Successful treatment of juvenile myelomonocytic leukemia relapsing after stem cell transplantation using donor lymphocyte infusion.

Juvenile myelomonocytic leukemia (JMML) is a rare pediatric malignancy. Hematopoietic stem cell transplantation (SCT) is the only curative approach. However, relapse after SCT remains the major cause of treatment failure.

Role of chest computed tomography at diagnosis in the management of Wilms' tumor: a study by the United Kingdom Children's Cancer Study Group.

Purpose: This study sought to determine whether the identification of minimal pulmonary metastatic disease by chest computed tomography (CT) performed at diagnosis in patients with Wilms' tumor and normal chest x-rays (CXR) could predict a subgroup of children at increased risk of pulmonary relapse.

Patients And Methods: A retrospective analysis was carried out of the records of 449 children entered onto the United Kingdom Childrens' Cancer Study Group Second Wilms' Tumor Study between July 1986 and September 1991. The imaging protocol did not stipulate chest CT at diagnosis, but 141 children who had normal frontal and lateral CXRs and a chest CT scan performed at diagnosis were eligible for analysis.

Respiratory infections following haemopoietic stem cell transplantation in children.

Disorders of the respiratory system are well recognised following the administration of chemotherapy schedules; although respiratory complications may occur following less intensive regimens, they are most frequently seen following the administration of high dose chemotherapy with or without radiotherapy which is used in preparation for haemopoietic stem cell transplantation (SCT). In this setting, respiratory complications may occur in up to 50% of patients and account for over 40% of all deaths; those patients who require admission to intensive care (ICU) requiring intubation and mechanical ventilation have a particularly poor prognosis, with less than 10% becoming long-term survivors.

The pore of the leaf cavity of Azolla species: teat cell differentiation and cell wall projections.

The differentiation of the specialized secretory teat cells of the leaf cavity pore of Azolla species was investigated at the ultrastructural level with emphasis on their peculiar cell wall projections. The results indicated that the projections are formed as soon as the teat cells complete their differentiation and that their production is principally associated with changes in endoplasmic reticulum profiles. The number of projections increases with the teat cell age and is stimulated under salt and P deficiency stresses.

Outcome for children after failed transplant for primary haemophagocytic lymphohistiocytosis.

Primary haemophagocytic lymphohistiocytosis is a rare disorder of childhood, which is usually fatal without allogeneic stem cell transplantation (SCT). For children who lack a matched family or closely matched unrelated donor, SCT using haploidentical parental stem cells has been used, but is associated with an increased risk of graft failure. The most appropriate subsequent management for those children who survive after graft rejection is currently unclear.

Non-myeloablative stem cell transplantation for congenital immunodeficiencies.

Allogeneic haematopoietic stem cell transplantation (HSCT) can be a highly successful treatment option for individuals with congenital immunodeficiency states. The strategy for HSCT is varied but in cases where there is preservation of residual T cell function, conditioning regimes have been used and have been based around a combination of busulphan and cyclophosphamide with or without serotherapy. In patients with coexisting organ damage this has resulted in significant morbidity and mortality.

Unexpected and variable phenotypes in a family with JAK3 deficiency.

Mutations of the Janus kinase 3 (JAK3) have been previously described to cause an autosomal recessive variant of severe combined immunodeficiency (SCID) usually characterized by the near absence of T and NK cells, but preserved numbers of B lymphocytes (T-B+SCID). We now report a family whose JAK3 mutations are associated with the persistence of circulating T cells, resulting in previously undescribed clinical presentations, ranging from a nearly unaffected 18-year-old subject to an 8-year-old sibling with a severe lymphoproliferative disorder. Both siblings were found to be compound heterozygotes for the same deleterious JAK3 mutations: an A96G initiation start site mutation, resulting in a dysfunctional, truncated protein product and a G2775(+3)C mutation in the splice donor site sequence of intron 18, resulting in a splicing defect and a predicted premature stop.

Fatal graft-versus-host disease following HLA-mismatched donor lymphocyte infusion.

We report the case of a 10-year-old boy with molecular relapse of CML following unrelated donor BMT who developed fatal grade 4 acute GVHD of the gut and liver following one antigen-mismatched donor lymphocyte infusion. Previous experience of donor lymphocyte infusion in the HLA-mismatched setting is reviewed and the role of adoptive immunotherapy in this situation is discussed.

Improved outcome of alternative donor bone marrow transplantation in children with severe aplastic anaemia using a conditioning regimen containing low-dose total body irradiation, cyclophosphamide and Campath.

The increasing success of human leucocyte antigen (HLA)-matched sibling donor (MSD) transplants and combination immunosuppressive treatments have dramatically improved the prognosis of severe aplastic anaemia (SAA) in children and young adults. For patients who lack a MSD there is a significant minority who fail immunosuppressive therapy or suffer from a severe constitutional aplastic anaemia in which immunosuppression would be ineffective. Alternative donor bone marrow transplantation (AD-BMT) has only had limited success in this context.

Cyclosporin for atopic dermatitis in children.

This paper details a UK consensus conference held in London in April 2000 to establish guidelines for the use of cyclosporin A for atopic dermatitis in children. It should be reserved for the severest refractory atopic dermatitis. In view of its potential toxicity, careful monitoring is mandatory, in particular blood pressure and renal function.

Analysis of chimaerism in thalassaemic children undergoing stem cell transplantation.

We have prospectively assessed the relative contribution of host and donor to haemopoiesis following stem cell transplantation (SCT) in children with beta-thalassaemia major (n = 35), using karyotype analysis or Southern blot/polymerase chain reaction analysis of variable number tandem repeats on genomic DNA from peripheral blood. Early haemopoiesis was fully donor in origin in 24 out of 35 cases and remained so throughout the post-transplant course in all but one patient, who evolved to stable mixed chimaerism. The remaining 11 cases (31%) initially showed mixed chimaerism: four of these rejected, one eventually eradicated host haemopoiesis to become fully donor haemopoietic, and the remaining six had persistent mixed chimaerism, with 5--38% host haemopoiesis.

Clinical course of patients with major histocompatibility complex class II deficiency.

The clinical course of 10 children who have been diagnosed with major histocompatibility complex (MHC) class II deficiency (bare lymphocyte syndrome) in the UK over the past eight years is described. They have had a generally poor prognosis, with only two of the 10 still alive despite eight attempts at bone marrow transplantation in six patients. Overwhelming viral infection was the predominant cause of death.

Nonmyeloablative stem cell transplantation for congenital immunodeficiencies.

The optimal approach for stem cell transplantation in children with immunodeficiency has yet to be determined. Conditioning therapy is necessary for reliable engraftment and full immune reconstitution; however, the beneficial effect of cytoreductive conditioning is counterbalanced by increased short- and long-term treatment-related toxicity. Whether bone marrow transplantation with a nonmyeloablative preparative regimen was sufficient for the establishment of donor immune reconstitution, with the resultant correction of disease phenotype, was investigated.

Intrinsic defects of B cell function in X-linked severe combined immunodeficiency.

The cytokine receptor common gamma chain mutation in X-linked SCID results in a failure of T and NK cell development and an as yet undefined defect of B cells. Using immunoglobulin isotype-specific reverse transcription-PCR we show that although hematopoietic stem cell transplantation restores a diverse repertoire of class-switched B cell clones, on further analysis these are almost all of donor origin. This suggests that host B cells, which predominate after unconditioned transplantation, are still defective even in the presence of normal T cells.

Itraconazole oral solution as antifungal prophylaxis in children undergoing stem cell transplantation or intensive chemotherapy for haematological disorders.

This was an open study of oral antifungal prophylaxis in 103 neutropenic children aged 0-14 (median 5) years. Most (90%) were undergoing transplantation for haematological conditions (77% allogeneic BMT, 7% autologous BMT, 6% PBSC transplants and 10% chemotherapy alone). They received 5.

Influence of severe combined immunodeficiency phenotype on the outcome of HLA non-identical, T-cell-depleted bone marrow transplantation: a retrospective European survey from the European group for bone marrow transplantation and the european society for immunodeficiency.

We analyzed the outcomes of 214 HLA non-identical T-cell-depleted bone marrow transplantations (BMTs), performed in 178 consecutive patients for treatment of severe combined immunodeficiencies (SCID). Patients were treated in 18 European centers between 1981 and March 1995. SCID variants, that is, absence of T and B lymphocytes (B-) or absence of T cells with presence of B lymphocytes (B+) were found to have a major influence on outcome.

Improved prognosis for acquired aplastic anaemia.

This study compared the prognosis of patients treated for aplastic anaemia at Great Ormond Street Hospital for Children from 1973-88 (group A; n = 38) with a more recent cohort from 1989-96 (group B; n = 37). The two groups were similar in terms of clinical history, age, and severity of aplasia. The main treatment differences included the use of androgen treatment in group A (21 of 38 patients) but not in group B, and the addition of cyclosporin A to immunosuppressive treatment for 14 patients in group B.

Salvage of patients with acute promyelocytic leukaemia with residual disease following ABMT performed in second CR using all-trans retinoic acid.

Detection of residual disease after completion of therapy or following bone marrow transplantation (BMT) in patients with acute promyelocytic leukaemia (APL) predicts relapse and is associated with a poor prognosis. Here we describe the successful treatment of residual disease post-transplant in APL using prolonged all-trans retinoic acid (ATRA) therapy in two children in whom autologous BMT (ABMT) had been performed in second complete remission (CR). ATRA treatment was well tolerated and found to be beneficial despite its prior use as a component of the initial induction protocol.

Long-term immune reconstitution and outcome after HLA-nonidentical T-cell-depleted bone marrow transplantation for severe combined immunodeficiency: a European retrospective study of 116 patients.

We have performed a retrospective analysis of the development of T- and B-cell functions after HLA-nonidentical T-cell-depleted bone marrow transplantation (BMT) performed in 193 patients with severe combined immunodeficiency (SCID) at 18 European centers between December 1982 and December 31, 1993. One hundred sixteen of 193 patients were alive with evidence of engraftment 6 months after BMT. Development of T-cell function occurred earlier than B-cell function and was achieved more frequently up to the time of last follow-up.

Haploidentical related transplants and unrelated donor transplants with T cell addback.

Only 30% of children have a matched family donor (MFD). Alternative donors can be found from volunteer unrelated donor (UD) panels, and almost every child has a haploidentical parental donor (Haplo). The outcome of alternative donor BMT has previously been inferior due to increased graft rejection and GVHD.

Anticardiolipin antibodies and thromboembolism after BMT.

We describe a 4-month-old child who developed unusual thrombotic complications following allogeneic BMT for Omenn syndrome, a form of SCID. Eight weeks after the procedure the child suffered a major cerebrovascular accident and developed acute pulmonary hypertension in association with persistently elevated anticardiolipin antibody titres. It is postulated that central line-derived microemboli caused these serious thrombotic complications in the context of an evolving hypercoaguable state.