Asymptomatic multicentric Castleman disease: a potential early stage of idiopathic MCD.

ABSTRACT: According to the diagnostic criteria for human herpesvirus 8 (HHV-8)-negative/idiopathic multicentric Castleman disease (iMCD) proposed by Castleman Disease Collaborative Network in 2017, there is a group of HHV-8-negative patients with multicentric Castleman disease (MCD) who do not have symptoms and hyperinflammatory state and do not meet the iMCD criteria. This retrospective study enrolled 114 such patients, described as asymptomatic MCD (aMCD), from 26 Chinese centers from 2000 to 2021. With a median follow-up time of 46.5 months (range, 4-279 months), 6 patients (5.3%) transformed to iMCD. The median time between a diagnosis of aMCD and iMCD in these 6 patients was 28.5 months (range, 3-60). During follow-up, 7 patients died; 3 of them died from progression of MCD. Despite that, 37.7% of patients received systemic treatment targeting MCD; this strategy was neither associated with a lower probability of iMCD transformation nor a lower death rate. The 5-year estimated survival of all patients with aMCD was 94.1% (95% confidence interval, 88.8-99.6). Transformation to iMCD was an important predictor of death (log-rank P = .01; 5-year estimated survival, 83.3%). This study suggests that patients with aMCD may represent a potential early stage of iMCD, who may not require immediate treatment but should be closely monitored.

Comprehensive geriatric assessment in newly diagnosed older myeloma patients: a multicentre, prospective, non-interventional study.

BACKGROUND: Multiple myeloma is a disease of the older people, whose prognoses are highly heterogeneous. The International Myeloma Working Group (IMWG) proposed a geriatric assessment (GA) based on age, functional status and comorbidities to discriminate between fit and frail patients. Given the multidimensional nature of frailty and the relatively recent exploration of frailty in the field of MM, reaching a consensus on the measurement of frailty in MM patients remains challenging. OBJECTIVE: We sought to assess the feasibility of performing a comprehensive GA (CGA) in older MM patients in a real-world and multicentre setting and to evaluate their baseline CGA profiles. RESULTS: We studied 349 older patients with newly diagnosed MM (age range, 65-86 years). Our results showed that a CGA is feasible for older MM patients. Using the IMWG-GA criteria, we identified significantly more frail patients in our cohort comparing to in the IMWG cohort (43% vs 30%, P = 0.002). In the IMWG-GA 'fit' group, risk of malnutrition, depression and cognitive impairment remains. The median follow-up time was 26 months (range 1-38). The median overall survival (OS) was 34.7 months, and the estimated 3-year OS rate was 50%. A high MNA-SF score (MNA-SF ≥ 12), low GDS score (GDS ≤ 5) and high CCI score (CCI ≥ 2) can be used to predict the OS of older patients with newly diagnosed MM. This study is registered at www.clinicaltrials.gov (NCT03122327). CONCLUSIONS: Our study justifies the need for a CGA in older patients with newly diagnosed MM.

Treatment and outcome patterns of patients with Waldenström's macroglobulinemia: a large, multicenter retrospective review in China.

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 <100 × 109/L, serum albumin <3.5 g/dl, ß2 microglobulin concentration ≥4 mg/L and LDH ≥250 IU/L predicted poor OS. In summary, our study showed that frontline treatment choices for WM are widely heterogeneous. We validated most of the established prognostic factors in the rIPSS (age >65 years, LDH ≥250 IU/L, ALB <3.5 g/dl and ß2 microglobulin ≥4 mg/L) together with PLT ≤ 100 × 109/L indicate a poor prognosis for patients with WM.

The anti-leukemic effect of carnosic acid combined with adriamycin in a K562/A02/SCID leukemia mouse model.

The effects of carnosic acid (CA) were investigated on the acute myeloid leukemia (AML) cell growth in vivo. A NOD/SCID AML mouse model, which was set up by inoculation with K562/A02 cells, was used to study whether tumor growth in vivo can be inhibited by CA combined with adriamycin. After being inoculated with K562/A02 cells, the NOD/SCID mice were expressed positive human mdr1 and bcr/abl genes. This result indicates that the K562/A02/SCID leukemia mouse model is successfully established. The mice treated with CA combined with adriamycin exhibit a significant lower number of leukemia cells (20%) than that of untreated animals (32.5%) (P<0.05), in particular with higher percentages of apoptotic cells than the mice treated by single adriamycin (control) group. The median of 95% CI survival time is 19 (10.0-44.2) and 33 (29.4-36.6) days for the control group and the CA-treated group, respectively. The difference is statistically significant (P<0.05). It is illustrated that the natural compound CA, combined with Adriamycin, has high potential to inhibit the growth of malignant cells in vivo, and is a promising adjuvant anti-cancer drug. Prospective studies should be conducted to understand the functional mechanism of CA at the molecular level.

[Relationship of TGF-ß and IL-4R gene polymorphisms with risk of classical Hodgkin lymphoma].

OBJECTIVE: This study was aimed to analyze the relationship between single nucleotide polymorphisms of transforming growth factor-ß1 G-800A and C-509T, interleukin-4 receptor V75I and susceptibility of CHL in adults. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied to analyze the expressed alleles of the selected SNP loca. The relationship between genomic polymorphisms of TGF-ß1 and IL-4R and susceptibility of CHL were coupled with clinical data. RESULTS: TGF-ß1G-800A and TGF-ß1C-509T had obvious linkage equilibrium (D' = 0.879, r(2) = 0.83, P = 0.020). GT haplotype distribution frequencies in mixed cellularity Hodgkin lymphoma cases and control group were of 53.1% and 34.2%, respectively, with statistically significant (OR = 2.35, P = 0.000); distribution frequencies of mutant gene T/T in disease and control groups were of 38.8% and 15.3%, respectively, also with statistically significant (OR = 3.654, P = 0.000); frequencies of nodular sclerosis CHL patients with IL-4R V75I mutant gene A/A in disease and control groups were of 19.2% and 41.75%, respectively, also with statistically significant (OR = 3.156, P = 0.000). CONCLUSION: Single nucleotide polymorphisms of TGF-ß1 G-800A, C-509T and IL-4R V75I has a significant correlation with Chinese susceptibility to classical Hodgkin lymphoma.

[Monitoring of plasma concentration of imatinib mesylate in patients with chronic myeloid leukemia].

OBJECTIVE: To analyze the clinical efficacy of imatinib mesylate (IM) for Ph-positive or BCR-ABL positive chronic myeloid leukemia (CML) to couple the trough plasma concentrations (C mins) of IM with clinical responses and adverse events (AEs). METHODS: One hundred and one CML patients received IM therapy, and Cmins of IM were determined in 30 patients. RESULTS: (1) Cumulative complete hematological response (CHR), major cytogenetic response (MCyR), complete cytogenetic response (CCyR) and negative BCR/ABL fusion gene rates were 96.6%, 86.5%, 77.5% and 47.2%, respectively, in CML-CP patients. In accelerated and blastic phases (AP and BC) patients, CHR, MCyR, CCyR and negative BCR-ABL fusion gene rates were 58.3%, 25.0%, 25.0%, 8.3%, respectively. (2) Mean Cmins of IM was significantly higher in the CCyR at 1 year [(1472 +/- 482) microg/L] group than in the non-CCyR at 1 years group [(1067 +/- 373) microg/L] (P < 0.05), and higher in the MMR at 1 year group than in the non-MMR at 1 years group [(1624 +/- 468) microg/L vs (1137 +/- 404) microg/L, P < 0.05]. CONCLUSION: IM significantly improves cytogenetic and molecular response, event-free survival, and overall survival for patients with Ph-positive CML. The Cmins of IM exerts a significant impact on clinical response (CCyR and MMR at 1 year).

Histone deacetylase inhibitor valproic acid inhibits proliferation and induces apoptosis in KM3 cells via downregulating VEGF receptor.

The expression of vascular endothelial growth factor receptor 1(VEGFR-1) in human multiple myeloma KM3 cells in vitro, effects of valproic acid (VPA), as a histone deacetylase inhibitor, on cell proliferation and apoptosis and the underlying molecular mechanism were investigated. The effects of VPA on the growth of KM3 cells were studied by MTT assay. The apoptosis rate was determined with flow cytometry. The mRNA level of VEGFR was determined by RT-PCR; and immunocytochemistry was used to detect the protein level of ac-H4 and VEGFR. VPA inhibited proliferation of KM3 cells in a time- and dose-dependent manner. Treatment with VPA (4, 2, 1 and 0.5 mmol/L) for 48h, the apoptosis rates of KM3 cells were (13.27+/-3.54)%, (22.13+/-1.20)%, (24.41+/-2.23)% and(40.62+/-4.28)% respectively. The expression of VEGFR-1 in KM3 cells were decreased in VPA-treated group by the immunochemistry and RT-PCR, whereas the acetylated histone H4(ac-H4) accumulated. It suggested VPA could decrease the expression of VEGFR-1 in KM3 cells, and it might play an important role in regulating the proliferation and apoptosis of multiple myeloma cell line KM3 cells. These results provide the framework for clinical trials.