ABSTRACT
We conducted a retrospective cohort study on 663 transfusion-dependent ß-thalassemia patients receiving the same iron chelation monotherapy with deferoxamine, deferiprone, or deferasirox for up to 10 years (median age 31.8 years, 49.9 % females). Patients on all three iron chelators had a steady and significant decline in serum ferritin over the 10 years (median deferoxamine: -170.7 ng/mL, P = 0.049, deferiprone: -236.7 ng/mL, P = 0.001; deferasirox: -323.7 ng/mL, P < 0.001) yet had no significant change in liver iron concentration or cardiac T2*; while noting that patients generally had low hepatic and cardiac iron levels at study start. Median absolute, relative, and normalized changes were generally comparable between the three iron chelators. Patients receiving deferasirox had the highest morbidity and mortality-free survival probability among the three chelators, although the difference was only statistically significant when compared with deferoxamine (P = 0.037). On multivariate Cox regression analysis, there was no significant association between iron chelator type and the composite outcome of morbidity or mortality. In a real-world setting, there is comparable long-term iron chelation effectiveness between the three available iron chelators for patients with mild-to-moderate iron overload.
Subject(s)
Blood Transfusion , Deferasirox , Deferiprone , Deferoxamine , Iron Chelating Agents , Iron , Pyridones , beta-Thalassemia , Humans , Iron Chelating Agents/therapeutic use , beta-Thalassemia/mortality , beta-Thalassemia/therapy , beta-Thalassemia/drug therapy , beta-Thalassemia/complications , Female , Male , Adult , Retrospective Studies , Deferoxamine/therapeutic use , Deferiprone/therapeutic use , Iron/metabolism , Deferasirox/therapeutic use , Pyridones/therapeutic use , Iron Overload/etiology , Iron Overload/drug therapy , Benzoates/therapeutic use , Ferritins/blood , Adolescent , Triazoles/therapeutic use , Young Adult , Child , Treatment Outcome , Middle Aged , Liver/metabolism , Liver/drug effects , Liver/pathology , Cohort StudiesABSTRACT
Data on iron overload status and change thresholds that can predict mortality in patients with transfusion-dependent ß-thalassemia (TDT) are limited. This was a retrospective cohort study of 912 TDT patients followed for up to 10 years at treatment centers in Italy (median age 32 years, 51.6% female). The crude mortality rate was 2.9%. Following best-predictive threshold identification through receiver operating characteristic curve analyses, data from multivariate Cox-regression models showed that patients with Period Average Serum Ferritin (SF) > 2145 vs ≤ 2145 ng/mL were 7.1-fold (P < 0.001) or with Absolute Change SF > 1330 vs ≤ 1330 ng/mL increase were 21.5-fold (P < 0.001) more likely to die from any cause. Patients with Period Average Liver Iron Concentration (LIC) > 8 vs ≤ 8 mg/g were 20.2-fold (P < 0.001) or with Absolute Change LIC > 1.4 vs ≤ 1.4 mg/g increase were 27.6-fold (P < 0.001) more likely to die from any cause. Patients with Index (first) cardiac T2* (cT2*) < 27 vs ≥ 27 ms were 8.6-fold (P < 0.001) more likely to die from any cause. Similarly, results at varying thresholds were identified for death from cardiovascular disease. These findings should support decisions on iron chelation therapy by establishing treatment targets, including safe iron levels and clinically meaningful changes over time.
Subject(s)
Blood Transfusion , Iron Overload , beta-Thalassemia , Humans , Female , Iron Overload/mortality , Iron Overload/blood , Iron Overload/etiology , Male , beta-Thalassemia/therapy , beta-Thalassemia/mortality , beta-Thalassemia/blood , beta-Thalassemia/complications , Adult , Retrospective Studies , Adolescent , Ferritins/blood , Young Adult , Middle Aged , Iron/blood , Iron/metabolism , Cohort Studies , Child , Follow-Up Studies , Italy/epidemiologySubject(s)
Anemia/complications , Iron Overload/complications , beta-Thalassemia/complications , Adult , Anemia/mortality , Anemia/therapy , Blood Transfusion , Female , Humans , Iron Overload/mortality , Kaplan-Meier Estimate , Male , Mortality , Risk , Young Adult , beta-Thalassemia/mortality , beta-Thalassemia/therapyABSTRACT
BACKGROUND: Worldwide, haemoglobin E ß-thalassaemia is the most common genotype of severe ß-thalassaemia. The paucity of long-term data for this form of thalassaemia makes evidence-based management challenging. We did a long-term observational study to define factors associated with survival and complications in patients with haemoglobin E thalassaemia. METHODS: In this prospective, longitudinal cohort study, we included all patients with haemoglobin E thalassaemia who attended the National Thalassaemia Centre in Kurunegala, Sri Lanka, between Jan 1, 1997, and Dec 31, 2001. Patients were assessed up to three times a year. Approaches to blood transfusions, splenectomy, and chelation therapy shifted during this period. Survival rates between groups were evaluated using Kaplan-Meier survival function estimate curves and Cox proportional hazards models were used to identify risk factors for mortality. FINDINGS: 109 patients (54 [50%] male; 55 [50%] female) were recruited and followed up for a median of 18 years (IQR 14-20). Median age at recruitment was 13 years (range 8-21). 32 (29%) patients died during follow-up. Median survival in all patients was 49 years (95% CI 45-not reached). Median survival was worse among male patients (hazard ratio [HR] 2·51, 95% CI 1·16-5·43), patients with a history of serious infections (adjusted HR 8·49, 2·90-24·84), and those with higher estimated body iron burdens as estimated by serum ferritin concentration (adjusted HR 1·03, 1·01-1·06 per 100 units). Splenectomy, while not associated with statistically significant increases in the risks of death or serious infections, ultimately did not eliminate a requirement for scheduled transfusions in 42 (58%) of 73 patients. Haemoglobin concentration less than or equal to 4·5 g/dL (vs concentration >4·5 g/dL), serum ferritin concentration more than 1300 µg/L (vs concentration ≤1300 µg/L), and liver iron concentration more than 5 mg/g dry weight of liver (vs concentration ≤5 mg/g) were associated with poorer survival. INTERPRETATION: Patients with haemoglobin E thalassaemia often had complications and shortened survival compared with that reported in high-resource countries for thalassaemia major and for thalassaemia intermedia not involving an allele for haemoglobin E. Approaches to management in this disorder remain uncertain and prospective studies should evaluate if altered transfusion regimens, with improved control of body iron, can improve survival. FUNDING: Wellcome Trust, Medical Research Council, US March of Dimes, Anthony Cerami and Ann Dunne Foundation for World Health, and Hemoglobal.
Subject(s)
beta-Thalassemia/complications , beta-Thalassemia/mortality , Adolescent , Adult , Blood Transfusion/statistics & numerical data , Chelation Therapy/methods , Chelation Therapy/statistics & numerical data , Child , Female , Ferritins/blood , Hemoglobin E/analysis , Hemoglobins , Humans , Kaplan-Meier Estimate , Longitudinal Studies , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , Splenectomy/statistics & numerical data , Sri Lanka/epidemiology , Young AdultABSTRACT
OBJECTIVE: Increased life span with regular transfusion and iron chelator treatments enhances the importance of nutrition in beta thalassemia. Controlling Nutritional Status (CONUT) score is a nutritional index calculated on serum albumin, total cholesterol and lymphocyte count. We aim to evaluate need for transfusion and the clinical conditions which cause morbidity with CONUT score in patients with adult transfusion dependent beta thalassemia (BTD). METHOD: We conducted a retrospective study at the Denizli Thalassemia Center. We used Mann Whitney Utest for comparing. We applied logistic regression analysis and ROC analysis to evaluate CONUT score and clinical effects. RESULTS: A total of 102 patients with BTD were included. 89 were beta thalassemia major and 13 were transfusion dependent thalassemia intermedia (44 male,58 female). The median age was 26. The mean follow up period was 26 months. The median of CONUT score was 3.0 (min: 0-max: 6). CONUT score of 54 patients (52.9%) was high (≥3). We found significant difference with CONUT score ≥3 (median:32 units) and CONUT score of <3 (median:26.5 units) in terms of annual erythrocyte transfusion amount (p = 0.001). Low bone mass, vitamin D deficiency / insufficiency and hypogonadism were found to be more common with high CONUT score (≥3) (p = 0.001). CONUT score is a distinguishing parameter for hypogonadism (p = 0.001; AUC = 0.922) and low bone mass (p = 0.001; AUC = 0.867). CONCLUSION: CONUT score can be used as a predictor to evaluate need for transfusion and morbidity of patients with BTD. If nutritional status is closely followed with CONUT score and nutritional deficiency is corrected, cost and complications will be decreased and expanctancy of life can be increased.
Subject(s)
Cholesterol/blood , Serum Albumin, Human/metabolism , beta-Thalassemia , Adolescent , Adult , Disease-Free Survival , Erythrocyte Transfusion , Female , Follow-Up Studies , Humans , Lymphocyte Count , Male , Middle Aged , Retrospective Studies , Risk Factors , Survival Rate , beta-Thalassemia/blood , beta-Thalassemia/mortality , beta-Thalassemia/therapyABSTRACT
ß-Thalassemia (ß-thal) is one of the most common inherited diseases all over the world. These patients are very susceptible to infection disease, and the mortality and morbidity of infected patients will increase. The object of this systematic review study was to determine mortality and morbidity of infected ß-thal patients with coronavirus disease 2019 (COVID-19). We searched PubMed, Elsevier, and Scholar Google to obtain related papers. The time of search was 21 June until 17 July 2020. All original and review articles and case reports were searched with key words: COVID 19, beta or ß-thalassemia (ß-thal), mortality and morbidity. Data were extracted after quality assessment of all articles. We obtained seven, 21 and six articles from PubMed, Scholar Google and Science Direct, respectively. Finally, seven articles were discussed in our study. The total number of enrolled patients was 34. Twenty-six patients carried transfusion-dependent ß-thal major (ß-TM). The most common symptoms were fever, cough, pain and dyspnea. Nine patients died. The result of this study has shown that the mortality and morbidity of infected ß-thal patients will escalate.
Subject(s)
COVID-19/epidemiology , Pandemics , SARS-CoV-2 , beta-Thalassemia/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , COVID-19/mortality , Comorbidity , Diabetes Mellitus/epidemiology , Female , Global Health , Hospitalization/statistics & numerical data , Humans , Hypertension, Pulmonary/epidemiology , Immunocompromised Host , Male , Middle Aged , Splenectomy/adverse effects , Thrombophilia/drug therapy , Thrombophilia/etiology , Young Adult , beta-Thalassemia/mortality , beta-Thalassemia/surgeryABSTRACT
Alternate donor HSCT for thalassemia major from a matched unrelated donor or haploidentical family donor is a feasible therapeutic option in children with no matched family donor. Aggressive pretransplant immunosuppression, reduced toxicity conditioning, and PTCY result in excellent thalassemia-free survival. We describe here our experience in this cohort. We performed a retrospective analysis of the data on children who underwent a haploidentical HSCT for thalassemia major with PTCY at our center from August 2017 to August 2019. All children received pretransplant immune suppression for 6 weeks with fludarabine and dexamethasone, hypertransfusion and chelation with intravenous desferrioxamine. Conditioning included thiotepa, fludarabine, rabbit ATG, and cyclophosphamide, and GvHD prophylaxis included PTCY with tacrolimus. Twenty children were included and nineteen children engrafted. Acute hypertension occurred in five children, bacterial infection in eight children and viral respiratory infection in three children. Three children suffered from graft rejection. Reactivation of viruses namely CMV, adenovirus, and BK virus was seen in 60% of children. Grades 1-2 acute GvHD of the skin in four children (20%) and limited chronic GvHD of the skin in four children (20%). Immune cytopenia was documented in three children (15%). Haploidentical HSCT offers a therapeutic option for children with thalassemia major with no suitably matched family or unrelated donors. Our reduced toxicity regimen with PTCY offers a DFS of 75% and OS of 95% with low transplant-related mortality of 5%.
Subject(s)
Cyclophosphamide/therapeutic use , Hematopoietic Stem Cell Transplantation/methods , Immunosuppression Therapy/methods , Immunosuppressive Agents/therapeutic use , Transplantation Conditioning/methods , Transplantation, Haploidentical/methods , beta-Thalassemia/therapy , Adolescent , Child , Child, Preschool , Drug Administration Schedule , Drug Therapy, Combination , Female , Follow-Up Studies , Graft Rejection/immunology , Graft Rejection/prevention & control , Graft vs Host Disease/immunology , Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation/mortality , Humans , Male , Retrospective Studies , Treatment Outcome , beta-Thalassemia/mortalityABSTRACT
A retrospective cohort analysis to explore 10-year mortality and prevalence of transfusion-dependent ß-thalassaemia (TDT)-associated co-morbidities in patients with TDT was undertaken using Hospital Episode Statistics (HES) data from the National Health Service (NHS) in England. A 10-year forward-looking cohort analysis for the period 2009-2018 was completed using HES admitted patient care (APC), outpatient data, and linked HES/Office of National Statistics mortality data for patients with ß-thalassaemia (ICD-10 diagnosis code D56.1). TDT-associated co-morbidity rates were high in the 612 patients with TDT, with 76% having at least one co-morbidity, 54% suffering from two of more, and 37% three or more. The three most common TDT-associated co-morbidities, occurring in more than one third of patients were: endocrine disorders (excluding diabetes) 40%, osteoporosis 40%, and diabetes 34%. Cardiac disease was observed in 18% of patients overall, with atrial fibrillation and heart failure being the most common with a prevalence of 11% and 9%, respectively. The crude 10-year mortality rate in the TDT cohort was 6·2% (38/612), significantly greater than the 1·2% age/sex-adjusted mortality rate of the general population (P < 0·001). These data support the notion that the unmet need in TDT remains significant, with high rates of co-morbidity and mortality.
Subject(s)
Diabetes Mellitus/mortality , Heart Diseases/mortality , Osteoporosis/mortality , beta-Thalassemia/mortality , Adolescent , Adult , Blood Transfusion , Child , Comorbidity , Diabetes Mellitus/therapy , England , Female , Follow-Up Studies , Heart Diseases/therapy , Humans , Male , Osteoporosis/therapy , Retrospective Studies , beta-Thalassemia/therapySubject(s)
Cord Blood Stem Cell Transplantation , Graft Rejection , Hematopoietic Stem Cell Transplantation , beta-Thalassemia , Adolescent , Adult , Allografts , Child , Child, Preschool , Disease-Free Survival , Female , Follow-Up Studies , Graft Rejection/mortality , Graft Rejection/prevention & control , Humans , Male , Survival Rate , beta-Thalassemia/mortality , beta-Thalassemia/therapyABSTRACT
Large deletions in the ß-globin gene cluster lead to increased HbF levels by delaying the γ- to ß-globin switch process. However, these deletions when inherited as a homozygous condition or when co-inherited with ß-thalassemia result in variable clinical phenotypes. Individuals or families with a clinically presenting child, where the parents had HbF levels ≥ 10%, were further screened for the presence of large ß-globin cluster deletions. Six deletions in the ß-globin gene cluster were screened by GAP-PCR, and the uncharacterized deletions were further analyzed by gene dosage or by multiplex ligation-dependent probe amplification (MLPA). Among 192 individuals suspected for the inheritance of large deletions, 138 were heterozygous for large deletions, 45 were compound heterozygous of a large ß-globin cluster deletion and ß-thalassemia, and 9 were found to be homozygous for deletions. Among the heterozygotes, the Asian Indian inversion-deletion was found to be the most common deletion (39.9%), followed by the HPFH-3 deletion (30.0%). Other deletions 49.3 kb, δß-thalassemia (21.2%), and 32.6 kb deletion (4.4%) were also found to be prevalent in our population. Patients compound heterozygous or homozygous for HPFH-3 and 32.6 kb deletions showed a milder clinical presentation, as compared with the patients compound heterozygous or homozygous for the Asian Indian inversion-deletion and 49.3 kb δß-thalassemia. This comprehensive study highlights the mutation spectrum of large ß-globin cluster deletions and the clinical heterogeneity in the patients homozygous or compound heterozygous with ß-thalassemia, thus asserting the need for molecular characterization of these deletions.
Subject(s)
Fetal Hemoglobin/genetics , Genetic Association Studies , Genetic Heterogeneity , beta-Thalassemia/epidemiology , beta-Thalassemia/genetics , delta-Thalassemia/epidemiology , delta-Thalassemia/genetics , Age of Onset , Child , Child Mortality , Child, Preschool , Female , Fetal Hemoglobin/analysis , Genetic Association Studies/statistics & numerical data , Humans , India/epidemiology , Infant , Inheritance Patterns/genetics , Male , beta-Thalassemia/blood , beta-Thalassemia/mortality , delta-Thalassemia/blood , delta-Thalassemia/mortalityABSTRACT
The consequence of regular blood transfusion in patients with thalassemia major (TM) is iron overload. Herein, we report the long-term impact of chelation on liver iron concentration (LIC) and cardiac T2* MR in patients with TM. This is a retrospective cohort study over 10 years of adolescents and adults with TM aged at least 10 years who had their first cardiac T2* MR between September 2006 and February 2007. One-year chelation therapy was considered the unit of analysis. A total of 99 patients were included in this study with a median age of 18 years. The median cardiac T2* MR and LIC at baseline were 19 ms and 11.6 mg/g dw, respectively. During follow-up, 18 patients died and six underwent successful bone marrow transplantation. Factors associated with decreased survival were older age (HR 1.12, p = 0.014) and high risk cardiac T2* (HR 8.04, p = 0.004). The median cardiac T2* and LIC significantly improved over the 10-year follow-up period (p = 0.000011 and 0.00072, respectively). In conclusion, this long-term "real-life" study confirms that low cardiac T2* adversely impacts the overall survival in patients with TM. Higher baseline LIC predicts a larger reduction in LIC, and lower baseline cardiac T2* predicts a larger improvement in T2*.
Subject(s)
Chelation Therapy/trends , Magnetic Resonance Imaging, Cine/methods , beta-Thalassemia/diagnostic imaging , beta-Thalassemia/drug therapy , Adolescent , Chelation Therapy/methods , Cohort Studies , Deferasirox/therapeutic use , Deferiprone/therapeutic use , Female , Follow-Up Studies , Humans , Iron Chelating Agents/therapeutic use , Iron Overload/diagnostic imaging , Iron Overload/drug therapy , Iron Overload/mortality , Male , Retrospective Studies , Survival Rate/trends , Time Factors , Young Adult , beta-Thalassemia/mortalityABSTRACT
BACKGROUND: The NIH protocol for non-myeloablative (NMA) conditioning allogeneic stem cell transplantation (alloSCT) with alemtuzumab and low-dose total body irradiation corrected the abnormal sickle cell disease (SCD) phenotype without the risk of graft-versus-host disease. However, alloSCT using NMA conditioning had been rarely applied to ß-thalassemia major (ß-TM) patients. METHODS: To avoid prolonged immunosuppression, we developed a two-stage strategy. Mixed donor chimerism was initially achieved using the protocol developed by the NIH protocol. Thereafter, we facilitated donor chimerism using the optional reinforced stem cell (SC) infusion in cases requiring protracted immunosuppression or experiencing impending graft failure. RESULTS: In this study, ß-TM (n = 9) and SCD (n = 4) patients were equally effectively treated with eradicating the abnormal hemoglobin phenotype. Five patients, including four ß-TM, achieved stable mixed chimerism without receiving optional reinforced SC infusion. All patients that received optional reinforced infusion achieved complete (n = 4) or mixed chimerism (n = 1). The overall survival rate and event-free survival at 4 years were 91.7% (95% CI; 53.9-98.8) in both groups, with a thalassemia-free survival rate in ß-TM patients of 87.5% (95% CI; 38.7-98.1). CONCLUSION: This study is the first to report successful NMA conditioning alloSCT to achieve stable mixed chimerism correcting the abnormal hemoglobin phenotype in adult ß-TM patients.
Subject(s)
Hematopoietic Stem Cell Transplantation , Hemoglobinopathies/therapy , Siblings , Transplantation Conditioning , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Hemoglobinopathies/diagnosis , Hemoglobinopathies/mortality , Humans , Prognosis , Transplantation Chimera , Transplantation Conditioning/adverse effects , Transplantation Conditioning/methods , Transplantation, Homologous , Treatment Outcome , beta-Thalassemia/mortality , beta-Thalassemia/therapyABSTRACT
We studied 1110 patients with ß-thalassemia major aged ≤25 years who received transplants with grafts from HLA-matched related (n = 677; 61%), HLA-mismatched related (n = 78; 7%), HLA-matched unrelated (n = 252; 23%), and HLA-mismatched unrelated (n = 103; 9%) donors between 2000 and 2016. Ninety percent of transplants were performed in the last decade. Eight-five percent of patients received ≥20 transfusions and 88% were inadequately chelated. All patients received myeloablative-conditioning regimen. Overall and event-free survival were highest for patients aged ≤6 years and after HLA-matched related and HLA-matched unrelated donor transplantation. The 5-year probabilities of overall survival for patients aged ≤6 years, 7 to 15 years, and 16 to 25 years, adjusted for donor type and conditioning regimen were 90%, 84%, and 63%, respectively (P < .001). The corresponding probabilities for event-free survival were 86%, 80%, and 63% (P < .001). Overall and event-free survival did not differ between HLA-matched related and HLA-matched unrelated donor transplantation (89% vs 87% and 86% vs 82%, respectively). Corresponding probabilities after mismatched related and mismatched unrelated donor transplantation were 73% vs 83% and 70% vs 78%. In conclusion, if transplantation is considered as a treatment option it should be offered early (age ≤6 years). An HLA-matched unrelated donor is a suitable alternative if an HLA-matched relative is not available.
Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Tissue Donors , beta-Thalassemia/therapy , Adolescent , Adult , Age Factors , Child , Child, Preschool , Hematopoietic Stem Cell Transplantation/mortality , Histocompatibility , Humans , Myeloablative Agonists/therapeutic use , Surveys and Questionnaires , Survival Analysis , Transplantation Conditioning/methods , Transplantation, Homologous , Unrelated Donors , Young Adult , beta-Thalassemia/mortalitySubject(s)
Anemia, Sickle Cell/complications , Heart Failure/etiology , Hypertension, Pulmonary/etiology , Renal Insufficiency, Chronic/etiology , Risk Assessment/methods , Severity of Illness Index , Tricuspid Valve Insufficiency/etiology , Adult , Anemia, Sickle Cell/mortality , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Risk , Sickle Cell Trait/complications , Sickle Cell Trait/mortality , Young Adult , beta-Thalassemia/complications , beta-Thalassemia/mortalityABSTRACT
OBJECTIVE: At present, cholecystectomy is carried out for thalassaemia patients with gall stone disease only if they develop symptoms of cholecystitis, except in the rare instance where an un-inflammed gall bladder is removed simultaneously with splenectomy. We carried out this retrospective analysis of case records to examine if patients with thalassaemia have a higher rate of peri operative complications compared to non-thalassaemics with gall stone disease, warranting a change of policy to justify elective cholecystectomy. RESULTS: Case records of 540 patients with thalassaemia were retrospectively analysed of which 98 were found to have gallstones. Records of 62 patients without thalassaemia with gall stone disease too were used for comparison. 19 of patients with thalassaemia and 52 of non-thalassaemic who had gallstones had undergone cholecystectomy. In all but 5 patients with thalassaemia cholecystectomy was done following attacks of acute cholecystitis as was the case in the non-thalassaemic controls. A significantly higher proportion of early and late complications had occurred in thalassaemia patients compared to non-thalassaemic patients post operatively. Six deaths related to sepsis following acute cholecystitis in the peri operative period were reported among 19 thalassaemia patients whereas no deaths were reported among 55 non-thalassaemic patients who underwent cholecystectomy for gallstones.
Subject(s)
Cholecystectomy, Laparoscopic/statistics & numerical data , Cholecystitis, Acute/surgery , Elective Surgical Procedures/statistics & numerical data , Splenectomy/statistics & numerical data , beta-Thalassemia/surgery , Adolescent , Adult , Aged , Case-Control Studies , Child , Child, Preschool , Cholecystectomy, Laparoscopic/methods , Cholecystectomy, Laparoscopic/mortality , Cholecystitis, Acute/complications , Cholecystitis, Acute/mortality , Cholecystitis, Acute/pathology , Elective Surgical Procedures/methods , Elective Surgical Procedures/mortality , Female , Gallbladder/pathology , Gallbladder/surgery , Gallstones/pathology , Gallstones/surgery , Humans , Infant , Male , Middle Aged , Retrospective Studies , Spleen/pathology , Spleen/surgery , Splenectomy/mortality , Survival Analysis , Time Factors , beta-Thalassemia/complications , beta-Thalassemia/mortality , beta-Thalassemia/pathologyABSTRACT
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only available curative treatment for patients with ß-thalassemia major (ß-TM). However, the problem of finding a suitable sibling donor with well-matched human leukocyte antigens is still a major obstacle to curing these patients. With the progress in high-resolution HLA typing technology and supportive care, outcomes after allogeneic HSCT from an HLA well-matched unrelated donor (UD) now approach those of well-matched sibling donors. However, UD HSCT is hampered by an increased risk of graft-versus-host disease and transplant-related mortality. Here we report the outcome of transplantation in patients with ß-TM using a novel WZ-14-TM transplant protocol, based on cyclophosphamide, intravenous busulfan, fludarabine, and antithymocyte globulin, in our center. Forty-eight patients between 2 and 11 years of age with ß-TM received HLA well-matched UD peripheral blood stem cell transplantation following the WZ-14-TM protocol. All of the transplanted patients achieved donor engraftment. The incidences of grade II to IV acute and chronic graft-versus-host disease were 8.3% and 8.3%, respectively. The overall survival and thalassemia-free survival rates were both 100%. This encouraging result suggests that the WZ-14-TM protocol is a feasible and safe conditioning regime for patients with ß-TM undergoing UD HSCT.
Subject(s)
Graft vs Host Disease/mortality , Graft vs Host Disease/prevention & control , Transplantation Conditioning , Unrelated Donors , beta-Thalassemia/mortality , beta-Thalassemia/therapy , Acute Disease , Adult , Allografts , Antilymphocyte Serum/administration & dosage , Busulfan/administration & dosage , Child , Child, Preschool , Chronic Disease , Cyclophosphamide/administration & dosage , Disease-Free Survival , Female , Humans , Infant , Male , Middle Aged , Peripheral Blood Stem Cell Transplantation , Risk Factors , Survival Rate , Vidarabine/administration & dosage , Vidarabine/analogs & derivativesABSTRACT
Thalassemia is a major public health problem in developing countries. Sibling matched hematopoietic stem cell transplantation (HCT) is the recommended treatment for thalassemia major (TM). We retrospectively analyzed our data of thalassemia major patients who underwent HCT at a tertiary care center in Northern India from January 2008 to September 2017. The primary end points were overall survival (OS) and thalassemia-free survival (TFS), and secondary end points were complications post HCT (graft-versus-host-disease [GVHD], hemorrhagic cystitis [HC], and sinusoidal obstruction syndrome [SOS]). Data of 203 transplants for 200 patients (3 s transplants) were evaluated. Median follow-up period was 29.1 months (range, 0.3 to 116.7 mo). The overall survival (OS) was 88.5% and TFS was 82%. Class risk analysis showed a significantly higher OS and TFS in class I and class II compared to class III high risk group (OS: P=0.0017; TFS: P=0.0005) and (OS: P=0.0134; TFS: P=0.0027) respectively. Acute and chronic GVHD was seen in 59 (29.5%) and 18 (9%) patients, respectively, and SOS and HC were seen in 23 (11.5%) and 11 (5.5%) patients, respectively. This study reconfirms that allogenic HCT is feasible in developing world with the overall survival and TFS comparable to that reported in Western literature and should be considered early in all TM patients with available matched sibling donors.
Subject(s)
Hematopoietic Stem Cell Transplantation/methods , beta-Thalassemia/therapy , Adult , Female , Follow-Up Studies , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Hemorrhage/etiology , Hepatic Veno-Occlusive Disease/etiology , Humans , India , Male , Middle Aged , Retrospective Studies , Siblings , Survival Analysis , Transplantation, Homologous/adverse effects , Transplantation, Homologous/methods , beta-Thalassemia/complications , beta-Thalassemia/mortalityABSTRACT
OBJECTIVES: Beta-thalassemias are a group of recessively autosomal inherited disorders of hemoglobin synthesis, which, due to mutations of the beta-globin gene, lead to various degrees of defective beta-chain production, an imbalance in alpha/beta-globin chain synthesis, ineffective erythropoiesis, and anemia. Improved survival in thalassemic patients has led to the emergence of previously unrecognized complications, such as renal disease. METHODS: A comprehensive literature review through PubMed was undertaken to summarize the published evidence on the epidemiology and pathophysiology of renal disease in thalassemia. Literature sources published in English since 1990 were searched, using the terms beta-thalassemia, renal disease. RESULTS: Renal disease is considered to be the 4th cause of morbidity among patients with transfusion dependent thalassemia. Chronic anemia, hypoxia and iron overload are the main mechanisms implicated in development of renal injury, whereas several studies also suggested a contributive role of iron chelators. DISCUSSION AND CONCLUSION: Kidney disease may develop through progressive renal tubular and glomerular damage; thus, its early recognition is important in order to prevent and/or reverse deterioration. This review will provide an insight on the involved mechanisms implicated in kidney disease in thalassemic patients and will discuss the updates on diagnosis and prevention of renal complications in thalassemia.
Subject(s)
Hypoxia , Iron Overload , Kidney Diseases , beta-Thalassemia , Female , Humans , Hypoxia/complications , Hypoxia/metabolism , Hypoxia/mortality , Hypoxia/therapy , Iron Overload/complications , Iron Overload/metabolism , Iron Overload/mortality , Iron Overload/therapy , Kidney Diseases/etiology , Kidney Diseases/metabolism , Kidney Diseases/mortality , Kidney Diseases/therapy , Male , beta-Thalassemia/complications , beta-Thalassemia/metabolism , beta-Thalassemia/mortality , beta-Thalassemia/therapyABSTRACT
Seventy-five percent of patients with beta thalassemia (ß-thalassemia) do not have human leukocyte antigen-matched siblings and until recently had no access to a curative treatment. Gene therapy is a promising treatment that can be proposed to these patients. This study estimates its cost and efficacy. In a monocentric retrospective study and cost-efficacy analysis, this study compared the two-year outcomes and costs of patients with ß-thalassemia treated by gene therapy and hematopoietic stem-cell transplantation (HSCT). Grade III and grade IV complications, hospitalizations, and length of stay were extracted from the hospital discharge data. Costs were estimated from hospital accounting information and national cost studies. A total of seven patients with ß-thalassemia treated between 2009 and 2016 were included, of whom four received gene therapy. Patients treated by gene therapy were older and had fewer complications and hospital admissions. Infectious complications were three times more frequent for patients treated with HSCT than for gene therapy. Average costs were 608,086 for patients treated by gene therapy and 215,571 for HSCT. The total cost of the vector was 48% of the total cost of gene therapy. Gene therapy as a curative alternative for patients lacking human leukocyte antigen-matched donors was costlier but resulted in fewer complications than HSCT.
Subject(s)
Genetic Therapy , Hematopoietic Stem Cell Transplantation , beta-Thalassemia/genetics , beta-Thalassemia/therapy , Adolescent , Child , Child, Preschool , Clinical Trials as Topic , Cost-Benefit Analysis , Genetic Therapy/economics , Genetic Therapy/methods , Genetic Vectors , Graft vs Host Disease/diagnosis , Graft vs Host Disease/etiology , Health Care Costs , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/economics , Hematopoietic Stem Cell Transplantation/methods , Humans , Infant , Prognosis , Retrospective Studies , Tissue Donors , Transplantation, Homologous , Treatment Outcome , beta-Thalassemia/diagnosis , beta-Thalassemia/mortalityABSTRACT
Beta-thalassemia (ß-thalassemia) is a frequently inherited monogenic disorder worldwide with severe physical and mental health comorbidities. The aim of this study is to evaluate the burden of psychiatric disorders in adult patients hospitalized with ß-thalassemia in the United States (US). We utilized the discharge data from the National Inpatient Sample (NIS) from 2010 through 2014 to identify hospitalized ß-thalassemia patients who are 18 years and older. We assessed categorical and continuous variables using chi-square test and Student's t test respectively. The burden of psychiatric disorders was assessed using descriptive statistics and represented in terms of frequency (n) and percentage (%). A p value threshold of < 0.05 was considered clinically significant. All statistical analyses were performed using SPSS version 22.0 (IBM Corp., Armonk, NY, USA). Of the 10,046 ß-thalassemia patients studied, 24.4% (n = 2448) reported psychiatric disorders. Mood disorders (15.2%; inclusive of 10.3% depression), followed by anxiety (9.4%), and substance abuse disorder (6.5%; 4.3% drug abuse, 2.2% alcohol abuse) were most prevalent. Comorbid mental illnesses increased the length of stay by 44.6% and total costs by 23.4%. All-cause mortality rate was reported at 1.9% in overall ß-thalassemia patients. This study highlights higher rates of psychiatric disorders such as depression and anxiety and correlated increases in length of stay and cost in hospitalized ß-thalassemia patients. To improve medical outcomes and curtail unnecessary health-care costs, implementation of an integrated care model can be considered.