PFS (52.2% vs. 97.0%, p = 0.005). The 3-year overall survival was 100%. Conclusions In our large cohort of adults with unifocal LCH, we found that prognosis of unifocal LCH in adults was very good, and age < 30 years at diagnosis was associated with increased relapse risk.

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Waldenström macroglobulinemia (WM) is a indolent B-cell lymphoma secreting IgM. CXCL13 is a chemokine expressed in the lymphoid tissue and is required for B lymphocyte. Studies have found elevated levels of CXCL13 in the serum and bone marrow of WM patients. Aims: To explore the value of elevated CXCL13 levels in the treatment response and prognosis evaluation of Waldenström macroglobulinemia (WM). Methods: Serum samples and clinical statistics of symptomatic WM patients were collected. Serum CXCL13 levels at baseline (0 month) and after six 6 months of treatments were measured by enzyme-linked immunosorbent assay. High CXCL13 levels were defined as higher than 2000pg/ml at baseline or higher than 200pg/ml at the 6th month. Treatment responses and overall survival were evaluated corresponding to different serum CXCL13 levels. The median follow-up period was 40 months. Results: Seventy-two patients diagnosed with WM were included in our study. The male-to female ratio was 48:24. The median age at baseline was 63 (39~81) years old. Indications for therapy included fatigue, B-symptoms, organ enlargement, anemia and IgM-related clinical complications. Sixty-nine patients received systemic therapy, including 16 patients treated with chemotherapy, 24 patients treated with rituximab combined with chemotherapy, 9 patients treated with bortezomib-based regimens, and 19 patients treated with BTK inhibitors. Three patients were not treated because of patients will. The median serum level of CXCL13 of all patients was 947 (range 10.0-21389.9) pg/ml at baseline and significantly decreased to 133.8 (range 0.0-6742.0) pg/ml after 6 months of treatments. Thirty-nine patients achieved partial remission or very good partial remission (PR/VGPR) at 6th month, and 30 patients achieved minimal remission or stable disease (MR/SD). The medium serum CXCL13 level at 6th month in PR/VGPR patients was lower than in MR/SD patients (70.2pg/ml vs 345.0pg/ml, p=0.002) (Figure 1). In chemotherapy group, patients achieved PR/VGPR had lower serum CXCL13 levels at baseline (588.4pg/ml vs 2574.0pg/ml, p=0.03). In chemotherapy group or combined with rituximab, serum CXCL13 decreased significantly in both PR/VGPR group and SD/MR group (p<0.005). In patients treated with bortezomib-based regimen or BTK inhibitors, the decrease of serum CXCL13 levels were not significant in SD/MR patients. Eight patients died in the follow-up period. The overall survival (OS) also differed corresponding to serum CXCL13 levels. Grouped by serum CXCL13 levels at baseline, the median OS was 60.0 months in patients with high CXCL13 levels, while was not reached in patients with low CXCL13 levels (p=0.0004). As for CXCL13 levels as 6th month, the median OS was 74.0 months and not reached, respectively in patients with high and low CXCL13 levels (p=0.0001). However, the survival predictive value of CXCL13 level was weakened in treatment subgroups. We further analyzed the serum CXCL13 levels in a series of 16 patients who received Orelabrutinib (BTKi). The CXCL13 levels decreased during the follow-up and most of them (12/16, 75%) were less than 10% of baseline after twelve months of BTKi treatment. Summary/Conclusion: Serum CXCL13 level decreased in WM patients treated with different regimen, and was parallel to the disease remission. Detection of serum CXCL13 at baseline or during the treatment may be helpful in evaluating treatment response and predicting prognosis.Keywords: Waldenstrom’s macroglobulinemia

Background Langerhans cell histiocytosis (LCH) is a myeloid dendritic cell disorder frequently affecting children more than adults. The presentation of LCH varies with age, however, the clinical characteristics and genetic profiles of adolescent LCH remain elusive. To address the knowledge gap, we performed a single-centre retrospective study of 36 adolescent LCH patients aged between 14 and 17 years at Peking Union Medical College Hospital. Results At the time of diagnosis, 10 patients were classified as unifocal single system LCH (27.8%), 2 patients had pulmonary single system LCH (5.6%), 5 patients had multifocal single system LCH with bone involvement (13.9%), and 19 patients had multisystem LCH (52.8%). The most prevalent involvement in multisystem patients was the pituitary gland (78.9%), followed by the bone (42.1%), lung (42.1%), and lymph nodes (42.1%). Eight (42.1%) patients had risk organ involvement. BRAF(N486_P490) was detected in 50% of patients who underwent next generation sequencing, and BRAF(V600E) was detected in one patient. Chemotherapies were the first line treatment in 24 patients. One patient died and thirteen patients relapsed during the follow-up. The estimated 5-year OS rate and EFS rate were 94.7% and 59.0%, respectively. Conclusions In this study, we report a large series of adolescent LCH patients. The clinical characteristics of adolescent LCH patients may be close to adult LCH. Compared with pediatric cases, adolescent LCH tends to have more pituitary lesions and pulmonary involvement, fewer skin and hematopoietic involvement, a higher frequency of BRAF deletion mutation, and a lower frequency of BRAF(V600E) mutation.

Plasma cell dyscrasias (PCDs), including multiple myeloma (MM), light-chain amyloidosis (AL), and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes), are malignancies of plasma cells but with diverse clinical features. Although they have the same precursor stage of monoclonal gammopathy of undetermined significance (MGUS), their shared mutational pathogeneses remain understudied. To investigate the common mutational signatures with clinical significance, we subjected bone marrow plasma cells from patients with MM (n=163), AL (n=121), POEMS syndrome (n=67), and MGUS (n=13) using a targeted gene sequencing (TGS) panel of 370 genes. This TGS panel is designed on the basis of our previous research on whole-exome sequencing of AL (Huang XF et al, Amyloid, 2020) and POEMS syndrome (Chen J et al, Leukemia, 2021). Strikingly, the principal component analysis of the top 100 variably mutated genes revealed two major subgroups among patients with PCDs: one subgroup with a high mutational burden of chromatin-modifying genes (namely the CMGmut subgroup), and the other subgroup with a subtly higher burden of classical mutations in MM (namely the non-CMGmut subgroup) (Figure 1A). The most heavily mutated chromatin-modifying genes in the CMGmut subgroup of PCDs included KMT2D, EP400, RUNX1, KDM5A, etc. The Least absolute shrinkage and selection operator (LASSO) regularization analysis revealed that the high mutational burden of RUNX1 and KMT2D was the biomarker to distinguish the CMGmut subgroup from the non-CMGmut subgroup. As for clinical significance, the patients with MM, early-stage AL (Mayo12, Stage 1,2), or POEMS syndrome of the CMGmut subgroup were more likely to have prolonged progression-free survival than those of the non-CMGmut subgroup (Figure 1B). Also, the patients with MM or AL of the CMGmut subgroup showed inferior responses to the first-line CyBorD (cyclophosphamide, bortezomib, and dexamethasone), whereas the patients with MM of the CMGmut subgroup showed non-inferior responses to the first-line VRD (bortezomib, lenalidomide, and dexamethasone). In summary, TGS panel-based mutational profiling provided mechanistic insights into a subgroup of patients with PCDs characterized by a high mutational burden of chromatin-modifying genes and relatively indolent clinical features. Our findings enable the identification of these patients who will potentially benefit from epigenetic therapy in future clinical management. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Background Elderly patients with acute myeloid leukemia (AML) can be treated with intensive therapy, low-intensity therapy, or best supportive care. Medical decision-making might be affected by physicians’ occupational and non-occupational factors. Objective To explore the impact of physicians’ personalities and behavioral traits on treatment-related decision-making for elderly AML patients. Design A nationwide cross-sectional survey. Participants Hematologists in mainland China ( N = 529; response rate 64.5%). Main Measures The medical decision-making for elderly AML patients was evaluated using 6 clinical vignettes. Hematologists’ attitudes toward risk and uncertainty, Big Five personality traits, and decision-making styles were assessed using binary lottery choices and well-recognized self-report inventories. Key Results The resulting binary regression model in predicting treatment intensity contained professional title group (OR = 0.012, 95% CI 0.001 to 0.136, P < 0.001), conscientiousness (OR = 0.336, 95% CI 0.121 to 0.932, P = 0.036), extraversion (OR = 0.403, 95% CI 0.166 to 0.974, P = 0.044), conscientiousness by title group (OR = 2.009, 95% CI 1.100 to 3.667, P = 0.023), and extraversion by title group (OR = 1.627, 95% CI 0.965 to 2.743, P = 0.068) as predictors of therapy intensity preference. Junior physicians with a higher level of extraversion (mean difference = 0.27; 95% CI 0.07 to 0.45; P = 0.009) or conscientiousness (mean difference = 0.19; 95% CI 0.01 to 0.36; P = 0.028) tended to prescribe more intensive therapy. Meanwhile, no significant correlation was found between physicians’ personalities or behavioral traits and treatment-related decision-making in senior physicians. Conclusions Physicians’ personalities contribute to treatment-related decision-making for elderly AML patients, depending on the professional titles. More extravert or conscientious attending physicians tended to prescribe more intensive therapy. Meanwhile, the decisions made by chief and associate chief physicians were not impacted by their personal traits. Junior physicians should be aware of such potential influence when making medical decisions.

Unicentric Castleman disease (UCD) is a rare lymphoproliferative disorder presenting as a single nodal mass with characteristic histopathology. Patients with UCD are typically asymptomatic with normal laboratory markers, whereas patients with multicentric Castleman disease (MCD) demonstrate multicentric lymphadenopathy and cytokine storm-induced systemic inflammatory symptoms. This retrospective analysis of 116 UCD cases identified 19 (16.4%) cases with an MCD-like inflammatory state (UCD-MIS). We compared treatments and outcomes between cases of UCD-MIS and UCD-non-MIS to evaluate the role of surgery and illuminate biological behavior of UCD-MIS. There were differences in the distribution of histopathological subtypes (plasmacytic histopathology was more frequently seen, 52.6% vs 13.4%; P<.001) between the 2 groups. However, both groups demonstrated good responses to surgical treatment, suggesting that UCD-MIS in some patients still shared common biological behavior with UCD in other patients. Sixteen (94.2%) patients with UCD-MIS underwent complete surgical excision alone, and the systemic inflammation resolved completely in all of them. This high response rate suggests surgical treatment as a potential cure for this unique subset of patients. After a median follow-up duration of 64 months (range, 2-239 months), neither lymphadenopathy nor the inflammatory state recurred. However, inflammation may progress in patients with irresectable disease, and treatment options other than surgery should be considered in these patients.

Adult Langerhans cell histiocytosis (LCH) remains poorly defined. We retrospectively studied 266 newly diagnosed LCH patients to understand the clinical presentation, treatment, and prognosis of adult LCH. The median age at diagnosis was 32 years (range, 18-79 years). At the time of diagnosis, 40 patients had single lesions within a single system, 18 patients had single pulmonary LCH, 26 patients had multiple lesions within a single system (SS-m), and 182 patients had multisystem disease (MS). The most common organ involved in MS patients was the bone (69.8%), followed by the pituitary (61.5%) and lung (61.0%). BRAFV600E , BRAF deletion, and MAP2K1 mutation were detected in 38.8%, 25.4%, and 19.4% patients, respectively. BRAF deletion was found more common in patients with MS LCH compared to single-system LCH (38.5% vs 7.1%, p = .004), also in patients with liver involvement (69.2% vs 14.3%, p < .001). The estimated 3-year overall survival (OS) and event-free survival (EFS) rates were 94.4% and 54.7%, respectively, in SS-m and MS LCH. Multivariate Cox regression showed that involvement of the liver or spleen at baseline predicted poor EFS and receiving cytarabine-based therapy as a first-line treatment and age older than 30 years at diagnosis predicted favorable EFS. The involvement of risk organs and age older than 50 years predicted poor OS, and receiving cytarabine-based therapy predicted favorable OS. Therefore, BRAF deletion was correlated with MS LCH, particularly those with liver involvement. Liver or spleen involvement at baseline indicates a poor prognosis, and a cytarabine-based regimen could be considered as first-line treatment for adult LCH patients.

Objectives:The clinical outcome of bullous pemphigoid appears worse in patients with infectious complications, and assessment of the prevalence and risk factors of infectious complications could be necessary to plan preventative strategies and to instruct the treatment plans. We sought to determine the risk factors of infection and compare associated factors in inpatients and outpatients with different system infections. Design:This is a single-centered retrospective study on the medical records of 252 patients from 2010 to 2018 at the dermatology department, Peking Union Medical College. Medical profiles of medical history, diagnosis, infectious complications, and treatment plans were analyzed. The associated factors were compared between the subgroups, including inpatients and outpatients, different body sites of infection. Results:Of the total 252 patients with bullous pemphigoid (BP), 81 patients (81/252, 32.1%) had infectious complications. Forty-eight patients died from pulmonary infections (11/48, 22.9%), cardiovascular diseases (6/48, 12.5%), and other diseases. Infections were most frequently found in skin/mucosa (44/252, 17.5%), respiratory system (32/252, 12.7%), and blood (10/252, 4.0%). On multivariate analysis, risk factors of infections in BP were maximal control dose of corticosteroids (OR 2.539, 95% CI 1.456-4.430,p= 0.001), low serum albumin level (OR 2.557, 95% CI 1.283, 5.092,p= 0.007), hospitalization (OR 4.025, 95% CI 2.289, 7.079,p< 0.001), comorbidities including respiratory disease (OR 4.060, 95% CI, 1.861, 8.858,p< 0.001), eye disease (OR 4.431, 95% CI 1.864, 10.532,p< 0.001), and diabetes (OR 2.667, 95% CI 1.437, 4.949,p= 0.002). The rate of infection was significantly higher in inpatients compared to that in outpatients (54.0 vs. 20.6%,p< 0.001), with diverse risk factors. Mucocutaneous infections were associated with a maximal control dose of corticosteroid and other dermatoses. Respiratory infections were related to respiratory disease and old age, and hematologic infection was associated with low serum hemoglobin levels and mucosal involvement of BP. Both of them were associated with mucosal involvement of BP and high titer anti-BP180 antibody. Conclusions:Infectious complications of bullous pemphigoid are common and are associated with mucosal involvement of BP, more comorbidities, the higher dose of corticosteroids, and the lower level of serum albumin.

Background: The clinical features and prognosis of adult Langerhans cell histiocytosis (LCH) remained poorly defined. Although recurrent somatic activating mutations of BRAFV600E and additional genetic drivers of MAPK pathway had been discovered in LCH, most genomic analyses were from children and the spectrum of genetic alterations and the impact of these genetic mutations on clinical presentation in adult LCH remains elusive. To address these questions, we retrospectively studied the clinical features, organ involvement, treatment approaches, genomic analyses and outcomes of adult LCH patients in our center. Methods: Patients diagnosed with LCH between January 2001 and June 2020 at Peking Union Medical College Hospital were included in this retrospective study. BRAF or MAP2K1 mutation was detected by a custom-designed NGS panel. Patients were classified according to the number of systems involved: SS-s, one lesion in a single system; SS-m, multiple lesions within one single system; and MS, multiple systems involved. The overall survival (OS) was defined as the duration from the diagnosis of LCH to the date of death. The event free survival (EFS) was defined as the duration from the initiation of treatment for LCH to reactivation after treatment and death from any cause. Results: Overall 266 patients were enrolled, 177 patients were male (66.5%). The median age at diagnosis was 32 years (range, 18-79 years). At the time of diagnosis, 58 patients had SS-s LCH (21.8%), 26 patients had SS-m LCH with bone involvement (9.8%) and 182 patients had MS LCH (68.4%). The most common organ involved in MS patients was bone (69.8%), followed by the pituitary (61.5%), lung (61.0%), lymph nodes (35.2%), skin (26.4%), liver (23.1%), thyroid (13.7%), spleen (8.2%), CNS (3.8%) and gastrointestinal tract (1.1%). No patients had hematopoietic system involvement. For 67 patients, BRAF and MAP2K1 mutation status were successfully determined with NGS. BRAFV600E was detected in 26 patients (38.8%), BRAFV600D was detected in 1 patient (1.5%), BRAFT599I in 1 patient (1.5%) and BRAFdeletion mutation in 17 patients (25.4%), including 15 BRAF N486_P490 and 2 BRAF N486_P491delinsS. MAP2K1 mutation was detected in 13 patients (19.4%). BRAF status was related to disease features and extent of disease. BRAF deletion was found in 38.5% of patients with MS LCH, 7.1% of patients with SS LCH (P= 0.004). BRAF deletion was apparent in 69.2% of patients with liver involvement (P <0.001). While bone involvement was associated with BRAFV600E mutation (46.2% vs 13.2%, P = 0.033). The initial treatment of the whole cohort is illustrated in the flow diagram of Figure 1. The estimated 4-year OS and EFS of patients with SS-s LCH were 97.2% and 57.0%, respectively. Totally 201 MS or SS-m patients received first-line treatment at our hospital. After a median 43-month follow-up (range 1-214 months), 92 patients had reactivation. The median EFS was 38.5 months (95% CI, 20.9-56.1 months). To evaluate the prognostic factors of EFS using multivariate Cox regression model, the involvement of liver (HR 0.545, 95% CI 0.335-0.885) or spleen (HR 0.416, 95% CI 0.205-0.844) at baseline were predictive of poor EFS, while receiving cytarabine-based therapy as a first-line treatment (HR 2.195, 95% CI 1.441-3.344) and age older than 30 years at diagnosis (HR 1.660, 95% CI 1.087-2.533) predicted favorable EFS. BRAF or MAP2K1 mutation status did not significantly affect EFS. Seventeen patients died during follow-up. The estimated 4-year OS was 94.4% of patients with MS or SS-m. Conclusion: We first found more than 25% of adult LCH patients carried BRAFdeletion (BRAF N486_P490 or BRAF N486_P491delinsS), which was related with MS and liver involvement. Also, we demonstrated that liver and spleen involvement indicates a worse prognosis in adult LCH, age older than 30 years at diagnosis predicted favorable EFS and a cytarabine-based regimen should be considered as a first-line treatment for adult MS or SS-m LCH patients. Disclosures No relevant conflicts of interest to declare.