ABSTRACT
Objectives: Acquired hemophilia affects approximately one in 1 million people. Timely diagnosis is key to appropriate disease management and the prevention of life-threatening complications. Patients with this condition may initially be seen by inexperienced physicians and remain underdiagnosed for several years. This consensus statement is aimed at providing guidelines for all practitioners in the Kingdom of Saudi Arabia (KSA) to diagnose and manage acquired hemophilia A. Methods: This consensus statement reflects the opinions drafted by a group of hematology specialists, who used an explicit systematic process to identify areas of agreement and disagreement. Results: This consensus statement provides a guide for all practitioners in the KSA regarding the diagnosis of clinical presentation, relevance, characteristics of bleeding symptoms, and case management; it additionally provides guidance for non-specialists. All management aspects, including diagnosis and treatment modalities, are discussed. Conclusions: Patients with acquired hemophilia may initially be seen by physicians who lack appropriate expertise in diagnosing and managing this condition. This consensus statement from the premier experts on the disease in the KSA provides details for diagnosing and managing acquired hemophilia.
ABSTRACT
Proteinuria is a manifestation of sickle cell anemia (SCA)-related renal disease and is a risk factor of renal impairment. Angiotensin-converting enzyme (ACE) inhibitors have benefits, but their role in SCA remains undefined. This study aimed to assess the role of lisinopril, an ACE inhibitor, in reducing proteinuria in SCA patients. Thirty-five patients older than 15 years with known SCA (HbSS or HbS-ß0) and a 24-h urinary protein level of 150 mg or more participated in this study. Urine was collected over 24 h to quantify proteinuria. The patients had a mean age of 28.5 ± 6.98 years. The median 24-h urinary protein before treatment was 0.3006 g and that after treatment was 0.150 g (P = 0.01). After a median follow-up of 38 months, 24-h urinary protein decreased in 27 (77%) patients and normalized in 18 (52%) patients. Urinary protein increased in 2 (6%) patients and remained stable (no change) in 6 (17%) patients. There was no significant difference in blood pressure (BP) before and after treatment. The average dose of lisinopril was 5 mg. Twenty patients were still on lisinopril at last follow-up. The reasons for stopping lisinopril included normalization of protein, noncompliance, adverse effects, and pregnancy. Lisinopril effectively reduced proteinuria in SCA patients, without significantly reducing BP. Only a few patients developed adverse effects, including coughing, dizziness, and diarrhea. It is unclear how long lisinopril should be continued and whether it can be stopped in patients with normalized urinary protein.
Subject(s)
Anemia, Sickle Cell , Angiotensin-Converting Enzyme Inhibitors , Lisinopril , Proteinuria , Humans , Lisinopril/therapeutic use , Proteinuria/drug therapy , Proteinuria/urine , Female , Male , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/drug therapy , Anemia, Sickle Cell/urine , Adult , Young Adult , Treatment Outcome , Time Factors , Blood Pressure/drug effects , AdolescentABSTRACT
ABSTRACT Objectives: Investigate the prevalence of Rh and the K antigens and their phenotypes in the red blood cells of blood donors in Riyadh, Saudi Arabia. Methods: This is a retrospective study. The five principal Rh antigens (D, C, c, E, e) and the Kell antigen from the Kell blood group were tested in 4,675 random samples collected from four blood bank centers in Riyadh. Data were collected for seven weeks (from January 4, 2019 to February 28, 2019). Antigens were tested using the TANGO Optimo system. Results: We found that approximately 86% of the donors had the D antigen, 66% had C, 78% had c, 26% had E, 97% had e and 14% had K. The most common Rh phenotypes were R1r (31%) and R1R1 (22%). Conclusion: The differences in the results between the study population and other populations, such as Caucasian, Indian and African populations indicate the importance of establishing a population-specific database.
Subject(s)
Blood Donors , Phenotype , AntigensABSTRACT
OBJECTIVES: Investigate the prevalence of Rh and the K antigens and their phenotypes in the red blood cells of blood donors in Riyadh, Saudi Arabia. METHODS: This is a retrospective study. The five principal Rh antigens (D, C, c, E, e) and the Kell antigen from the Kell blood group were tested in 4,675 random samples collected from four blood bank centers in Riyadh. Data were collected for seven weeks (from January 4, 2019 to February 28, 2019). Antigens were tested using the TANGO Optimo system. RESULTS: We found that approximately 86% of the donors had the D antigen, 66% had C, 78% had c, 26% had E, 97% had e and 14% had K. The most common Rh phenotypes were R1r (31%) and R1R1 (22%). CONCLUSION: The differences in the results between the study population and other populations, such as Caucasian, Indian and African populations indicate the importance of establishing a population-specific database.
ABSTRACT
ABSTRACT: Prevalence of bleeding disorders vary due to several factors including geographical location. Mild bleeding disorders can lead to iron deficiency, morbidity, and in severe cases mortality. Quantification of haemorrhagic symptoms is a key component in management of bleeding disorders and a challenging task for clinicians.An abridged version of MCMDM-1vWD questionnaire with validated Arabic translation was used to quantify bleeding disorders in adult students (nâ=â1138) in 4 different regions of Kingdom of Saudi Arabia. Statistical analysis was performed to indicate gender disparity and prevalence.74.5% of respondents answered at least 1 question with affirmation, with 32.3% affected in Riyadh showing the highest prevalence and 14.03% affected in Dammam showing the least prevalence (P-valueâ<â.001). Gender-wise, higher prevalence of bleeding disorders in females 54.9% than in males 45.1% was observed (P-value .01). Epistaxis prevalence was significantly higher in males 30.7% vs 23.2% in females (P-value .0004), while cutaneous symptoms were reported significantly more by female participants 29.7% vs 12.3% in males (P-valueâ<â.001). Menorrhagia was reported by 28% of females, with heavy bleeding experienced by 57.6% female participants forâ<7âdays while in 42.4% of females for >7âdays.The current study signifies the ethnic distribution and gender disparity of mild bleeding disorders, and highlights the need for national surveillance system in order to improve management of patients with bleeding disorders.
Subject(s)
Hemorrhage/epidemiology , Adolescent , Adult , Cross-Sectional Studies , Epistaxis/epidemiology , Female , Humans , Male , Menorrhagia/epidemiology , Prevalence , Saudi Arabia/epidemiology , Severity of Illness Index , Sex Factors , Students, Medical/statistics & numerical data , Young AdultABSTRACT
Importance: Although effective agents are available to prevent painful vaso-occlusive episodes of sickle cell disease (SCD), there are no disease-modifying therapies for ongoing painful vaso-occlusive episodes; treatment remains supportive. A previous phase 3 trial of poloxamer 188 reported shortened duration of painful vaso-occlusive episodes in SCD, particularly in children and participants treated with hydroxyurea. Objective: To reassess the efficacy of poloxamer 188 for vaso-occlusive episodes. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled, multicenter, international trial conducted from May 2013 to February 2016 that included 66 hospitals in 12 countries and 60 cities; 388 individuals with SCD (hemoglobin SS, SC, S-ß0 thalassemia, or S-ß+ thalassemia disease) aged 4 to 65 years with acute moderate to severe pain typical of painful vaso-occlusive episodes requiring hospitalization were included. Interventions: A 1-hour 100-mg/kg loading dose of poloxamer 188 intravenously followed by a 12-hour to 48-hour 30-mg/kg/h continuous infusion (n = 194) or placebo (n = 194). Main Outcomes and Measures: Time in hours from randomization to the last dose of parenteral opioids among all participants and among those younger than 16 years as a separate subgroup. Results: Of 437 participants assessed for eligibility, 388 were randomized (mean age, 15.2 years; 176 [45.4%] female), the primary outcome was available for 384 (99.0%), 15-day follow-up contacts were available for 357 (92.0%), and 30-day follow-up contacts were available for 368 (94.8%). There was no significant difference between the groups for the mean time to last dose of parenteral opioids (81.8 h for the poloxamer 188 group vs 77.8 h for the placebo group; difference, 4.0 h [95% CI, -7.8 to 15.7]; geometric mean ratio, 1.2 [95% CI, 1.0-1.5]; P = .09). Based on a significant interaction of age and treatment (P = .01), there was a treatment difference in time from randomization to last administration of parenteral opioids for participants younger than 16 years (88.7 h in the poloxamer 188 group vs 71.9 h in the placebo group; difference, 16.8 h [95% CI, 1.7-32.0]; geometric mean ratio, 1.4 [95% CI, 1.1-1.8]; P = .008). Adverse events that were more common in the poloxamer 188 group than the placebo group included hyperbilirubinemia (12.7% vs 5.2%); those more common in the placebo group included hypoxia (12.0% vs 5.3%). Conclusions and Relevance: Among children and adults with SCD, poloxamer 188 did not significantly shorten time to last dose of parenteral opioids during vaso-occlusive episodes. These findings do not support the use of poloxamer 188 for vaso-occlusive episodes. Trial Registration: ClinicalTrials.gov Identifier: NCT01737814.
Subject(s)
Anemia, Sickle Cell/drug therapy , Pain/drug therapy , Poloxamer/therapeutic use , Vasodilator Agents/therapeutic use , Adolescent , Adult , Analgesics, Opioid/therapeutic use , Anemia, Sickle Cell/complications , Child , Double-Blind Method , Female , Humans , Male , Pain/etiology , Placebos/adverse effects , Placebos/therapeutic use , Poloxamer/adverse effects , Vasodilator Agents/adverse effects , Young AdultABSTRACT
BACKGROUND: Congenital fibrinogen deficiency is an ultra-rare disorder in which patients can experience severe and/or frequent bleeding episodes (BEs). Here, we present the largest prospective study to date on the treatment of this disorder. METHODS: Hemostatic efficacy of human fibrinogen concentrate (HFC; FIBRYGA® , Octapharma AG) for treatment of bleeding or surgical prophylaxis was assessed by investigators and adjudicated by an independent data monitoring and endpoint adjudication committee (IDMEAC) according to a four-point scale, using objective criteria. Thromboelastometry maximum clot firmness (MCF) was also determined. RESULTS: Twenty-five afibrinogenemia patients were treated with HFC: 24 for on-demand treatment of 89 BEs, and nine as prophylaxis for 12 surgeries. For BEs, treatment success (rating of excellent or good) evaluated by investigators was 96.6% (90% confidence interval [CI], 0.92-0.99; two missing ratings, classified as failures) and by the IDMEAC was 98.9% (90% CI, 0.95-0.999). Mean ± standard deviation (SD) increase in MCF was 5.8 ± 2.5 mm one hour after the first HFC infusion (mean ± SD dose, 61.88 ± 11.73 mg/kg). For the 12 surgeries (median [range] HFC dose/surgery, 85.80 mg/kg [34.09-225.36]), intraoperative and postoperative treatment success were both rated 100% (90% CI, 0.82-1.00) by investigators and the IDMEAC. Three adverse events were possibly treatment related, including a moderate case of thrombosis. There were no deaths, no severe allergic or hypersensitivity reactions, and no clinical evidence of neutralizing antifibrinogen antibodies. CONCLUSIONS: Human fibrinogen concentrate was efficacious for on-demand treatment of bleeding and as surgical prophylaxis, with a favorable safety profile, in patients with congenital afibrinogenemia.
Subject(s)
Afibrinogenemia , Hemostatics , Afibrinogenemia/diagnosis , Afibrinogenemia/drug therapy , Fibrinogen , Humans , Prospective Studies , ThrombelastographyABSTRACT
Iron deficiency is the most prevalent nutritional deficiency worldwide. According to an estimate by the World Health Organization, up to 27% of the world's population experience iron deficiency anemia (IDA). Studies conducted in the Middle East, including Saudi Arabia, have suggested that IDA is the most common cause of anemia, especially among females. This study aimed to determine the prevalence of IDA and iron deficiency (ID) among apparently healthy young university students from four regions in Saudi Arabia. Students were asked to complete a simple survey questionnaire; blood samples were then collected and analyzed after obtaining informed consent. A total of 981 students completed the survey, with 11% of the participants reporting symptoms of anemia; 34% of participants were diagnosed with IDA and 6% reported a diagnosis of hemoglobinopathy. Blood analysis confirmed the prevalence of ID and IDA in 28.6% and 10.7% of the participants, respectively; those with ID and IDA were mostly females (88.5% and 94%, resp.). Thalassemia trait and sickle cell trait were detected in 1.3% and 7% of participants, respectively. Our findings from a national survey among young university in Saudi Arabia indicate a high prevalence of ID and IDA.
ABSTRACT
Background: With acute myeloid leukemia (AML), there are limited data about the accuracy of day 14 bone marrow (BM) biopsies for predicting complete remission as compared to day 28 BM biopsy results. We here aimed to estimate the correlation between, and the diagnostic accuracy of, both approaches. Materials and Methods: We reviewed 84 patients with AML treated with standard induction chemotherapy to evaluate the remission rate and treatment decisions based on day 14 BM biopsy from 2000-2012. Results: Sixty five patients (77%) demonstrated remission (CR) with less than 5% blasts on their day 14 BM. Thirteen patients (16%) had residual disease (RD), and 6 (7%) were classified as indeterminate response (IR) i.e., blasts 5-20%. Two patients with RD on day 14 underwent re-induction. Out of the 17 remaining cases with RD+IR, 14 (all 6 with IR and 8 out of 11 with residual disease with no re-induction) demonstrated a morphologic complete remission (CR) on day 28 BM. The percentages for complete remissions on days 28 and 14 were significantly different [94% versus 79.3%, respectively; p=0.004, (OR= 0.143, 95% CI: 0.032-0.63)]. Day 14 BM had 82% sensitivity in predicting CR on Day 28; however, it had insufficient specificity (60%) in predicting failure of CR. Conclusions: Induction treatment response assessment based on day 14 BM does not accurately predict the response rate on day 28 and the use of day 14 BM as a sole marker of response to therapy might expose patients to unnecessary interventions.
Subject(s)
Bone Marrow/surgery , Decision Support Techniques , Induction Chemotherapy , Leukemia, Myeloid, Acute/drug therapy , Neoplasm, Residual/drug therapy , Remission Induction , Adolescent , Adult , Aged , Biopsy , Bone Marrow/pathology , Female , Follow-Up Studies , Humans , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged , Neoplasm, Residual/pathology , Prognosis , Time Factors , Young AdultABSTRACT
BACKGROUND: Fibrinogen concentrate is the preferred choice for fibrinogen replacement in congenital fibrinogen deficiency. This study investigated hemostatic efficacy of a new plasma-derived, double virus-inactivated (using two dedicated virus inactivation/elimination steps) human fibrinogen concentrate for on-demand treatment of bleeding episodes (BEs) and surgical prophylaxis. STUDY DESIGN AND METHODS: In this planned interim analysis of a prospective, multinational Phase III study (NCT02267226), 13 patients with afibrinogenemia (≥12 years) received fibrinogen concentrate (FIBRYGA, Octapharma AG). Hemostatic efficacy was assessed by investigators and an independent data monitoring and endpoint adjudication committee (IDMEAC) using objective four-point criteria and by thromboelastometry maximum clot firmness (MCF). RESULTS: Fibrinogen concentrate was used on-demand to treat 23 BEs in 11 patients, with 21 (91.3%) requiring a single infusion only. Treatment success was 95.7% (90% confidence interval [CI], 0.81-1.00; assessment missing for one BE) by investigators and 100% (90% CI, 0.88-1.00) by IDMEAC. Mean MCF increased significantly from 0.0 to 6.5 mm (95% CI, 5.65-7.40; p < 0.0001) at 1 hour postinfusion of a median (range) dose of 58.8 (33.9-101.7) mg/kg per BE. Four patients received fibrinogen concentrate as surgical prophylaxis, with intraoperative and postoperative treatment success rated 100% (90% CI, 0.50-1.00) by investigators and IDMEAC (median [range] dose per surgery 93.5 [34.1-225.4] mg/kg). No additional hemostatic interventions were required. No deaths, thromboses, or seroconversions were reported. CONCLUSION: These data showed that the new fibrinogen concentrate was efficacious for on-demand treatment of acute bleeding and surgical prophylaxis in congenital afibrinogenemia patients.
Subject(s)
Afibrinogenemia/drug therapy , Blood Loss, Surgical/prevention & control , Fibrinogen/administration & dosage , Adolescent , Adult , Afibrinogenemia/blood , Female , Fibrinogen/adverse effects , Humans , Male , Middle Aged , Prospective StudiesABSTRACT
Home therapy for uncomplicated mild/moderate bleeding can decrease healthcare burden, promote self-esteem, reduce complications, and provide near-normal quality of life. To evaluate recombinant activated factor VII (rFVIIa) as home therapy for joint bleeds in Algeria, Morocco, Oman, Saudi Arabia, and United Arab Emirates. Twenty-seven patients aged more than 2 years with congenital haemophilia and inhibitors were monitored for up to 8 months after a first haemarthrosis episode treated with rFVIIa. Assessments were made by patients/caregivers with a standardized diary. The main measures included home-managed bleeds, haemostasis, and pain relief within 9âh after first injection. Additional analyses included convenience, time to pain resolution, and doses given within 48âh. Of 132 bleeds, 84 (63.6%) were managed at home. Of these, successful haemostasis (partial or complete) was achieved at 9âh in 87.8%, with pain relief for 84.0%. For all treatment settings, successful haemostasis at 9âh was achieved for 86.3% of bleeds, with pain relief achieved for 74.8% of bleeds. Higher initial dosing was associated with fewer injections. Median time to complete haemostasis was 48âh (spontaneous bleeds) and 24âh (traumatic bleeds). Median time to complete pain relief was 24âh for both bleed types. Satisfaction with treatment was high. No safety concerns were reported. Results from this observational study agree with previous data on the safety and efficacy of home treatment with rFVIIa and will help to increase awareness and aggregate experience, fostering confidence in home management of haemophilia patients with inhibitors in developing countries.
Subject(s)
Factor VIIa/therapeutic use , Hemarthrosis/therapy , Hemophilia A/complications , Hemophilia B/complications , Recombinant Proteins/therapeutic use , Developing Countries , Feasibility Studies , HumansABSTRACT
OBJECTIVE: To compare direct smear technique with ethylenediaminetetraacetic acid (EDTA) preserved smear technique in terms of preparing bone marrow aspirate slides. METHODS: This prospective study was carried out between September 2009 and July 2012 at the Haematology/Oncology Department, King Khalid University Hospital, Riyadh, Saudi Arabia. With a standard gauge disposable bone marrow aspirate needle, 0.5 to 1.0 ml bone marrow was aspirated with a 10ml syringe. Half of the marrow was immediately transferred to an EDTA tube with gentle mixing, while slides were prepared directly from the rest of the sample in the syringe. The tube sample was used to prepare slides at the end of the procedure. A score of 1-4 was assigned to each slide depending on the quality and number of particles. RESULTS: A total of 245 bone marrow aspirate samples were evaluated related to 216 patients. Of the total, 238 (97%) samples were included in the study. The mean score for the direct smear group was 3.40±0.79 and for the EDTA smear group it was 3.34±0.75 (p=0.27), which was not statistically significant. An informal comparison of the morphological analysis of the samples did not reveal any differences. CONCLUSIONS: Bone marrow aspirate slides prepared at the end of the procedure from EDTA preserved samples were not inferior to slides prepared directly from the aspirated sample.
Subject(s)
Bone Marrow/pathology , Histocytological Preparation Techniques , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy, Needle , Edetic Acid , Female , Humans , Male , Middle Aged , Prospective Studies , Young AdultABSTRACT
Among many complications of sickle cell disease, renal failure is the main contributor to early mortality. It is present in up to 21% of patients with sickle cell disease. Although screening for microalbuminuria and proteinuria is the current acceptable practice to detect and follow renal damage in patients with sickle cell disease, there is a crucial need for other, more sensitive biomarkers. This becomes especially true knowing that those biomarkers start to appear only after more than 60% of the kidney function is lost. The primary purpose of this study is to determine whether lactate dehydrogenase (LDH) correlates with other, direct and indirect bio-markers of renal insufficiency in patients with sickle cell disease and, therefore, could be used as a biomarker for early renal damage in patients with sickle cell disease. Fifty-five patients with an established diagnosis of sickle cell disease were recruited to in the study. Blood samples were taken and 24-h urine collection samples were collected. Using Statcrunch, a data analysis tool available on the web, we studied the correlation between LDH and other biomarkers of kidney function as well as the distribution and relationship between the variables. Regression analysis showed a significant negative correlation between serum LDH and creatinine clearance, R (correlation coefficient) = -0.44, P = 0.0008. This correlation was more significant at younger age. This study shows that in sickle cell patients LDH correlates with creatinine clearance and, therefore, LDH could serve as a biomarker to predict renal insufficiency in those patients.
Subject(s)
Anemia, Sickle Cell/complications , Biomarkers/blood , Creatinine/metabolism , L-Lactate Dehydrogenase/blood , Renal Insufficiency/diagnosis , Renal Insufficiency/etiology , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
Arsenic poisoning may occur from sources other than drinking water such as rice, seafood, or insecticides. Symptoms and signs can be insidious, non-specific, atypical, and easily overlooked. We present a 39-year-old woman with celiac disease who was on gluten-free diet for 8 years and presented with diarrhea, headache, insomnia, loss of appetite, abnormal taste, and impaired short-term memory and concentration, but with no skin lesions. Arsenic concentration in her 24-hour urine was 682.77 micro g/g creatinine (normal < 15). She responded very well to chelation therapy with dimercaptosuccinic acid given orally and recovered within 2 weeks. The suspected source of arsenic poisoning was rice, as drink.ing contaminated ground water is not known in Saudi Arabia and she had not taken seafood. Therefore, arsenic poisoning should be suspected based on the meticulous medical history in cases of patients with celiac disease whose main food is rice and who present with unusual symptoms.
Subject(s)
Arsenic Poisoning/diagnosis , Celiac Disease/diet therapy , Oryza/chemistry , Adult , Arsenic Poisoning/drug therapy , Arsenic Poisoning/etiology , Chelating Agents/therapeutic use , Diet, Gluten-Free , Female , Humans , Saudi Arabia , Succimer/therapeutic useABSTRACT
Platelet refractoriness may lead to life-threatening gastro-intestinal, intracranial or pulmonary hemorrhage that is difficult to control despite massive platelet and red cell transfusion, antifibrinolytic agents, high dose corticosteroids, immunoglobulin and intravenous (I.V.) recombinant activated factor VII (rFVIIa). In cases with pulmonary hemorrhage, intrapulmonary administration of rFVIIa may be more effective in non-responsive cases. We report a 51-year-old man with relapsing acute lymphoblastic leukemia (ALL) and platelet refractoriness, who suffered a life-threatening pulmonary hemorrhage that was refractory to massive platelet transfusion, tranexamic acid, high dose corticosteroids, immunoglobulin and intravenous rFVIIa, but responded immediately to a single intrapulmonary dose of rFVIIa that was inhaled with a jet nebulizer assistance through the endotracheal tube.
Subject(s)
Blood Platelets , Factor VIIa/administration & dosage , Hemorrhage/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Administration, Inhalation , Hemorrhage/etiology , Humans , Lung Diseases/etiology , Male , Middle Aged , Platelet Transfusion , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Recombinant Proteins/administration & dosage , RecurrenceABSTRACT
Thalassemia syndrome has diverse clinical presentations and a global spread that has far exceeded the classical Mediterranean basin where the mutations arose. The mutations that give rise to either alpha or beta thalassemia are numerous, resulting in a wide spectrum of clinical severity ranging from carrier state to life-threatening, inherited hemolytic anemia that requires regular blood transfusion. Beta thalassemia major constitutes a remarkable challenge to health care providers. The complications arising due to the anemia, transfusional iron overload, as well as other therapy-related complications add to the complexity of this condition. To produce this consensus opinion manuscript, a PubMed search was performed to gather evidence-based original articles, review articles, as well as published work reflecting the experience of physicians and scientists in the Arabian Gulf region in an effort to standardize the management protocol.
Subject(s)
beta-Thalassemia/diagnosis , beta-Thalassemia/epidemiology , Arabia/epidemiology , Consensus , Humans , beta-Thalassemia/complicationsABSTRACT
BACKGROUND: Elderly patients with acute myeloid leukemia (AML) have a poor outcome because of co- morbidities, poor tolerance to intensive chemotherapy and inherently more resistant disease. Clofarabine is a second generation nucleoside analogue which has shown promising activity in elderly patients with AML. This study was conducted to review the outcome of treatment with clofarabine in a group of such patients. METHODS: The records of 5 elderly patients who were diagnosed to have AML and treated with clofarabine over a 12 month period were reviewed retrospectively. RESULTS: There were 2 female and 3 male patients with a median age of 68 years (range 65-82). At the time of treatment, 2 patients had newly diagnosed AML not considered suitable for intensive therapy, while 3 patients had partial or no response to conventional chemotherapy. The overall response rate was 100%, all patients achieving a complete remission. Induction and consolidation were well tolerated. All patients developed neutropenia with a median duration of 20 days (range 17-42). One patient developed hand and foot syndrome and a generalized rash but recovered. There was no mortality and all patients remained in remission after a median follow-up of 5.2 months (Range 3-10). CONCLUSION: Clofarabine (alone or in combination) is active in elderly AML patients with an acceptable safety profile and should be considered a potential option in this group.
Subject(s)
Adenine Nucleotides/therapeutic use , Antimetabolites, Antineoplastic/therapeutic use , Arabinonucleosides/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Adenine Nucleotides/adverse effects , Aged , Aged, 80 and over , Aging , Antimetabolites, Antineoplastic/adverse effects , Arabinonucleosides/adverse effects , Clofarabine , Disease-Free Survival , Female , Hand-Foot Syndrome , Humans , Leukemia, Myeloid, Acute/mortality , Male , Neutropenia/chemically induced , Remission Induction , Retrospective Studies , Survival , Treatment OutcomeABSTRACT
BACKGROUND: Clinical immunology has traditionally relied on accurate phenotyping of the patient's immune dysfunction for the identification of a candidate gene or genes for sequencing and molecular confirmation. Although this is also true for other branches of medicine, the marked variability in immune-related phenotypes and the highly complex network of molecules that confer normal host immunity are challenges that clinical immunologists often face in their quest to establish a specific genetic diagnosis. OBJECTIVE: We sought to identify the underlying genetic cause in a consanguineous family with chronic inflammatory bowel disease-like disorder and combined immunodeficiency. METHODS: We performed exome sequencing followed by autozygome filtration. RESULTS: A truncating mutation in LPS-responsive beige-like anchor (LRBA), which abolished protein expression, was identified as the most likely candidate variant in this family. CONCLUSION: The combined exome sequencing and autozygosity mapping approach is a powerful tool in the study of atypical immune dysfunctions. We identify LRBA as a novel immunodeficiency candidate gene the precise role of which in the immune system requires future studies.