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Objectives To explore the distinct mutation profiles between acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) and de novo AML and their relationships with prognosis. Methods Next-generation sequencing of 42 myeloid neoplasm-related genes in 293 newly diagnosed patients with AML. Results Eighty-four patients had AML-MRC, and 161 patients had de novo AML. The mutation rates of ASXL1 (25% vs 8.7%, P = .001), NRAS (17.9% vs 8.1%, P = .022), PTPN11 (11.9% vs 5%, P = .048), SETBP1 (6% vs 0.6%, P = .033), SRSF2 (11.9% vs 5.6%, P = .08), TP53 (16.7% vs 1.2%, P < .001), and U2AF1 (17.9% vs 7.5%, P = .014) in AML-MRC were higher than those in de novo AML, while the rates of FLT3-ITD (3.6% vs 15.5%, P = .005), KIT (0% vs 6.2%, P = .046), WT1 (3.6% vs 9.9%, P = .077), NPM1 (1.2% vs 21.7%, P < .001), and CEBPA (4.8% vs 24.2%, P < .001) mutation were lower. The appearance of ASXL1, TP53, U2AF1, SRSF2, and SETBP1 mutation could predict AML-MRC–like features in de novo AML, which was related to older age (60 vs 51 years, P = .001), low WBC counts (4.7 × 109/L vs 11.6 × 109/L, P = .001), and inferior outcomes (median overall survival, 15 months vs not reached, P = .003). Conclusions The presence of AML-MRC–related mutations can reveal a subset of patients with de novo AML similar to patients with AML-MRC.

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis that typically affects many organs, including the lung and pleura. However, there are few studies concerning pulmonary involvement in ECD patients, as well as the difference of pulmonary involvement between ECD and Langerhans cell histiocytosis (LCH). We performed a retrospective study of 54 ECD patients, and compared the pulmonary manifestations with those of adult LCH patients in our centre. The median age of diagnosis of the 54 ECD patients was 48 years (range 9-66 years). Chest computed tomography (CT) scans revealed lung involvement in 49 (91%) patients and pleural involvement in 34 (63%). Thirty-three (61%) patients had interstitial lung disease (ILD) with varying degrees of interlobular septal thickening, micronodules, and ground-glass opacities. ECD and LCH patients with pulmonary involvement showed significant differences in smoking status (P < 0·001), respiratory symptoms (P = 0·001) such as cough and pneumothorax (P < 0·001), and radiological findings, including cysts (P < 0·001), opacities (P < 0·001), and pleural thickening (P < 0·001). With a median follow-up duration of 24 months (range, 1-84 months), the estimated three-year overall survival (OS) of this entire ECD cohort was 90·2%. Patients with ILD tended to have worse progression-free survival (PFS) than those with no ILD (P = 0·29).

POEMS syndrome is a rare plasma cell dyscrasia with distinct lipid metabolism abnormalities at disease onset. However, the serum lipidomic characteristics in patients with POEMS syndrome were not investigated. The study performed an untargeted lipidome screening by liquid chromatography‐tandem mass spectrometry (LS‐MS/MS) in the pre‐ and post‐treatment serum of 24 patients with POEMS syndrome, together with the serum of 24 paired healthy controls. Patients with POEMS syndrome had a distinct serum lipid composition compared with healthy controls, and a 3‐lipid model had a predictive accuracy of 93.5% in distinguishing patients and healthy controls consisting of fatty acyl 17‐oxo‐20Z‐hexacosenoic acid, phosphatidylcholine(16:0/18:1(9Z)) and sterol lipid 5b‐pregnanediol. Four lipids including 17‐oxo‐20Z‐hexacosenoic acid (r = 0.423, P = .040) were correlated with risk stratification, and 2 lipids including Cer(d18:0/13:0) were inversely related to serum vascular endothelial growth factor level (r=−0.465, P = .022). Eleven lipids were related to disease activity, including arachidonic acid which was inversely related and lysoPC(20:4) which was positively related. The study indicated a distinct lipid characteristic profile of patients with POEMS syndrome different from healthy controls and identified several lipids that may serve as potential diagnostic markers and monitors of therapeutic efficacy, as well as indicating potential metabolism pathways involved in the pathological process.

To achieve prompt and comprehensive assessment of treatment, we investigated the feasibility of composite hematologic and organ response (CHOR) model in a Chinese light chain (AL) amyloidosis cohort. Three hundred and eighty-eight newly diagnosed patients were assigned scores of 0-3 for complete response, very good partial response, partial response, no response, or progression at 6 months. Organ response (OR) was scored as follows: 0 - all OR (AOR), 1 - mixed OR (MOR), and 2 - no OR (NOR). Finally, patients were divided into CHOR group 1 (total score 0-3) and group 2 (total score 4-5). The patients who achieved AOR and MOR had similar outcomes, which were much better than those of patients with NOR. Group 1 had significantly better overall survival than group 2 (

Objectives The aim of this retrospective analysis was to assess the incidence of hepatitis B virus (HBV) reactivation among patients with myeloproliferative neoplasms (MPN) during and after ruxolitinib treatment. Methods Between February 2013 and February 2020, 224 patients with MPN were treated using ruxolitinib at Peking Union Medical College Hospital. Of these, 6 had chronic, and 56 had resolved HBV infection, including 43 patients who received combination treatment with thalidomide, prednisone, and stanozolol (TSP) during ruxolitinib treatment. Results Two patients with chronic HBV infection who did not take any antiviral prophylaxis developed HBV reactivation and hepatitis flare. The other four patients with chronic HBV infection, who took antiviral prophylaxis before ruxolitinib treatment, did not develop HBV reactivation. Also, no patients with resolved HBV infection received antiviral prophylaxis and developed HBV reactivation. Conclusion This study demonstrated that HBV reactivation and hepatitis flare might commonly occur a few months after initiating ruxolitinib treatment in patients with chronic HBV infection who did not take antiviral prophylaxis, especially in combination with TSP. Still, it was extremely rare in patients with resolved HBV infection.

To illuminate the prognostic value of ADC (apparent diffusion coefficient), an important quantitative parameter of diffusion-weighted MRI, for multiple myeloma (MM). A prospective single-center study which enrolled 114 consecutive newly diagnosed MM patients with baseline whole-body diffusion-weighted MRI (WB DW-MRI) results was conducted. Baseline clinical and MRI parameters were analyzed with univariate and multivariate approaches to identify independent risk factors for progression-free survival (PFS) and overall survival (OS). Five different DW-MRI patterns were seen, and the mean ADC value of the representative background bone marrow was 0.4662 ± 0.1939 × 10−3 mm2/s. After a mean follow-up of 50.2 months (range, 15.7–75.8 months), twenty-four patients died and seven were lost to follow-up. The mean ADC value of the representative background bone marrow was showed to be an independent risk factor for both PFS (HR 4.664; 95% confidence interval (CI) 1.138–19.121; p = 0.032) and OS (HR 14.130; 95% CI 1.544–129.299; p = 0.019). Normal/salt-and-pepper pattern on DW-MRI was associated with PFS using univariate analysis (p = 0.035) but lost the significance with multivariate Cox regression. Mean ADC value of the representative background bone marrow predicts both PFS and OS which suggests the role of baseline DW-MRI for risk stratification in newly diagnosed MM patients. • Whole-body diffusion-weighted MRI (WB DW-MRI) might be helpful to improve the current risk stratification systems for newly diagnosed multiple myeloma (MM). • Morphological parameters as MRI pattern and focal lesion–associated parameters have been reported to be related to survival. However, important functional parameters such as apparent diffusion coefficient (ADC) values were not incorporated into the current risk stratification model. • This study is one of the first endeavors to delineate the correlation of baseline ADC values and survival in MM patients. It is revealed that the mean ADC value of the representative background bone marrow (L3-S1 and iliac bone) was an independent risk factor for both PFS and OS.

Background The study aimed to investigate the clinical features and prognosis factors of adult patients with Langerhans cell histiocytosis (LCH) with pulmonary involvement, especially multisystem (MS) LCH with pulmonary involvement. Methods We retrospectively analyzed the demographic materials, clinical features and treatment outcomes of 119 adult LCH patients with pulmonary involvement at our center from January 1990 to November 2019. Results Among 119 patients, 13 (10.9%) had single-system (SS) LCH, and 106 (89.1%) had MS-LCH with pulmonary involvement. SS-LCH patients had higher smoking rate (84.6% vs 52.8%, P = 0.026) and smoking index (300 vs 200, P = 0.019) than MS-LCH patients. The percentage of respiratory symptoms of SS-LCH patients was higher than MS-LCH patients (84.6% vs 53.8%, P = 0.034). Pulmonary function was impaired in 83.8% of the patients, and DLCO was the parameter most frequently impaired, accounting for 81.1%. The median DLCO was 65.1% predicted. Patients with pneumothorax had significantly worse DLCO (P = 0.022), FEV1 (P = 0.000) and FEV1/FVC (P = 0.000) than those without pneumothorax. During the follow-up, 72.4% of the patients had stable pulmonary function, and 13.8% showed improvements after chemotherapy. The estimated 3-year OS and EFS were 89.7 and 58.3%, respectively. Patients with a baseline FEV1 ≤ 55% predicted had worse OS. A history of pneumothorax indicated worse EFS and cytarabine based therapy predicted better EFS. Conclusions An FEV1 ≤ 55% predicted and a history of pneumothorax at diagnosis indicated a poor prognosis. Cytarabine based regimen may arrest the decline in pulmonary function in LCH patients with pulmonary involvement and improve EFS.

Background In order to study the CXCR4 expression with [68Ga]pentixafor PET in different types of non-Hodgkin lymphoma, we performed a retrospective study to describe the [68Ga]pentixafor PET/CT imaging in a spectrum of lymphomas and to compare it with [18F]FDG PET/CT. Results Twenty-seven patients with newly diagnosed non-Hodgkin lymphoma were recruited retrospectively. [68Ga]pentixafor PET showed increased radioactivity in lymphoplasmacytic lymphoma (n = 8), marginal zone lymphoma (n = 4), diffuse large B cell lymphoma (n = 3), follicular lymphoma (n = 2), mantle cell lymphoma (n = 1), unclassified indolent B cell lymphoma (n = 3), and enteropathy associated T cell lymphoma (n = 3). However, peripheral T cell lymphoma, not otherwise specified (n = 1), and NK/T cell lymphoma (n = 2) were not avid for [68Ga]pentixafor. In comparison to [18F]FDG PET, [68Ga]pentixafor PET demonstrated more extensive disease and higher radioactivity in lymphoplasmacytic lymphoma and marginal zone lymphoma. Conclusion CXCR4 expression varies in different types of non-Hodgkin lymphoma. Overexpression of CXCR4 was detected with [68Ga]pentixafor PET/CT in lymphoplasmacytic lymphoma, marginal zone lymphoma, diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma, unclassified indolent B cell lymphoma, and enteropathy associated T cell lymphoma. The uptake of [68Ga]pentixafor was higher than [18F]FDG in lymphoplasmacytic lymphoma and marginal zone lymphoma.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes (POEMS) syndrome is associated with increased risk for ischemic stroke (IS). Because POEMS syndrome is rare, little is known regarding the underlying mechanism and prognosis for IS in patients in whom it occurs. The medical records of patients with POEMS syndrome were screened between January 2018 and January 2000 at Peking Union Medical College Hospital to identify those with IS. The baseline characteristics, IS features, and patient outcomes were analyzed. Forty-one (8.0%) of 510 POEMS patients were documented to have IS. Patients with IS were older, had a higher percentage of Overall Neuropathy Limitation Scale score >4, and had a higher level of fibrinogen compared with those who did not have IS. Ninety-three percent of IS events occurred before or within 3 months after a diagnosis of POEMS. Of 41 occurrences of IS, 29 (46.3%) were multifocal. Recurrent IS was observed in 13 (31.7%) of 41 patients, but not in patients with successful anti-plasma cell therapy. The 3-year overall survival rate in patients with IS was 71.0% and for those without IS, it was 88.5% (P = .002). We showed that 8.0% of POEMS patients had IS, and most IS events occurred in POEMS patients not being treated effectively. Having IS was a predictor of unfavorable prognosis. Early diagnosis, immediate initiation of treatment for POEMS, and control of POEMS syndrome is key to reducing the occurrence of IS, improving survival, and preventing recurrence of IS.

We aimed to detect the MYD88L265P and CXCR4S338X mutations in cell-free DNA (cfDNA) in patients with Waldenstrom macroglobulinemia (WM). We collected peripheral blood and paired bone marrow aspirates from 27 WM patients (including 16 patients with newly diagnosed WM, 3 patients with WM in relapse and 8 patients with WM during treatment). cfDNA was extracted from peripheral blood using a QIAamp Circulating Nucleic Acid Kit. The MYD88L265P and CXCR4S338X mutations were detected by real-time allele-specific PCR (AS-PCR) in cfDNA and genomic DNA (gDNA) extracted from bone marrow aspirates. The sensitivity of real-time AS-PCR for detecting MYD88L265P in cfDNA was determined using a serial dilution of 10%, 2%, 0.4% and 0.08% MYD88L265P cfDNA in wild-type cfDNA. Among the 27 patients, MYD88L265P was detected in 88.9% of them in gDNA and in 85.2% of them in cfDNA, with a concordance rate of 96.3%. The concordance rates were 93.8%, 100% and 100% in patients with newly diagnosed WM, patients with WM in relapse and patients with WM during treatment, respectively. The sensitivity of real-time AS-PCR for detecting MYD88L265P in cfDNA was 0.4%. CXCR4S338X was detected in 6.3% of the 16 newly diagnosed WM patients in both gDNA and cfDNA, with a concordance rate of 100.0%. It is feasible to apply cfDNA to detect MYD88L265P and CXCR4S338X in WM patients with a high concordance rate.

To explore the clinical characteristics and outcomes in Chinese patients with type I cryoglobulinemia (CG), we retrospectively analyzed the clinical data, management, and outcomes of 45 patients diagnosed with type I CG in our hospital from January 2015 to March 2019. In our study, all type I CGs were secondary to hematologic diseases, and monoclonal gammopathy of unknown significance was the most common primary disease, accounting for 48.9% (n = 22). Additionally, B cell non-Hodgkin lymphoma, Waldenström's macroglobulinemia, and multiple myeloma accounted for 24.4% (n = 11), 20.0% (n = 9), and 6.7% (n = 3), respectively. In patients with type I CG, skin damage was the most common symptom, presenting in 57.8% of the patients, followed by peripheral neuropathy (22.2%) and renal involvement (15.6%). Treatment was initiated in 29 patients (64.4%), and the most common choice was a rituximab-based regimen in 13 patients (44.8%), followed by bortezomib-based regimen in 11 patients (37.9%). Clinical symptoms were significantly improved after treatment, and the clinical remission rate was 86.2%, including 34.5% of complete clinical remission, while the laboratory response rate was 88.9%, including 33.3% of complete response and 55.6% of partial response. The expected 1-year overall survival was 97.8%. In conclusion, for patients with multisystemic involvement, such as skin damage, kidney damage, or peripheral neuropathy, the diagnosis of type I CG should be considered, and the underlying disease needs to be explored. Symptoms and primary diseases should be taken into consideration before choosing initial management.

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= 0.004), also in patients with liver involvement (69.2% vs 14.3%, P

Background: Doxycycline was demonstrated in a retrospective study to be associated with greater survival in patients with light chain amyloidosis. Therefore, we prospectively compared the efficacy of bortezomib-cyclophosphamide-dexamethasone (CyBorD) and CyBorD combined with doxycycline for cardiac light chain amyloidosis. Methods: This was a multicenter, open-label, randomized controlled trial. Patients with Mayo 2004 stage II to III light chain amyloidosis were included. Patients were randomized to doxycycline 100 mg twice daily along with 9 cycles of CyBorD (doxycycline group) or to 9 cycles of CyBorD alone (control group). The primary outcome was 2-year progression-free survival (PFS). PFS was defined as the time from randomization to death, hematologic progression, or organ progression (heart, kidney or liver). Hematologic progression was defined on the basis of a substantial increase in free light chain. An increase in either NT-proBNP (N-terminal pro B-type natriuretic peptide) or cardiac troponin was the main criterion for defining cardiac progression. Cardiac PFS, defined as the time from randomization to cardiac progression or death, was compared between groups in an exploratory analysis. The corresponding treatment hazard ratio was estimated with a Cox regression model. Results: One hundred forty patients underwent randomization, with 70 in each group. The median age was 61 years (range, 33–78 years) with a male:female ratio of 1.75:1. Stage II disease was present in 34 (48.6%) and 33 (47.1%) patients in the doxycycline and control groups, respectively. After a median follow-up duration of 24.4 months, 32 of 70 (45.7%) patients in the doxycycline group and 30 of 70 (42.9%) patients in the control group experienced progression. PFS was not significantly different between groups (hazard ratio, 0.97 [95% CI, 0.59–1.60]; P =0.91). Cardiac progression occurred in 29 of 70 (41.4%) patients in the doxycycline group and 26 of 70 (37.1%) patients in the control group. The death rates for both groups by the end of follow-up was the same, 25 of 70 (35.7%). No significant differences were observed for either cardiac PFS (hazard ratio, 0.91 [95% CI, 0.54–1.55]; P =0.74) or overall survival (hazard ratio, 1.04 [95% CI, 0.60–1.81]; P =0.89). Conclusions: Our trial demonstrated that doxycycline combined with CyBorD failed to prolong PFS or cardiac PFS compared with CyBorD alone in cardiac light chain amyloidosis. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03401372.

Ga-pentixafor PET/CT in a 66-year-old woman with newly diagnosed multiple myeloma showed extensive disease in bone and bone marrow. After 6 cycles of chemotherapy, the patient was in complete remission but complained of fever and coughing. Follow-up Ga-pentixafor PET/CT showed significantly reduced uptake in bone and bone marrow, consistent with her clinical outcome of myeloma. However, patches, nodules, and ground-grass opacities in bilateral lungs with moderate to intense uptake of Ga-pentixafor were noted. The histopathology of the biopsy for the pulmonary nodule confirmed pulmonary cryptococcosis.

Erdheim–Chester disease (ECD) is a rare non-Langerhans histiocytosis with a broad, nonspecific clinical spectrum from asymptomatic to life-threatening multi-organ involvement [1,2]. Diagnosis of EC...

To summarize the clinical features and outcomes in Chinese patients with immunoglobulin light-chain (AL) amyloidosis with ≥10% bone marrow plasma cells (BMPCs).We retrospectively compared the clinical features and outcomes between patients with ≥10% BMPCs (high-BMPC group; n = 56) and those with10% BMPCs (low-BMPC group; n = 311).Patients in the high-BMPC group had significantly higher levels of N-terminal pro-brain natriuretic peptide, significantly lower levels of 24 h urine protein, and significantly higher levels of difference between the involved and uninvolved serum free light chains (485.3 versus 121.1 mg/L, P 0.001). Patients in the high-BMPC group had significantly higher early mortality within 3 months of diagnosis (21.4% versus 10.9%, P = 0.018). In a 3-month landmark analysis, median progression-free survival durations were 17.3 and 34.5 months (P = 0.01), and the median overall survival durations were 24.4 months and not reached in the high- and low-BMPC groups, respectively (P = 0.005).Patients with AL amyloidosis and ≥10% BMPCs have higher mortality within 3 months of diagnosis and poorer prognosis compared with patients with10% BMPCs.

Purpose Smoldering multiple myeloma (SMM) is a rare asymptomatic plasma cell disorder. Even with emerging therapeutic approaches and risk stratification, the optimal time to treat SMM remains controversial. This meta-analysis aimed to compare early treatment with deferred treatment of SMM, especially high-risk SMM. Methods Early treatment was defined as treatment immediately after diagnosis. Deferred treatment was initiated after progression. The primary outcome was progression. Secondary outcomes were mortality, response, and safety. PubMed, EMBASE, Medline, Cochrane, and ClinicalTrials.gov databases were searched from January 1990 to March 2019. Randomized controlled trials (RCTs) comparing early treatment with deferred treatment in SMM patients were eligible. Risk ratios (RRs) with 95% confidence interval (CI) were pooled. Results Eight RCTs covering 885 SMM patients were included. Considering all the different treatment approaches, early treatment significantly decreased progression of SMM (RR=0.53, 95% CI 0.33-0.87, P=0.01). In subgroup analysis, melphalan plus prednisone (RR=0.22, 95% CI 0.08-0.64, P=0.005) and immuno-modulatory drugs (RR=0.43, 95% CI 0.31-0.59, P

Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder. The anti–interleukin 6 (IL-6) therapy siltuximab is not available everywhere, and is not effective for over one-half of patients. Alternative treatment approaches are urgently needed. In the first iMCD clinical trial directed against a target other than IL-6 signaling, we investigated a thalidomide-cyclophosphamide-prednisone (TCP) regimen in newly diagnosed iMCD patients. This single-center, single-arm, phase 2 study enrolled 25 newly diagnosed iMCD patients between June 2015 and June 2018. The TCP regimen (thalidomide 100 mg daily for 2 years; oral cyclophosphamide 300 mg/m2 weekly for 1 year; prednisone 1 mg/kg twice a week for 1 year) was administered for 2 years or until treatment failure. The primary end point was durable tumor and symptomatic response for at least 24 weeks. Twelve patients (48%) achieved the primary end point with no relapse, 3 patients (12%) demonstrated stable disease, and 10 patients (40%) were evaluated as treatment failure. Even when considering all patients, there were significant (P < .05) improvements in median symptom score, IL-6 level, hemoglobin, erythrocyte sedimentation rate, albumin, and immunoglobulin G. Among responders, the median levels of all evaluated parameters significantly improved, to the normal range, after treatment. The regimen was well tolerated. One patient died of pulmonary infection and 1 patient had a grade 3 adverse event (rash); 2 patients died following disease progression. Estimated 1-year progression-free survival and overall survival were 60% and 88%, respectively. The TCP regimen is an effective and safe treatment of newly diagnosed iMCD patients, particularly when siltuximab is unavailable. This trial was registered at www.clinicaltrials.gov as #NCT03043105.

BACKGROUND Cardiac involvement occurs in more than half of the patients with light-chain amyloidosis (AL), but the characteristics, treatment and prognosis of cardiac AL (CAL) are not fully described. Methods and Results: A total of 227 patients with CAL diagnosis between January 2009 and March 2017 at Peking Union Medical College Hospital were included. Patients with Mayo stages I, II and III AL accounted for 0.9%, 49.8% and 49.3%, respectively. Autologous stem cell transplantation, bortezomib combinations, non-bortezomib regimens and palliative treatment were given as first line therapy in 3.1%, 44.1%, 30.8% and 22.0% of patients, respectively. Overall hematological response and cardiac response were achieved in 60.6% and 37.2% of evaluable patients, respectively. The median overall survival (OS) was 17 months in all patients, and 10 months in those with Mayo stage III. In patients with Mayo stage III disease who survived for >1 month, the bortezomib group survived significantly longer than the non-bortezomib group (median OS, not reached vs. 12 months, P=0.019). Three independent prognostic factors for survival were identified: N-terminal fragment of B-type natriuretic peptide (NT-proBNP) ≥5,000 pg/mL, bone marrow plasma cells ≥10%, and systolic blood pressure

POEMS syndrome is a rare plasma cell dyscrasia. This study compared the responses to and survival of 347 POEMS syndrome patients given three first-line treatment regimens: autologous stem cell transplantation (ASCT, N = 165) and melphalan + dexamethasone (MDex, N = 79), or lenalidomide + dexamethasone (LDex, N = 103). After a median 45-month follow-up, overall hematologic complete remission (CRH) was 46.4%, vascular endothelial growth factor complete remission (CRV) was 55.1%, and neurological remission (RN) was 93.8%. CRH was better with ASCT (49.7%) than with MDex (37.7%, p = 0.001). CRV was better with ASCT (66.2%) than with MDex (38.5%, p = 0.001) or LDex (47.7%, p = 0.008). Differences in RN achieved by three regimens (91.5% vs. 100% vs. 93.8%, p = 0.234) were not significant. Overall 3-year progression-free survival (PFS) was 80.5% and overall 3-year overall survival (OS) was 90.8%. PFS was 87.6% with ASCT and 64.9% with LDex (p = 0.003). OS in the three regimens did not differ (p = 0.079). In medium-high risk patients, ASCT had better CRH and CRV than MDex, and better PFS than LDex. Therefore, although all three treatments had reasonable responses and survivals, patients with higher risk may benefit more from ASCT treatment.

The diagnosis of polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome requires polyneuropathy and monoclonal plasma cell proliferation as two mandatory criteria. Our aim was to summarize clinical manifestations and treatment responses of POEMS variants with no evidence of monoclonal gammopathy. We queried all medical documentation of patients referred to Peking Union Medical College Hospital from August 2012 to July 2017, and reviewed the clinical and laboratory features of 13 patients with atypical POEMS syndrome with undetectable monoclonal gammopathy, and compared to prototypes published. The prevalence of polyneuropathy, organomegaly, skin changes, and extravascular fluid overload were 100%, 100%, 92%, and 100%, respectively. Other clinical manifestations, such as endocrinopathy, pulmonary hypertension, papilledema, thrombocytosis, and polycythemia affected similar percentages of patients as seen in prototypes. POEMS variants enrolled had a median serum vascular endothelial growth factor (VEGF) level of 4998 pg/ml (range 2155-11,029 pg/ml). Long-term follow-up found that all 12 patients received autologous stem cell transplant, melphalan-based therapy or lenalidomide/thalidomide-based therapy obtained clinical improvement, of which eight experienced decreased levels of VEGF by 50% or back to normal. The median progression-free survival was 101.5 months. Our findings raised a variant of POEMS syndrome variants with featured clinical manifestations, elevated VEGF levels, and good response to therapies targeting plasma cell.

In this study, we aimed to investigate treatment options and the prognosis of patients with WM in China. This retrospective study included 1141 patients diagnosed with symptomatic WM between January 2003 and December 2019 at 35 tertiary hospitals in 22 provinces of China. Fifty-four patients (7.3%) received monotherapy, 264 (36.0%) received chemoimmunotherapy, 395 (53.8%) received other combination regimens without rituximab, and 21 (2.9%) received ibrutinib. Using a multivariable Cox regression model, age > 65 years old, platelets 65 years, LDH ≥250 IU/L, ALB

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare plasma cell dyscrasia without standard front-line treatment. Merely, few studies have reported the responses and outcomes of bortezomib plus dexamethasone (BDex) in POEMS syndrome. In this study, a total of 69 patients (40 males) treated with front-line BDex were included. The median age at diagnosis was 50 years (range, 30–78 years). After a median of 9 cycles BDex (range 1–9), fifty-two (88.1%), thirty-two (46.4%), and forty-seven (71.2%) patients achieved the best neurologic response, hematological complete response, and serum vascular endothelial growth factor (VEGF) response, respectively. The extravascular overload, pulmonary hypertension, and renal impairment also substantially improved. No treatment-related death occurred. Two patients developed grade-1 bortezomib-induced peripheral neuropathy and were reversible after drug withdrawal. After a median follow-up of 22.5 months, the estimated 2-year overall survival and time to next treatment were 95.7% and 65.6%, respectively. In conclusion, the combination of bortezomib and dexamethasone is effective, with a high response rate and safety profile for patients with newly diagnosed POEMS syndrome.

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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-020-06467-w.

Recently, a difference between involved and uninvolved free light chains (dFLC) less than 10 mg/L after treatment (stringent dFLC response) was reported to be associated with superior survival in light-chain (AL) amyloidosis. We conducted a retrospective study of AL amyloidosis patients treated with bortezomib to investigate the predictive value of a stringent dFLC response. Two hundred and thirty-five patients were included. The cardiac and renal responses were much higher in patients achieving a stringent dFLC response (86.5% versus 42.7% and 75.9% versus 38.2%

A 38-year-old man with newly diagnosed multiple myeloma underwent Ga-pentixafor PET/CT for baseline assessment. Ga-pentixafor PET/CT demonstrated multiple focal bone and bone marrow lesions with intense radioactivity. After 9 cycles of chemotherapy against multiple myeloma, the patient experienced serologically complete remission of myeloma. Consistently, the follow-up Ga-pentixafor PET/CT for PET response showed significantly reduced uptake in the previously chemokine receptor 4-positive bone lesions. However, intense and homogeneous uptake of Ga-pentixafor was noted in the thymus with a smooth contour and slightly increased density, which is possibly caused by thymic hyperplasia after chemotherapy.

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.

Background Rosai–Dorfman disease (RDD) and IgG4-related (IgG4-RD) disease are both rare diseases, but in some cases, RDD mimics IgG4-RD clinically and pathologically. RDD mimicking IgG4-RDs (RDD mimic IgG4-RD), referring to disease initially diagnosed as IgG4-RD but finally pathologically confirmed to be RDD, is a clinically rare and confusing disease. To summarize the characteristics of this disease, we prospectively analyzed the clinical features, laboratory parameters, pathological characteristics, treatment and prognosis of patients diagnosed with RDD mimic IgG4-RD. Moreover, by analyzing characteristics of RDD mimic IgG4-RD, RDD and IgG4-RD, we further compared the similarities and differences between RDD and IgG4-RD. Results 7 patients with RDD mimic IgG4-RD were included in this study and all of them had extranodal organ involvement, especially the central nervous system, which occurred in 5 patients (71.4%). Although serum IgG4 level was elevated in 6 cases (1360–54,100 mg/L), overall, it was still lower than that in IgG4-RD patients. Furthermore, we found a new cut-off value of serum IgG4 concentration for differentiating RDD and IgG4-RD with higher specificity. Pathological findings of RDD also showed features resembling IgG4-RD: IgG4-positive plasma cell enrichments were observed in all RDD mimic IgG4-RD patients, and the proportion of IgG4/IgG in tissues was 10–40% in 4 patients and more than 40% in 2 patients. However, none of the RDD mimic IgG4-RD patients or RDD patients displayed obliterative phlebitis or storiform fibrosis. Most of the RDD mimic IgG4-RD patients were treated with glucocorticoids combined with immunosuppressants, and a good prognosis was obtained following treatment. Conclusions RDD has clinical manifestations that mimic IgG4-RD. However, detailed differences in laboratory parameters and pathological characteristics are present between these two diseases. Our study underlines the necessity to rule out RDD while diagnosing IgG4-RD using pathological findings as the identification criteria and provides advice for both differentiating these two diseases and clinical treatment of RDD mimic IgG4-RD.

Endocrinopathy is an important characteristic of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome. However, endocrine responses to different regimens were unknown so far. Here we investigated endocrine characteristics in 383 patients with newly diagnosed POEMS syndrome and thyroid responses 1 year after treatment with autologous peripheral stem cell transplantation, melphalan plus dexamethasone, or lenalidomide plus dexamethasone. Overt hypothyroidism and subclinical hypothyroidism were noted in 20.6% (79/383) and 36.0% (138/383) of patients. Adrenal insufficiency was noted in 13.6% (43/316) of patients. Hyperprolactinemia was noted in 62.7% (207/330) of patients. Hypogonadism was noted in 48.0% (60/125) of female and 22.6% (51/226) of male patients. Thyroid function was significantly related with baseline risk stratification (p < 0.001) and significantly improved regardless of initial regimens. Patients with baseline hypothyroidism had a significant inferior progression-free survival (PFS) (p = 0.028) and overall survival (OS) (p = 0.006). Three-year PFS in patients with and without baseline hypothyroidism were 68.9 vs. 82.5%, respectively. Three-year OS rates in patients with and without baseline hypothyroidism were 82.8 vs. 92.8%, respectively. In summary, hypothyroidism, hyperprolactinemia, and hypogonadism are common endocrinopathies in POEMS syndrome. Thyroid function significantly improved regardless of the initial regimens. Thyroid function parallels with baseline risk stratification, and patients with baseline hypothyroidism have significantly inferior OS and PFS.

Background ETV6-ACSL6 is a fusion gene rarely reported in myeloid malignancies, and its clinical characteristics, proper treatment strategies, and effect on prognosis are poorly understood. Results Sixteen patients with the ETV6-ACSL6 fusion gene were identified, with a median age of 50 years. Twelve patients were male. Clinical diagnoses included chronic eosinophilic leukemia, not otherwise specified, acute myeloid leukemia, and other types of myeloproliferative and myelodysplastic disorders. Ten out of 12 patients had increased levels of eosinophils, and four out of five had increased levels of basophils in peripheral blood. Treatment with tyrosine kinase inhibitors was ineffective. The prognosis of the patients was poor, with seven patients dying within 1 year. Conclusions Patients with the ETV6-ACSL6 fusion gene mainly present with myeloproliferative and myelodysplastic disorders, typically with increased eosinophils and/or basophils and poor survival. Intensive therapies such as allogenic stem cell transplantation should be an initial consideration for eligible patients.

Cold agglutinin disease (CAD) is a rare form of autoimmune haemolytic anaemia, and because of its rareness, there is no standard treatment for CAD patients. We retrospectively analysed the response to rituximab-containing therapy in CAD patients at our hospital. All patients received rituximab-containing therapy for at least 1 month. A total of 16 patients (11 males and 5 females) were included. The median age at the onset of the disease was 63.5 years (range 41–79). Most patients had manifestations including anaemia (81.3%) or cold-induced circulatory symptoms (75.0%). The median haemoglobin level was 72 g/L (range 29–101), and the median cold agglutinin titre was 1,024 (range 64–2,048). Thirteen of 16 patients (81%) responded to the therapy. Responders achieved a median increase in haemoglobin levels of 45 g/L. Grade 3–4 neutropenia occurred in 3 patients (19%), but only 1 (6%) of them experienced infection. Anaphylaxis related to rituximab occurred in 1 patient. During follow-up, five patients experienced relapse, and two patients died. The estimated median progression-free survival was 36 months, and median overall survival was not yet reached. In conclusion, A rituximab-based therapy in accordance with individual patient characteristics may be a reasonable choice for CAD patients.

BACKGROUND Progressive nodular histiocytosis (PNH) is a rare, clinically distinct non-Langerhans cell histiocytic neoplasm affecting the skin and mucous membranes with no signs of spontaneous regression of the lesions. Patients typically have hundreds of lesions of superficial xanthomatous papules to nodules and deep larger fibrous nodules, which can be life-threatening if laryngeal mucosa was involved. So far, few cases of PNH have been reported and no effective treatment has been shown to reverse the progressive clinical course. CASE PRESENTATION Here we describe a case of PNH presenting as diffuse, progressively enlarging papules, nodules and even leonine appearance in a young woman. The diagnosis was confirmed by histological and immunohistochemical findings. Next-generation sequencing (NGS) showed identical missense mutation in XIAPY404C and in-frame deletion in MAPK1A2[6>5]. Since ERK inhibitor has not been on the market yet, the patient received chemotherapy instead. Traditional chemotherapy with intermediate-dose of cytarabine (500 mg/m2 cytarabine by 3-hour infusion every 12 hours for 3 days every 5 weeks) achieved favorable therapeutic effect as confirmed by clinical symptoms and PET/CT imaging. CONCLUSIONS PNH is a rare, proliferative disorder with disfiguring lesions and deteriorative quality of life. Mutations in MAPK1, XIAP may play crucial roles in the pathogenesis of PNH. Intermediate-dose cytarabine can be considered as a promising treatment option for PNH patients.

A 59-year-old man with history of POEMS syndrome was found with a painless mass in the right neck for 9 months. In F-FDG and Ga-pentixafor PET/CT, there were multiple neck nodes and left inguinal nodes that showed intense F-FDG and Ga-pentixafor uptake. In addition, osteoblastic bone lesions with mild F-FDG and Ga-pentixafor uptake were noted in the pelvis, which was consistent with posttreated osseous involvement of POEMS syndrome. However, considering lymphoadenopathy with such intense F-FDG uptake is not usually seen in POEMS syndrome, the patient underwent biopsy of the right cervical nodes. The histopathology with immunohistochemistry confirmed follicular lymphoma.

Extranodal natural killer/T cell lymphoma, nasal type (ENKL) is a highly aggressive tumor with relatively poor prognosis. In this prospective study, we investigated the efficacy and toxicity of a novel GDP-ML regimen (combined gemcitabine, cisplatin, dexamethasone, methotrexate, and pegaspargase) as front-line treatment in newly diagnosed ENKL. Eligible newly diagnosed stage I/II ENKL patients received sandwich chemoradiation therapy. Patients with stage III/IV disease received an initial 4 cycles of GDP-ML regimen. After 4 cycles, responding patients continued to receive either autologous transplantation or additional two courses of GDP-ML. A total of 44 patients were enrolled with a median follow-up of 26 months. The overall response rate (ORR) were 78.6% for the whole cohort, 84.6% for stage I/II, and 66.7% for stage III/IV, and corresponding complete remission (CR) rates were 61.9%, 76.9%, and 33.3%. The 1- year and 2- year progression-free survival (PFS) rates were 69.3% and 62.9%, and 1- year and 2-year overall survival (OS) rates were 76.5% and 67.4%, respectively. Patients with stage I/II disease showed better 2-year OS rate compared with stage III/IV patients (88.1% vs. 33.2%, p

Background Acute myeloid leukemia (AML) is a clinically and biologically heterogeneous disease. The survival of older patients is generally poor. In the current study, we sought to investigate the differences in molecular gene mutations between younger and older AML patients, and to identify those newly diagnosed AML patients who are more likely to respond to standard cytarabine and daunorubicin induction chemotherapy. Methods We retrospectively evaluated 179 patients who were newly diagnosed with non-M3 AML. A next-generation sequencing assay covering 34 genes was used to investigate recurrently mutated genes. The mutational status of fusion genes was determined by real time PCR. Results The median age at diagnosis was 53 years (range 18–88 years). Sixty-eight patients were 60 years or older with a median age of 67 years (range 60–88 years). Eighteen patients (10.1%) carried t(8;21)(q22;q22.1) or RUNX1–RUNX1T1 gene fusion, and there was a significantly higher incidence in younger patients (p = 0.019). At least one non-synonymous gene mutation was detected in 159 patients (88.8%). The median number of gene mutations was two (range 0–6). The mean number of molecular gene mutations at diagnosis was higher in older patients than younger patients (2.5 vs 1.83, p = 0.003). Older patients had significantly higher incidences of ASXL1 (22.1% vs 13.5%, p = 0.025) and TP53 mutations (13.2% vs 3.6%, p = 0.034). In total, 78 patients received DA60 (daunorubicin 60 mg/m2 per day on days 1–3 and cytarabine 100 mg/m2 twice per day on days 1–7) as the induction therapy, and information was available on their response to induction treatment. Patients with RUNX1–RUNX1T1 gene fusion were significantly more likely to achieve complete remission (CR) after DA60 induction therapy (p = 0.026), as were patients without the ASXL1 mutation (p = 0.007). Conclusion Older AML patients had a lower incidence of favorable cytogenetics and higher frequencies and burdens of molecular mutations that are associated with poor prognosis compared to younger patients. Patients with RUNX1–RUNX1T1 gene fusion or without the ASXL1 gene mutation had a better chance of achieving CR when treated with cytarabine and daunorubicin induction chemotherapy.

Hypothyroidism is the most common endocrine disorder in POEMS syndrome. In this single-center prospective study, 36 patients with newly diagnosed POEMS syndrome were treated with lenalidomide (10 mg daily for 21 days) and dexamethasone (40mg once per week) for 12 cycles. Hypothyroidism was demonstrated in 58.5% (24/41) at baseline, including 25% (6/24) of clinical hypothyroidism and 75% (18/24) of subclinical hypothyroidism. After 12-month treatment, the percentages of clinical hypothyroidism and subclinical hypothyroidism had decreased 11.8% and 27.2%, respectively. Percentage of euthyroidism had increased from 41.5% to 80.5%. There was a strong relation between VEGF response and thyroid function improvement (p = .028). Patients with clinical hypothyroidism at baseline had an inferior 1-year OS (50% vs. 100%, p .043) than euthyroidism and subclinical hypothyroidism groups. Clinical hypothyroidism was associated with decreased overall survival and this combination treatment was effective in improving thyroid function in POEMS syndrome.

The incidence and clinical implications of autoimmune diseases (ADs) in patients with non-Hodgkin's lymphoma(NHL) remain unclear. The aim of this study was to examine the prevalence of ADs in NHL and define the clinical characteristics and prognosis of AD-associated NHL patients. Patients diagnosed with NHL in our institute between 1995 and 2017 were retrospectively reviewed to assess the incidence of ADs. Of 4880 patients with NHL, 140 (2.9%) presented with autoimmunity, with a total of 24 ADs. The most common AD was Sjögren syndrome, followed by autoimmune cytopenia, psoriasis, rheumatoid arthritis, etc. Psoriasis and rheumatoid arthritis were significantly associated with pre-existing ADs, whereas autoimmune cytopenia was significantly associated with secondary AD. Sjögren syndrome was significantly associated with B-cell lymphoma, and systemic vasculitis was significantly associated with T-cell lymphoma. Patients with AD-associated NHL had a high frequency of extranodal involvement(87%), with significant associations between specific extranodal sites of lymphoma and subtypes of ADs. Among patients with available data on pre-treatment peripheral blood Epstein-Barr virus (EBV) DNA(n = 68), elevated EBV-DNA load was observed in a variety of NHL subtypes, including 20% of marginal zone lymphoma and 14.3% of follicular lymphoma patients. In a matched-pair analysis, survival did not differ significantly between NHL patients with and without ADs. However, for NHL patients with pre-existing ADs, a prior history of systemic corticosteroids therapy was significantly associated with worse survival (HR = 7.33, P = 0.006). Taken together, our data suggest that a broad spectrum of ADs is associated with NHL, and AD-associated NHL has distinct features with regard to clinical manifestations and prognosis.

Peripheral T cell lymphomas (PTCL) are less responsive to anthracycline-containing regimen such as CHOP and carry a poor prognosis. In this prospective study, we investigated gemcitabine, cisplatin, and dexamethasone (GDP) combined with methotrexate (MTX) and pegaspargase (PEG-L) as front-line treatment in PTCL. Eligible newly diagnosed PTCL patients received 4 cycles of the GDP-ML chemotherapy every 28 days. After 4 cycles, responding patients continued to receive either autologous stem cell transplantation or the MTX/cytarabine (MA) regimen for consolidation. This trial is registered with www.chictr.org.cn (ChiCTR-ONC-12002055). A total of 65 patients were enrolled with a median follow-up of 38.5 months. The overall response rate (ORR) was 55.4%, and complete remission rate (CR) was 33.8%. The median overall survival (OS) was 16 months, and the 1-year and 2-year OS were 59.1% and 38.2%, respectively. The median PFS was only 8 months. The main adverse event was hematologic toxicity: 50% patients showed grade III/IV neutropenia. GDP-ML for the first-line treatment of PTCL patients is an effective induction regimen compared with standard CHOP, and the toxicity was more significant but acceptable. However, future studies exploring new drug combinations are warranted to overcome relapse after remission. ClinicalTrials.gov Identifier: NCT02987244

A 48-year-old man and a 55-year-old woman, who were diagnosed with follicular lymphoma and small B lymphocytic cell lymphoma, respectively, underwent initial "watch-and-wait" approach against lymphoma. The initial F-FDG PET/CT of both patients showed multiple FDG-avid lymph nodes in the neck, mediastinum, abdomen, and inguinal regions. During their active surveillance, the follow-up PET/CT of both patients revealed spontaneous regression of lymphoma.

This study is to retrospectively evaluate the prevalence of MYD88 and CD79B mutations and the clinicopathologic characteristics of patients with primary diffuse large B cell lymphoma (DLBCL) of the female genital tract and breast. The characteristics, treatments, and outcomes of 19 patients diagnosed with primary DLBCL of the female genital tract and breast, who had formalin-fixed and paraffin-embedded tissues obtained from diagnostic samples diagnosed between January 2004 and June 2016, were analyzed retrospectively. Nineteen female patients (7 with primary breast and 12 with primary female genital tract DLBCL) were included in this retrospective study. Eleven patients (57.9%) carried a MYD88 mutation, including 10 with MYD8 L265P and 1 with the MYD88 L265S mutation. Seven patients (36.8%) harbored a CD79B mutation, which included two cases with CD79B Y196H, two cases with CD79B Y196N, one case with CD79B Y196D, one case with CD79B Y196F, and one case with CD79B Y196X. Four cases had both MYD88 and CD79B mutations. The clinicopathologic parameters, progression-free survival (PFS), and overall survival (OS) of the MYD88 mutation-carrying group were not significantly different from those of the MYD88 wild-type group except for higher LDH levels. Six patients received cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP), while 13 patients received rituximab plus CHOP, and 13 patients received central nervous system prophylaxis. The median OS and PFS were 73 and 56 months, respectively. Patients with primary breast and primary female genital tract DLBCL have a high frequency of MYD88 and CD79B mutations. The presence of these mutations does not affect survival but may offer additional therapeutic options.

Objective To determine the efficacy and prognosis of autologous hematopoietic stem cell transplantation (ASCT) as frontline treatment for peripheral T cell lymphoma (PTCL). Methods Clinical data from 46 PTCL patients who achieved complete (CR) or partial remission (PR) after ASCT from October 1996 to July 2014 were analysed retrospectively. Results Median patient age was 32 (range: 15–68) years. Disease types included PTCL, unspecified type, in 23 patients, anaplastic large cell lymphoma in eight, angioimmunoblastic lymphoma in eight, extranodal NK/T-cell lymphoma in five, and hepatosplenic T-cell lymphoma and enteropathy associated T-cell lymphoma in one each. Of these patients, 80% had Prognostic Index for Peripheral T-cell Lymphoma scores ≥1. Thirty-four patients had pre-transplantation CR and 12 had PR. Median follow up was 37 (6–176) months. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 77.1% and 61.9%, respectively. Multivariate analysis showed that pre-transplantation CR was an independent risk factor for survival, and CR was more common than PR (OS 81% vs 59.3%; PFS 71.8% vs 17.8%). Conclusion Frontline consolidation treatment with ASCT was associated with favourable outcomes in patients with PTCL. Pre-transplantation CR was a prognostic factor for survival, suggesting that ASCT may be favoured as front-line consolidation therapy after first complete remission.

Background Lemzoparlimab (also known as TJC4 or TJ011133), a novel, RBC-sparing CD47 antibody with a unique epitope, is in early phase clinical development in both the U.S. and China. Like other anti-CD47 antibodies, lemzoparlimab blocks the interaction of CD47 and SIRPα, leading to phagocytosis of various CD47+ tumor cell lines and primary AML cells. Mono-treatment of lemzoparlimab inhibited tumor growth completely and extended the overall survival of treated mice in a patient-derived AML xenograft model. Here we report initial findings in the ongoing phase I trial which is to determine the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of lemzoparlimab in relapsed and/or refractory (r/r) AML and MDS patients. Methods The trial (NCT04202003) adopted a modified 3+3 dose escalation design with weekly lemzoparlimab at dose levels of 1, 3, 10, 20 and 30 mg/kg. The initial two lower dose cohorts (1 mg/kg and 3 mg/kg) was designed to enroll one patient each, and the study would escalate to the next level (10 mg/kg) if no DLT and no predefined toxicity events (e.g. grade 2 or above drug-related non hematologic toxicity, except for isolated lab abnormality with no clinical manifestation) were observed. If the first DLT or predefined toxicity event was observed, the cohort size would be expanded at the current dose level and the study would revert to the standard 3+3 design. Safety, PK/PD parameters, and preliminary efficacy were evaluated. Results As of 24 July 2020, 5 r/r AML patients (pts) including 1 relapsed, 1 relapsed/refractory and 3 primary refractory, were enrolled across 3 dose cohorts (1 at 1 mg/kg, 1 at 3 mg/kg and 3 at 10 mg/kg). Patients had 2-4 prior therapies. Median age was 45 years (range 25-66). Four of 5 pts developed treatment emergent AEs. Most of the AEs were grade 1 or 2. Treatment-related AEs that occurred in > 1 patient included thrombocytopenia (2/5 pts, 1 with grade 1 and 1 with grade 3) and positive anti-erythrocyte antibody (2/5 pts). No dose dependent hematologic toxicities have been observed so far. There was no treatment-related dose interruption or dose discontinuation. No patient developed treatment-related SAE or death. The maximum tolerated dose (MTD) has not yet been reached and the drug was well tolerated in r/r AML pts in the background of significantly impaired hematopoietic function with or without supportive blood transfusion. The anti-CD47 interferences on the blood bank testing were mitigated before blood transfusion. With doses from 1 mg/kg to 10 mg/kg, lemzoparlimab exhibited a supraproportional increase in exposure, which can be attributed to target (CD47) mediated drug disposition at low doses. CD47 receptor occupancy (RO) was evaluated as a PD marker. The mean RO on peripheral T cells at Cmax was 74.0%, 82.0% and 84.9% for 1, 3 and 10 mg/kg, respectively. The mean RO on CD33+ tumor cells at Cmax was 45.9%, 75.8% and 82.2% for 1, 3 and 10 mg/kg, respectively. Of note, one patient with primary refractory AML achieved morphologic leukemia-free state (MLFS) after 2 cycles of lemzoparlimab treatment at 1 mg/kg. Conclusion Lemzoparlimab was well tolerated in r/r AML pts in the doses tested and importantly, consistent with preclinical data, there were no serious hematological AEs so far. No DLTs or MTD was observed up to 10 mg/kg weekly dosing so far. The PK/PD profile of lemzoparlimab is also consistent with preclinical findings. The preliminary efficacy observed was encouraging. Dose escalation will continue until MTD or RP2D is reached. Disclosures No relevant conflicts of interest to declare.

Objective: Castleman disease (CD) is a group of rare lymphoproliferative disorders which are divided into unicentric CD (UCD) and multicentric CD (MCD) according to the number of lymph node regions involved. In the case of UCD, no or only local compressive symptoms are present with normal biochemistry, and prognosis is great after complete surgical resection. However, we have noticed that a small portion of UCD patients presenting with severe constitutional symptoms accompanied by high inflammatory state might resemble MCD in clinical presentations and biochemical features. Since our current understanding of this group of patients is far from enough, we are here to summarize the characteristics, treatments and outcomes of these high inflammatory patients and compare them with other UCD patients to see whether surgery still serves well as first-line treatment, so as to illuminate the biological behavior of these hyper-inflammatory UCD patients. Method: We retrospectively analyzed 123 cases of UCD diagnosed between Jan 2000 and Dec 2019 in Peking Union Medical College Hospital. The patients with high inflammatory state who met the laboratory and clinical criteria for idiopathic MCD (Blood, 2017) were included in the hyper-inflammatory group (Figure 1). We summarized their clinical characteristics, treatments and outcomes. Response criteria of iMCD defined by Castleman Disease Collaborative Network (CDCN) were cited to evaluate treatment response in symptoms and biochemistry. Kaplan-Meier analysis were used to analyze the progress-free survival (PFS) and overall survival (OS), and comparison was made with other UCD patients through Log-rank test. Result: Among 24 UCD patients with high inflammatory state (19.5%), when compared to others without, constitutional symptoms, organomegaly, fluid retention and complication of paraneoplastic pemphigus (PNP) or bronchiolitis obliterans (BO) were more common. ESR or CRP elevation, anemia, abnormal platelet count, albumin decrease, renal function impairment and IgG increase were also more usually discovered (Table 1). Meanwhile, plasmacytic (PC) histopathology was more frequently seen (45.8% vs 14.1%, P=0.001) (Table 2), but no statistical significance was shown on the lymph node region involved. As for first-line treatments (Figure 1), 18 UCD patients with high inflammatory state (75.0%) underwent complete surgical excision alone; there was no recurrence of lymphadenopathy after surgery, and the inflammation resolved completely except 2 cases of disease progression (both complicated by PNP), achieving a response rate of 88.9%. 2 patients (8.3%) received chemotherapy together with surgery, and all disease completely resolved. Among the 3 patients (12.5%) treated only with chemotherapy, 1 experienced symptomatic and biochemical progression of disease. Finally, there was one patient (4.17%), after a watch-and-wait period, experienced progression in symptoms. In contrast, disease progression was not seen in UCD without high inflammatory state. There was no statistical difference between median follow-up time of the two groups. UCD patients without high inflammatory state have a better PFS curve [P Conclusion: UCD patients with high inflammatory state are not uncommon. Although they resemble MCD with more PC histopathology, more severe symptoms and abnormal lab results, the good response to surgical treatment suggested that patients with high inflammatory state still shared common biological behavior with other UCD. However, recurrence of symptoms and progression of inflammation might still happen in patients with PNP or unresectable disease, so treatment options other than surgery should be considered in these patients. Figure Disclosures No relevant conflicts of interest to declare.

Backgroud: Waldenström macroglobulinemia (WM) is an uncommon indolent B cell non-Hodgkin lymphoma, which has heterogeneous clinical presentations and indications for treatment. Mostly the choice of first-line therapy is based on the individual patient's characteristic and indications for treatment. In China, previous studies on WM are mostly from single-center with small sample size, limiting the information available on treatment and outcome patterns. To address this knowledge gap, we present data from an analysis based on a nationwide multicenter registry with 17-years follow-up. Our study focuses on the clinical presentation, first-line therapies, as well as outcome and prognosis of WM in China. Methods: Patients diagnosed with WM between January 2003 and December 2019 at 35 academic hospitals in China, which have been entered in the database of the China Waldenström macroglobulinemia Registration (CWMG), were included in this retrospective study. Data including baseline clinical features, symptoms requiring treatment, treatment and survival were collected. The overall survival (OS) was defined as the duration from the diagnosis of WM to the date of death or last follow-up. Results: Overall 1141 patients were enrolled, 829 patients were male (72.7%), with a male-to-female ratio of 2.7:1. The median age at diagnosis was 64 years (range, 29-89 years), which 472 patients (41.4%) were older than 65 years, and 126 patients (11.0%) were older than 75 years. The patients' family histories included 6 WM and 4 other lymphoproliferative disorders. Symptoms leading to treatment initiation including anemia in 828 patients (72.6%), organomegaly in 441 patients (38.7%), thrombocytopenia in 302 (26.5%), neutropenia in 246 (21.6%), constitutional symptoms in 203 (17.8%), Bing-Neel syndrome in 13 (1.1%), IgM-related symptoms in including secondary amyloidosis in 32 (2.8%), secondary autoimmune hemolysis in 25 (2.2%), peripheral neuropathy in 23 (2.0%), secondary cold agglutinin disease in 21 (1.8%), secondary cryoglobulinemia in 11 (1.0%). At the time of diagnosis, 1125 patients had full information for IPSS-WM risk stratification. Among them, 194 patients (17.2%) were classified as low risk, 436 patients (38.8%) were intermediate risk, and 495 patients (44.0%) were high risk. Overall, 734 patients had documented treatment information. 75 patients (10.2%) received monotherapy, 264 (36.0%) received chemoimmunotherapy, and 395 (53.8%) receive other combination regimens (Figure 1). The most frequently used monotherapy was chlorambucil (3.1%), followed by ibrutinib (2.9%) and rituximab (2.5%). Rituximab, cyclophosphamide and dexamethasone or prednisone (DRC or RCP) were the most frequently used chemoimmunotherapy (10.8%). Followed by rituximab plus cyclophosphasmide, vincristine/vincristine and prednisone/prednisolone (R-COP) (6.8%), R-COP plus doxorubicin/epirubicin (R-CHOP) (6.1%), rituximab plus fludarabine, cyclophosphamide (R-FC) (4.5%), rituximab plus bortezomib based regimen (3.5%). Other combination regimens including bortezomib based regimen (18.6%), FC (10.6%), CHOP (9.3%), immunomodulatory drug based regimen (5.7%), chlorambucil plus prednisone (4.4%). After a median of 23 months (range 1-201 months) follow-up, 123 patients died. The estimated 5-year OS was 74.9%. Median OS were similar among patients who received monotherapy, chemoimmunotherapy or other combination regimens. To evaluate the prognostic factors of OS using multivariate Cox regression model, age > 65 years old (P=0.011, HR 0.622, 95% CI 0.431-0.898), platelet < 100×109/L (P=0.006, HR 0.570, 95% CI 0.381-0.853), serum albumin Conclusion: Frontline treatment choices of WM are wide heterogeneity due to various clinical presentations and the rarity of the disease. Old age, low platelet, low albumin, high β-2 microglobulin, high LDH and secondary amyloidosis indicate worse prognosis in WM. These findings may provide guidance for management of WM and better prognostic stratification of risk-adapted treatment strategies. Figure 1 Disclosures No relevant conflicts of interest to declare.

Background: Patients with amyloid light-chain (AL) amyloidosis who have advanced cardiac damage are at risk of premature mortality. Currently, bortezomib is the mainstay in the treatment of...

Background Erdheim–Chester disease (ECD) is a rare multi-systemic form of histiocytosis. Treatment with BRAF inhibitors has markedly improved outcomes of ECD; however, this targeted therapy is expensive (estimated annual cost is $50,000). Since estimated annual cost of interferon-α (IFN-α) is only approximately $1600 in China, we retrospectively evaluated the long-term therapeutic efficacy of IFN-α and the value of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) as an assessment method among 32 ECD patients who received high dose IFN-α therapy at Peking Union Medical College Hospital. Results The median age at diagnosis was 48 years (range, 6–66 years). The median duration of treatment was 18.5 months (range, 1–51 months). The overall clinical response rates were 80.0%, including 33.3% complete response, 36.7% partial response and 10.0% stable disease. Thirty-one patients underwent a total of 81 scans by FDG-PET. Seventeen patients had serial FDG-PET results, nine patients had experienced a partial metabolic response at the last follow-up. The median reduction of ratios between the most active target lesion standardized uptake value (SUV) and liver SUV from baseline to last FDG-PET scan was 61.4% (range, 8.8–86.6%). Eight of thirteen patients who experienced continuous clinical improvement during follow-up had at least one target lesion SUV increased by FDG-PET which decreased in subsequent scans without changing treatment strategy. The estimated 3-year progression-free survival (PFS) and overall survival (OS) were 64.1 and 84.5%, respectively. Central nervous system (CNS) involvement was the only predictor for poor PFS and OS. Conclusions High-dose IFN-α treatment is a cost-effective option, especially for patients without CNS involvement. Single target lesion SUV elevation according to FDG-PET do not accurately demonstrate disease progression, but serial FDG-PET imaging effectively discriminate treatment response.