Long-Term Effects of Haematopoietic Stem Cell Transplantation after Pediatric Cancer: A Qualitative Analysis of Life Experiences and Adaptation Strategies

Haematopoietic stem cell transplantation (HSCT) improves the survival rate of children and adolescents with malignant and non-malignant conditions; however, the physical, psychological and social burden of such a procedure is considerable both during and after treatment. The present qualitative study investigated the long-term effects of HSCT after pediatric cancer. Thirty adolescent and young adult (AYA) survivors (Mage = 23.61 years, SD = 5.21) participated in individual interviews and were invited to speak about their life experiences following their treatment and strategies they use to deal with their past medical experiences and the long-term sequelae. Our results showed the presence of ongoing physical and psychosocial consequences of their past illness and its treatments with wide ranging psychosocial impacts, such as affected self-image, social withdrawal, sense of lack of choice, and need for specific attention. Different strategies were reported to overcome these consequences, such as talking about illness, giving a sense to their past medical experiences, and developing meaningful social relationships. Clinical and research implications are also discussed

Low Penetrance, Broad Resistance, and Favorable Outcome of Interleukin 12 Receptor β1 Deficiency: Medical and Immunological Implications

The clinical phenotype of interleukin 12 receptor β1 chain (IL-12Rβ1) deficiency and the function of human IL-12 in host defense remain largely unknown, due to the small number of patients reported. We now report 41 patients with complete IL-12Rβ1 deficiency from 17 countries. The only opportunistic infections observed, in 34 patients, were of childhood onset and caused by weakly virulent Salmonella or Mycobacteria (Bacille Calmette-Guérin -BCG- and environmental Mycobacteria). Three patients had clinical tuberculosis, one of whom also had salmonellosis. Unlike salmonellosis, mycobacterial infections did not recur. BCG inoculation and BCG disease were both effective against subsequent environmental mycobacteriosis, but not against salmonellosis. Excluding the probands, seven of the 12 affected siblings have remained free of case-definition opportunistic infection. Finally, only five deaths occurred in childhood, and the remaining 36 patients are alive and well. Thus, a diagnosis of IL-12Rβ1 deficiency should be considered in children with opportunistic mycobacteriosis or salmonellosis; healthy siblings of probands and selected cases of tuberculosis should also be investigated. The overall prognosis is good due to broad resistance to infection and the low penetrance and favorable outcome of infections. Unexpectedly, human IL-12 is redundant in protective immunity against most microorganisms other than Mycobacteria and Salmonella. Moreover, IL-12 is redundant for primary immunity to Mycobacteria and Salmonella in many individuals and for secondary immunity to Mycobacteria but not to Salmonella in most

Sickle cell anaemia and bone marrow transplantation

Sickle cell anaemia is an hereditary autosomal recessive disorder characterized by chronic haemolytic anaemia, painful episodes due to the occlusion of small vessels and an increased susceptibility to severe, often fatal infections. It is a disease commonly seen in equatorial Africa, particularly in the west, where 40 to 50% of the members of certain ethnic groups are carriers of the sickle cell gene. The gene is not restricted to blacks however, as it appears in parts of Turkey, Saudi Arabia, southern India, Sicily, Cyprus and Greece. Thirty years ago, most internists would have been surprised when they encountered an adult with sickle cell anaemia. At the present time, early diagnosis and comprehensive supportive care result in a better survival, although morbidity from vaso-occlusive crises and mortality from progressive organ failure persist especially for people living in third world countries.The aim of this work is to summarise the clinical problems encountered by these patients, to try to delineate factors influencing the natural course of the disease, to study the therapeutical options availed, and mainly to examine the value of bone marrow transplantation in this conditionThèse d'agrégation de l'enseignement supérieur -- UCL, 199

Sickle cell anaemia: current therapies

Tremendous progress has been made in the treatment of patients with sickle cell anaemia. This paper emphasises the benefit of early therapy with hydroxyurea, the indication for blood transfusions including iron chelation and the role of hematopoietic stem cell transplantation. In order to offer transplantation to a larger number of patients including adolescents and young adults, it is important to find less toxic, but still effective conditioning therapy and to evaluate the feasability of using alternative donors

Hematopoietic stem cell transplantation in sickle cell disease.

Since the first report of a young girl affected by sickle cell anemia, treated successfully by bone marrow transplantation (BMT) for acute myeloid leukemia, more than 200 patients have been transplanted worldwide for sickle cell anemia. The disease-free survival (DFS) is good (80-85% in several series), even though many children who received allografts had already significant sickle-related complications. The best results are obtained in young children who have HLA-identical sibling donors and are transplanted early in the course of the disease (DFS: 93%). Future directions in the field of stem cell transplantation of sickle cell anemia include (1) the establishment of new protocols with less toxicity, but still effective, (2) adapted conditioning regimen for adult patients, and (3) new sources of stem cells for broader application: umbilical cord blood and volunteer unrelated donors

What is new in iron overload?

Children with severe chronic hemolytic anemia or congenital erythroblastopenia are transfusion dependent. Long-term transfusion therapy prolongs life but results in a toxic accumulation of iron in the organs. The human body cannot actively eliminate excess iron. Therefore, the use of a chelating agent is required to promote excretion of iron. So far, iron chelation has been done by subcutaneous infusion of deferoxamine given over 10 h, 5-6 days per week. Compliance is poor and chelation often insufficient. Ferritin measurements and sometimes liver biopsies are used to evaluate the iron burden in the body. At the present time, new iron chelators that can be given orally are available. Furthermore, magnetic resonance imaging (MRI) assessment of tissue iron is a noninvasive and highly reproducible method, which is able to quantitate organ iron burden. In conclusion, iron overload can be measured more accurately with noninvasive methods such as MRI. Deferasirox is a once-daily oral therapy for treating transfusional iron overload, which improves patient compliance and quality of life

Hematopoietic stem cell transplantation for sickle cell anemia

Hematopoietic stem cell transplantation is the only therapy able to cure sickle cell anemia at the present time. So far, transplantations have been undertaken in approximatively 140 sickle cell patients all over the world, with good results. The selection of patients for transplantation remains a subject of dilemma because of the unpredictable course of the disease and the lack of valuable prognostic markers. The selection criteria accepted so far concern young patients under the age of 16, with a morbid course of the disease and having a HLA-compatible sibling. In Belgium, patients going back to their country of origin were also considered for transplantation. For 100 patients who underwent transplantation in Europe, the current Kaplan-Meier estimates of overall survival, event-free survival, and disease-free survival rates are 90%, 79%, and 81%, respectively. Benefits and side effects are analyzed

Bone marrow transplantation in sickle cell anaemia.

Sickle cell anaemia is a hereditary disorder commonly seen in the black population, due to a point mutation in the beta globin gene. The sickle mutation is responsible for an increased rigidity and adherence of the red blood cell leading to haemolytic anaemia and vaso-occlusive episodes. Symptoms include dactylitis, painful crisis, splenic sequestration and the development of multi-organ damage and failure. The progressive loss of splenic function increases the risk of infections. The morbidity and mortality can be reduced by the maintenance of an adequate nutrition, the prevention of infection and the treatment of complications. In some patients severely affected, a chronic transfusion program has to be instigated to maintain a level of haemoglobin S below 50%. New therapeutic strategies include the use of hydroxyurea and maybe, in the future, butyrates to increase the level of foetal haemoglobin. Further studies are needed to evaluate the benefits of such therapies. Bone marrow transplantation represents an attractive therapeutic tool and its role in other haemoglobinopathies like thalassaemia is now well demonstrated. As far as sickle anaemia is concerned, the first report concerned a child with acute myeloblastic leukaemia. The patient is now cured of both the sickle cell anaemia and the leukemia. Since April 1986, 21 patients underwent an allogeneic bone marrow transplantation for sickle cell anaemia in our department. 20 patients became asymptomatic and have an electrophoretic pattern of the haemoglobin similar to that of the donor. One patient died of bone marrow transplantation related complications