Currently, multiple myeloma (MM) is an incurable disease. Despite the fact that arsenic trioxide (ATO) shows promising results in vitro, data from treatment of patients with MM are disappointing. Due to these discrepancies, we compared the efficacy and selectivity of ATO at two different concentrations in samples from MM patients.
Methods
The extent of apoptosis induced by 2 and 5 µM ATO was evaluated by flow cytometry using annexin V. 34 diagnostic bone marrow samples obtained from MM patients were analysed.
Results
5 µM ATO efficiently induced apoptosis in primary samples. Besides efficacy, also selectivity of action on MM cells in comparison to remaining haematopoietic cells was demonstrated for 5 µM ATO but not for 2 µM ATO.
Discussion
Our study on primary samples confirmed that ATO has a potential role in therapeutic management of MM. Further controlled studies on MM patients are needed. 相似文献
To evaluate the influence of age on the relationships between biochemical and hematological variables and stability of erythrocyte membrane in relation to the sodium dodecyl sulfate (SDS) in population of 105 female volunteers between 20 and 90 years.
Methods
The stability of RBC membrane was determined by non-linear regression of the dependency of the absorbance of hemoglobin released as a function of SDS concentration, represented by the half-transition point of the curve (D50) and the variation in the concentration of the detergent to promote lysis (dD).
Results
There was an age-dependent increase in the membrane stability in relation to SDS. Analyses by multiple linear regression showed that this stability increase is significantly related to the hematological variable red cell distribution width (RDW) and the biochemical variables blood albumin and cholesterol.
Discussion
The positive association between erythrocyte stability and RDW may reflect one possible mechanism involved in the clinical meaning of this hematological index. 相似文献
To screen two important FLT3 mutations (internal tandem duplication (ITD) and D835 point mutations) in chronic myeloid leukemia (CML) patients from Southern India and report their incidence.
Methods
Screened 350 CML patients and 350 controls for the two FLT3/mutations through polymerase chain reaction and restriction fragment length polymorphism methods.
Results
ITDs were detected in 12 of the 350 CML patients (3.4%) and D835 mutations in only four cases (1.14%), relatively low in frequency as compared to those reported earlier from non-Indian populations. None of the cases showed simultaneous occurence of both ITD and D835 mutations.
Discussion
These FLT3 mutations seem to be very rare in CML, and it is possible that these could be found only in a subset of patients who are in the progressive stage and/or with varied drug response. Prospective studies are needed to confirm the role of FLT3 mutations in CML pathogenesis, which may help devising therapeutic interventions. 相似文献
Post-transplant lymphoproliferative disorder (PTLD) is a severe complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) associated with Epstein–Barr virus (EBV).
Clinical presentations
Among 263 individuals treated with allo-HSCT for severe aplastic anemia, pure white cell aplasia, T-prolymphocytic leukemia, and relapsed Hodgkin lymphoma, we diagnosed EBV-PTLD in 5 patients. Median age was 29 years (range 19–70 years) and four of five patients were EBV-seropositive prior to HSCT. All five had unrelated EBV-positive donors. In all cases, PTLD occurred within the first year post-transplant (median 4 months).
Intervention
There were two rapidly fatal courses with extensive organ involvement. Both patients showed lymphopenia and thrombocytopenia. In contrast, the three surviving patients had higher lymphocytes and normal platelet counts, while PTLD was restricted to one site and resolved after 2–4 cycles of rituximab.
Conclusion
In this case series courses of PTLD showed substantial diversity. 相似文献
We aimed to investigate the acute physiological responses (APR) to physiotherapy applications in patients undergoing autologous stem cell transplantation (ASCT), the difference between pre- and post-ASCT according to APR.
Methods
Twenty-six patients who were hospitalized for ASCT attended regular physiotherapy program. APR was recorded in the beginning and at the end of each exercise session. The differences in APR were calculated for each session. The mean values of the differences in APR were computed in pre-conditioning, pre-, and post-ASCT. Daily complete blood counts were also recorded during ASCT.
Results
Hemoglobin and platelet counts were significantly lower pre- and post-ASCT. Neutrophil counts were significantly lower post-ASCT. The difference in systolic blood pressure (SBP) in the beginning and at the end of the exercise sessions was significantly higher post-ASCT in comparison to pre-ASCT.
Conclusion
There was no significant change in APR except the SBP which suggests that similar level of exercise intensity could be tolerated in pre- and post-ASCT periods as well as preconditioning. 相似文献
This article reviews recent clinical experiences with first-line and second-line second-generation BCR-ABL inhibitors and discusses considerations for selection of therapy for patients with chronic-phase chronic myeloid leukemia.
Methods
We reviewed recent publications on PubMed and abstracts from major congresses relevant to the topic.
Results
Therapeutic options for front-line treatment have increased with the approval of two second-generation BCR-ABL inhibitors, dasatinib and nilotinib. Both agents are also treatment options for patients with resistance or intolerance to front-line imatinib. More recently, bosutinib, ponatinib, and omacetaxine have also been approved for patients with resistance or intolerance to prior therapy.
Discussion
Expanded treatment options coupled with rapidly changing treatment guidelines have led to numerous questions regarding the selection and monitoring of therapy. Common concerns include how to best select therapy based upon patient-specific comorbidities, monitoring and interpretation of treatment outcomes, and optimization of dosing when side effects occur. 相似文献
Angiogenesis is a word of Greek origin, ‘angeio’ refers to blood vessel, and genesis refers to creation, meaning the generation of new blood vessels. This process is essential for vertebrate development and plays a key role in human diseases. Angiogenesis is generally understood to be essential for the growth and metastasis of solid tumors and is also important in acute myeloid leukemia (AML).
Methods
This review summarizes the essential features of physiological and tumoral angiogenesis and the methods used for their assessment.
Results
Technologies for evaluating angiogenesis in AML are discussed and the prognostic significance of angiogenic factors is considered in the context of optimizing treatment.
Conclusion
As acute myelogenous leukemia and endothelial cells depend on each other for survival and proliferation, therapy directed against several pro-angiogenic factors might help to enhance the AML outcome. 相似文献
The group of unstable hemoglobins are associated with congenital non-spherocytic hemolytic anemia due to instability of the hemoglobin molecule. They often lead to formation of the characteristic inclusion bodies or Heinz bodies.
Aim
To identity the cause of mild anemia, reticulocytosis, and hepatosplenomegly in a case of non-spherocytic hemolytic anemia.
Materials and methods
A 34-year-old female patient originating from Maharashtra, western India presented with mild anemia and jaundice which had persisted since childhood. Investigations included a complete blood count, screening for red cell membrane protein defects, Hb analysis by high-performance liquid chromatography (HPLC) and cellulose acetate electrophoresis (pH 8.9), heat instability test and DNA sequencing.
Results
Hemoglobin analysis by HPLC showed an abnormal peak in the Hb C window (9.8%) with a retention time of 4.90 minutes. Cellulose acetate electrophoresis (pH 8.9) showed a slow moving band (6.15%) between Hb A2 and Hb S. The heat instability test was positive. DNA analysis of α globin genes showed absence of both deletional and non- deletional α thalassemia. DNA sequencing of the β globin gene revealed heterozygosity for a mutation at codon 98 [GTG → ATG, Val → Met], which gives rise to Hb-Koln.
Conclusion
Hb Koln is the commonest unstable Hb variant reported from many populations in the world. However, this is the first report of this unstable Hb variant from India. 相似文献
To describe the risky behaviours of Jamaican teens with sickle cell disease (SCD) and compare them to a national sample of Jamaican youth.
Methods
One hundred twenty two SCD adolescents, 15–19 years old, completed the standardized questionnaire used in the Jamaican Youth Risk and Resiliency Behaviour Survey (JYRRBS), which was a nationally representative survey of 1317 Jamaican youths. Information was obtained on socio-demographics, smoking, alcohol use, and sexual activity. Secondary data from the JYRRBS were extracted to measure the difference in risky behaviours between the groups.
Results
Almost 50% of SCD and 58% of national teens reported having had sexual intercourse. More SCD teens used alcohol (77.7% vs. 60.7%; P value = 0.001). Risky behaviours tended to coexist and living with a parent (odds ratio: 0.62, P value <0.01) and currently attending school (odds ratio: 0.43, P value <0.001) lowered the likelihood of having had sex.
Discussion
SCD teens engage in many risky behaviours and health care professionals should screen and counsel them at each visit. 相似文献
This study aimed to investigate the expression levels of T-cell immune response cDNA 7 (TIRC7) in immune thrombocytopenia (ITP) patients before and after high-dose dexamethasone (HD-DXM) treatment.
Methods
Forty-four patients with ITP were enrolled and received dexamethasone (40 mg/day) for 4 consecutive days. Patients who had platelet counts more than 50 × 109/l or less were defined as responders or non-responders, respectively. Quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were used to measure RNA level and plasma level of TIRC7, respectively.
Results
TIRC7 levels (RNA and plasma level) were significantly higher in ITP than that in control (P < 0.0001). However, after treatment, TIRC7 levels were significantly decreased in responders (P < 0.0001) but not in non-responders (P > 0.05).
Discussions
TIRC7 might be associated with the pathogenesis of ITP, and TIRC7 levels could be used as an indicator to evaluate patients’ response to HD-DXM treatment. 相似文献
Introduction of high-dose chemotherapy and the novel agents including bortezomib, Lenalidomide, and Thalidomide has provided a significant progress in the treatment of multiple myeloma (MM) with an increase in median overall survival up to 6–8 years. However, the advances in myeloma treatment comes at a price with new spectrum of treatment-related infectious complications which should be taken into consideration while treating these patients.
Clinical presentation
We report here two patients with Ig G λ MM presenting with intracerebral mass lesions in the abscence of constitutional symptoms that would suggest an infectious etiology. Both patients had severe hypogammaglobulinemia and lymphopenia, which was attributed to treatment regimens including bortezomib.
Intervention
The surgical intervention-revealed abscess in both cases caused by Nocardia cyriacigeorgica, a relatively new pathogen which rarely causes infections in humans and also an unexpected pathogen in myeloma patients.
Conclusion
Although every aspect of immune system is known to be affected in MM, humoral immune deficiency is the hallmark of the inherent immune defect in this disease. Introduction of the novel agents, bortezomib in particular seems to have changed the characteristics of the immune dysfunction and the spectrum of the opportunistic infections by causing qualitative and quantitative changes in cellular immunity. The new spectrum of infectious agents might not be limited to hepatitis B and herpes zoster. Monitoring lymphopenia and administration of prophylactic antimicrobial agents accordingly could be considered in patients treated with bortezomib. 相似文献
Acquired haemophilia is a rare hemorrhagic disease caused by inhibitory autoantibodies against coagulation factor VIII. Rituximab has become a popular choice for immunosuppressive therapy in acquired haemophilia, almost with the same schedule of 375 mg/m2 per week for 4–6 doses. While the effect of low-dose rituximab has seldom been reported.
Clinical presentation
We report a patient, aged 88 years, who developed acquired haemophilia with severe hemorrhage and elevation of carbohydrate antigen 125 (CA125), but in the absence of a detectable cause.
Intervention
We prescribed a low-dose rituximab alone (100 mg per week for a total of four infusions) for the patient, different from the conventional usage, but received a similar effect. In addition, the patient was diagnosed with immune thrombocytopenia 22 months after rituximab, while FVIII activity and activated partial thromboplastin time remained within the normal range. After four infusions of low-dose rituximab, the platelet count recovered.
Conclusion
At a follow-up of 34 months, the patient remains in remission without further treatment, suggesting low-dose rituximab seems to be a safe and effective regimen for the elderly patients with acquired haemophilia. 相似文献
High-performance liquid chromatography (HPLC) has been evaluated as useful technique for detection of variant hemoglobins in newborn screening, ethnicity-based screening, and patients with abnormal hemoglobin electrophoresis. This study aimed at evaluating this technique as ‘reflex’ testing in a pediatric referral center.
Methods
This study included 1317 children visiting the pediatric hospital, who underwent HPLC analysis on anticoagulated blood samples. These patients were divided into clinician-requisitioned HPLC (group A), ‘reflex’ testing for anemia (group B), and unrelated etiologies (group C). HPLC graphs were evaluated for various hemoglobins. Statistical analysis was performed for comparison between these groups for frequency of abnormal HPLC assay and various red cell parameters.
Results
The frequency of abnormal HPLC assay was 22.89% in group A (125 of 546 cases), 26.89% in group B (78 of 290 cases), and 31.8% in group C (153 of 781 cases) with statistically significant difference. The most frequent variant in all three groups was thalassemia trait. Thalassemia intermedia and major, both were detected in few patients in groups B and C.
Conclusion
‘Reflex’ testing for hemoglobin variants can be undertaken for pediatric samples to enhance detection of these variants and avoid an additional venepuncture. 相似文献
To explore the combination therapy of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO, As2O3) on acute promyelocytic leukemia (APL).
Methods
A meta-analysis of six studies was performed. Among 415 included cases, 165 cases were in the ATRA + ATO group, 129 cases in the ATRA-alone group, and 121 cases in the ATO-alone group. The complete remission (CR) rate and incidences of three groups were compared, respectively, between the therapies of ATRA + ATO with ATRA-alone, ATRA + ATO with ATO-alone, and ATRA with ATO.
Results
The assessment results showed that ATRA + ATO therapy significantly improved the CR rate and decreased the incidences of cutaneous reaction compared with ATRA-alone (P < 0.05). However, incidence of liver injury was higher in the ATRA + ATO and ATO-alone groups than that in ATRA-alone group (P < 0.05). Difference in the complications between ATRA + ATO therapy and ATO-alone was not significant (P > 0.05).
Conclusions
In conclusion, we suggest low-dose ATRA and ATO combination therapy may be more effective for the treatment of APL. 相似文献
To determine whether the values of mean cell volume (MCV) and mean sphered cell volume (MSCV) can distinguish hereditary spherocytosis (HS) from thalassemia.
Methods
The MCV, MSCV, and other erythrocyte indexes were measured in totally 263 people, 57 HS patients, 109 thalassemia patients, and 107 normal control subjects. All indexes were derived from measurements obtained by the Beckman–Coulter LH 750 Hematology Analyzer.
Results
The MSCV was significantly lower in the HS group compared with the thalassemia group (P < 0.001), but the MCV was significantly higher in the HS group compared with the thalassemia group (P < 0.001). Among 57 patients with HS, the MCV was higher than the MSCV in 56 patients. The MCV was lower than the MSCV in one patient combined with β-thalassemia. In the control and thalassemia groups, the MCV was lower than the MSCV.
Conclusion
Measurements of the MCV higher than the MSCV can be considered an ideal index to distinguish rapidly HS from thalassemia. 相似文献
Nucleostemin (NS), a recently discovered nucleolar protein, is essential for maintaining self-renewal and proliferation of embryonic and adult stem cells as well as cancerous cells. The aim of this study was to determine biological function of NS in MOLT-4 cells as a human T-cell acute lymphocytic leukemia (T-ALL) model.
Methods
Efficacy of a specific small interference RNA on NS depletion was studied by quantitative polymerase chain reaction and western blotting. The growth rate and viability were analyzed by trypan blue exclusion test. Fluorescent microscopy was used for detecting apoptosis. Cell cycle and apoptosis were mechanistically studied by flow cytometry and western blotting.
Results
Knockdown of NS inhibited proliferation, arrested the cell cycle, and induced apoptosis through p53 and p21Waf1/Cip1 pathways in MOLT-4 cells.
Discussion
These findings demonstrate critical roles of NS in MOLT-4 cells and may implicate on its therapeutic potential in this human T-ALL model. 相似文献
To study the features of bleeding conditions apparently not associated with vascular, platelet, or clotting dysfunctions.
Method
Conditions that may meet these criteria are: Münchausen syndrome factitious or fictitious, suicidal or homicidal bleeding, bleeding due to self-punishment, stigmatization, the battered child syndrome, and psychogenic bleeding.
Results
The importance of these variegate conditions is not trivial in clinical practice. Differential diagnosis may be difficult and involve other specialists besides hematologists. Occasionally, invasive procedures are involved.
Discussion
The occurrence of bleeding in patients, without a clotting defect or a systemic disorder and a negative family history for bleeding represents a diagnostic challenge. A careful examination of the physical and psychological status of the patient and an appropriate evaluation of the environment in which bleeding occurs, is always needed. 相似文献
Patients with beta-thalassemia intermedia tend to present later in life with milder anemia than beta-thalassemia major patients. The incidence of mortality and its causes in this patient population remains unknown. We aim to reveal the incidence and most common causes of death in this population.
Methods and results
We reviewed the charts of all of the beta-thalassemia intermedia patients who had been followed at the Chronic Care Center in Hazmieh, Lebanon during a 10-year period. A total of 18 patients out of 127 had died during the follow-up period giving a cumulative 10-year mortality incidence of 14%. The most common causes of cardiac deaths were due to renal and cardiac causes.
Discussion
Most causes of death have been linked to the high levels of iron coupled with anemia present in this patient population. Many of deaths could be prevented by adequate treatment.
Conclusion
Larger studies with more comprehensive data capture on risk factors of mortality in this patient population are called for. 相似文献