Successful treatment of refractory pure red cell aplasia with eltrombopag after ABO-incompatible allogeneic hematopoietic stem cell transplantation.

Pure red cell aplasia (PRCA) is a well-recognized complication of ABO major mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a reported incidence of 10%-20% (Zhidong et al., 2012; Busca et al., 2018). It is clinically characterized by anemia, reticulocytopenia, and the absence of erythroblasts in a normal-appearing bone marrow biopsy (Shahan and Hildebrandt, 2015). The mechanism for PRCA has been presumed to be persistence of recipient isoagglutinins, produced by residual host B lymphocytes or plasma cells, which can interfere with the engraftment of donor erythroid cells (Zhidong et al., 2012). Several risk factors of PRCA at presentation are known, such as presence of anti-A isoagglutinins before transplantation, reduced intensity conditioning, absence of acute graft-versus-host disease (GVHD), sibling donors, and cyclosporin A (CsA) as GVHD prophylaxis (Hirokawa et al., 2013). PRCA is not considered to be a barrier to HSCT, as some patients can recover spontaneously or benefit from various approaches including high-dose steroids, erythropoietin (EPO), plasma exchange, immunoadsorption, donor lymphocyte infusion (DLI), treatment with rituximab, bortezomib, or daratumumab, and tapering or discontinuation of immunosuppression (Hirokawa et al., 2013; Bathini et al., 2019). However, there are still some patients who fail to respond even to aggressive treatment; they become red cell transfusion-dependent and iron-overloaded, and their life quality is impaired.

Modulation of hippocampal dopamine and synapse-related proteins by electroacupuncture improves memory deficit caused by sleep deprivation.

BACKGROUND: Sleep is crucial for proper functioning of the brain, whereas lack of sleep is very common in modern society and can cause memory impairment. Hence, it is of great significance to find effective methods to intervene in the pathogenesis of memory impairment. OBJECTIVE: We designed this study to explore the mechanism underlying the therapeutic effects of electroacupuncture (EA) on the deficits caused by sleep deprivation (SD). METHODS: In this study, we first utilized the modified multiple platform method (MMPM) to establish a rat model of SD, which was followed by use of the Y-maze and Morris water maze (MWM) to assess the performance of rats following EA treatment. RESULTS: We found that EA at GV20 and ST36 significantly decreased the number of error reactions, increased the number of active avoidance responses in the Y-maze and shortened the latency of finding the platform in the MWM test in SD + EA versus untreated SD groups. Moreover, EA treatment partially restored SD-induced reductions in hippocampal dopamine (DA) content and significantly increased the levels of phosphorylated (p) synapsin I, calcium/calmodulin-dependent protein kinase (CaMK) II, and tyrosine hydroxylase, which are related to the synthesis and release of DA. CONCLUSIONS: In summary, we it appears that EA at GV20 and ST36 may improve SD-induced memory deficits by restoring the quantity of DA in the hippocampus, which is related to activation of CaMK II, synapsin I, and tyrosine hydroxylase. EA may have potential as an alternative therapy for SD and could improve learning and memory deficits among those suffering from sleep deficiency, although this needs verification by prospective clinical studies.

Acute myeloid leukemia patient with FLT3-ITD and NPM1 double mutation should undergo allogeneic hematopoietic stem cell transplantation in CR1 for better prognosis.

Background: According to the recent National Comprehensive Cancer Network (NCCN) guidelines, the risk level in acute myeloid leukemia (AML) patients with FLT3-ITD and NPM1 double mutation (AML FLT3-ITD+/NPM1+ ) depends on the allelic ratio of FLT3-ITD. But despite a low or high allelic ratio of FLT3-ITD, AML FLT3-ITD+/NPM1+ patients belong to the favorable or intermediate risk, for whom allogeneic stem cell transplantation is not obligated. However, some latest studies pointing out that NPM1 and FLT3-ITD double mutation patients showed an inferior prognosis, which have raised concern about the risk categorization and more effective treatment of AML FLT3-ITD+/NPM1+ patients. Methods: A total of 76 patients were selected for coexisting FLT3 and NPM1 mutations with normal cytogenetics. The prognostic risk factors were analyzed, and treatment strategies including allogeneic stem cell transplantati1on and chemotherapy were compared. Results: In 76 AML FLT3-ITD+/NPM1+ patients, 36.8% of patients had hyperleukocytosis (HL) and DNMT3A R882 mutation was the most common concomitant gene (23.7%). For 53 patients in the complete remission (CR), 22 had received allogeneic hematopoietic stem cell transplantation (allo-HSCT) on first complete remission (CR1). Patients in transplantation group had better overall survival (OS) and disease-free survival (DFS) than chemotherapy only (P=0.002 and 0.001, respectively). In multivariable Cox model analyses, HL and DNMT3A R882 mutation were independent adverse prognostic factors (all P<0.05) for AML FLT3-ITD+/NPM1+ patients. Nevertheless, allo-HSCT was an independent good factor of OS and DFS (P=0.001 and 0.000; HR =0.173 and 0.138; 95% CI were 0.062-0.483 and 0.049-0.389). And allo-HSCT could moderately improve the poor prognosis of AML FLT3-ITD+/NPM1+/DNMT3A R882+. Conclusion: Although, AML FLT3-ITD+/NPM1+ patients are categorized as favorable or intermediate risk levels according to recent NCCN and ELN guidelines, these patients should receive allo-HSCT in CR1 for a longer survival. AML FLT3-ITD+/NPM1+ patients with DNMT3A R882 mutation had a very poor prognosis, and allo-HSCT could moderately improve their survival.

Acupuncture combined with methylcobalamin for the treatment of chemotherapy-induced peripheral neuropathy in patients with multiple myeloma.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) seriously affects the quality of life of patients with multiple myeloma (MM) as well as the response rate to chemotherapy. Acupuncture has a potential role in the treatment of CIPN, but at present there have been no randomized clinical research studies to analyze the effectiveness of acupuncture for the treatment of CIPN, particularly in MM patients. METHODS: The MM patients (104 individuals) who met the inclusion criteria were randomly assigned into a solely methylcobalamin therapy group (500 µg intramuscular methylcobalamin injections every other day for 20 days; ten injections) followed by 2 months of 500 µg oral methylcobalamin administration, three times per day) and an acupuncture combined with methylcobalamin (Met + Acu) group (methylcobalamin used the same way as above accompanied by three cycles of acupuncture). Of the patients, 98 out of 104 completed the treatment and follow-ups. There were 49 patients in each group. The evaluating parameters included the visual analogue scale (VAS) pain score, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx) questionnaire scores, and electromyographic (EMG) nerve conduction velocity (NCV) determinations. We evaluated the changes of the parameters in each group before and after the therapies and made a comparison between the two groups. RESULTS: After 84 days (three cycles) of therapy, the pain was significantly alleviated in both groups, with a significantly higher decrease in the acupuncture treated group (P < 0.01). The patients' daily activity evaluated by Fact/GOG-Ntx questionnaires significantly improved in the Met + Acu group (P < 0.001). The NCV in the Met + Acu group improved significantly while amelioration in the control group was not observed. CONCLUSIONS: The present study suggests that acupuncture combined with methylcobalamin in the treatment of CIPN showed a better outcome than methylcobalamin administration alone. TRIAL REGISTRATION: China Clinical Trials Register (registration no. ChiCTR-INR-16009079 , registration date August 24, 2016).