M.H. van Weel-Sipman

Final height and hormonal function after bone marrow transplantation in children.

AIM To analyze final height and hormonal function in long-term survivors of bone marrow transplantation (BMT). PATIENTS Group 1 consisted of 16 patients (10 boys) with a hematologic malignancy, mostly leukemia, conditioned for BMT with total body irradiation (TBI), 7.5 to 12 Gy, and cyclophosphamide. Group 2 consisted of 14 patients (9 boys) with severe aplastic anemia, conditioned with chemotherapy only. RESULTS In group 1, patients achieved a reduced final height after BMT. The difference between the height standard deviation score (SDS) at BMT and the height SDS at final height was -1.96 (0.82) SDS in boys and -0.92 (0.71) SDS in girls (p = 0.0001, and p = 0.02 respectively). Final height was also lower than target height (boys, p = 0.01; girls, p = 0.03). Prepubertal growth in the first 3 years after BMT was normal but pubertal height gain was decreased. The patients in group 2 achieved normal height. Thyroid function and adrenal function were normal in all patients, and no growth hormone deficiency was detected. Serum follicle-stimulating hormone values after BMT were increased in all group 1 patients, with return to normal in two patients. Serum luteinizing hormone values were increased in all group 1 girls, with recovery in one girl. Normal serum luteinizing hormone values and spontaneous puberty were found in all group 1 boys. In group 2, disturbances in gonadotropins were seen only in three boys and two girls. CONCLUSION In patients treated in childhood with BMT after chemotherapy and TBI with 7.5 Gy or more, final height is compromised because of blunted growth in puberty. Patients who had not received TBI suffered no height loss. In the majority of patients, the combination of chemotherapy and TBI also resulted in irreversible disturbances of gonadal function.

Pubertal development and growth after total-body irradiation and bone marrow transplantation for haematological malignancies

Abstract Pubertal development after total-body irradiation (TBI) was investigated in 40 children (21 boys) treated with allogeneic bone marrow transplantation (BMT) for haematological malignancies at a mean age of 11.3 years. The mean age at the last visit was 19.0 years. Twenty-five patients (15 boys) were prepubertal at BMT. Data on secondary sexual characteristics, the pituitary-gonadal axis and longitudinal growth were retrospectively collected from the medical records. In boys not receiving additional testicular irradiation (n = 19), penile growth and pubic hair development was normal and all had serum testosterone levels within the adult range. The majority of them, however, had incidental elevations of LH, suggesting minor Leydig cell damage. Testicular volume at last measurement was small (mean: 10.5 ml) and serum FSH levels were elevated in all boys, with normalisation in only one, suggesting severe impairment of reproductive gonadal function. Of the ten girls who received BMT before puberty, six had a spontaneous onset of puberty and menarche; the four other girls needed hormonal substitution therapy. Recovery of gonadal function after cessation of substitution was seen in one girl, who became pregnant but had a spontaneous abortion. Decrease in height SDS was seen in the majority of patients and was positively correlated with male gender and lower age at the time of BMT. Conclusion Careful monitoring of both gonadal function and growth after bone marrow transplantation and total body irradiation is warranted in order to detect disturbances early and ensure normal pubertal development in children treated for haematological malignancies.

Unrelated donor bone marrow transplantation in Fanconi anaemia: the Leiden experience

Fanconi anaemia (FA) is an accepted indication for treatment with allogeneic HLA-identical BMT. Most patients, however, lack a suitable HLA-identical donor. In our centre, six FA patients were transplanted with a matched unrelated donor. Due to hypersensitivity to DNA cross-linking agents, a low-dose cyclophosphamide (CY) and thoraco-abdominal irradiation (TAI) regimen is recommended for conditioning in FA. We added Ara-C upfront and anti-T cell antibodies to enhance engraftment and to prevent GVHD, in combination with T cell depletion in four out of six of the first transplants. One patient did not engraft. In three patients rejection was observed. In three of these four patients a second BMT, using full bone marrow grafts, resulted in successful engraftment. The other patient died before a second BMT could be performed. The incidence and severity of acute GVHD was low: only one patient with grade III acute GVHD was seen. Two out of four surviving patients suffered from chronic GVHD. Four patients survived (median survival time 43 months after BMT), three with good and one with acceptable quality of life. Two patients died, one patient due to adenoviral reactivation with multi-organ failure, and one due to sepsis complicated by ARDS. In conclusion, MUD BMT is feasible in FA patients with bone marrow failure in whom no HLA-identical sibling donor is available. In our study group, the major problem was graft rejection, despite the administration of a combination of graft enhancing anti-T cell antibodies. Multicentre studies are needed to determine a more intensive, but still tolerable, conditioning regimen.

A female patient with “Aase syndrome”

Summary A girl with congenital hypoplastic anemia and triphalangeal thumbs (Aase syndrome) is described. This is the second report of these features in a female patient, making autosomal recessive inheritance a probable explanation.

Late effects of total body irradiation and cytostatic preparative regimen for bone marrow transplantation in children with hematological malignancies

Twenty-seven children, surviving disease-free for more than 1 year after allogeneic bone marrow transplantation (BMT) for hematological malignancy were evaluated for the long-term effects on endocrine function, sexual development, physical growth, appearance of ocular cataract and psychological sequelae. The growth rate was not decelerated in the prepubertal period in children not affected by chronic graft-versus-host (GVH) disease and without previous cranial irradiation. Development of sexual characteristics was delayed in 4 relevant cases. Thyroid function was not adversely affected, gonadal function was impaired in girls, transplanted after menarche, ocular cataract developed in all cases, irradiated without shielding of the eyes after 4 years. Psychologically, children after BMT had an advantageous social development.

Colony Forming Units in Culture in Childhood Aplastic Anemia

The results of the determination of the numbers of colony forming units in culture of the bone marrow of 17 children with aplastic anaemia before and after bone marrow transplantation, of 4 children treated with antilymphocyte globulin and of 16 children treated conventionally are presented.

Effective D-penicillamine treatment of an early diagnosed patient with Wilson's disease.

Sir, Early detection and diagnosis of patients with Wilsons disease [1] is of utmost importance. Beneficial results of treatment of the disease with D-penicillamine have been repeatedly described [2] but reports of long-term results in young children treated before any symptoms were present, are rare. We report here the encouraging results of 15 years of prophylactic treatment of a patient with Wilsons disease diagnosed before any clinical signs were present. A one year old boy was brought for examination. Two brothers had died, one from unclassified liver cirrhosis at the age of 81//2 years and the second at the age of 13 years from chemically and histologically proven Wilsons disease. Though there were still no physical or neurological abnormalities in this boy, we decided to investigate him also.

An infant with severe combined immunodeficiency syndrome, an α-thalassemia trait and renal Fanconi syndrome

We describe an infant with severe combined immunodeficiency syndrome and an α-thalassemia trait who developed a renal Fanconi syndrome after his first stem cell transplantation. This syndrome consists of a generalized failure of proximal tubular reabsorption, which leads to a large number of metabolic disturbances. The etiology varies from inherited causes, including an idiopathic form, to acquired causes such as intoxications, immunological disorders and hemoglobinopathies. In this case report we discuss possible explanations of the Fanconi syndrome in our patient. Bone Marrow Transplantation (2000) 26, 97–99.We describe an infant with severe combined immunodeficiency syndrome and an α-thalassemia trait who developed a renal Fanconi syndrome after his first stem cell transplantation. This syndrome consists of a generalized failure of proximal tubular reabsorption, which leads to a large number of metabolic disturbances. The etiology varies from inherited causes, including an idiopathic form, to acquired causes such as intoxications, immunological disorders and hemoglobinopathies. In this case report we discuss possible explanations of the Fanconi syndrome in our patient. Bone Marrow Transplantation (2000) 26, 97–99.