Figure 1c. is with numeric error. The error can not result in any change of discussion and conclusion. The proper figures corresponding to Fig 1c are in supplement file, see figure 5 and 6.
The prognostic value of anaplastic lymphoma kinase (ALK) expression in patients with anaplastic large-cell lymphoma (ALCL) remains controversial. Data on the clinical features of ALCL in a Chinese population are limited. We retrospectively reviewed 1293 patients with pathologically diagnosed lymphoma at Guangdong General Hospital from June 2007 through August 2016. We evaluated the incidence of ALCL, clinical characteristics, survival status, and outcome of crizotinib use in four relapsed/refractory ALK-positive patients. Among the 1293 patients, 1193 (92.3%) were non-Hodgkin's lymphoma, and 53 (4.4%) of whom were ALCL. Of the 50 ALCL patients, with a median age of 34 years, were evaluated. Among them, 33 (66.0%) were ALK-positive and 17 (34.0%) were ALK-negative. Significantly, more patients younger than 40 years old were ALK-positive than ALK-negative (66.7 vs. 23.5%; P = 0.003). The 5-year progression-free survival (PFS) for ALK-positive and ALK-negative patients were 61 and 11%, and the 5-year overall survival (OS) were 70 and 22%, respectively. Median PFS and OS were significantly better for patients with ALK-positive than ALK-negative (60.1 vs. 9.4 months, P = 0. 017; not reached vs. 32.7 months, P = 0.021). Multivariate analyses identified ALK expression, stage, and bone marrow involvement as independent prognostic factors for PFS and OS. Four relapsed ALK-positive patients were treated with crizotinib and two died. Our results suggest that ALK expression has different prognostic significance in patients with ALCL. Mechanisms underlying early relapse after chemotherapy and resistance to crizotinib need further investigation.
Pneumonitis is a rare but severe and potentially fatal adverse effect in chemotherapy of lymphoma. This study is aimed to investigate the incidence of interstitial pneumonitis in non-Hodgkin's lymphoma (NHL) patients receiving immunochemotherapy with pegylated liposomal doxorubicin and rituximab. Lymphoma patients were retrospectively reviewed, and eligible patients were included in this study. According to the chemotherapy regimens, patients were classified in four groups: combination of vincristine, cyclophosphamide, doxorubicin, and prednisone (CHOP group) with rituximab (RCHOP group) and combination of vincristine, cyclophosphamide, pegylated liposomal doxorubicin and prednisone (CDOP group) with rituximab (RCDOP group). Incidence and severity of interstitial pneumonitis were compared among the four groups. Among 757 patients reviewed, 207 patients were included in final analysis. Thirteen patients developed chemotherapy-induced interstitial pneumonitis, and the mean cycle of chemotherapy before the onset of pneumonitis was 4. Incidence rates of pneumonitis were 0, 1.8, 17.4, and 21.1% in CHOP, RCHOP, CDOP, and RCDOP groups, respectively (p < 0.001). The mean grades of pneumonitis were 0, 2, 2.5, and 3 in four groups, respectively (p < 0.001). After adjustment of confounders, chemotherapy regimens (OR 3.491, 95% CI 1.527-7.981, p = 0.003) and neutropenia in previous cycles (OR 2.186, 95% CI 1.281-3.731, p = 0.004) were independently associated with the incidence of pneumonitis. Interstitial pneumonitis should be highlighted in NHL patients who received more than 4 cycles of RCDOP chemotherapy regimen, especially in those who had grade 4 neutropenia in the previous cycles of chemotherapy.
Newly diagnosed acute myeloid leukemia (AML) failed to achieve complete remission after two courses of intensive chemotherapy. This was considered as primary refractory AML (PRR-AML), and still has a dismal prognosis. Allogeneic hematopoietic stem cell transplantation could be the only cure for these patients. However, the role of haploidentical hematopoietic stem cell transplantation (HID-HCT) for PRR-AML is still undetermined. We retrospectively analyzed the outcomes of 45 adult patients with PRR-AML who underwent HID-HCT, and compared it with the result of 53 patients who received HLA-matched related or unrelated donor transplantation (MD-HCT) during the same treatment period. The 3-year overall survival (OS), leukemia-free survival (LFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM) rates in the HID-HCT group were 19.0, 16.5, 70.0, and 35.2%, respectively, but showed no significant differences from the results of MD-HCT. Multivariate analysis showed that complex karyotype with del(7) and time >6months from diagnosis to transplantation were associated with lower OS and LFS, and chronic GVHD demonstrated better OS and LFS in the entire cohort. Complex karyotype with del(7) was related with higher CIR and chronic GVHD with lower CIR. In conclusion, HID-HCT could be an alternative treatment strategy to improve the long-term survival in PRR-AML adult patients who have no HLA-matched donors.
Although the survival rate of diffuse large B cell lymphoma (DLBCL) has increased with years, there are still patients who do not achieve complete remission or who relapse, especially patients with activated B cell-like (ABC) DLBCL. Bortezomib, a proteasome inhibitor, has shown activity in diffuse large B cell lymphoma, especially in the subtype of ABC DLBCL. We conducted a meta-analysis to compare the efficacy and adverse events in bortezomib-containing regimens with standard R-CHOP regimen in treating DLBCL. Our results show that comparing to standard R-CHOP regimen, bortezomib-containing regimen could not prolong the survival in patients with ABC DLBCL. And patients who received bortezomib had a trend of higher risk with peripheral neuropathy, although there is no significant statistical difference.
Acquired pure red cell aplasia (aPRCA) is a kind of anemia characterized by severe reticulocytopenia and obvious bone marrow erythroblastic cells decreased. Some patients are refractory or intolerant to the first-line therapy (cyclosporine A with/without steroids). The effects of the second-line therapy are not satisfactory and sometimes not available. In this study, we analyzed the efficacy and side effect of sirolimus on refractory/relapsed aPRCA and investigated the possible mechanism of sirolimus on immune regulation. Twenty-one patients with refractory/relapsed aPRCA were enrolled in this study and were administered with sirolimus. Totally, 76.2% of patients responded to the sirolimus with 42.9% complete response during the experimental period. The median time for reaction was 4months. Side effects were tolerable including infections; mild oral mucositis; sinus tachycardia, the increase of creatinine, transaminase, triglyceride, or cholesterol; and thrombocytopenia. Most patients stayed in remission or remained stable during the follow-up period. Early drug withdrawal may lead to quick relapse. Compared with healthy control, T-reg levels in patients with aPRCA reduced significantly before sirolimus but recovered after successful treatment. Level of T-reg cells correlated with hemoglobin level after effective sirolimus treatment. Thus, sirolimus was effective and tolerable for refractory/relapsed aPRCA. Effective sirolimus treatment may lead to the upregulation of T-reg cells which may partly explain the underlying mechanism.
Azacitidine and decitabine, two hypomethylating agents, are known to be effective in the treatment of high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients who cannot endure intensive cytotoxic chemotherapy or are not eligible for transplantation. However, the treatment response rate is low. The molecular mechanisms underlying the resistance to demethylation therapy are unclear. Though a wide range of predictors of treatment response have been investigated, no consensus has been reached. It is imperative to identify certain parameters that can help distinguish between patients who will obtain a favorable outcome from demethylation therapy and those who will not. Here, we describe currently researched potential predictors based on clinical characteristics, DNA methylation, gene mutation, gene expression, microRNAs, and protein expression. Although these parameters are not currently used in clinical practice, this review provides new sights into available clinical and experimental research. Moreover, this paper provides useful information on AML/MDS management.
Background: Status epilepticus seizures are distressing events for hospice and palliative care patients. Currently, rectal diazepam is the only abortive therapy approved by the U.S. Food and Drug Administration for seizures occurring out of hospital. However, transmucosal (buccal and intranasal) midazolam hydrochloride is a less expensive, equally effective, and a more socially acceptable alternative. Objective: To explore the use of transmucosal midazolam in out-of-hospital hospice patients in the State of Alabama. Design: A cross-sectional survey was used explore hospice providers' knowledge and use of transmucosal midazolam in clinical practice within Alabama. Setting Subjects: Hospice providers (physicians, nurses, and administrators) in the State of Alabama (n=27). Measurements: An electronic survey was used to elicit transmucosal midazolam use among hospice providers. Results: Transmucosal midazolam has been documented throughout the literature and reported by expert clinicians as an efficacious, safe, and appropriate pharmaceutical intervention for the abortive treatment of seizures in adult and pediatric out-of-hospital patients. However, barriers to the use of transmucosal midazolam with hospice patients included unfamiliarity with transmucosal route and lack of provider orders. None of the participants reported transmucosal midazolam use in out-of-hospital hospice settings. Conclusion: Evidence in the literature supports the use of transmucosal midazolam; however, further research is necessary to understand and address barriers in a more diverse and generalizable population.
Adult hemophagocytic lymphohistiocytosis (HLH) is a fatal disease with poor survival and a limited role of drug therapies. To help to recognize virus and enhance survival, we infused leukocytes derived from human leukocyte antigen (HLA) haplo-identical familial donors to patients. We retrospectively investigated 26 adult virus-associated hemophagocytic syndrome (VAHS) patients' medical records from 2006-2017. Eleven of the 26 patients accepted relatives' derived leukocytes infusions in addition to drug therapies recommended in the HLH-2004 protocol. The leukocyte doses ranged from 0.75 to 3.30x10(8) per kilogram of body weight. The other 15 patients accepted immunosuppressive and supportive therapies referred to in the HLH-2004 protocol. We compared the treatment outcomes of the two groups of patients. Patients in the cell infusion group had a lower viral load (P = 0.023) and better laboratory results and prolonged overall survival (60.44 vs. 20.18 weeks, P = 0.047). A factor that might relate to overall survival is platelet count (P = 0.032), except for the leukocyte infusions (P = 0.012). For patients without acceptable donors, infusions of leukocytes from HLA haplo-identical familial donors could be a feasible treatment to prolong overall survival as an adjuvant to drug therapies.
We sought to evaluate the activity and safety of carfilzomib-/ixazomib-containing combinations for patients with relapsed/refractory multiple myeloma (RRMM). We searched published reports including carfilzomib-/ixazomib-containing combinations for RRMM. Finally, we identified 11 prospective studies covering 2845 relapsed/refractory patients. Carfilzomib- and ixazomib-containing combinations respectively resulted in an impressive overall response rate (ORR 77 vs. 64%, P = 0.14), very good partial response or better (>= VGPR 48 vs. 21%, P = 0.001), complete response or better (>= CR 14 vs. 7%, P = 0.23), and clinical benefit rate (CBR 84 vs. 59%, P = 0.0002). Subgroup analysis showed that the carfilzomib (CFZ) +lenalidomide (LEN) + dexamethasone (DEX) triplet regimen resulted into similar response outcomes to those from CFZ + DEX doublet regimen in ORR (77 vs. 78%, P = 0.91), >= VGPR (50 vs. 53%, P = 0.84), and >= CR (13 vs. 12%, P = 0.96) analysis in these previously heavily pretreated population. And, there were no statistically significant differences between IXA + LEN + DEX triplet regimen and CFZ + LEN + DEX triplet regimen in ORR (85 vs. 78%, P = 0.55), >= VGPR (37 vs. 53%, P = 0.19), and >= CR (18 vs. 12%, P = 0.70) analysis. There were favorable trend towards proteasome inhibitors (PIs) + IMiDs + DEX in comparison with PIs + alkylating agent + Dex in ORR (79 vs 49%, P < 0.00001), >= VGPR analysis (36 vs. 16%, P = 0.008), and >= CR (16 vs. 3%, P < 0.00001). Compared with current standard chemotherapy, carfilzomib containing combinations clearly improved overall survival (HR, 0.79; P = 0.01), progression free survival (HR, 0.61; P = 0.0001). Carfilzomib-/ixazomib-containing combinations produced clinical benefit for patients with R/RMM. PIs + IMiDs + DEX triplet regimens could be good options for such relapsed/refractory patients.
Tumor cells can evade immune surveillance through overexpressing the ligands of checkpoint receptors on tumor cells or adjacent cells, leading T cells to anergy or exhaustion. Growing evidence of the interaction between tumor cells and microenvironment promoted the emergence of immune-checkpoint blockade. By targeting programmed cell death-1 (PD-1) pathway, cytotoxic activity of T cell is enhanced significantly and tumor cell lysis is induced subsequently. Currently, various antibodies against PD-1 and programmed death-ligand 1 (PD-L1) are under clinical studies in lymphomas. In this review, we outline the rationale for investigation of PD-1-PD-L1 immune-checkpoint blockade in lymphomas and discuss their prospect of applications in clinical treatment.