Eltrombopag plus diacerein vs. eltrombopag in patients with ITP: a multicenter, randomized, open-label, phase 2 trial.

This study aimed to compare the efficacy and safety of eltrombopag plus diacerein vs. eltrombopag alone in patients with primary immune thrombocytopenia (ITP) who were previously unresponsive to 14 days of eltrombopag treatment at the full dose. Recruited patients were randomly assigned 1:1 to receive either eltrombopag plus diacerein (n=50) or eltrombopag monotherapy (n=52). Overall response rate, defined as a platelet count at or above 30×109/L, at least doubling of the baseline platelet count, and no bleeding, was reached in 44% of patients in the eltrombopag plus diacerein group compared with 13% in the eltrombopag group at day 15 (P = .0009), and reached in 42% of patients in the combination group compared with 12% in the monotherapy group at day 28 (P = .0006). The addition of diacerein to eltrombopag also led to a longer duration of response (P = .0004). The two most common treatment-emergent adverse events were respiratory infection and gastrointestinal reactions in the combination group, and fatigue and respiratory infection in the eltrombopag group. In conclusion, eltrombopag plus diacerein was well tolerated, and induced higher overall response rates and longer duration of response than eltrombopag alone, offering a rejuvenating salvage therapy for ITP patients unresponsive to 14 days of full dosage eltrombopag. Our work has the potential to enhance the care of patients treated with thrombopoietin receptor agonists, reducing the need for rapid transitions to less-preferable therapies. This study is registered at ClinicalTrials.gov as NCT04917679.

Autologous hematopoietic stem cell transplantation improves survival outcomes in peripheral T-cell lymphomas: a multicenter retrospective real-world study.

The aim of this study is to evaluate the survival benefit of consolidative autologous hematopoietic stem cell transplantation (ASCT) in patients with peripheral T-cell lymphomas (PTCL). In this retrospective study, the ASCT group underwent consolidative ASCT after first-line therapy at 14 transplantation centers in China between January 2001 and December 2019. Data were collected over the same time frame for the non-ASCT group from the database of lymphoma patient records at Peking University Cancer Hospital & Institute. A total of 120 and 317 patients were enrolled in the ASCT and non-ASCT groups, respectively, and their median ages were 43 years and 51 years, respectively. In the ASCT group, 101 patients had achieved complete remission (CR) and 19 patients had achieved partial remission at the time of ASCT. The median follow-up time was 40.2 months and 68 months, and the 3-year overall survival (OS) rate was 80.6% and 48.9% (p < 0.001) for the ASCT and non-ASCT groups, respectively. The beneficial effect of ASCT for OS remained even after propensity score-matched (PSM) analysis (81.6% vs 68.3%, p = 0.001). Among the 203 patients who were aged ≤ 65 years and achieved CR, ASCT conferred a significant survival benefit (3-year progression-free survival [PFS]: 67.4% vs 47.0%, p = 0.004; 3-year OS: 84.0% vs 74.1%, p = 0.010), and this was also maintained after PSM analysis (3-year PFS: 66.6% vs 48.4%, p = 0.042; 3-year OS: 84.8% vs 70.5%, p = 0.011). Consolidative ASCT improved the survival outcome of PTCL patients, even those who achieved CR after first-line therapy.

Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients with CMML.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.

A Prognostic Model of Pseudogenes in Acute Myeloid Leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the abnormal proliferation of myeloid hematopoietic cells and it is urgently needed to develop new molecular biomarkers to predict clinical outcomes and improve therapeutic effects. METHODS: The differentially expressed genes were identified by comparing TCGA with GETx data. Univariate LASSO and multivariate cox regression analysis were performed to identify prognosis-associated pseudogenes. Based on the overall survival of related pseudogenes, we used them to construct a prognostic model for AML patients. Moreover, we built the pseudogenes-miRNA-mRNA ceRNA networks and explored their involved biological functions and pathways via GO and KEGG enrichment analysis. RESULTS: Seven prognosis-associated pseudogenes were identified, including CCDC150P1, DPY19L1P1, FTH1P8, GTF2IP4, HLA-K, NAPSB, and PDCD6IPP2. The risk model based on these 7 pseudogenes could accurately predict the 1-year, 3-year, and 5-year survival rates. The GO and KEGG enrichment analyses demonstrated that these prognosis-associated pseudogenes were significantly enriched in cell cycle, myeloid leukocyte differentiation, regulation of hemopoiesis, and other critical cancer-related biological functions and pathways. We systematically and comprehensively analyzed the prognostic role of pseudogenes in AML. CONCLUSIONS: The prognostic model of pseudogenes we identified is an independent predictor of overall survival in AML and could be used as biomarker for AML treatment.

Single-dose versus low-dose rituximab in corticosteroid-resistant or relapsed ITP: A multicenter, randomized, controlled study.

Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder, in which rituximab (RTX) induces the best long-term effect among recommended second-line treatments. Nevertheless, the optimal regimen of RTX remains unclear. We herein conducted a prospective, multicenter, open-label, randomized controlled trial to compare the efficacy and safety of RTX at two different dosage regimens in patients with corticosteroid-resistant or relapsed ITP. Recruited patients were randomly assigned (1:1) to receive either RTX at a repeated low dose (100 mg weekly for 4 weeks, LD-RTX) or at a single dose (375 mg/m2 , S-RTX). Overall response was achieved in 64.3% of patients who received LD-RTX versus 67.4% of those receiving S-RTX (p = .759). The complete response (CR) rate was 23.8% after LD-RTX and 28.3% after S-RTX (p = .635). In health-related quality of life, S-RTX improved patients' psychological status, quality of life, social activities, and work compared with LD-RTX. Furthermore, S-RTX significantly reduced physician visits without compromising efficacy. Our findings demonstrate that a S-RTX is comparable to LD-RTX in effectiveness and safety for treatment of corticosteroid-resistant or relapsed ITP. The single-dosage regimen optimizes the use of medical resources, improves the cost-effectiveness of RTX, and represents a promising and more convenient replacement for LD-RTX in ITP. This study has been completed and is registered with ClinicalTrials.gov, number NCT03258866.

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.

High-dose dexamethasone plus recombinant human thrombopoietin vs high-dose dexamethasone alone as frontline treatment for newly diagnosed adult primary immune thrombocytopenia: A prospective, multicenter, randomized trial.

We conducted a prospective, multicenter, randomized, controlled clinical trial to compare the efficacy and safety of high-dose dexamethasone (HD-DXM) plus recombinant human thrombopoietin (rhTPO), vs HD-DXM alone in newly diagnosed adult immune thrombocytopenia (ITP) patients. Enrolled patients were randomly assigned to receive DXM plus rhTPO or DXM monotherapy. Another 4-day course of DXM was repeated if response was not achieved by day 10 in both arms. One hundred patients in the HD-DXM plus rhTPO arm and 96 patients in the HD-DXM monotherapy arm were included in the full analysis set. So, HD-DXM plus rhTPO resulted in a higher incidence of initial response (89.0% vs 66.7%, P < .001) and complete response (CR, 75.0% vs 42.7%, P < .001) compared with HD-DXM monotherapy. Response rate at 6 months was also higher in the HD-DXM plus rhTPO arm than that in the HD-DXM monotherapy arm (51.0% vs 36.5%, P = .02; sustained CR: 46.0% vs 32.3%, P = .043). Throughout the follow-up period, the overall duration of response was greater in the HD-DXM plus rhTPO arm compared to the HD-DXM monotherapy arm (P = .04), as estimated by the Kaplan-Meier analysis. The study drugs were generally well tolerated. In conclusion, the combination of HD-DXM with rhTPO significantly improved the initial response and yielded favorable SR in newly diagnosed ITP patients, thus could be further validated as a frontline treatment for ITP. This study is registered as clinicaltrials.gov identifier: NCT01734044.

A prospective, multicenter study of low dose decitabine in adult patients with refractory immune thrombocytopenia.

We conducted a prospective, multicenter study to evaluate the efficacy and safety of low-dose decitabine in adult patients with refractory immune thrombocytopenia. Adult patients who did not respond to, did not tolerate, or were unwilling to undergo splenectomy, with either a baseline platelet count less than 30 × 109 /L or the presence of bleeding symptoms and further need of ITP-specific treatments, were enrolled. Patients received decitabine at 3.5 mg/m2 intravenously for three consecutive days per cycle, for three cycles with a four-week interval between cycles. All patients were assessed every week during the first 12 weeks and at four-week intervals thereafter. We screened 49 patients for eligibility. Four patients were excluded and 45 received decitabine. At the end of decitabine treatment, complete response was achieved in eight patients (17.78%), and partial response was achieved in 15 patients (33.33%). The median time to initial response was 28 days (range, 14-70 days). Furthermore, seven relapsed patients received decitabine retreatment and all showed platelet response, including one complete response and six partial responses. Sustained response rates at 6, 12 and 18 months were 44.44% (20/45), 31.11% (14/45) and 20.0% (9/45), respectively. For responders, immune thrombocytopenia-related symptoms, fatigue, psychological health, fear, and overall quality of life were significantly improved. Adverse events were observed in 13 (28.89%) patients. No serious adverse events were recorded. In conclusion, low dose decitabine is potentially effective and safe in the management of adults with refractory immune thrombocytopenia. This trial is registered with clinicaltrials.gov identifier: NCT01568333.

A multicenter randomized open-label study of rituximab plus rhTPO vs rituximab in corticosteroid-resistant or relapsed ITP.

This study aimed to compare the efficacy and safety of rituximab (RTX) plus recombinant human thrombopoietin (rhTPO) with RTX alone in patients with immune thrombocytopenia (ITP) who had failed to respond to corticosteroids or relapsed. Recruited patients were randomized at a ratio of 2:1 into 2 groups: the combination group (RTX + rhTPO, n = 77) and the monotherapy group (RTX, n = 38). Overall response was achieved in 79.2% of patients in the combination group vs 71.1% in the monotherapy group (P = .36), and the complete response (CR) rate was 45.4% in the combination group compared with 23.7% in the monotherapy group (P = .026). The combination group had significantly shorter time to response (TTR; median and range, 7 and 4-28 days) compared with the monotherapy group (28 and 4-90 days) (P < .01). There was no difference between these 2 groups in terms of the long-term response (P = .12). Our findings demonstrated that the combination of RTX and rhTPO significantly increased the CR rate and shortened TTR compared with RTX monotherapy in the treatment of corticosteroid-resistant or relapsed ITP but failed to show a beneficial effect on the long-lasting response. This study is registered at www.clinicaltrials.gov as #NCT01525836.

E3 ubiquitin ligase casitas B-lineage lymphoma-b modulates T-cell anergic resistance via phosphoinositide 3-kinase signaling in patients with immune thrombocytopenia.

BACKGROUND: The E3 ubiquitin ligase casitas B-lineage lymphoma-b (CBLB) is a newly identified component of the ubiquitin-dependent protein degradation system and is considered an important negative regulator of immune cells. CBLB is essential for establishing a threshold of T-cell activation and regulating peripheral T-cell tolerance through various mechanisms. However, the involvement of CBLB in the pathogenesis of immune thrombocytopenia (ITP) is unknown. OBJECTIVES: We aimed to investigate the expression and role of CBLB in CD4+ T cells obtained from patients with ITP through quantitative proteomics analyses. METHODS: CD4+ T cells were transfected with adenoviral vectors overexpressing CBLB to clarify the effect of CBLB on anergic induction of T cells in patients with ITP. DNA methylation levels of the CBLB promoter and 5' untranslated region (UTR) in patient-derived CD4+ T cells were detected via MassARRAY EpiTYPER assay (Agena Bioscience). RESULTS: CD4+ T cells from patients with ITP showed resistance to anergic induction, highly activated phosphoinositide 3-kinase-protein kinase B (AKT) signaling, decreased CBLB expression, and 5' UTR hypermethylation of CBLB. CBLB overexpression in T cells effectively attenuated the elevated phosphorylated protein kinase B level and resistance to anergy. Low-dose decitabine treatment led to significantly elevated levels of CBLB expression in CD4+ T cells from 7 patients showing a partial or complete response. CONCLUSION: These results indicate that the 5' UTR hypermethylation of CBLB in CD4+ T cells induces resistance to T-cell anergy in ITP. Thus, the upregulation of CBLB expression by low-dose decitabine treatment may represent a potential therapeutic approach to ITP.

DNA methylation-based subtypes of acute myeloid leukemia with distinct prognosis and clinical features.

Acute myeloid leukemia (AML) is a malignancy of the stem cell precursors of the myeloid lineage. DNA methylation is an important DNA modification that regulates gene expression. Investigating AML heterogeneity based on DNA methylation could be clinically informative for improving clinical diagnosis and prognosis. The AML subtypes based on DNA methylation were identified by unsupervised consensus clustering. The association of these subtypes with gene mutation, copy number variations, immune infiltration and clinical features were further explored. Finally, univariate, LASSO and multivariate cox regression analyses were used to identify prognosis-associated genes and construct risk model for AML patients. In addition, we validated this model by using other datasets and explored the involved biological functions and pathways of its related genes. Three CpG island methylator phenotypes (CIMP-H, CIMP-M and CIMP-L) were identified using the 91 differential CpG sites. Overall survival, morphology, macrophages M0 and monocytes were distinct from each other. The most frequently mutated gene in CIMP-L was DNMT3A while which in CIMP-M that was RUNX1. In addition, the TIDE scores, used to predict the response to immune checkpoint inhibitors, were significantly different among CIMPs. The CIMP-associated prognosis risk model (CPM) using 32 key genes had convinced accuracy of prediction to forecast 0.5-year, 1-year, 3-year and 5-year survival rates. Moreover, the risk score-related genes were significantly enriched in pattern specification process, regionalization, embryonic organ morphogenesis and other critical cancer-related biological functions. We systematically and comprehensively analyzed the DNA methylation in AML. The risk model we constructed is an independent predictor of overall survival in AML and could be used as prognostic factor for AML treatment.

SLED1 Promoting Cell Proliferation and Inhibiting Apoptosis in Acute Myeloid Leukemia: a Study.

In this study, we aimed to explore long non-coding RNA (lncRNA) sustained low-efficiency dialysis (SLED1) correlated with Bcl-2 apoptosis pathway in acute myeloid leukemia (AML). This study further aimed to determine its role in the regulation of AML progression and its action as a potential biomarker for better prognosis. AML microarray profiles GSE97485 and probe annotation from the Gene Expression Omnibus (GEO) database from the National Center for Biotechnology Information (NCBI) were detected using the GEO2R tool ( http://www.ncbi.nlm.nih.gov/geo/geo2r/ ). The expression of AML was downloaded from the TCGA database ( http://cancergenome.nih.gov/ ). The statistical analysis of the database was processed with R software. Bioinformatic analysis found that lncRNA SLED1 is highly expressed in AML patients and is associated with poor prognosis. We found that the increased SLED1 expression levels in AML were significantly correlated with FAB classification, human race, and age. Our study has shown that upregulation of SLED1 promoted AML cell proliferation and inhibited cell apoptosis in vitro; RNA sequencing showed increased expression of BCL-2 and indicated that SLED1 might promote the development of AML by regulating BCL-2. Our results showed that SLED1 could promote the proliferation and inhibit the apoptosis of AML cells. SLED1 might promote the development of AML by regulating BCL-2, but the mechanism involved in the progression of AML is unclear. SLED1 plays an important role in AML progression, may be applied as a rapid and economical AML prognostic indicator to predict the survival of AML patients, and help guide experiments for potential clinical drag targets.

Dexamethasone plus oseltamivir versus dexamethasone in treatment-naive primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trial.

BACKGROUND: Primary immune thrombocytopenia is an autoimmune bleeding disorder. Preclinical reports suggest that the sialidase inhibitor oseltamivir induces a platelet response in the treatment of immune thrombocytopenia. This study investigated the activity and safety of dexamethasone plus oseltamivir versus dexamethasone alone as initial treatment in adult patients with primary immune thrombocytopenia. METHODS: This multicentre, randomised, open-label, parallel group, phase 2 trial was done in five tertiary medical hospitals in China. Eligible patients were aged 18 years or older with newly diagnosed, treatment-naive primary immune thrombocytopenia. Participants were randomly assigned (1:1), using block randomisation, to receive either dexamethasone (orally at 40 mg per day for 4 days) plus oseltamivir (orally at 75 mg twice a day for 10 days) or dexamethasone monotherapy (orally at 40 mg a day for 4 days). Patients who did not respond to treatment (platelet counts remained <30 × 109 cells per L or showed bleeding symptoms by day 10) were given an additional cycle of dexamethasone for 4 days in each group. Patients in the dexamethasone plus oseltamivir group who relapsed (platelet counts reduced again to <30 × 109 cells per L) after an initial response were allowed a supplemental course of oseltamivir (75 mg twice a day for 10 days). The coprimary endpoints were 14-day initial overall response and 6-month overall response. Complete response was defined as a platelet count at or above 100 × 109 cells per L and an absence of bleeding. Partial response was defined as a platelet count at or above 30 × 109 cells per L but less than 100 × 109 cells per L and at least a doubling of the baseline platelet count and an absence of bleeding. A response lasting for at least 6 months without any additional primary immune thrombocytopenia-specific intervention was defined as sustained response. All patients who were randomly assigned and received the allocated intervention were included in the modified intention-to-treat population analysis. This study has been completed and is registered with ClinicalTrials.gov, number NCT01965626. FINDINGS: From Feb 1, 2016, to May 1, 2019, 120 patients were screened for eligibility, of whom 24 were ineligible and excluded, 96 were enrolled and randomly assigned to receive dexamethasone plus oseltamivir (n=47) or dexamethasone (n=49), and 90 were included in the modified intention-to-treat analysis. Six patients did not receive the allocated intervention. Patients in the dexamethasone plus oseltamivir group had a significantly higher initial response rate (37 [86%] of 43 patients) than did those in the dexamethasone group (31 [66%] of 47 patients; odds ratio [OR] 3·18; 95 CI% 1·13-9·23; p=0·030) at day 14. The 6-month sustained response rate in the dexamethasone plus oseltamivir group was also significantly higher than that in the dexamethasone group (23 [53%] vs 14 [30%]; OR 2·17; 95 CI% 1·16-6·13; p=0·032). During the median follow-up of 8 months (IQR 5-14), two of 90 patients discontinued treatment due to serious adverse events (grade 3); one (2%) patient with general oedema in the dexamethasone plus oseltamivir group and one (2%) patient with fever in the dexamethasone group. The most frequently observed adverse events of any grade were fatigue (five [12%] of 43 in the dexamethasone plus oseltamivir group vs eight [17%] of 47 in the dexamethasone group), gastrointestinal reactions (eight [19%] vs three [6%]), insomnia (seven [16%] vs four [9%]), and anxiety (five [12%] vs three [6%]). There were no grade 4 or 5 adverse events and no treatment-related deaths. INTERPRETATION: Dexamethasone plus oseltamivir offers a readily available combination therapy in the management of newly diagnosed primary immune thrombocytopenia. The preliminary activity of this combination warrants further investigation. Multiple cycles of oseltamivir, as a modification of current first-line treatment, might be more effective in maintaining the platelet response. FUNDING: National Natural Science Foundation of China.

1q21 gain but not t(4;14) indicates inferior outcomes in multiple myeloma treated with bortezomib.

Chromosome 1q21 aberrations in multiple myeloma have attracted much attention for a long time, however, the prognostic value is still under investigation. We confirmed the independent prognostic impact of 1q21 aberrations in this non-randomized clinical study. Our study noted that additional copies and larger clonal size of 1q21 gain did not worsen the outcome. We discovered that 1q21 gain was associated with the acquisition of new chromosome abnormalities and genomic instability, evidenced by the strong correlation between 1q21 gain and complex karyotypes or the acquisition of more than two cytogenetic aberrations. Moreover, 1q21 gain and/or del(17p) were powerful enough to discriminate high-risk patients. Furthermore, 1q21 gain retained unfavorable even when stratified by concurrent presence of t(4;14), especially in the bortezomib arm. Finally, although bortezomib might benefit patients with 1q21 gain, it could not completely overcome its adverse effects, suggesting the necessity of more effective therapies for these patients.

Monitoring the cytogenetic architecture of minimal residual plasma cells indicates therapy-induced clonal selection in multiple myeloma.

Recent attempts have focused on identifying fewer magnitude of minimal residual disease (MRD) rather than exploring the biological and genetic features of the residual plasma cells (PCs). Here, a cohort of 193 patients with at least one cytogenetic abnormalities (CA) at diagnosis were analyzed, and interphase fluorescence in situ hybridization (iFISH) analyses were performed in patient-paired diagnostic and posttherapy samples. Persistent CA in residual PCs were observed for the majority of patients (63%), even detectable in 28/63 (44%) patients with MRD negativity (<10-4). The absence of CA in residual PCs was associated with prolonged survival regardless of MRD status. According to the change of the clonal size of specific CA, patients were clustered into five groups, reflecting different patterns of clone selection under therapy pressure. Therapy-induced clonal selection exerted a significant impact on survival (HR = 4.0; P < 0.001). According to the longitudinal cytogenetic studies at relapse, sequential cytogenetic dynamics were observed in most patients, and cytogenetic architecture of residual PCs could to some extent predict the evolutional pattern at relapse. Collectively, the repeat cytogenetic evaluation in residual PCs could not only serves as a good complementary tool for MRD detection, but also provides a better understanding of clinical response and clonal evolution.

The impact of response kinetics for multiple myeloma in the era of novel agents.

Rapid remission by induction therapy has long been recognized as an important predictor for long-time survival in acute leukemia. However, the impact of response kinetics on multiple myeloma (MM) seems to be different and remains unexplored. The relationship between response kinetics and outcome were assessed in 626 patients with newly diagnosed MM who were included in a prospective, nonrandomized clinical trial (BDH 2008/02). Patients were assigned to either immunomodulatory drug- or proteasome inhibitor-based therapy. The response depth, time to best response (TBR) and duration of best response (DBR) were collected. Depth of response was associated with superior outcomes, consistent with findings from other studies. However, the early responders (defined as TBR ≤3 months) showed significantly worse survival compared with late responders. We found that patients with rapid complete remission experienced inferior survivals comparable to those attaining a gradual partial remission. Moreover, 4 distinct response kinetics patterns were identified. Patients with gradual and sustained remission ("U-valley" pattern) experienced superior outcomes, whereas poor outcomes were observed in rapid and transient responders ("roller coaster" pattern) (median overall survival, 126 vs 30 months). The effects of response patterns on survival were confirmed in patients at different stages of disease and cytogenetic risk, including transplant-eligible patients and those attaining different extents of response depth. Collectively, our data indicated that slow and gradual response is a favorable prognostic factor in MM. In addition to response depth, the kinetic pattern of response is a simple and powerful predictor for survival even in the era of novel agents.

Synchronous Hodgkin lymphoma and gastric adenocarcinoma: A rare case report and literature review.

Hodgkin lymphoma (HL) is a lymphoproliferative disease arising in the lymphoid tissue, which is characterized by Reed-Sternberg cells. Adenocarcinoma is the most frequent pathological type of stomach cancer. Improved survival in HL patients leads to the development of secondary malignancies. However, synchronous occurrence of these 2 malignancies is extremely rare. Here, we present a 45-year-old male complaining of a lymph node mass in the neck, without any abdominal symptoms, diagnosed as HL and gastric adenocarcinoma with hepatitis B carrier status. We treated the patient with 8 courses of pirarubicin bleomycin, vincristine, and dacarbazine (modified ABVD), and 4 courses of capecitabine therapy concurrently along with oral entecavir, as the patient survived longer than 20 months.The prognosis of multiple primary malignancies is poor because therapy is difficult, without a standard treatment. The frequency of multiple primary malignancies is increasing in recent years, and second malignancies in patients with cancer should be taken into consideration.

The functional TP53 rs1042522 and MDM4 rs4245739 genetic variants contribute to Non-Hodgkin lymphoma risk.

As a heterogeneous kind of malignances, Non-Hodgkin lymphoma (NHL) is the most common hematologic cancer worldwide with the significantly increased morbidity in China. Accumulated evidences demonstrated that oncoprotein MDM4 plays a crucial role in the TP53 tumor suppressor signaling pathway. An rs4245739 A>C polymorphism locating in the MDM4 3'-untranslated region creates a miR-191 target site and results in allele-specific MDM4 expression. In this study, we examined the association between this polymorphism as well as the TP53 Arg72Pro (rs1042522 G>C) genetic variant and Non-Hodgkin Lymphoma (NHL) risk in a Chinese Han population. Genotypes were determined in 200 NHL cases and 400 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. We found significantly increased NHL risk among carriers of the TP53 72Pro allele compared with those with the 72Arg allele (P = 0.002 for the Pro/Pro genotype). We also observed a significantly decreased NHL risks among carriers of the MDM4 rs4245739 C allele compared with those with the A allele in Chinese (P = 0.014 for the AC genotype). Stratified analyses revealed the associations between these SNPs and NHL risk are especially noteworthy in young or male individuals. Additionally, the associations are much pronounced in NHL patients with B-cell lymphomas or grade 3 or 4 disease. Our results indicate that the TP53 Arg72Pro and the MDM4 rs4245739 polymorphisms contribute to NHL susceptibility and support the hypothesis that genetic variants in the TP53 pathway genes can act as important modifiers of NHL risk.