- A Case of Bing-Neel Syndrome Successfully Treated with Ibrutinib. [Journal Article]
- CRCase Rep Hematol 2018; 2018:8573105
- Bing-Neel syndrome is a rare manifestation of Waldenström macroglobulinemia characterized by lymphoplasmacytic cells' infiltration into the central nervous system. We present a case of a 74-year-old ...
Bing-Neel syndrome is a rare manifestation of Waldenström macroglobulinemia characterized by lymphoplasmacytic cells' infiltration into the central nervous system. We present a case of a 74-year-old patient with a known diagnosis of Waldenström macroglobulinemia and newly depressed consciousness. Flow cytology of his cerebral spinal fluid demonstrated a lambda light chain-restricted population of B-cells consistent with a CD5+ CD10+ B-cell lymphoma. Magnetic resonance imaging suggested involvement of the left optic nerve sheath and the bilateral orbital and parietal parenchyma and leptomeninges. He was diagnosed with Bing-Neel syndrome and treated with intrathecal liposomal cytarabine, intravenous high-dose methotrexate, and rituximab without improvement. Subsequently, he started treatment with ibrutinib 560 mg daily and concurrent rituximab. Within three months, he showed clinical and radiologic improvement. The patient has continued on ibrutinib and has now been stable for over 36 months. This represents the longest reported period of successful treatment of Bing-Neel syndrome with ibrutinib.
- A Bayesian Network Meta-Analysis Comparing the Efficacies of Eleven Novel Therapies with the Common Salvage Regimen for Relapsed or Refractory Acute Myeloid Leukemia. [Journal Article]
- CPCell Physiol Biochem 2018 Sep 17; 49(4):1589-1599
- CONCLUSIONS: Referring to the network outcome and SUCRA value, clofarabine plus Ara-C (CR: 79.05%, ORR: 80.02%) and Ara-C plus vosaroxin (CR: 75.42%, ORR: 73.43%) were potentially the top two choices for both CR and ORR. CPX-351 (1-year OS: 91.36%), HiDAC plus MK-8776 (3-year OS: 94.23%) and clofarabine plus Ara-C (1-year EFS: 97.34%) yielded the highest probabilities to be the optimal choices for 1-year OS, 3-year OS and 1-year EFS, respectively.
- Recently approved therapies in acute myeloid leukemia: A complex treatment landscape. [Review]
- LRLeuk Res 2018 Sep 08; 73:58-66
- Acute myeloid leukemia (AML) is a heterogeneous disease. Until recently, treatment for patients with AML was limited to induction chemotherapy with cytarabine and anthracycline or hypomethylating age...
Acute myeloid leukemia (AML) is a heterogeneous disease. Until recently, treatment for patients with AML was limited to induction chemotherapy with cytarabine and anthracycline or hypomethylating agents, and, in some instances, allogeneic hematopoietic stem cell transplant. With the recent approval of new therapies-i.e., CPX-351, enasidenib, ivosidenib, gemtuzumab ozogamicin, and midostaurin-a new era in AML treatment has emerged. Comprehensive diagnostic testing, such as cytogenetic and molecular testing, is necessary for establishing patient eligibility for these new agents and should be performed in a timely manner. However, choosing a therapy for patients who are eligible for multiple treatments may be a complex process, particularly for patients with newly diagnosed AML. This review discusses data, including associated safety profiles that supported these recent approvals, and provides insights to help clinicians navigate new therapy options for this devastating disease. Given the heterogeneity of AML, the treatment landscape will likely continue to grow and evolve as additional agents (and their combinations) are approved for the treatment of subpopulations of patients with AML. Physicians will need to remain abreast of the ever-changing treatment landscape.
- The efficacy of sapacitabine in treating patients with acute myeloid leukemia. [Journal Article]
- EOExpert Opin Pharmacother 2018 Sep 17
- Acute myeloid leukemia (AML) remains a poor prognosis hematological malignancy. The introduction of aggressive chemotherapy with allogeneic stem cell transplantation has resulted in improved clinical...
Acute myeloid leukemia (AML) remains a poor prognosis hematological malignancy. The introduction of aggressive chemotherapy with allogeneic stem cell transplantation has resulted in improved clinical outcomes in younger patients. However, the treatment results in unfit elderly AML population remain disappointing. New strategies should be introduced to improve the prognosis in this group of patients. Areas covered: This review presents and discusses the mechanism of action, safety and efficacy of sapacitabine in AML patients. Expert opinion: Sapacitabine, a novel nucleoside analog, seemed to be a promising new agent for AML treatment. Its oral bioavailability and tolerable toxicity profile allow the drug to be used in an outpatient setting, especially in elderly unfit patients. Sapacitabine is known to have antileukemic activity in randomized clinical trials. In AML patients, sapacitabine monotherapy offered no advantage over low-intensity cytarabine treatment, and the combination of sapacitabine with decitabine was not significantly more effective than decitabine alone. However, the oral administration of sapacitabine allows it to be used in AML maintenance therapy.
- New FDA-Approved and Emerging Novel Treatment Options for Acute Myeloid Leukemia. [Journal Article]
- PPharmacotherapy 2018 Sep 16
- Advancements in the treatment of acute myeloid leukemia (AML) have been sparse over the last several decades, and the disease continues to have a poor prognosis. However, in 2017 alone, four new medi...
Advancements in the treatment of acute myeloid leukemia (AML) have been sparse over the last several decades, and the disease continues to have a poor prognosis. However, in 2017 alone, four new medications approved by the United States Food and Drug Administration (FDA) for the treatment of AML reached the market. Midostaurin, liposomal cytarabine and daunorubicin, enasidenib, and gemtuzumab ogozamicin all showed benefit in respective clinical trials to gain approval for the treatment of AML in various patient populations. Additionally, many phase II and III clinical trials are currently ongoing to assess the safety and efficacy of other potential therapies for the treatment of AML. In this review, we summarize the results of the landmark clinical trials associated with the newly approved agents as well as the current ongoing clinical trials for treatment of AML. A literature search was performed to retrieve data on agents currently being studied for use. Although the overall prognosis for patients with AML remains poor, the addition of the newly FDA-approved medications is a step in the right direction for a disease state that has proven difficult to treat. This article is protected by copyright. All rights reserved.
- Evolving treatment strategies in mantle cell lymphoma. [Review]
- BPBest Pract Res Clin Haematol 2018; 31(3):270-278
- Mantle cell lymphoma is an incurable, moderately aggressive B cell lymphoma. While a small proportion of patients with indolent disease can be managed expectantly, most patients require treatment. Th...
Mantle cell lymphoma is an incurable, moderately aggressive B cell lymphoma. While a small proportion of patients with indolent disease can be managed expectantly, most patients require treatment. The therapeutic approach is driven by physician recommendation, patient choice, age, fitness and comorbidities. Young, fit patients often receive combination chemoimmunotherapy, including high dose cytarabine, with autologous stem cell transplant. Recent data has indicated benefit from maintenance rituximab following autologous stem cell transplant. Ongoing trials are investigating combinations of chemotherapy and targeted agents as well as the role of minimal residual disease guided therapy. Older, less fit patients often receive bendamustine and rituximab or anthracycline based regimens. Maintenance rituximab is typically administered in older MCL patients after anthracycline based chemotherapy although its use after bendamustine based therapy is not supported by current data. Current trials focus on refining this regimen with the addition of targeted agents. In the relapsed and refractory setting, novel agents have demonstrated activity although durability of responses remains unsatisfactory.
- Gemcitabine, cisplatin, and dexamethasone (GDP) in combination with methotrexate and pegaspargase is active in newly diagnosed peripheral T cell lymphoma patients: a phase 2, single-center, open-label study in China. [Journal Article]
- AHAnn Hematol 2018 Sep 12
- 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, ...
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.
- Up-regulated miR-146a expression induced by G-CSF enhanced low dosage chemotherapy response in aged acute myeloid leukemia patients. [Journal Article]
- EHExp Hematol 2018 Sep 09
- The selection of chemotherapy regimen for elderly patients with acute myeloid leukemia (AML) remains challenging. Here, we report that granulocyte colony-stimulating factor (G-CSF) upregulates the ex...
The selection of chemotherapy regimen for elderly patients with acute myeloid leukemia (AML) remains challenging. Here, we report that granulocyte colony-stimulating factor (G-CSF) upregulates the expression of microRNA (miR)-146a in a nuclear factor (NF)-κB-dependent manner, leading to direct decreases in the expression of the target proteins CXCR4 and Smad4 in AML cells in vitro. The reduction in CXCR4 expression suppressed the migration abilities of leukemia cells. Downregulation of Smad4 promoted cell cycle entry in leukemia cells. Furthermore, an increase in apoptosis was observed when leukemia cells were treated sequentially with G-CSF and cytosine arabinoside (Ara-C) in vitro. These findings suggest that G-CSF treatment may disrupt the protection of bone marrow niches from leukemia cells. In a review of data from 78 cases of primary AML, we found that a high miR-146a expression and/or upregulation of this miRNA during G-CSF priming chemotherapy was predictive of better clinical outcomes. Our findings suggest that miR-146a may be a novel biomarker for evaluating the clinical prognosis and treatment effects of a G-CSF priming protocol in elderly patients with AML.
- Central diabetes insipidus in pediatric patients with Langerhans cell histiocytosis: Results from the JLSG-96/02 studies. [Journal Article]
- PBPediatr Blood Cancer 2018 Sep 11; :e27454
- CONCLUSIONS: In the JLSG-96/02 studies, CDI developed in 15.8% of the cohort in which half as pre- and the other half as post-CDI. Relapse, particularly at the CNS risk sites, was linked with the development of post-CDI.
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- Enhanced Anti-Leukemic Effects through Induction of Immunomodulating Microenvironment by Blocking CXCR4 and PD-L1 in an AML Mouse Model. [Journal Article]
- IIImmunol Invest 2018 Sep 11; :1-10
- Previously, we found that dual therapy by the CXCR4 inhibitor Plerixafor and cytosine arabinoside (Ara-C) effectively eradicated leukemia cells and concurrently activated immune cells in acute myeloi...
Previously, we found that dual therapy by the CXCR4 inhibitor Plerixafor and cytosine arabinoside (Ara-C) effectively eradicated leukemia cells and concurrently activated immune cells in acute myeloid leukemia (AML). To reveal the significance of programmed death-ligand1 (PD-L1) in AML and as a strategic approach, we investigated the anti-leukemic effect of a triple combinational therapy by utilizing Plerixafor and anti-PD-L1 in combination with chemotherapy in an AML mouse model. We examined leukemic myeloid blast cells in multiple organs after the successive treatment with Ara-C, Plerixafor, and anti-PD-L1. The results showed that noticeable benefits of triple combinational therapy for eradication of myeloid blast cells in vivo with prolonged survival rates. The frequencies of regulatory T cells (Tregs), monocytic-myeloid-derived suppressor cells (M-MDSCs), and granulocytic-myeloid-derived suppressor cells (G-MDSCs), in the peripheral blood of leukemic mice were consistently decreased, even when mice were sacrificed alive at D + 26 after completion of the triple combinational therapy, compared to the other subgroups. These findings imply that the modulation by the triple combinational therapy may lead to more efficient leukemic myeloid blast cell ablation through the suppression of Tregs or M-MDSCs and G-MDSCs in AML. Although Plerixafor and PD-L1 antagonist do not have a direct anti-leukemic role, our results provide some clues and guidelines to develop clinically therapeutic strategies for chemotherapy-resistant patients by the modulation of leukemic microenvironments.