Patient Versus Physician Perspective in the Management of Chronic Myeloid Leukemia During Treatment with Tyrosine Kinase Inhibitors.

INTRODUCTION: Chronic myeloid leukemia (CML) is a chronic disease with treatment-free remission (TFR) increasingly regarded as a feasible goal of treatment. However, various factors may influence adherence to international guidelines for CML management. This study aimed to compare the reporting of care between patients with CML and their treating doctors. METHODS: Parallel patient and physician online surveys were conducted between September 22, 2021, and March 15, 2022, which focused on the perceptions of 1882 adult patients with CML and 305 physicians regarding tyrosine kinase inhibitor (TKI) treatment options, monitoring and toxicities, TFR, and challenges faced. RESULTS: Among the enrolled patients, 69.9% received first-line imatinib treatment, 18.6% received nilotinib, and 4.7% received dasatinib. Among the patients treated with imatinib, 36.7% switched to other TKIs due to imatinib resistance/intolerance (71.1%), exploration of more potent TKIs to achieve TFR (8.9%), and treating physicians' recommendation (14.0%), with a median duration of initial treatment of 14 months [interquartile range (IQR) 6-36]. Most (91.8%) physicians agreed that the breakpoint cluster region-Abelson 1 (BCR::ABL1) transcript level should be assessed every 3 months, but only 42.7% of individuals committed to 3-monthly testing and only 17.8% strictly followed their treating physicians' recommendation. Half of the patients aimed for TFR; however, just 45.2% of physicians considered TFR as one of the top three goals for their patients. The major concern in obtaining TFR was patients' adherence. Fatigue was often distressing for patients with TKIs, while physicians were more concerned about platelet and neutrophil counts. A total of 12% and 20.8% of patients reported moderate/severe anxiety and depression, respectively, while only 53.7% of physicians had concerns about their patients' mental health. During the coronavirus disease 2019 (COVID-19) pandemic, 69.2% of patients reported a reduction in their income. Among these patients, 61.8% maintained their current treatment, while 7.3% switched to cheaper alternatives or discontinued treatment, with over 80% of these patients belonging to the low-income group. CONCLUSIONS: Overcoming challenges in patient-physician communication and treatment access is key to improving disease management and quality of life, especially for patients with low income. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05092048.

18 months follow-up of deep molecular response 4.5 (MR4.5) with nilotinib in patients with newly diagnosed chronic-phase chronic myeloid leukemia: a prospective, multi-center study in China.

Introduction: Early stable deep molecular response (DMR) to nilotinib is associated with goal of treatment-free remission (TFR) in patients with chronic-phase chronic myeloid leukemia (CML-CP). It is important to early distinguish between patients who can achieve a DMR and those who are fit for TFR. Methods: We performed a multicenter study to explore the early cumulative MR4.5 rate at 18 months with nilotinib in patients with newly diagnosed CML-CP (ND-CML-CP) in China. Of the 29 institutes, 106 patients with ND-CML-CP received nilotinib (300 mg BID). Results and discussion: The cumulative MR4.5 rate of nilotinib treatment at 18 months was 69.8% (74/106). The cumulative MMR and MR4.0 rates for nilotinib at 18 months were 94.3% (100/106) and 84.9% (90/106), respectively. Patients with an ultra-early molecular response (u-EMR) at 6 weeks were not significantly different in obtaining DMR or MMR by 24 months compared with those without u-EMR (p = 0.7584 and p = 0.9543, respectively). Our study demonstrated that nilotinib treatment in patients with ND-CML-CP contributed to obtain high early MR4.5.

Synthesis, characterization and in vitro biological evaluation of two matrine derivatives.

Matrine is a traditional Chinese medicine and botanical pesticide with broad biological activities, including pharmacological and agricultural activities. In present work, two matrine derivatives have been successfully synthesized via introducing indole and cyclohexylamino to 13 position of matrine, respectively, with sophocarpine as starting material, and structurally characterized via infrared spectroscopy(IR), MS, 1 H NMR, 13 C NMR and X-ray crystal diffraction. The results of the in vitro biological activity tests showed that these two matrine derivatives exhibited even better activities against human cancer cells Hela229 and insect cell line Sf9 from Spodoptera frugiperda (J. E. Smith) than that of parent matrine, suggesting that the heterocyclic or cyclic group can dramatically increase the biological activity of matrine. It is worth to mention that 13-indole-matrine could possibly inhibit the growth of insect cells or human cancer cells by inducing cell apoptosis. The results of the present study provide useful information for further structural modifications of these compounds and for exploring new, potent anti-cancer agents and environment friendly pesticides.

[Establishment of a Xenografted Acute Myeloid Leukemia Model by using Zebrafish].

Objectve: To investigate the feasibility of establishing xenografted leukemia model by zebrafish, so as to provide the more direct model in vitro and experimental evidence for study of acute myeloid leukemia and screening of the drugs for targeting therapy. METHODS: Acute myeloid leukemia cell line KG-1a was labeled with red fluorescent dye-MitoRed, then the labeled cells were injected into the yolk sac of zebrafish embryos. Morphological observation, cell count and histopathological detection were used to analyse the infiltration and metastasis of KG-1a cells in zebrafish. RESULTS: KG1a cells could proliferate and gradually spread to the entire abdominal cavity of the zebrafish after KG-1a cells were injected into the yolk sac during 1-7, the results of cell counting in vitro also proved a significant proliferation of KG-1a cells in zebrafish, suggesting that the implanted leukemia stem cells could survive, proliferate and spread in zebrafish. Further study showed that the implanted cells could be transfered to the liver of zebrafish, these cells displayed the signature of KG-1a cells by hematoxylin-eosin(HE) staining. CONCLUSIONS: Human acute myeloid leukemia cells KG1a can survive, proliferate and migrate in zebrafish, suggesting xenografted leukemia model of zebrafish has been successfully established. This model may be benefitcial for the study of acute myeloid leukemia and the screening of the drugs for targeting therapy of acute myeloid leukemia.

[Impact of human cytomegalovirus viremia on relapse after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia patients].

OBJECTIVE: To explore the relationship between cytomegalovirus (CMV) infection and risk factors for relapsing patients with acute myeloid leukemia (AML) (non- acute promyelocytic leukemia) after hematopoietic stem cell transplantation (HSCT). METHODS: A total of 62 allo-HSCT patients from January 2005 to January 2014 were enrolled and analyzed retrospectively. And the clinical characteristics of donors and recipients and post-transplantation relapse were recorded. RESULTS: Single factor analysis indicated that there were 5 risk factors correlated with disease relapse (P < 0.05). Leucocytosis (>100×10(9)/L), high-risk AML and cyclosporine A concentration under 200 µg/L were correlated with high relapsing rates while CMV reaction and chronic graft versus host disease had a low relapsing rate. Cox regression analysis revealed that high-risk AML (RR = 3.296, 95%CI:1.274-8.530, P = 0.014), CMV negativity (RR = 0.285, 95%CI:0.084-0.973, P = 0.045) and non-chronic GVHD (RR = 0.167, 95%CI:0.042-0.668, P = 0.011) were major risk factors of relapse. CONCLUSION: Human CMV viremia after allo-HSCT has a decreased relapsing risk in patients with AML.

Low-dose arsenic trioxide combined with aclacinomycin A synergistically enhances the cytotoxic effect on human acute myelogenous leukemia cell lines by induction of apoptosis.

Acute myeloid leukemia (AML) is a common disorder in the elderly. Although remarkable progress has been made over recent decades, the outcome remains poor. Thus, the development of a more effective method to overcome this problem is necessary. In this study, we aimed to investigate the synergistic cytotoxic effect of low-dose arsenic trioxide (As2O3) combined with aclacinomycin A (ACM) on the human AML cell lines KG-1a and HL-60, and to clarify the underlying mechanism. Results showed that As2O3 combined with ACM exerted a synergistic cytotoxic effect by activation of the apoptosis pathway. Additionally, we found that the combination treatment decreased Bcl-2, c-IAP and XIAP expression but increased SMAC and caspase-3 expression more significantly than the single drug treatments. Furthermore, combination index (CI) values were < 1 in all matched combination groups. Additional evaluation of As2O3 combined with ACM as a potential therapeutic benefit for AML seems warranted.

[Effects of recombinant human interleukin 11 on hematological malignancy after allogeneic hematopoietic cell transplantation].

OBJECTIVE: To investigate the effects of recombinant human interleukin 11 (rhIL-11) on hematological malignancy after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 48 patients with hematological malignancy from January 2006 to June 2010 were alternately enrolled into a prospective randomized study. And they were assigned into the control and rhIL-11 injection groups. Later the investigators compared two groups with regards to hematopoietic reconstitution, graft versus host disease (GVHD) classification, clinical recurrence rate and disease-free survival. RESULTS: With the therapy of rhIL-11, the absolute neutrophil counts recovering to 0.5 × 10(9)/L and platelet recovering to 20 × 10(9)/L were (15.1 ± 1.6) and (18.2 ± 3.3) days respectively. And they were significantly lower than those in control group [(16.1 ± 1.6) vs (22.4 ± 5.5) days, P = 0.032, 0.003]. The incidence of acute GVHD was surprisingly low in the study group (26.1% vs 50.0%, P = 0.048). There was no significant difference in chronic GVHD (36.8% vs 38.9%, P = 0.899) or relapse rate (5.1% vs 7.7%, P = 0.662) between two groups during a median follow-up period of 11.7 months. A trend of improved 3-year-disease-free survival was observed in the study group (65.4% vs 50.9%, P = 0.637). CONCLUSION: The application of rhIL-11 after allo-HSCT may accelerate both neutrophil and platelet engraftment and lower the occurrence of acute GVHD.