ABSTRACT
Objective: To evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (auto-HSCT) in elderly patients (≥65 years old) with multiple myeloma (MM) . Methods: From June 1, 2006 to July 31, 2020, 22 MM patients (≥65 years old) who were diagnosed in the First Affiliated Hospital, Sun Yat-sen University and received novel drug induction followed by auto-HSCT were analyzed retrospectively. These patients were evaluated for important organ functions before transplantation, and the International Myeloma Working Group frail score was used in 2016 to screen out transplant-eligible patients. Results: The median (interquartile range, IQR) age at the time of transplantation of the 22 patients was 66.75 (IQR 4.50) years. A total of 20 patients received stem cell mobilization. The median number of mononuclear cells collected was 4.53×10(8)/kg, that of CD34(+) cells was 3.37×10(6)/kg, and the median number of apheresis procedures performed was 2. After stem cell transfusion, the median time of neutrophil implantation was 11 days, that of platelet implantation was 13 days, and the treatment-related mortality was 0 at 100 days after transplantation. The median follow-up was 48.7 months. The median time to progression time was not reached, and the median overall survival time was 111.8 months. Conclusion: Auto-HSCT is a safe and effective treatment for selected elderly patients of 65 years or older with MM.
Subject(s)
Aged , Humans , Hematopoietic Stem Cell Mobilization/methods , Hematopoietic Stem Cell Transplantation/adverse effects , Multiple Myeloma/drug therapy , Retrospective Studies , Transplantation, Autologous/methods , Treatment OutcomeABSTRACT
Objective: To study the efficacy, safety and long-term outcomes of integrated strategy of bortezomib-based induction regimens followed by autologous hematopoietic stem cell (ASCT) and maintenance therapy in Chinese multiple myeloma (MM) patients. Methods: 200 MM patients receiving integrated strategy of bortezomib--based induction regimens followed by ASCT and maintenance therapy were retrospectively and prospectively analyzed from December 1. 2006 to April 30. 2018. Results: The complete remission rates (CR) and better than very good partial remission rates (VGPR) after induction therapy, transplantation and maintenance therapy were respectively 31% and 75.5%, 51.8% and 87.7%,73.6% and 93.4%. There was no difference between 4 cycles and more than 5 cycles induction chemotherapy. The negative rate of MRD detection by flow cytometry was 17.6% and 38.2% respectively after induction and 3 months after transplantation. The negative rate of MRD gradually increased during the maintenance therapy. The success rate of high dose CTX combined with G-CSF mobilization was 95.5% and transplantation related mortality (TRM) was zero. The median time to progress (TTP) was 75.3 months and the median overall survival (OS) was 99.5 months. TTP of patients obtaining CR and negative MRD after induction were longer that those of no CR and positive MRD. TTP and OS of patients receiving triple-drug induction and ASCT in early stage were longer than those of double-drug induction and ASCT in late stage. LDH≥240 U/L, high risk cytogenetics, ISS II+III stage and HBsAg positive were prognostic factors at diagnosis. However, only MRD and high risk cytogenetics were independent prognostic factors after transplantation and maintenance therapy. The clinical characteristics of patients of TTP ≥6 years were listed below: light-chain type M protein, ISS I stage, normal level of hemoglobin and platelet, normal LDH, HBsAg negative, chromosome 17p-negative, good response and sustained good response. Conclusions: Integrated strategy of bortezomib-based induction regimens followed by ASCT and maintenance therapy can significantly improve the short-term and long-term efficacy. The prognostic factors of TTP in different disease stages were different. Response to treatment, especially MRD, played a more important role in prognostic factors.
Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols , Bortezomib/therapeutic use , Follow-Up Studies , Hematopoietic Stem Cell Transplantation , Induction Chemotherapy , Multiple Myeloma/therapy , Retrospective Studies , Stem Cell Transplantation , Transplantation, Autologous , Treatment OutcomeABSTRACT
Objective: To compare the efficacy, response and survival between high-dose melphalan (HDM) and cyclophosphamide+ etoposide+ busulfan (CVB) as the conditioning regimen in autologous stem cell transplantation (ASCT) for newly diagnosed multiple myeloma (NDMM) . Methods: Retrospectively enrolled 123 consecutive NDMM patients who had received PAD induction with subsequent ASCT from Jan 2011 to Aug 2017. The CVB group and HDM group had 82 and 41 patients respectively. Results: ①No differences existed between these 2 groups in non-hematological side effects. ②Patients of CVB group had faster neutrophil and platelet engraftment time, with the median neutrophil engraftment time of 10 (9-35) day vs 11 (9-12) day for patients of HDM group (z=-3.433, P=0.001) , and with median platelet engraftment time of 11 (7-55) day vs 13 (10-35) day for patients of HDM group (z=-3.506, P<0.001) . CVB group entered neutropenia and severe thrombocytopenia more earlier than the HDM group, resulting similar neutropenia duration and severe thrombocytopenia duration between the CVB group and HDM group. However, patients of CVB group had significantly longer fever persistent time and antibiotic administration time. ③The response rate was significantly lower in patients of CVB group vs. patients of HDM group (9/46 vs 14/28, P=0.021) . Further, the minimal residual disease (MRD) negative rate at 3(rd) month post-transplantation seemed to be lower in CVB group than that in HDM group (31.7%vs 48.8%, P=0.065) . ④Both the univariate and multivariate analysis showed that HDM and CVB groups had similar duration to progression (TTP) (P=0.619) and overall survival (OS) (P=0.295) . Conclusion: HDM conditioning regimen is superior to CVB regimen in hematological side effects, tumor burden reduction and administration convenience. However, these two regimen had similar TTP and OS in MM patients receiving ASCT.
Subject(s)
Humans , Busulfan , Cyclophosphamide , Drug Combinations , Etoposide , Hematopoietic Stem Cell Transplantation , Melphalan , Multiple Myeloma/therapy , Retrospective Studies , Stem Cell Transplantation , Transplantation Conditioning , Transplantation, AutologousABSTRACT
<p><b>OBJECTIVE</b>To study the clinical significance of abnormal protein bands (APB) in multiple myeloma (MM) patients treated with bortezomib-based induction regimen and autologous stem cell transplantation (ASCT).</p><p><b>METHODS</b>Sixty-eight MM patients submitted to bortezomib-based induction therapy and ASCT from January 2007 to July 2012 were retrospectively studied. Monoclonal protein was detected by immunofixation electrophoresis (IFE).</p><p><b>RESULTS</b>Of all 68 patients, 33 (48.5%) patients had APB. At the first emergence of an APB, two patients with light chain type achieved CR and before transplantation, and thirty-one patients were after transplantation with median time of 104 (ranged 33-404) days. The median duration of APB appearance was 105 (ranged 35-801) days. Patients who developed APB compared with those without APB, had a significantly higher CR plus very good partial response (VGPR) rates (100.0% vs 85.7%%, P=0.017) and CR rates (87.9% vs 62.9%) (P=0.03). There were no significant differences in gender, age, HGB, ALB, β2-microglobulin, M protein type, Durie-Salmon and ISS stages, the case number of first line or second line treatment, induction courses of bortezomib-based regimen, and the mode of ASCT. With a median follow-up of 33.4 (ranged 7.0-71.7) months, patients with APB tended to have a longer overall survival (OS) versus non-APB patients, although no significant difference obtained (P>0.05). Among APB patients, OS was longer in patients whose appearance of APB occurred <6 months after transplantation than those ≥ 6 months, but the significant difference was not obtained yet (P>0.05).</p><p><b>CONCLUSIONS</b>Patients who developed APB had a significantly better response to bortezomib-based induction regimen followed ASCT. APB emergence has a good prognostic significance.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Boronic Acids , Therapeutic Uses , Bortezomib , Hematopoietic Stem Cell Transplantation , Multiple Myeloma , Metabolism , Therapeutics , Myeloma Proteins , Metabolism , Prognosis , Pyrazines , Therapeutic Uses , Retrospective Studies , Transplantation, AutologousABSTRACT
<p><b>OBJECTIVE</b>To study the humoral immunity reconstitution and its relationship with infection in patients with multiple myeloma (MM) after undergoing autologous hematopoietic stem cell transplantation (auto-HSCT).</p><p><b>METHODS</b>Forty-two MM patients undergoing auto-HSCT were included in this study. Peripheral blood were obtained for immunoglobulin detection, including IgG, IgA and IgM before transplantation and 1, 3, 6, 12, 18 and 24 months after transplantation. The time, type, pathogen of infection between 1 and 24 month after transplantation were analyzed.</p><p><b>RESULTS</b>The level of IgA at 6 month [(0.75±0.59) g/L] after auto-HSCT was lower than that of pre-auto-HSCT [(1.04±0.70) g/L], and reached the level of pre-auto-HSCT at 9 months [(0.99±0.52) g/L] after auto-HSCT. The level of IgM reached the level of pre-auto-HSCT [(0.45±0.26) g/L] at 3 months after auto-ASCT [(0.50±0.26) g/L]. The level of IgG reached the level of pre-auto-HSCT [(9.80±2.98) g/L] at 1 month after auto-HSCT [(11.09±2.69) g/L], and higher than that of pre-auto-HSCT at 9 months after auto-HSCT [(12.07±3.57) g/L]. The level of IgG with IgG-type MM was higher than that of patients with light-chain type and IgD-type MM at 6, 9 and 12 months after auto-HSCT. The IgA level of patients who obtained complete remission (CR) is much higher than that of patients who obtained nCR in IgG-type patients. The incidence of infection in 6 month after auto-HSCT was higher than that of (6-12) month and >12 month after auto-HSCT. The incidence of infection was strongly negative correlated with IgA (r =-0.943, P=0.005) and IgG (r=-0.943, P=0.005) level. The frequency of viral infection was also negatively correlated with IgA and IgG.</p><p><b>CONCLUSION</b>The reconstitution time of IgG, IgA and IgM was different in MM patients after auto-HSCT. IgG recovered first, then IgM, and IgM the last. The incidence of infection was negatively correlated with IgA and IgG. With the recovery of IgG and IgA, the incidence of infection was decreased accordingly.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Hematopoietic Stem Cell Transplantation , Immunity, Humoral , Multiple Myeloma , Allergy and Immunology , Therapeutics , Transplantation, Autologous , Virus Diseases , Allergy and ImmunologyABSTRACT
<p><b>BACKGROUND</b>Incomplete right bundle branch block (ICRBBB) is commonly associated with atrial septal defect (ASD), but lacks sufficient diagnostic test characteristics. An abnormal T wave is also often observed in ASD, with horizontal or inverted displacement of the proximal T wave limb in the right precordial leads, termed "defective T wave" (DTW).</p><p><b>METHODS</b>We examined the diagnostic test characteristics of combining ICRBBB with DTW as a new index to diagnose ASD. A total of 132 consecutive patients with ASD and 132 cases of age/gender-matched controls without ASD were enrolled.</p><p><b>RESULTS</b>Sensitivities of DTW, ICRBBB, and both were 87.1% - 87.9%. Specificities were 97.0%, 96.2%, and 100%, respectively. Positive predictive values were 1.3%, 1.1%, and 100.0% respectively, while negative predictive values were 99.9% for each.</p><p><b>CONCLUSION</b>Combining ICRBBB with DTW in electrocardiogram (ECG) as a new index significantly increased the specificity and positive predictive values while maintaining a high sensitivity in diagnosing ASD.</p>
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Bundle-Branch Block , Diagnosis , Electrocardiography , Heart Septal Defects, Atrial , Diagnosis , Predictive Value of Tests , Sensitivity and SpecificityABSTRACT
<p><b>BACKGROUND AND OBJECTIVE</b>Vascular endothelial growth factor (VEGF) is the most important angiogenic factor of multiple myeloma (MM). This study was to investigate the effect of transfection of human soluble vascular endothelial growth factor receptor-1 (sFlt-1) gene on the proliferation of human MM cell line RPMI8226.</p><p><b>METHODS</b>The recombinant plasmid pcDNA3-sFlt-1 was constructed and transfected into RPMI8226 cells. The expression of sFlt-1 was identified by reverse transcription-polymerase chain reaction (RT-PCR) and ELISA. The effects of sFlt-1 protein on the proliferation and VEGF expression of RPMI8226 cells were investigated by MTT assay and ELISA, respectively.</p><p><b>RESULTS</b>The recombinant plasmid pcDNA3-sFlt-1 was successfully transfected into RPMI8226 cells. sFlt-1 protein expression was identified by ELISA, which inhibited the proliferation of RPMI8226 cells and reduced VEGF concentration in the culture supernatant.</p><p><b>CONCLUSION</b>RPMI8226 cells can express sFlt-1 protein with high biological activity when transfected with the sFlt-1 gene, which inhibits the proliferation of RPMI8226 cells.</p>
Subject(s)
Humans , Cell Line, Tumor , Cell Proliferation , Enzyme-Linked Immunosorbent Assay , Gene Expression Regulation, Neoplastic , Multiple Myeloma , Genetics , Metabolism , Pathology , Plasmids , Recombinant Proteins , Genetics , Metabolism , Reverse Transcriptase Polymerase Chain Reaction , Transfection , Vascular Endothelial Growth Factor A , Metabolism , Vascular Endothelial Growth Factor Receptor-1 , Genetics , Metabolism , PhysiologyABSTRACT
In order to investigate the central nervous mechanism and the diseases involved in catecholamine transmitter secretion, the dynamics of catecholamine release is studied in single cell, brain slice or in vivo. Noradrenaline is an important neurotransmitter and modulator in the central nervous system (CNS) and the peripheral nervous system (PNS). In the present paper, we first compared three real-time methods used to measure noradrenaline secretion in single cells (membrane capacitance, amperometry and confocal fluorescence microscopy imaging). Compared to the electrophysiological method and fluorescence microscopy, the basic usage of the carbon fiber electrode (CFE) in neuroscience research was presented as an example. Then, we presented a primary description of ion channels, including voltage-gated Na(+), K(+) and Ca(2+) channels in locus coeruleus (LC) neurons in rat brain slices. Finally, we presented example recordings of combined patch-clamp and amperometry measurements in LC neurons, indicating Ca(2+)-dependent quantal noradrenaline release following Ca(2+) influx through Ca(2+) channels.
Subject(s)
Animals , Rats , Central Nervous System , Physiology , Ion Channels , Physiology , Norepinephrine , Bodily Secretions , Patch-Clamp TechniquesABSTRACT
<p><b>OBJECTIVE</b>Capsule endoscopy (CE) has been demonstrated to be safe and well tolerated in adults. However, its value in pediatric patients has not been well studied. The present study aimed to evaluate the safety and effectiveness of CE in pediatric patients with suspicious small bowel disorders.</p><p><b>METHODS</b>Fifteen children and adolescents (less than 18 years) were referred to our study for suspected small bowel diseases from Aug. 2002 to May 2005. They aged from 3 to 18 years. Among them, 5 patients were less than 10 years old. The range of weight was from 17 to 83 kg and height was from 49 to 176 cm. Clinical indications included obscure gastrointestinal bleeding (n = 12) and abdominal pain (n = 3). All the patients had normal results on upper and lower gastrointestinal examinations before they underwent CE. The procedures for capsule placement, gastric transit time, small bowel transit time, the average time of the elimination of the capsule, capsule findings, and complications were recorded.</p><p><b>RESULTS</b>All the patients described that the capsule was easy to swallow except 3 youngest children. Finally the capsule was delivered via gastroscopy with overtube for these three children under intravenous anesthesia. No capsule retention occurred during the study. Median recording time was (464 +/- 40) min. In 5 patients, the capsule did not pass the ileal valve by the end of the recording time. Median gastric transit time was (85 +/- 90) min. Median small bowel transit time was (283 +/- 106) min. The average time of the elimination of the capsule was (34.3 +/- 21.8) h. The detective yield of CE was 80%. These positive findings included Crohn's disease (5), hemangioma (2), angiodysplasia (2), Meckel diverticulum (1), polyp (1), and granulomatous lesions (1).</p><p><b>CONCLUSION</b>CE was performed safely in pediatric patients after ingestion or endoscopic placement of the capsule. The high yield of abnormal findings was comparable to those of adult patients.</p>
Subject(s)
Adolescent , Child , Child, Preschool , Humans , Abdominal Pain , Diagnosis , Pathology , Capsule Endoscopy , Methods , Diagnosis, Differential , Diagnostic Imaging , Methods , Gastrointestinal Hemorrhage , Diagnosis , Pathology , Intestinal Diseases , Diagnosis , Pathology , Intestine, Small , Pathology , Retrospective StudiesABSTRACT
Objective To analyze the cost of capsule endoscopy in diagnosing small bowel bleeding and to compare it with traditional diagnostic methods.Methods The patients suspected with small bowel bleeding were divided into group A(n=58,collected during 1998 to 2005)diagnosed with traditional processes and group B (n=93,collected during 2002 to January 2005)diagnosed with capsule endoscopy.The diagnostic yield,specific treatments,examination costs and other accumulated costs of two groups was compared.The examination cost ratio and the integration cost ratio were evaluated.The sensitivity analysis was performed.Results The diagnostic yield of small bowel bleeding in group A and group B were 22.4%(13/58) and 86%(80/93),respectively.The total of examination costs were 133 750 RMB and 790 500 RMB,respectively.The examination costs in group B(RMB 9881.3/each) was slightly lower than group A(RMB 10 288.5/each).Furthermore,as the diagnostic yield of group B was significantly higher than group A(P=0.001).The specific treatments based on the results of the diagnosis was 37.4% higher in group B(49.5%) than group A(12.1%).That means the cost of repeat- ed consultations,emergencies room visit,examinations,supporting treatments and hospitalizations in group B were significantly decreased.After the adjustment,the cost in group B(RMB 9881/patient) was lower than group A(16 361.5 RMB in one month—97 424.0 over 5 years/patient).The total cost of each patient in group A was 6480.2—87 542.7 RMB more than group B,which represented 1.7—9.9 folds increase.Conclusions The patients who suspected with small bowel bleeding and had a negative results of gastroscopy and colonoscopy were recommended to have capsule endoscopy which yields early diagnosis and less cost.