Low serum ferritin levels signify low iron stores and this could predispose to iron deficiency anemia.
To determine the rate and predictors of low serum ferritin levels during the puerperium in Enugu, Southeast Nigeria.
A hospital-based prospective longitudinal study involving parturient women who delivered singleton fetuses at term. Venous blood samples were collected to determine the serum ferritin concentration at 48 hours and 6 weeks postpartum. Data analysis involved descriptive and inferential statistics at 95% confidence interval (CI) using Statistical Package for Social Sciences (SPSS) computer software version 20.0.
Two-hundred and two women who carried singleton pregnancies to term were studied. The mean serum ferritin levels at 48 hours and 6 weeks were 27.82±18.41 µg/L and 36.12±21.53 µg/L, respectively. Forty-eight hours postdelivery, 29.2% had low ferritin levels and this decreased to 12.4% at 6 weeks postpartum. There was a significant positive correlation between the serum ferritin level at 48 hours postdelivery and the serum ferritin level at 6 weeks postpartum (r=0.89, P<0.001). Predictors of the low ferritin level at 6 weeks included age <20 years (odds ratio [OR] =0.70, 95% CI =0.53, 0.93), multiparity (OR =63.7, 95% CI =3.18, 127.5), anemia at 48 hours postpartum (OR =61.7, 95% CI =13.27, 116.6), a low ferritin level at 48 hours (OR =78.1, 95% CI =8.8, 108.3), and intake of antenatal hematinics for <3 months (OR =0.04, 95% CI =0.01, 0.20).
There was a significant occurrence of low ferritin levels during the puerperium in the study centers, and this was associated mainly with pregnancy and delivery factors. Efforts to improve the iron stores in parturient women could benefit from early booking and compliance with antenatal hematinics and optimizing hemoglobin and iron levels before delivery.
iron deficiency; iron stores; puerperium; predictors; postpartum
Hypereosinophilic syndrome (HES) encompasses numerous diverse conditions resulting in peripheral hypereosinophilia that cannot be explained by hypersensitivity, infection, or atopy and that is not associated with known systemic diseases with specific organ involvement. HES is often attributed to neoplastic or reactive causes, such as chronic eosinophilic leukemia, although a majority of cases remains unexplained and are considered idiopathic. Here, we review the current diagnosis and management of HES and present a unique case of profound hypereosinophilia associated with warm autoimmune hemolytic anemia requiring intensive management. This case clearly illustrates the limitations of current knowledge with respect to hypereosinophilia syndrome as well as the challenges associated with its classification and management.
hypereosinophilia; eosinophils; myeloproliferative disorder; autoimmune hemolytic anemia; idiopathic autoimmune hemolytic anemia; leukemia
The evolution of care in hemophilia is a remarkable story. Over the last 60 years, advances in protein purification, protein chemistry, donor screening, viral inactivation, gene sequencing, gene cloning, and recombinant protein production have dramatically enhanced the treatment and lives of patients with hemophilia. Recent efforts have produced enhanced half-life (EHL) clotting factors to better support prophylaxis and decrease the frequency of infusions. Medical needs remain in the areas of alternate modes of administration to decrease the need for venous access, better treatment, and prophylaxis for patients who form antibodies to clotting factors, and ultimately a cure of the underlying genetic defect. In this brief review, the authors summarize data on EHL clotting factors, introduce agents whose mode of action is not clotting factor replacement, and list current gene therapy efforts.
extended half-life clotting factors; gene therapy; anti-tissue factor pathway inhibitor antibodies; clotting factor analogs; nonfactor replacement therapy
Total joint arthroplasty can be associated with major blood loss and require subsequent blood transfusions for postoperative anemia. Measures to effectively and safely decrease blood loss and reduce the need for blood transfusions would help improve patient safety and lower health care costs. A possible pharmacological option to reduce surgical blood loss in total joint arthroplasty is the use of tranexamic acid. Abundant literature has shown that intravenous and/or topical administration of tranexamic acid is effective in reducing blood loss and blood transfusions, with no increased risk of venous thromboembolic events or other complications.
tranexamic acid; total hip arthroplasty; total knee arthroplasty; antifibrinolytic; blood transfusion; blood loss
Hematopoietic stem cell transplantation remains the only curative treatment currently in use for patients with sickle cell disease (SCD). The first successful hematopoietic stem cell transplantation was performed in 1984. To date, approximately 1,200 transplants have been reported. Given the high prevalence of this disorder in Africa, and its emergence in the developed world through immigration, this number is relatively small. There are many reasons for this; primary among them are the availability of a donor, the risks associated with this complex procedure, and the cost and availability of resources in the developing world. Of these, it is fair to say that the risks associated with the procedure have steadily decreased to the point where, if currently performed in a center with experience using a matched sibling donor, overall survival is close to 100% and event-free survival is over 90%. While there is little controversy around offering hematopoietic stem cell transplantation to symptomatic SCD patients with a matched sibling donor, there is much debate surrounding the use of this modality in “less severe” patients. An overview of the current state of our understanding of the pathology and treatment of SCD is important to show that our current strategy is not having the desired impact on survival of homozygous SCD patients, and should be changed to significantly impact the small proportion of these patients who have matched siblings and could be cured, especially those without overt clinical manifestations. Both patient families and providers must be made to understand the progressive nature of SCD, and should be encouraged to screen full siblings of patients with homozygous SCD for their potential to be donors. Matched siblings should be referred to an experienced transplant center for evaluation and counseling. In this review, we will discuss the rationale for these opinions and make recommendations for patient selection.
sickle cell disease; morbidity; stem cell transplantation; patient selection; matched sibling donor
Glanzmann’s thrombasthenia (GT) is a genetic platelet surface receptor disorder of GPIIb/IIIa (ITG αIIbβ3), either qualitative or quantitative, which results in faulty platelet aggregation and diminished clot retraction. Spontaneous mucocutaneous bleeding is common and can lead to fatal bleeding episodes. Control and prevention of bleeding among patients with GT is imperative, and remains challenging. Local measures, including anti-fibrinolytic therapy, with or without platelet transfusions, used to be the mainstay of therapy. However, in recent years the use of recombinant factor VIIa (rFVIIa) has increased significantly, with excellent response rates in treating and preventing hemorrhage among GT patients. Gene therapy and stem cell transplantation offer a potential cure of this disease, but both are costly and remain experimental at this point. This manuscript offers a comprehensive review of our understanding of GT and the available treatment options.
Glanzmann; thrombasthenia; treatment
Cryoballoon ablation (CA) is a safe and efficient method for pulmonary vein isolation in the treatment of paroxysmal atrial fibrillation (AF). There are conflicting results about the predictors of AF recurrence. The aim of this study is to evaluate the role of hematological indices to predict AF recurrence after CA.
A total of 49 patients (mean age 58.3±12.2 years, 51.02% female) with symptomatic paroxysmal AF underwent CA procedure. One hundred and sixty-eight pulmonary veins were used for pulmonary vein isolation with the second-generation cryoballoon. The hematological samples were obtained before and 24 hours after ablation.
At a mean follow-up of 10.2±2.4 months, the probability of being arrhythmia-free after a single procedure was 86%. Patients with AF recurrence had higher red cell distribution width levels (16.10%±1.44% vs 14.87%±0.48%, P=0.035). The neutrophil/lymphocyte ratio, erythrocyte sedimentation rate, and C-reactive protein levels were detected in the patients with or without recurrence. Left atrial diameter (46.28±4.30 mm vs 41.02±4.10 mm, P=0.002), duration of AF (6.71±4.57 years vs 3.59±1.72 years, P=0.003), and age (65.01±15.39 years vs 54.29±11.32 years, P=0.033) were the other independent predictors of clinical recurrence after CA. Multiple regression analysis revealed that left atrial diameter was the only independent predictor for AF recurrence (P=0.012).
In this study of patients with paroxysmal AF undergoing cryoablation, increased preablation red cell distribution width levels, and not C-reactive protein or erythrocyte sedimentation rate, was associated with a higher rate of AF recurrence. Our results support the role of a preablation, proinflammatory, and pro-oxidant environment in the development of AF recurrence after ablation therapy but suggest that other factors are also important.
ablation; atrial fibrillation; cryoballoon; neutrophil; CRP; oxidative stress
Transfusional iron overload is a major target in the care of patients with transfusion-dependent thalassemia (TDT) and other refractory anemias. Iron accumulates in the liver, heart, and endocrine organs leading to a wide array of complications. In this review, we summarize the characteristics of the approved iron chelators, deferoxamine, deferiprone, and deferasirox, and the evidence behind the use of each, as monotherapy or as part of combination therapy. We also review the different guidelines on iron chelation in TDT. This review also discusses future prospects and directions in the treatment of transfusional iron overload in TDT whether through innovation in chelation or other therapies, such as novel agents that improve transfusion dependence.
thalassemia; transfusion-dependent thalassemia; iron overload; iron chelation therapy; transfusion
Following the obviation of the pathogen safety threats posed by previous generations of clotting factor concentrates for the treatment of hemophilia, the principal issue facing the patient community is timely access to adequate supplies of continuously improving therapies. The application of evidence-based medicine has enhanced the basis of hemophilia therapy, while resulting in some challenges to patient care. Increasingly, the criteria used for the approval and payment of treatment products by regulatory and reimbursement agencies, respectively, are becoming inflexible and unrealistic. This is occurring particularly in the requirements for demonstrating product efficacy. Concurrently, emerging evidence of the interpatient variability in the clinical response to therapy has led to the proposed personalization of therapeutic regimens. Possible impediments to optimal care include competitive tensions among suppliers who seek to gain label claims for reimbursement purposes, which result in clinical trial designs of, arguably, unethical design, carried out in poor countries. We synthesize these converging developments to suggest some changes to the current hemophilia treatment paradigm, which should make it more patient-centric and enable speedier access to new therapies.
hemophilia; treatment products; clinical trials; standards; reimbursement
To compare the safety and efficacy of dabigatran to warfarin for the treatment of deep vein thrombosis and pulmonary embolism.
Venous thromboembolism (VTE) is a disease comprised of two conditions: deep vein thrombosis and pulmonary embolism. VTE is a major cause of morbidity and mortality worldwide with an annual incidence estimated at 1–3 cases per 1,000 individuals. This incidence increases with age from 0.1 per 1,000 in adolescence to eight per 1,000 in those 80 years of age and older. As the proportion of patients 65 years of age and older expands, the number of patients presenting with VTE will also increase. Anticoagulation remains the cornerstone of VTE treatment. Traditionally, vitamin K antagonists have been used to minimize the risk of thrombus extension and for secondary prevention. Unpredictable pharmacokinetics and pharmacodynamics, routine monitoring, drug–food and drug–drug interactions, and potentially severe adverse events have all been cited as barriers to optimal care. Dabigatran has been proposed as a suitable alternative to warfarin therapy in the treatment of VTE. Therefore, a critical appraisal of dabigatran’s safety and efficacy is necessary to determine its role in therapy.
Dabigatran remains an alternative to warfarin therapy for the treatment of VTE. However, dabigatran also has distinct disadvantages that warrant consideration. Clinicians must ensure that drug characteristics align with patient characteristics to optimize patient outcomes.
venous thromboembolism; pulmonary embolisms; venous thrombosis; anticoagulants; warfarin sodium; dabigatran etexilate mesylate
Despite insights into the genetic basis of Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs), a significant proportion of essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients present with no known MPN disease alleles. There were no previous studies investigating the impact of ASXL1 mutations in Ph-negative MPNs in Turkey. In the current study, we investigated the prognostic significance of ASXL1 mutations in Turkish MPN patients. We also aimed to determine the prognostic significance of JAK2V617F allele burden and the relationship of JAK2V617F mutation with ASXL1 mutations in Ph-negative MPNs.
About 184 patients from a single center diagnosed with Ph-negative MPNs were screened for ASXL1, JAK2V617F mutations, and JAK2V617F allele burden: 107 ET and 77 PMF.
A total of 29 ASXL1 mutations were detected in 24.7% of PMF and 8.4% of ET patients. ASXL1-mutated ET patients showed a trend toward an increase in the incidence of cerebrovascular events and higher total leukocyte counts. ASXL1-mutation in PMF was associated with older age and a higher prevalence of bleeding complications. In univariate analysis, overall survival (OS) was significantly reduced in ASXL1-mutated PMF patients. In multivariate analysis, Dynamic International Prognostic Scoring System-plus high-risk category and ASXL1 mutation status were independently associated with shorter survival in PMF. In PMF, mutational status and allele burden of JAK2V617F showed no difference in terms of OS and leukemia-free survival.
We conclude that ASXL1 mutations are molecular predictors of short OS in PMF.
Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs); ASXL1; JAK2V617F; JAK2V617F allele burden
Rheumatic heart disease (RHD) is a serious health concern in developing countries. Rheumatic mitral stenosis (RMS) is the most long-term sequel in RHD. The neutrophil to lymphocyte ratio (NLR) is a novel marker, and a higher NLR has been associated with poor clinical outcomes in various cardiovascular disorders. We evaluated the availability of NLR to predict severity of mitral stenosis (MS) in patients with RHD.
We analyzed 300 consecutive patients with RMS. The patients were divided into tertiles according to NLR: 0.85< NLR ≤1.85 (n=100, tertile 1), 1.86≤ NLR ≤2.46 (n=100, tertile 2), and 2.47≤ NLR ≤7.08 (n=100, tertile 3). Patients with RMS were divided into three groups based on the degree of MS as mild, moderate, and severe MS. After the initial evaluation, 187 patients with moderate-to-severe RMS (Group 1) and 113 patients with mild RMS (Group 2) were reassessed.
The patients with severe RMS had significantly elevated NLR, mean platelet volume, and pulmonary artery systolic pressure values compared to patients with moderate and mild MS (P<0.001, P<0.001, P<0.001 respectively). Multivariate binary logistic regression analysis revealed that high levels of NLR was an independent predictor of severe RMS (odds ratio =0.68, P=0.008). Moderate-to-severe RMS incidence was significantly higher among patients in the tertile 3 (odds ratio =2.8, P=0.001).
NLR is a new inflammatory marker and a simple, rapid, and easily accessible prognostic parameter that can be associated with severity of RMS in patients with RHD.
rheumatic heart disease; rheumatic mitral stenosis; neutrophil to lymphocyte ratio
Acquired hemophilia A is a rare autoimmune disorder caused by an autoantibody (inhibitor) to factor VIII (FVIII) that interferes with its coagulant function and predisposes to severe, potentially life-threatening hemorrhage. Disease management focuses on controlling bleeding, primarily with the use of bypassing therapy and recombinant porcine FVIII, and permanently eradicating the autoantibody using various immunosuppressants. Treatment challenges include delayed diagnosis, difficulty achieving hemostasis and durable remissions, and complications associated with the use of hemostatic and immunosuppressive therapy in a primarily older patient population.
autoantibodies; factor VIII; hemostasis; inhibitors; inhibitor eradication
Hemophilia care has improved dramatically over the past 50 years, evolving from plasma concentrates, to purified plasma proteins, to recombinant clotting factors. These collective developments allowed for home delivery of on-demand and prophylactic treatment, resulting in the reduction of hemophilia morbidity and mortality and improved quality of life. Although efficacious in treating bleeding, conventional factor products’ half-lives require frequent venipuncture, which remains a significant burden to patients. Despite the remarkable advances in hemophilia care, no improvements have, until now, been made to the pharmacokinetic properties of factor products. Multiple strategies have more recently been employed to generate novel bioengineered products that, with great hope, represent the next wave of progress in hemophilia care. The use of these products will undoubtedly raise important discussion about choosing conventional factor over new long-acting factor products. Incorporation of these therapies into clinical care is accompanied by unanswered safety questions that will likely be evaluated only in postmarketing surveillance analysis. Further, these products may change current treatment paradigms with unclear cost repercussions and feasibility. This paper will review efraloctocog alfa (FVIII-Fc) and its role in the treatment of hemophilia A.
hemophilia A; factor VIII; Fc fusion; bioengineered products; efraloctocog alfa
This study was undertaken to determine the distribution of ABO/RhD (rhesus D antigen) blood phenotypes, prevalence of anti-D alloantibodies, and the risk factors for alloimmunization among pregnant women in Kasese District, Western Uganda.
Materials and methods
Ethylenediamine tetraacetic acid-containing plasma samples and serum samples were taken from pregnant women attending the antenatal clinic. The blood groups were identified using the microplate grouping method, while the presence of anti-D alloantibodies was detected by the indirect antiglobulin test (IAT). Data were also collected from the pregnant women on the risk factors associated with anti-D alloantibody formation.
Among the 726 participants, the blood group distribution was as follows: O: 356 (49.%); A: 190 (26.%); B: 152 (21%); and AB: 28 (4%). A total of 28 (3.86%) pregnant women were RhD negative. Anti-D alloantibodies were detected in 88 (12.1%) of the participants; and of these, 13 (14.8%) were RhD negative. Statistically significant risk factors for anti-D alloimmunization included miscarriage, stillbirth, and postpartum hemorrhage.
Blood group O was the most common among the pregnant women in this study and the prevalence of Rh negativity was 3.8%. The frequency of anti-D alloimmunization among pregnant women in Kasese District was 12.12%, with 85.5% of these being RhD positive. Risk factors such as a history of stillbirths, miscarriages, and incidence of postpartum hemorrhage were significantly associated with anti-D alloimmunization. There is a need to routinely carry out antenatal blood grouping and IAT screening on pregnant women in Uganda to detect anti-D alloimmunization. Given the high prevalence of anti-D alloantibody formation among RhD-positive women, we recommend additional research studies on the role of autoimmunity among antigen-positive women, as well as the occurrence of RhD variants plus their implications on hemolytic disease of the fetus and newborn, in Uganda.
ABO/RhD; blood groups; anti-D alloimmunization; indirect antiglobulin test; pregnant women; Western Uganda
Hereditary angioedema (HAE) is characterized as an episodic swelling disorder with autosomal dominant inheritance. Clinical features include nonpitting edema of external or mucosal body surfaces, and patients often present with swelling of the extremities, abdominal pain, and swelling of the mouth and throat, which can lead to asphyxiation. Patients with HAE classically have no associated urticaria, which is often referred to as nonhistaminergic angioedema. Treatment for HAE involves long-term prophylaxis, short-term prophylaxis, and management of acute attacks. Up until the past few years, acute HAE episodes were predominately treated with supportive measures. Three classes of medications have recently been approved by the US Food and Drug Administration (FDA) for the management of acute HAE attacks. Ecallantide, a recombinant protein that acts as a reversible inhibitor of kallikrein, is currently indicated for acute attacks of HAE in those aged ≥12 years. In two randomized, double-blind, placebo-controlled, multicenter trials, EDEMA3 and EDEMA4, patients treated with 30 mg of ecallantide demonstrated statistically significant improvement in symptoms compared to those on placebo. In addition to its use as treatment for HAE, ecallantide has been used off label in the management of nonhistaminergic angioedema, not due to HAE. Ecallantide has shown promise in the treatment of these other forms; however, data are limited to mainly case reports at this time. Ecallantide is generally a safe and well-tolerated medication; however, based on reports of anaphylaxis, ecallantide does contain a black box warning. Due to the risk of anaphylaxis, ecallantide cannot be self-administered and must be given by a health care professional. Overall, ecallantide is a safe and effective medication for the treatment of acute attacks of HAE.
idiopathic angioedema; ACE-Inhibitor induced angioedema; nonhistaminergic angioedema; bradykinin; acquired angioedema; Kallikrein; 7- C1-Inhibitor
We aimed to determine the prevalence and correlates of thrombocytopenia among people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and to assess occurrence of antiplatelet antibodies, among thrombocytopenic HIV clients at Mbarara Regional Referral Hospital, southwestern Uganda.
Materials and methods
This was a retrospective review of hematologic results at enrollment to HIV care from 2005 to 2013. The prevalence and correlates of thrombocytopenia were estimated based on the Immune Suppressed Syndrome (ISS) Clinic electronic database. A cross-sectional study determined the occurrence of antiplatelet antibodies, using the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) technique.
We reviewed 15,030 client records. The median age was 35.0 (range 18–78; interquartile range [IQR] 28–42) years, and there were 63.2% (n=9,500) females. The overall prevalence of thrombocytopenia was 17.4% (95% confidence interval [CI]: 16.8%–18.0%). The prevalence of thrombocytopenia was 17.8% (95% CI: 17.1%–18.4%) among antiretroviral therapy (ART)-naïve clients (n=2,675) and was 13.0% (95% CI: 0.3%–21.9%) for clients who were on ART (n=6). The study found a significant association between thrombocytopenia and other cytopenias, CD4 counts, ART, and deteriorating HIV stage (P<0.05). Two of the 40 participants (5.0%) had antiplatelet antibodies.
This study has showed a high prevalence of HIV-related thrombocytopenia. Antiplatelet antibodies were found in 5.0% of HIV-infected thrombocytopenic participants. Our study shows a significant association of thrombocytopenia burden in a high-HIV study population (Southwest Uganda); therefore, there is need to monitor platelet counts and initiate platelet transfusion in our blood banking practices, to avert possible risks of bleeding.
antiplatelet antibodies; cytopenia; AIDS
The effect of pesticides on nicotinamide adenine dinucleotide phosphate hydrogen (NADPH), including its level and relationship with the T helper 1 (Th1)/Th2 ratio, in patients suffering from non-Hodgkin lymphoma (NHL) was investigated. One hundred newly diagnosed patients with aggressive NHL (53 men, 47 women) and 40 healthy age-, sex-, and body mass index-matched controls (23 men, 17 women), exposed or not to pesticides, were recruited for a cross-sectional study conducted at the Clinical Hematology Departments of Tlemcen and Sidi Bel-Abbès University Medical Centers in the northwest of Algeria. NADPH levels were significantly increased in patients compared with controls; and in exposed patients compared with those not exposed, and controls (one-way analysis of variance; P=0.000). Albumin, glutathione peroxidase, superoxide dismutase, catalase activity, and oxygen radical absorbance capacity levels were significantly decreased in patients compared with in the control group. Oxygen radical absorbance capacity levels were significantly decreased in exposed patients compared with in unexposed patients; however, malondialdehyde levels were significantly increased in exposed patients when compared with controls and unexposed patients. Protein carbonyl and xanthine oxidase levels were significantly increased in exposed patients compared with controls; meanwhile, there were no significant differences between the two patient groups or between unexposed patients and controls. The Th1/Th2 ratio was significantly decreased in patients when compared with controls; the neutrophil-to-lymphocyte ratio was significantly increased (for both comparisons, P<0.001). In addition, NADPH was strongly associated with NHL (Mantel–Haenszel common odds ratio estimate =5.55; 95% confidence interval, 2.22–13.88; P=0.000). Moreover, NADPH levels were significantly negatively related to the Th1/Th2 ratio, either in exposed patients or in unexposed patients (respectively, r=−0.498 [P=0.004] and r=−0.327 [P=0.006]). In conclusion, pesticide exposure was strongly associated with NADPH alteration in NHL. The relationship between NADPH and Th1/Th2 ratio should focus on new therapeutic strategies for the disease.
non-Hodgkin lymphoma; pesticides; NADPH; Th1/Th2 ratio
Hodgkin’s lymphoma (HL) originates from clonal B cells and is the most common malignancy in the second decade of life. Liver involvement is uncommon at presentation in patients with HL and there is a paucity of data for treatment of patients with severely impaired liver function. We present an unusual case of HL with severe hepatic impairment, splenomegaly and multiple chromosomal abnormalities that was treated initially with gemcitabine and steroids. Once liver function tests improved, six cycles of Adriamycin, bleomycin, vinblastine, and dacarbazine were administered. The patient remains in remission at 3.5 years of follow-up.
hepatomegaly; cytogenetics; remission
The aim of this study was to evaluate the role of consolidation radiotherapy (RT) in advanced-stage Hodgkin’s disease (HD) with initial bulky sites after radiological complete remission (CR) or partial response (PR) with positron emission tomography-negative (metabolic CR) following standard chemotherapy (ABVD [Adriamycin, bleomycin, vinblastine, and dacarbazine]) six to eight cycles.
Patients and methods
Adult patients with advanced-stage HD treated at our institute during the period 2006 to 2012 were retrospectively evaluated. One hundred and ninety-two patients with initial bulky disease size (>7 cm) who attained radiological CR/PR and metabolic CR were included in the analysis. One hundred and thirteen patients who received radiotherapy (RT) as consolidation postchemotherapy (RT group) were compared to 79 patients who did not receive RT (non-RT group). Disease-free (DFS) and overall survival (OS) rates were estimated using the Kaplan–Meier method and were compared according to treatment group by the log-rank tests at P ≤0.05 significance level.
The mean age of the cohort was 33 (range: 14 to 81) years. Eighty-four patients received involved-field radiation and 29 patients received involved-site RT. The RT group had worse prognostic factors compared to the non-RT group. Thirteen (12%) relapses occurred in the RT group, and 19 (24%) relapses occurred in the non-RT group. Nine patients (8%) in the RT group died, compared to eleven patients (14%) in the non-RT group. Second malignancies were seen in only five patients: three patients in the RT group compared to two patients in the non-RT group. At 5 years, overall DFS was 79%±9% and OS was 85%±9%. There was significant statistical difference between the RT group and the non-RT group regarding 5-year DFS: 86%±7% and 74%±9%, respectively (P ≤0.02). However, the 5-year OS was 90%±5% for the RT group and 83%±8% for the non-RT group, with no statistical difference (P ≤0.3). Conclusion: The results of our study suggest that consolidation RT in patients with advanced-stage HD with initial bulky disease who had postchemotherapy radiologic CR or PR with metabolic CR improved the DFS.
Hodgkin’s disease; radiological and metabolic complete remission; involved-field radiation; involved-site radiation
The β-thalassemias are a group of hereditary hematological diseases caused by over 300 mutations of the adult β-globin gene. Together with sickle cell anemia, thalassemia syndromes are among the most impactful diseases in developing countries, in which the lack of genetic counseling and prenatal diagnosis have contributed to the maintenance of a very high frequency of these genetic diseases in the population. Gene therapy for β-thalassemia has recently seen steadily accelerating progress and has reached a crossroads in its development. Presently, data from past and ongoing clinical trials guide the design of further clinical and preclinical studies based on gene augmentation, while fundamental insights into globin switching and new technology developments have inspired the investigation of novel gene-therapy approaches. Moreover, human erythropoietic stem cells from β-thalassemia patients have been the cellular targets of choice to date whereas future gene-therapy studies might increasingly draw on induced pluripotent stem cells. Herein, we summarize the most significant developments in β-thalassemia gene therapy over the last decade, with a strong emphasis on the most recent findings, for β-thalassemia model systems; for β-, γ-, and anti-sickling β-globin gene addition and combinatorial approaches including the latest results of clinical trials; and for novel approaches, such as transgene-mediated activation of γ-globin and genome editing using designer nucleases.
Thalassemia; gene therapy; HbF induction; transcription factors; induced pluripotent stem cells; genome editing; TALEN; CRISPR; ZFN
Hematopoietic stem and progenitor cell (HSPC) transplantations require prior harvesting of allogeneic or autologous HSPCs. HSPCs are usually present in bone marrow (BM) during the entire life, in cord blood (CB) at birth, or in peripheral blood (PB) under particular circumstances. HSPCs were first harvested in BM and later in CB and PB, as studies showed interesting features of such grafts. All harvesting methods were in use throughout the years, except BM harvesting for HSPC autologous transplantation, which was replaced by PB harvesting. BM, CB, and PB harvesting methods have been developed, and materials and devices technically improved to increase the number of HSPCs harvested. In parallel, knowing the features of the donors or patients associated with successful numbers of HSPCs allows the adaptation of appropriate harvesting methods. Moreover, it is important to ensure the safety of donors or patients while harvesting. This review describes the methods used for harvesting based on recent studies or developments around these methods, and more particularly, the means developed to increase the numbers of HSPCs harvested in each method. It also explains briefly the influence of technical improvements in HSPC harvesting on potential changes in HSPC graft composition.
hematopoietic stem cell; harvesting; cord blood; bone marrow; mobilization; peripheral blood; apheresis
The infused autograft lymphocyte to monocyte ratio (A-LMR) as a surrogate marker of host immunity (ie, absolute lymphocyte count) and CD14+ HLA-DRlow/neg immunosuppressive monocytes (ie, absolute monocyte count) is a prognostic factor for patients with diffuse large B-cell lymphoma after autologous peripheral hematopoietic stem cell transplantation (APHSCT). Thus, we set out to investigate if A-LMR can also affect survival post-APHSCT in classical Hodgkin lymphoma. From 1994 to 2012, 183 patients with classical Hodgkin lymphoma who underwent APHSCT were studied. The patients were randomly divided into a training set (n=122) and a validation set (n=61). The receiver operating characteristic and area under the curve identified an A-LMR ≥1 as the best cut-off value and validated by the k-fold cross-validation in the training set. Multivariate analysis showed A-LMR to be an independent prognostic factor for survival in the training set. Patients with an A-LMR ≥1.0 experienced a superior overall survival (OS) versus patients with an A-LMR <1.0 (median OS not reached versus 40.4 months, 5-year OS rates of 86% [95% CI 72–93] versus 43% [95% CI 28–58], P<0.0001, respectively) in the training set. In the validation set, an A-LMR ≥1 showed a median OS of not reached versus 41.4 months for an A-LMR <1, 5-year OS rates of 90% (95% CI 73–97) versus 48% (95% CI 28–68; P<0.0001). A-LMR provides a platform to engineer an autograft versus tumor effect to improve clinical outcomes in patients with classical Hodgkin lymphoma undergoing APHSCT.
autograft absolute lymphocyte to monocyte count ratio; survival; autologous peripheral hematopoietic stem cell transplantation; classical Hodgkin lymphoma
“Immune thrombocytopenia” (ITP) is an autoimmune disorder that leads to peripheral destruction, as well as a decreased production of platelets. ITP most commonly presents as mild mucocutaneous bleeding. Though it is rare, the leading cause of mortality in persons with ITP is intracranial hemorrhage and those that do not respond to therapy are at increased risk. Our understanding of the pathophysiology of ITP has evolved immensely, especially over the last 60 years. The discovery of the platelet-production stimulator, thrombopoietin (TPO), lent clarity to an earlier hypothesis that inhibition of platelet production at the level of the megakaryocyte, at least in part, accounts for thrombocytopenia in adults with ITP. This facilitated the development of TPO-based therapies to treat ITP. Thrombopoietin receptor agonists are one of the most recent treatments to enter the landscape. Original production of a recombinant human TPO was halted after clinical trials revealed the untoward effect of autoantibodies to the recombinant human TPO with cross-reactivity to endogenous TPO. Next-step development focused on stimulation of the TPO receptor with fewer immunogenic agents. Currently, two such thrombopoietin receptor agonists, romiplostim and eltrombopag, are licensed in the USA to treat thrombocytopenia in adults with persistent or chronic ITP. Ongoing research will assess their efficacy in other immune-mediated and nonimmune-mediated primary and secondary thrombocytopenias.
thrombopoietin; thrombopoietin receptor agonist; megakaryocyte; peptibody
Human T-cell lymphotrophic/leukemia virus (HTLV-1) is a retrovirus implicated in transfusion-transmitted infection.
The objective of this study was to determine the seroprevalence of HTLV-1 antibodies among blood donors at the University of Nigeria Teaching Hospital, Enugu, Eastern Nigeria.
A cross-sectional study was carried out on consented participants over 4 months. A total of 300 blood donors were recruited consecutively from the blood bank. The serum of the collected 5 mL of blood obtained from each participant was stored at −20°C until required for analysis. The serum samples were then analyzed for antibodies to HTLV-1 using a one-step incubation double-antigen sandwich ELISA (enzyme-linked immunosorbent assay) kit. Participants’ demographic characteristics and degree of exposure to the risk factors associated with HTLV-1 infection were captured using a questionnaire. Statistical analysis of results was done using SPSS version 17.
Of the 300 blood donors, 288 (96%) were male, while 12 (4%) were female. The average age of the blood donors was 26.85±8.52 years. The age group with the highest representation among the blood donors were those aged between 21 and 25 years. Only 22.3% of the blood donors were above 30 years. None of the 300 screened blood donors tested positive to HTLV-1 antibodies. Hence, the seroprevalence of HTLV-1 infection among blood donors was 0%. Of the blood donors, 5% had history of previous sexually transmitted disease, while 34.7% used condoms during sexual intercourse.
The seroprevalence obtained in this study cannot statistically support the justification of routine screening of blood donors for HTLV-1 infection. More prospective and multicentered studies are required to determine the infectivity of HTLV-1 in blood donors in Nigeria.
retrovirus; transfusion; blood-borne infection; screening; Africa