Chongmei Huang

A homoharringtonine-based induction regimen for the treatment of elderly patients with acute myeloid leukemia: a single center experience from China

Background and purposeThe response to remission induction in elderly patients with acute myeloid leukemia (AML) remains poor. The purpose of this paper is to evaluate the efficacy and toxicity of a plant alkaloid, homoharringtonine, in combination with cytarabine as an induction therapy for AML in elderly patients (≥60 years).ResultsTwenty-three patients were treated with the HA regimen consisting of homoharringtonine (2 mg/m2/day for 7 days) and cytarabine (Ara-C, 100 mg/m2/day for 7 days). The overall response rate was 56.5% with complete remission (CR) rate of 39.1% and partial remission of 17.4%. There was no early death in this cohort of patients. The estimated median overall survival (OS) time of all patients was (12.0 ± 3.0) months. The estimated OS time of the CR patients was 15 months. The estimated one-year OS rate of all patients treated with HA protocol was (49.3 ± 13.5) %. The estimated one-year OS rate of the CR patients was (62.5 ± 17.1) %.ConclusionHA is a suitable induction regimen for elderly patients with AML, with relatively low toxicity and reasonable response rate.

Mouse bone marrow-derived mesenchymal stem cells inhibit leukemia/lymphoma cell proliferation in vitro and in a mouse model of allogeneic bone marrow transplant

The allogeneic hematopoietic stem cell (HSC) transplantation of mesenchymal stem cells (MSCs) contributes to the reconstitution of hematopoiesis by ameliorating acute graft-versus-host disease (aGVHD). However, the role of MSCs in graft-versus-leukemia remains to be determined. In the present study, we co-cultured C57BL/6 mouse bone marrow (BM)-derived MSCs with A20 murine B lymphoma, FBL3 murine erythroleukemia and P388 murine acute lymphocytic leukemia cells. Cell proliferation, apoptosis, cell cycle progression and the amount of cytokine secretion were then measured using a Cell Counting kit-8, Annexin V/propidium iodide staining, flow cytometry and ELISA, respectively. We also established a model of allogeneic bone marrow transplantation (BMT) using BALB/c mice. Following the administration of A20 cells and MSCs, we recorded the symptoms and the survival of the mice for 4 weeks, assessed the T cell subsets present in peripheral blood, and, after the mice were sacrifice, we determined the infiltration of MSCs into the organs by histological staining. Our results revealed that the MSCs inhibited the proliferation of the mouse lymphoma and leukemia cells in vitro, leading to cell cycle arrest and reducing the secretion of interleukin (IL)-10. In our model of allogeneic BMT, the intravenous injection of MSCs into the mice injected wth A20 cells decreased the incidence of lymphoma, improved survival, increased the fraction of CD3+CD8+ T cells, decreased the fraction of CD3+CD4+ T cells and CD4+CD25+ T cells in peripheral blood, and ameliorated the manifestation of aGVHD. The results from the present study indicate that MSCs may be safe and effective when used in allogeneic BMT for the treatment of hemotological malignancies.

Bortezomib in combination with epirubicin, dexamethasone and thalidomide is a highly effective regimen in the treatment of multiple myeloma: a single-center experience

The aim of the present study was to evaluate the effectiveness of bortezomib combined with epirubicin, dexamethasone, and thalidomide (BADT) for the treatment of multiple myeloma (MM). The BADT regimen consisted of a maximum of eight 4-week cycles of: intravenous bortezomib (1.0 mg/m2) and intravenous epirubicin (12 mg/m2) on days 1, 4, 8, and 11; dexamethasone (20 mg) on days 1, 2, 4, 5, 8, 9, 11, and 12; and oral thalidomide (100 mg/m2) on days 1–28. Twelve patients with MM were included in the study, of whom four had not been previously treated and eight had been previously treated with at least one cycle of a systemic combined regimen. All the patients completed at least two cycles of treatment, with an average of five cycles; the complete response (CR) rate was 83.3% (10/12) and stabilization of disease was 16.7% (2/12). The average number of cycles required to achieve CR was 1.9 (range 1–6). In three patients, mobilization of peripheral blood stem cells allowed a sufficient quantity of CD34+ cells to be harvested for future autotransplantation. The main adverse reactions included peripheral neuropathy (4/12), thrombocytopenia (3/12), electrocardiographic abnormalities (4/12), neutropenia (5/12), and liver function impairment (4/12), primarily grade I–II. Infection occurred in four patients with neutropenia, including one patient who developed sepsis. The estimated 1-year overall survival rate was 91.7 ± 8.0%, and the estimated 1-year disease-free survival was 75.0 ± 12.5%. BADT is a highly effective combined regimen, with acceptable toxicity, for the treatment of multiple myeloma.

A New Mutation Identified in an Imatinib and Nilotinib Resistant ChronicMyeloid Leukemia Patient

Chronic myeloid leukemia (CML) is a heterogeneous disease induced by BCR-ABL oncogene. Since the emergence of Tyrosine kinase inhibitors(TKIs), treatment of CML has been drastically changed. However, resistance and intolerance of TKIs have frequently been reported, especially in advanced-stage patients. The most critical reason for TKIs resistance is point mutations within the ABL1 kinase domain that interfere the binding of ABL1 with TKIs. The types and frequencies of mutations have been reported in different population. In this study, we identified a new mutation A2387G (N796S) within the BCR domain (exon 10) via next generation exon sequencing in an imatinib and nilotinib resistant CML patient.

Impact of clinical utility of MRD assessment with different techniques on survival in acute B lymphoblastic leukemia

Abstract We investigated the impact of minimal residual disease (MRD) obtained from different approaches on the outcomes of 141 B lymphoblastic leukemia (B-ALL) patients. Among 169 samples with more than 5% blasts by morphology, 3.6% (6/169) were Flow-MRD negative. Of the 212 positive molecular-MRD samples from Ph+ ALL patients, 55 (25.9%) were Flow-MRD negative. Before consolidation or allogeneic stem cell transplantation (allo-HSCT), negative Flow-MRD was associated with improved survival (p = .019 and .041, respectively) for Ph− ALL patients, but not for Ph+ ALL (p = .111 and .812, respectively). There was no difference in overall survival (OS) by achievement of complete molecular response at complete remission (CR, p = .333 and .863, respectively). Our results indicated that the results of MRDs detected with different methods varied. Flow-MRD can be used as a reliable prognostic marker for Ph− ALL patients. MRD either by flow cytometry or quantitative reverse transcription-polymerase chain reaction (qRT-PCR) at CR did not affect OS or DFS for Ph+ ALL.

Interleukin 10 enhanced CD8+ T cell activity and reduced CD8+ T cell apoptosis in patients with diffuse large B cell lymphoma

Abstract The pleiotropic cytokine interleukin (IL)‐10 is best characterized by its ability to downregulate inflammation and promote peripheral tolerance. On the other hand, IL‐10 was also found to maintain the effector response of CD8+ T cells and promote the expansion of tumor‐resident CD8+ T cells. In diffuse large B cell lymphoma (DLBCL), the role of IL‐10 has been characterized in tumor cells but not in CD8+ T cells. We found that CD8+ T cells in DLBCL presented robust interferon (IFN)‐&ggr; expression early during TCR‐activation but could not maintain this response later on, which was characterized by significantly lower CD8+ T cell degranulation and higher apoptosis. These observations were associated with higher PD‐1 expression in DLBCL CD8+ T cells. Furthermore, the PD‐1+ cells were strongly enriched in the IFN‐&ggr;+, but not the IFN‐&ggr;−, fraction. Interestingly, exogenous IL‐10 significantly improved the survival of DLBCL CD8+ T cells, and resulted in significantly higher IFN‐&ggr;, ganzyme A and granzyme B expression in the absence of CD19+ tumor cells, and significantly improved CD8+ T cell‐mediated specific lysis of CD19+ tumor cells. IL‐10 did not alter the expression of PD‐1 in DLBCL CD8+ T cells, but curiously, IL‐10‐treated DLBCL CD8+ T cells were less susceptible to PD‐L1‐mediated apoptosis. We then demonstrated that IL‐10 treatment significantly elevated the expression of pro‐survival factor Bcl‐2. Blocking IL‐10 resulted in higher apoptosis, fewer IFN‐&ggr;+ CD8+ T cells, and lower Bcl‐2 expression. IL‐10 also significantly increased STAT3, but not STAT1, phosphorylation in CD8+ T cells. Together, these results suggested that IL‐10 could enhance CD8+ T cell inflammation in DLBCL patients.