Prevalence, clinical characteristics and treatment outcome of factor X deficiency in a consecutive cohort of primary light-chain amyloidosis.

Factor X (FX) deficiency is prevalent in light-chain (AL) amyloidosis but its clinical significance was not investigated deeply. We conducted a retrospective analysis of a consecutive cohort with 207 primary AL amyloidosis patients. FX deficiency was present in 129 patients (62.3%). Those with FX deficiency had higher dFLC (299.6 mg/L vs. 102.3 mg/L, P < 0.001), higher cardiac troponin I (0.05 µg/L vs. 0.02 µg/L, P < 0.001) and N-terminal pro-brain natriuretic peptide (3115 ng/L vs. 392 ng/L, P < 0.001), and more patients with bone marrow plasma cells > 10% (18.0% vs. 4.3%, P = 0.008). The prevalence of FX deficiency increased with the Mayo 2004 stage. FX-deficient patients exhibited inferior overall survival (P < 0.001) and progression-free survival (P < 0.001) than others. Fifty-five patients with FX deficiency received retesting of FX activity after anti-plasma cell therapy. The median variation in FX activity was + 6.8% (range, -24.5% ~ +73.4%). Better improvement of FX activity was observed in patients with complete hematologic response (+18.2% vs. +4.0%, P = 0.036) and at least one organ response (+14.4% vs. +3.4%, P = 0.024). FX deficiency is associated with a heavier disease burden and poorer survival in primary AL amyloidosis. Improvement of FX activity tends to appear in patients with better hematologic and organ responses after chemotherapy.

Benefit of high-dose idarubicin as induction therapy in acute myeloid leukemia: a prospective phase 2 study.

Idarubicin 12 mg/m2 has been recommended as a standard induction therapy for acute myeloid leukemia (AML). It is unknown whether a higher dose of idarubicin can improve the remission rate. This phase 2 prospective single-arm study enrolled 45 adults with newly diagnosed AML between September 2019 and May 2021 (NCT 04,069,208). Induction therapy included administration of idarubicin 14 mg/m2 for 3 days and cytarabine 100 mg/m2 every 12 h subcutaneously for 7 days. The primary endpoint was the composite complete response rate (complete response (CR) plus complete response with incomplete blood count recovery (CRi)). The median age was 45 years (range 14-60 years). Forty (88.9%) patients had CR or CRi, including 39 patients with CR and 1 patient with CRi after one course of induction therapy. The median times to recovery of absolute neutrophil and platelet counts were 21 days. Only 1 patient died of intracranial hemorrhage during induction therapy. After a median follow-up of 14 months (range 3.5-24 months), the estimated 18-month overall survival and disease-free survival (DFS) were 66.9% and 57.5%, respectively. In conclusion, idarubicin 14 mg/m2 plus cytarabine was a safe and efficient intensive regimen for younger and fit patients with newly diagnosed AML.

Impact of Physicians' Personalities and Behavioral Traits on Treatment-Related Decision-making for Elderly Acute Myeloid Leukemia.

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.

Amyloidosis secondary to intrapulmonary Castleman disease mimicking pulmonary hyalinizing granuloma-like clinical features: A rare case report.

RATIONALE: Amyloidosis secondary to intrapulmonary Castleman disease (CD) is a rare benign disease diagnosed by histopathology. It seems to be associated with chronic inflammation, and large amounts of IL-6 produced in the germinal center of CD may enhance the production of precursor of amyloid. PATIENT CONCERNS: We reported a case of an 18-year-old woman presenting with dry cough and dyspnea on exertion for 6 months and detailed exams revealed multiple pulmonary nodules, positive antinuclear antibodies, hypocomplementemia, and thrombocytopenia. DIAGNOSES: A computed tomography-guided percutaneous lung biopsy revealed the histopathological features of pulmonary hyalinizing granuloma (PHG), but video-assisted pulmonary wedge resection for biopsy with immunohistochemical stains finally demonstrated a corrected diagnosis of intrapulmonary CD with secondary amyloidosis. INTERVENTIONS: The patient had received prednisone and Tacrolimus for 6 months. OUTCOMES: There was no significant improvement in pulmonary lesions or platelet level. Chemotherapy to CD was needed. LESSONS: Intrapulmonary CD should be considered in patients with multiple pulmonary nodules irresponsive to corticosteroid and diagnosis of PHG should be carefully considered based on small lung biopsy sample. The treatment of amyloidosis secondary to CD remains to be uncertain.

Correction to: Next-generation sequencing-based genetic landscape and its clinical implications for Chinese acute myeloid leukemia patients.

[This corrects the article DOI: 10.1186/s12935-018-0716-7.].

Bortezomib-based chemotherapy can improve renal and tubular functions in patients with light chain-associated Fanconi syndrome.

Light chain-associated Fanconi syndrome (LCFS) is a disorder of renal proximal tubule due to immunoglobulin light chains. Cases of LCFS are rare and mostly sporadically reported, and treatment of this entity is still controversial. This single-center retrospective study included 22 patients diagnosed with LCFS in Peking Union Medical College Hospital. Monoclonal gammopathy of undetermined significance was diagnosed in 13 patients, and overt multiple myeloma in six patients, with two smoldering myeloma and one Waldenstrom macroglobulinemia. Light chain was mostly kappa type (90.9%). Baseline median estimated glomerular filtration rate was 66 (13-126) ml/min/1.73 m2, with one patient presented as end-stage renal disease. After a median follow-up of 37 months, three patients died. Twelve patients were treated with chemotherapy, including 7 with bortezomib-based regimens. Renal function was significantly improved in the group of patients who received chemotherapy (p = 0.026). Compared with other chemotherapy regimens, patients with bortezomib-based treatment had a better hematological response (p = 0.027) as well as a better proximal tubule outcome (p = 0.015). Chemotherapy likely outweighs supportive treatment in patients with LCFS. Bortezomib-based regimen seems to be a safe first-line therapy for management of those patients.

Successful Treatment of Erdheim-Chester Disease With Coronary Artery Involvement.

Erdheim-Chester disease (ECD) is a rare non-Langerhans histiocytosis and inflammatory myeloid neoplasm with poor prognosis. Symmetric long bone osteosclerosis occurs in nearly all patients, but other organs are often involved. Coronary artery involvement is rare, but was encountered in a patient who experienced angina. Radiologic presentation and histologic findings were consistent with diagnosis of ECD. A soft-tissue mass was found surrounding the right atrium, ascending aorta, and all branches of coronary artery. Interferon-alfa treatment was successful. In conclusion, we recommend coronary artery computed tomography angiography for cardiovascular evaluation of ECD and interferon-alfa to treat ECD.

The prognostic value of T1 mapping and late gadolinium enhancement cardiovascular magnetic resonance imaging in patients with light chain amyloidosis.

BACKGROUND: Cardiac impairment is associated with high morbidity and mortality in immunoglobulin light chain (AL) type amyloidosis, for which early identification and risk stratification is vital. For myocardial tissue characterization, late gadolinium enhancement (LGE) is a classic and most commonly performed cardiovascular magnetic resonance (CMR) parameter. T1 mapping with native T1 and extracellular volume (ECV) are recently developed quantitative parameters. We aimed to investigate the prognostic value of native T1, ECV and LGE in patients with AL amyloidosis. METHODS: Eighty-two patients (55.5 ± 8.5 years; 52 M) and 20 healthy subjects (53.2 ± 11.7 years; 10 M) were prospectively recruited. All subjects underwent CMR with LGE imaging and T1 mapping using a Modified Look-Locker Inversion-recovery (MOLLI) sequence on a 3 T scanner. Native T1 and ECV were measured semi-automatically using a dedicated CMR software. The left ventricular (LV) LGE pattern was classified as none, patchy, and global groups. Global LGE was considered when there was diffuse, transmural LGE in more than half of the short axis images. Follow-up was performed for all-cause mortality using Cox proportional hazards regression analysis and Kaplan-Meier survival curves. RESULTS: The patients demonstrated an increase in native T1 (1438 ± 120 ms vs. 1283 ± 46 ms, P = 0.001) and ECV (43.9 ± 10.9% vs. 27.0 ± 1.7%, P = 0.001) compared to healthy controls. Native T1, ECV and LGE showed significant correlation with Mayo Stage, and ECV and LGE showed significant correlation with echocardiographic E/E' and LV ejection fraction. During the follow-up for a median time of 8 months, 21 deaths occurred. ECV ≥ 44.0% (hazard ratio [HR] 7.249, 95% confidence interval (CI) 1.751-13.179, P = 0.002) and global LGE (HR 4.804, 95% CI 1.971-12.926, P = 0.001) were independently prognostic for mortality over other clinical and imaging parameters. In subgroups with the same LGE pattern, ECV ≥ 44.0% remained prognostic (log rank P = 0.029). Median native T1 (1456 ms) was not prognostic for mortality (Tarone-Ware, P = 0.069). CONCLUSIONS: During a short-term follow-up, both ECV and LGE are independently prognostic for mortality in AL amyloidosis. In patients with a similar LGE pattern, ECV remained prognostic. Native T1 was not found to be a prognostic factor.

Next-generation sequencing-based genetic landscape and its clinical implications for Chinese acute myeloid leukemia patients.

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.

The clinical spectrum of IgM monoclonal gammopathy: A single center retrospective study of 377 patients.

OBJECTIVES: We retrospectively evaluated the clinical features, serum levels of IgM, and prevalence of IgM related diseases in patients with serum immunofixation electrophoresis (sIFE) confirmed IgM monoclonal gammopathy at our center. METHODS: We included patients with sIFE confirmed IgM monoclonal gammopathy between January 2008 and December 2014 in this retrospective study. We evaluated clinical data, sIFE, serum IgM levels, and diagnosis. RESULTS: In total, 7107 patients had sIFE confirmed monoclonal gammopathy, with 377 (5.3%) patients having the IgM type. The median age was 62 years (range, 19-105 years). The median level of serum IgM is 8.3g/L (range, 0.24-150g/L). The diagnosis included monoclonal gammopathy of undetermined significance (MGUS, 157 patients, 41.6%), Waldenstrom macroglobulinemia (WM, 105 patients, 27.9%), B cell non-Hodgkin's lymphoma (69 patients, 18.3%), primary cold agglutinin disease (pCAD, 16 patients, 4.2%), primary amyloidosis (14 patients, 3.7%), cryoglobulinaemia (six patients, 1.6%), IgM MGUS associated neuropathy (five patients, 1.3%), multiple myeloma (three patients, 0.8%), and POEMS syndrome (two patients, 0.5%). Levels of serum IgM>15.5g/L were 80.6% sensitive and 89.2% specific for the diagnosis of WM. Kappa type light chain indicated the diagnosis of WM, pCAD, IgM MGUS associated neuropathy and cryoglobulinaemia, while lambda type light chain indicated POEMS and amyloidosis. There were 41/157 (26.1%) MGUS patients diagnosed with complications due to IgM-unrelated autoimmune diseases. CONCLUSION: IgM monoclonal gammopathy contains a broad spectrum of diseases. Levels of serum IgM and the type of light chain can be used to help with differential diagnosis. The association between MGUS and some autoimmune diseases requires further investigation.