Sarcopenia and gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation

Objective: The aim of this study was to investigate the prevalence of sarcopenia(SP) and its relationship with gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation(HSCT).Methods: A total of 108 patients with various hematological disorders were selected from Peking University People’s Hospital. SP was screened and diagnosed based on the 2019 Asian Sarcopenia Diagnosis Strategy. Physical measurements and fecal samples were collected, and 16S rRNA gene sequencing was conducted. Alpha and beta diversity analyses were performed to evaluate gut microbiota composition and diversity.Results: After HSCT, significant decreases in calf circumference and body mass index(BMI) were observed,accompanied by a decline in physical function. Gut microbiota analyses revealed significant differences in the relative abundance of Enterococcus, Bacteroides, Blautia and Dorea species before and after HSCT(P<0.05). Before HSCT, sarcopenic patients had lower Dorea levels and higher Phascolarctobacterium levels than non-sarcopenia patients(P<0.01). After HSCT, no significant differences in species abundance were observed. Alpha diversity analysis showed significant differences in species diversity among the groups, with the highest diversity in the postHSCT 90-day group and the lowest in the post-HSCT 30-day group. Beta diversity analysis revealed significant differences in species composition between pre-and post-HSCT time points but not between SP groups. Linear discriminant analysis effect size(LEfSe) identified Alistipes, Rikenellaceae, Alistipes putredinis, Prevotellaceae defectiva and Blautia coccoides as biomarkers for the pre-HSCT sarcopenia group. Functional predictions showed significant differences in anaerobic, biofilm-forming and oxidative stress-tolerant functions among the groups(P<0.05).Conclusions: This study demonstrated a significant decline in physical function after HSCT and identified potential gut microbiota biomarkers and functional alterations associated with SP in patients with hematological disorders. Further research is needed to explore the underlying mechanisms and potential therapeutic targets.

Carrimycin in the treatment of acute promyelocytic leukemia combined with pulmonary tuberculosis: A case report

BACKGROUND Pulmonary tuberculosis(PTB)is prevalent in immunocompromised populations,including patients with hematologic malignancies,human immunodeficiency virus infections,and chronic diseases.Effective treatment for acute promyelocytic leukemia(APL)combined with PTB is lacking.These patients show an extremely poor prognosis.Therefore,studies should establish efficient treatment options to improve patient survival and prognosis.CASE SUMMARY A 60-year-old male with pain in the right side of his chest and a fever for 4 d visited the outpatient department of our hospital.Peripheral blood smear revealed 54%blasts.Following bone marrow examinations,variant APL with TNRC18-RARA fusion gene was diagnosed.Chest computed tomography scan showed bilateral pneumonitis with bilateral pleural effusions,partial atelectasis in the lower lobes of both lungs,and the bronchoalveolar lavage fluid gene X-Pert test was positive,indicative of PTB.Carrimycin,ethambutol(EMB),and isoniazid(INH)were administered since he could not receive chemotherapy as the WBC count decreased continuously.After one week of treatment with carrimycin,the patient recovered from fever and received chemotherapy.Chemotherapy was very effective and his white blood cells counts got back to normal.After being given five months with rifampin,EMB and INH and chemotherapy,the patient showed complete remission from pneumonia and APL.CONCLUSION We report a case of PTB treated successfully with carrimycin with APL that requires chemotherapy.

Comprehensive evaluation of nutritional status before and after hematopoietic stem cell transplantation in 170 patients with hematological diseases

Objective： To investigate the nutritional status of patients before and after hematopoietic stem cell transplantation（HSCT）, and explore optimal methods for assessing nutritional status in patients with hematological diseases.Methods： This cohort study enrolled 170 patients who were diagnosed with hematological diseases and underwent allogeneic HSCT in the Department of Hematology, Peking University People＇s Hospital between May2011 and April 2013. We used fixed-point continuous sampling and four nutritional screening tools, Nutritional Risk Screening 2002（NRS-2002）, Mini Nutritional Assessment（MNA）, Subjective Global Assessment（SGA） and Malnutrition Universal Screening Tools（MUST）, in combination with body measurements, to extensively screen and evaluate nutritional risks and status in patients receiving HSCT before entering and after leaving laminar air flow rooms.Results： After HSCT, patients had significant reduction in weight, hip circumference, waist-hip ratio, calf circumference, mid-upper arm circumference, and suprailiac skinfold thickness compared with pre-HSCT measurements. Before HSCT, NRS-2002 identified that 21.2% of patients were at nutritional risks, compared with100% after HSCT. MUST indicated that before HSCT, 11.77% of patients were at high nutritional risk,compared with 59.63% after HSCT. MNA assessed that 0.06% of patients were malnourished before HSCT,compared with 19.27% after HSCT. SGA identified that before HSCT, 1.76% of patients had mild to severe malnutrition, which increased to 83.3% after HSCT. There is a significant increase in the nutritional risk and malnutrition in patients who received HSCT.Conclusions： Before HSCT, some patients already had nutritional risk or nutritional deficiencies, and prompt and close nutritional screening or assessment should be performed. The nutritional status of patients after HSCT was generally deteriorated compared with that before transplantation. Body measurements should be taken more frequently during the subsequent treatment window in the laminar air flow rooms. After HSCT, it is recommended to combine MNA and SGA to fully evaluate the nutritional status, and thus provide timely and reasonable nutritional support.

Is the traditional Chinese medicine helpful for patients with hematologic malignant diseases? A meta-analysis of randomized controlled trials

AIM:To evaluate the efficacy of traditional Chinese medicine(TCM)for the treatment of hematologic malignant diseases.METHODS:We searched the Cochrane CENTRAL,PubM ed,Embase,Web of Science,AMED,CNKI,Wanfang Platform;China Sinomed and the clinical trial registry web sites and Googlescholar electronically up to June19th,2014 and hand searched related publications.Only randomized controlled trials(RCTs)researching on whether TCM as the adjuvant treatment improved the effect for hematologic malignant diseases were included.Two reviewers extracted data and evaluated the studies independently.Pooled risk ratios(RR)were calculated as outcome measures.Our primary outcomes were the overall response(OR)rate.RESULTS:We retrieved 13143 references and included11 RCTs involved 891 participants after screening.Because the non-significant heterogeneity we used the fixed effect model to combine data and TCM had a significantly higher OR and CR(complete response)rates than the control[RR=1.17,95%CI:(1.10,1.25),P<0.00001;RR=1.24,95%CI:(1.11,1.37),P<0.0001,respectively].Only three studies included in the survival rate analysis.We combined them with random effects model and there was no significant difference between the TCM and control arms.Becauseof the low heterogeneity we used the fixed effect model to combine the non-hematologic adverse effects(AEs)data.Our results showed that TCM significantly decreased non-hematologic AEs rates we researched,the gastrointestinal reaction[RR=0.50,95%CI:(0.37,0.68),P<0.0001],liver and/or kidney injury[RR=0.37,95%CI:(0.26,0.53),P<0.00001]and heart injury[RR=0.24,95%CI:(0.09,0.68),P=0.007].Additionally,TCM had a trend to decrease the infection rate[RR=0.16,(0.02,1.12),P=0.07],but not statistically significantly.CONCLUSION:TCM increases OR and CR rates for hematologic malignances and reduces treatment associated serious non-hematologic AEs.Therefore,TCM should be included in the treatment of hematologic malignances.

Hematologic diseases: High risk of Clostridium difficile associated diarrhea

AIM: To investigate the incidence and clinical outcome of Clostridium difficile (C. difficile) associated diarrhea (CDAD) in patients with hematologic disease.

Methods and New Developments in the Treatment of Hematological Diseases with Integrated Traditional Chinese and Western Medicine

Objective:To understand the methods and progress of integrated Chinese and Western medicine in the treatment of hematological diseases,and to provide ideas for integrated Chinese and Western medicine in the treatment of hematological diseases.Methods:Searching the CNKI,Wanfang and Weipu databases with"integrated traditional Chinese and Western medicine","hematological disease",and"traditional Chinese medicine"as the key words,for related literature of integrated traditional Chinese and Western medicine in the treatment of hematological disease,screening and analyzing the literature.Results:After decades of development,the methods of integrated traditional Chinese and Western medicine in the treatment of hematological diseases have been developed from initial exploration to clinical practice,from wide application to recent progress.The combination methods include the combination of Western medicine and traditional Chinese medicine,as well as the combination of Western medicine and non-medicine of traditional Chinese medicine.The combination of traditional Chinese and Western medicine includes the combination of Chinese and Western medicine,sequential and alternate methods,etc.The combination of traditional Chinese and Western medicine in the treatment of hematological diseases has significant effects in enhancing efficiency and reducing toxicity,improving the quality of life and prolonging the survival period.Conclusion:The combination of traditional Chinese and Western medicine has obvious curative effect,high safety and various methods in treating hematologic diseases.

Ailogeneic hematopoietic cell transplantation for malignant hematological diseases in patients older than 50 years of age

Objective To investigate the efficiency and safety of allogeneic hematopoietic cell transplantation for malignant hematological diseases in patients older than 50 years of age. Methods From May 2002 to January 2010,35 patients P 】 50 years with malignant hematological diseases received allogeneic hematopoietic

Diagnostic performance of Neutrophil CD64 index,procalcitonin,and C-reactive protein for early sepsis in hematological patients

BACKGROUND Patients with hematological diseases are immunosuppressed due to various factors,including the disease itself and treatments,such as chemotherapy and immunotherapy,and are susceptible to infection.Infections in these patients often progress rapidly to sepsis,which is life-threatening.AIM To evaluate the diagnostic efficacy of the neutrophil CD64(nCD64)index,compared to procalcitonin(PCT)and high-sensitivity C-reactive protein(hs-CRP),for the identification of early sepsis in patients with hematological diseases.METHODS This was a prospective analysis of patients with hematological diseases treated at the Fuxing Hospital affiliated with Capital Medical University,between March 2014 and December 2018.The nCD64 index was quantified by flow cytometry and the Leuko64 assay software.The factors which may affect the nCD64 index levels were compared between patients with different infection statuses(local infection,sepsis,and no infection),and the control group and the nCD64 index levels were compared among the groups.The diagnostic efficacy of the nCD64 index,PCT,and hs-CRP for early sepsis was evaluated among patients with hematological diseases.RESULTS A total of 207 patients with hematological diseases(non-infected group,n=50;locally infected group,n=67;sepsis group,n=90)and 26 healthy volunteers were analyzed.According to the absolute neutrophil count(ANC),patients with hematological diseases without infection were divided into the normal ANC,ANC reduced,and ANC deficiency groups.There was no statistically significant difference in the nCD64 index between these three groups(P=0.586).However,there was a difference in the nCD64 index among the non-infected(0.74±0.26),locally infected(1.47±1.10),and sepsis(2.62±1.60)groups(P<0.001).The area under the diagnosis curve of the nCD64 index,evaluated as the difference between the sepsis and locally infected group,0.777,which was higher than for PCT(0.735)and hs-CRP(0.670).The positive and negative likelihood ratios were also better for the nCD64 index than either PCT and hs-CRP.CONCLUSION Our results indicate the usefulness of the nCD64 index as an inflammatory marker of early sepsis in hematological patients.

Active Tuberculosis in Children Receiving Chemotherapy

Tuberculosis infections is a serious illness and can be life threatening for patients with hematologic malignancies. We are reporting the observations of two children aged 7 and 5 years undergoing anticancer treatment for hematological malignancies. The symptoms were, in the first case, cough, purulent sputum and signs of tuberculosis impregnation, for the second case, cervical adenopathies (PDA) with inflammatory signs. The evolution under antituberculosis treatment was favorable for both patients, with a 5-year follow-up for the first patient and one year for the second case. The tuberculosis did not affect chemotherapy. The goal of our work is to specify the etio-pathogenic mechanisms, the clinical, therapeutic and evolutionary particularities of this rare association.

Cytogenetic and Molecular Characterization of Hematological Neoplasm in an Ecuadorian Population

Cancer is one of the major causes of mortality in Ecuador and annually, hematological malignancies are within the top ten most common cancers. In this multicentric study, we analyzed a series of patients diagnosed with different hematological disorders between the years 1984 and 2012. Chromosome abnormalities were detected in 1886 (45.9%) patients. FISH and RT-PCR techniques were used in order to determine the presence of genetic rearrangements and complement conventional cytogenetics results. Using FISH and RT-PCR, positive cases were increased by 1.8% and 6.9% respec- tively. We analyzed fusion genes resulting from t(8;21), t(15;17), inv(16), t(9;22), 11q23 rearrangements, t(4;11) and t(1;19). The frequency of transcripts of some of these fusion genes was of particular interest as our results differ from studies on other populations. Specifically, the fusion gene BCR-ABL was present in the form of the b2/a2 transcript in 95% of CML patients and in the form of b3/a2 transcript in the remaining 5%. The PML-RARA fusion gene also showed a distinct pattern of transcript expression. This fusion gene exhibited the bcr2 (36%) and bcr3 (64%) transcripts, how- ever the bcr1 transcript was absent from our sample population. All cases carrying the CBFB-MYH11 fusion gene ex- hibited the F transcript. This was also of interest due to the rarity of this particular transcript worldwide. Finally all cases carrying the MLL-AF4 fusion gene displayed the e7-e8 transcript. The frequency of the subtypes of some fusion genes differ from those reported in other populations, possibly due to the particular genetic make-up of the Ecuadorian population, mostly mestizo, as well as environmental factors.

Hematologic Emergencies

Hematological emergencies are defined as acute life-threatening conditions in hematological diseases due to benign blood disorders or hematological malignancies or as a result of its treatment. This article deals of the most common emergencies encountered by hematologists. Emerging clinical situations, predictable or not, are common in the treatment of hematological diseases. However, the rapid development of new targeted drugs in cancer medicine has led to an increase in chronically ill cancer and hematology patients, who are being treated aggressively despite significant comorbidities and higher age. This development will lead to an increase in the number of hematologic emergencies, and these patients will be seen by various specialists. The knowledge of most hematological emergencies is crucial in daily practice. In this review, we discuss the epidemiology, pathophysiology and clinical with an emphasis on the early diagnosis and treatment of these conditions that can significantly affect the patient’s clinical outcome.

Polymorphism analysis of Glutathione S-transferase A1 in patients with hematological diseases and its effect on GST enzyme activity

Glutathione S-transferases(GSTs)are important drug-metabolizing enzymes that catalyze the binding of glutathione(GSH)to electrophilic substances.GST has genetic polymorphism,and the enzyme activity of GST affects the metabolism of certain drugs in vivo.In the present day,we investigated the GST enzyme activity and GSTA1 gene polymorphism in 170 patients with hematological diseases and explored their relationship.The GSTA1 gene polymorphism of the patient was analyzed by PCR-restriction fragment length polymorphism(PCR-RFLP)technique,and the base sequences of the four mutation sites(-631,-567,-69,and-52)in the promoter region were determined by DNA-Sequencer.The patient’s GST enzyme activity was calculated by measuring the rate at which it catalyzed the reaction between 1-chloro-2,4-dinitrobenzene(CDNB)and GSH.The average GST enzyme activities of males and females were 5.20±0.13 and 5.17±0.12 nmol/min/mL,respectively,and the difference was not significant(P=0.91).The frequencies of genotypes GSTA1*A*A(wild genotype),GSTA1*A*B(heterozygous genotype),and GSTA1*B*B(homozygous mutant genotype)were 75.3%,22.9%,and 1.8%,respectively.Alleles GSTA1*A and*B were distributed at 86.8%and 13.2%,respectively.The genotype frequency distribution between males and females was no significant difference by Pearson’s chi-square test(P=0.743).The average GST activity of the heterozygous mutant genotype(4.83±0.76 nmol/min/mL)was lower than the wild genotype(5.34±1.26 nmol/min/mL,P=0.018),and higher than that of the homozygous mutant genotype(3.32±0.07 nmol/min/mL,P=0.022).These findings might help us improve the individualized treatment of patients with hematological diseases in the future and promote the development of precision medicine for blood diseases.

Roles of ribosomal proteins in hematologic disorders and cancers:a review

Ribosomes are important organelles for synthesizing proteins in cells.They are composed of ribosomal RNA and more than 80 ribosomal proteins.It is well known that an essential function of ribosomal proteins is to participate in protein translation.In addition,ribosomal proteins also perform extra-ribosomal functions,such as participating in DNA replication,transcription,and damage repair,regulating cell growth,proliferation,apoptosis,and transformation.In recent years,studies have shown that alterations in ribosomal protein synthesis or function can lead to various hematologic diseases,including Diamond-Blackfan anemia,5q-syndrome,Shwachman-Diamond syndrome,and other blood system diseases.Moreover,abnormal expressions of specific ribosomal protein genes have been reported in many malignant tumors.In this review,we elaborated on the changes in ribosomal proteins in hepatocellular carcinoma and colorectal,prostate,gastric,esophageal,and other cancers and discussed the relationship between ribosomal proteins and the occurrence of hematologic disorders and cancers.

Application and Assessment of Chinese Arsenic Drugs in Treating Malignant Hematopathy in China

Chinese arsenic drugs have been applied in Chinese medicine for several centuries. Beginning from 1970s, arsenic containing drugs have been generally used for the treatment of malignant hematologic diseases including acute promyelocytic leukemia, myelodysplastic syndrome, and multiple myeloma. No matter what ingredients of arsenic drugs were applied, either arsenic trioxide, arsenic disulfide, or arsenic containing Chinese herbal compositions including Qinghuang Powder （青黄散） and Realgar-lndigo naturalis formula （复方黄黛片）, they all provided the distinct approaches for the management of malignant hematologic diseases, and good clinical efficacy was obtained with mild adverse reactions. Moreover, the mechanisms of action have been continuallv elucidated.

Post-hematopoietic stem cell transplantation in patients with hematologic disorders:Chinese herbal medicine for an unmet need

While much progress has been made in the field of hematopoietic stem cell transplantation （HSCT）, headway in the promotion of recovery following this procedure has been limited. Data regarding the potential of Chinese herbal medicine （CHM） for patients with hematologic disorders who received HSCT are gradually increasing; however, these data are mostly in Chinese. Therefore, we set out to summarize the existing data. We searched PubMed, the Cochrane Library and the China National Knowledge Infrastructure and retrieved 9 clinical studies related to this group of patients, in whom CHM was used as an intervention. Of the 9 papers, 6 were published by the same group of researchers. The focus of the reviewed studies was heterogeneous, and the objectives varied widely. With the exception of one randomized control trial, all of the studies were retrospective and observational; the median number of patients was 11.5, with the largest study containing 104 patients. CHM treatment was largely divided into two stages： （1） pre-HSCT, which was initiated as soon as conditioning chemotherapy was administered and aimed to counterbalance the adverse effects of these potent agents; （2） post-HSCT, which began immediately after transplantation and was intended to promote engraftment, control graft- versus-host disease and prolong survival. In addition, the 9 Chinese materia medica most commonly prescribed （appearing in four studies） were： Shengdihuang （Rehmannia glutinosa）, Baizhu （Atractylodes macrocephala）, Renshen （Panax ginseng）, Dangshen （ Codonopsis pilosula）, Maimendong （ Ophiopogon japonicus）, Danggui （Angelica sinensis）, Taizishen （Pseudostellaria heterophylla）, Huangqi （Astragalus membranaceus） and Ejiao （Equus asinus）.