Keith Quirolo

Quality of Life in Patients with Thalassemia Intermedia Compared to Thalassemia Major

Abstract: The impact of thalassemia major and thalassemia intermedia and their associated complications on quality of life (QOL) is largely unknown. Determining the degree of health impairment as perceived by the patient is essential information needed to recommend suitable therapy. The objective of this study was to evaluate QOL in transfusion‐independent patients with thalassemia (non‐Tx) compared with that in transfused patients (Tx) and to identify the factors that affect QOL in thalassemia. A convenient sample of 48 thalassemia patients (29 Tx and 19 non‐Tx) with mean age of 14.6 years (SD = 7.5 years) were selected during a comprehensive visit to complete a Dartmouth Primary Care Cooperative Information Chart System (COOP) questionnaire. Patients rated QOL from excellent (1) to poor (5) on five dimensions of health status. Scores of 4 or 5 represent major limitations. These results were augmented by a brief medical history and chart review. Forty‐one percent of Tx patients and 47% of non‐Tx patients reported severe impairments in 1‐6 and 1‐2 domains, respectively. The most commonly reported affected domains were feelings such as anxiety, depression, and concern of overall health status or indications of recent deterioration in health. In contrast with previous beliefs, transfusion‐independent thalassemia patients also suffer serious impairment in QOL. Presented data suggest that all patients with thalassemia undergo QOL assessment so that interventions focused on affected domains can be implemented.

Erythrocytapheresis for chronically transfused children with sickle cell disease: An effective method for maintaining a low hemoglobin S level and reducing iron overload

Cerebrovascular accident (CVA) is a major complication of sickle cell disease during childhood. Long‐term transfusion reduces the hemoglobin S level and generally prevents recurrent stroke, but it also results in progressive iron overload that requires regular chelation therapy. Erythrocytapheresis offers an alternative approach aimed at reducing the iron accumulation. We reviewed the results of erythrocytapheresis in eight sickle cell patients (mean age of 12.1 years) at high risk for a first or recurrent stroke. They were maintained at the standard pre‐transfusion hemoglobin S (Hb S) level of 30%.

Current issues in blood transfusion for sickle cell disease.

PURPOSE OF REVIEW Although blood transfusion has been felt to be a beneficial therapy for sickle cell disease (SCD) since the 1950s, associated complications initially limited this therapy for these patients. With advances now reducing the side effects of transfusion and several landmark studies over the last decade clearly defining the efficacy for decreasing sickle cell morbidity, the indications for transfusion have increased. This review will discuss the indications, methods and goals of transfusion as well as complications and recent changes in transfusion therapy for SCD. RECENT FINDINGS Recently studies have established the efficacy of transfusion for prevention of stroke, treatment of acute chest syndrome and perioperative transfusion management of SCD. Pulmonary hypertension is increasingly recognized as a significant source of morbidity and mortality and is an evolving indication for transfusion therapy. Phenotypically matching transfused blood has been shown to decrease alloimmunization, and genotyping for antigen matching may help match donors to patients in the future. SUMMARY The increased use of transfusions may ultimately be balanced by hydroxyurea and other newer therapies developed as the complex pathophysiology of SCD is better understood; however, red cell transfusion is currently the most studied and accepted therapy for most acute and many chronic complications of SCD. Physicians caring for patients with sickle cell disease should be aware of the unique complications and transfusion requirements in this population.

Use of hydroxyurea in children ages 2 to 5 years with sickle cell disease

The efficacy and side effects of hydroxyurea in young children with sickle cell disease are unknown. The authors followed-up eight young children (mean age 3.7 years) during therapy with hydroxyurea for an average of 137 weeks. Total and fetal hemoglobin levels rose with hydroxyurea therapy. Hospital admission rates and total hospital days decreased during hydroxyurea therapy. No unexpected toxicity occurred, and growth and development were unaffected. This pilot study suggests that hydroxyurea is safe and effective in young children with sickle cell disease.

Changing outcome of homozygous α-thalassemia : Cautious optimism

Only a few long-term survivors of homozygous alpha-thalassemia, a usually fatal condition, have been reported. The authors present a surviving infant with this disorder and discuss the complications, treatments, and implications of this genetic hemoglobinopathy. The child had no antenatal intervention and has been treated with regular transfusions. She has had normal growth and development and is currently 2.5-years-old. A literature review of survivors with Bart hemoglobinopathy reveals an intense perinatal course and a great prevalence of congenital urogenital and limb defects. Advances in antenatal diagnosis, intrauterine intervention, and postnatal treatments have resulted in extended survival of children with congenital defects that until recently were considered invariably fatal. Transfusion and chelation therapy and bone marrow transplantation provide long-term treatment and potential curative options.

Sibling Donor Cord Blood Transplantation for Thalassemia Major: Experience of the Sibling Donor Cord Blood Program

Abstract: The Sibling Donor Cord Blood (SDCB) Program was initiated in 1998 as a resource to collect, characterize, and release cord blood units (CBUs) from families affected by malignant and nonmalignant disorders for transplantation. Families in the United States were recruited by telephone after referrals by community and academic physicians. Collection kits were mailed to prospective participants and family members were instructed about CBU procurement from community hospitals and shipping to a central laboratory. Data about the infants delivery and CBU harvest, CBU processing, prethaw characteristics, sterility, and human leukocyte antigen (HLA) typing were collected. Standard outcome data were collected after CBU release for transplantation. Descriptive analyses of CBU collections, processing, release, and transplantation outcomes were performed. Currently, 1617 CBU collections have been processed from families with thalassemia (6%), sickle cell disease (28%), malignant disorders (49%), and other rare hematological disorders (17%). Thirty‐two of 96 donor‐recipient pairs with thalassemia major were HLA identical and 14 have received cord blood transplantation, either alone or in combination with bone marrow or peripheral blood progenitor cells (N= 4) from the same donor. Eleven of the 14 survive free of thalassemia after transplantation. These preliminary results confirm the feasibility and utility of remote‐site sibling donor cord blood collection and subsequent transplantation for hematological disorders, with a very high rate of usage from a cord blood bank dedicated to performing these unique collections. It was concluded that cord blood transplantation from sibling donors represents a suitable alternative to bone marrow transplantation.

Barriers to adherence of deferoxamine usage in sickle cell disease.

We hypothesized that child cognitive disability would be a significant risk factor for non‐adherence with home deferoxamine (DFO) administration and that a factor that would contribute to improved adherence would be sharing of responsibilities for chelation between parents and patients. We explored the influences on adherence of behavioral and psychological adjustment; family stress; perceived convenience of and satisfaction with the DFO regimen; and parent and patient knowledge about DFO.

Lower alloimmunization rates in pediatric sickle cell patients on chronic erythrocytapheresis compared to chronic simple transfusions.

BACKGROUND: Erythrocytapheresis (ECP), automated red blood cell exchange, is increasingly being used for chronic transfusion therapy in sickle cell disease (SCD) as it is an isovolumetric transfusion, is more effective in lowering hemoglobin (Hb)S, and can limit iron overload. Because ECP requires increased blood exposure compared to simple transfusions there is concern for increased transfusion complications, including alloimmunization. We compared alloimmunization rates between patients receiving simple or exchange chronic transfusions.

Autonomic reactivity and clinical severity in children with sickle cell disease

Individual differences in autonomic nervous system reactivity have been studied in relation to physical and mental health outcomes, but rarely among children with chronic disease. The purpose of this study was to examine the associations among autonomic reactivity, clinical severity, family stressors, and mental health symptoms in children with homozygous sickle cell disease. Nineteen children with homozygous sickle cell disease participated in a cross-sectional study involving parent-completed measures, medical record reviews and laboratory-based measures of autonomic nervous system responses to social, cognitive, physical and emotional challenges. Autonomic reactivity was significantly associated with both clinical severity and externalizing behavior symptoms. Children with greater parasympathetic withdrawal during challenges compared to rest had significantly more severe disease (r=–0.45, p<0.05); greater sympathetic activation during challenges compared to rest was associated with more externalizing behavior symptoms (r=0.44, p<0.05). Children experiencing major family stressors had internalizing behavior symptoms but no difference in autonomic reactivity or clinical severity compared to children experiencing fewer family stressors. Individual differences in autonomic reactivity may offer a new, biologically plausible account for observed variation in painful episodes, other physical complications and behavioral symptoms among children with sickle cell disease.

Outcomes of Preimplantation Genetic Diagnosis Therapy in Treatment of β‐Thalassemia: A Retrospective Analysis

Abstract: Thalassemia is one of the most common single‐gene disorders that can be cured by hematopoietic stem cell transplantation (HCT) from a human leukocyte antigen (HLA)‐identical sibling donor. In families that have an affected child, preimplantation genetic diagnosis (PGD) can be used to select an unaffected, HLA‐identical embryo. In brief, this procedure requires in vitro fertilization, oocyte retrieval, fertilization, and blastomere biopsy for identification of unaffected HLA‐identical embryos. After delivery, umbilical cord blood from the sibling donor is collected for HCT. The objective of this study was to determine the outcomes of families using PGD therapy for cure of β‐thalassemia and to review the limitations of PGD therapy. Families affected with β‐thalassemia who attempted PGD therapy were retrospectively identified and reviewed for indication, attempted cycles, successful pregnancy, and transplantation outcomes. Eight identified families affected by thalassemia underwent PGD. The diagnosis of their affected children included six cases of β‐thalassemia major and two cases of transfusion‐dependent hemoglobin E‐β‐thalassemia patients. A total of 14 cycles of PGD were attempted, ranging from one to four attempts per family. Following successful identification of HLA‐identical cells, two pregnancies occurred, of which one resulted in engraftment of a β‐thalassemia child. PGD therapy offers the possibility of recruiting a suitable donor for HCT, yet is limited by financial cost due to labor‐intensive techniques, low probability of obtaining an HLA‐matched unaffected embryo, variable implantation capacity, and significant emotional impact. Improvements in PGD therapys efficacy and cost will make this a more viable option for affected families.