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Background: Late-onset noninfectious pulmonary complications (LONIPCs) are life-threatening complications of bone marrow transplantation (BMT). Several pathological patterns are described in the literature with different prognoses, and with different relationships to graft-versus-host disease (GVHD). The role of high-resolution CT (HRCT) is not yet well established., Objective: To illustrate different patterns of LONIPCs on HRCT in allogeneic versus autologous BMT in order to investigate the correlation with chronic GVHD (cGVHD)., Materials and Methods: A total of 67 HRCT scans were performed in 24 patients with noninfectious pulmonary disease at least 3 months after BMT (16 allogeneic, 8 autologous). Abnormality patterns and extension on HRCT images were correlated with the clinical outcome and with the severity of cGVHD., Results: Of 24 patients, 9 showed LONIPCs (1 autologous, 8 allogeneic). There was a significant association between abnormalities on HRCT and severe cGVHD (P = 0.038), with no specific pattern. Prognosis seemed to be related to the severity of cGVHD and not to the extent of abnormalities on HRCT., Conclusion: The significant association between abnormalities on HRCT and severe GVHD suggests that LONIPCs can be a pulmonary manifestation of the disease. HRCT is a useful tool when combined with clinical data.

Two hereditary human leukemia syndromes are severe congenital neutropenia (SCN), caused by mutations in the gene ELA2, encoding the protease neutrophil elastase, and familial platelet disorder with acute myelogenous leukemia (AML), caused by mutations in the gene AML1, encoding the transcription factor core-binding factor alpha (CBFalpha). In mice, CBFalpha regulates the expression of ELA2, suggesting a common link for both diseases. However, gene-targeted mouse models have failed to reproduce either human disease, thus prohibiting further in vivo studies in mice. Here we investigate CBFalpha regulation of the human ELA2 promoter, taking advantage of bone marrow obtained from patients with either illness. In particular, we have identified novel ELA2 promoter substitutions (-199 C to A) within a potential motif for lymphoid enhancer factor-1 (LEF-1), a transcriptional mediator of Wnt/beta-catenin signaling, in SCN patients. The LEF-1 motif lies adjacent to a potential CBFalpha binding site that is in a different position in human compared with mouse ELA2. We find that LEF-1 and CBFalpha co-activate ELA2 expression. In vitro, the high mobility group domain of LEF-1 interacts with the runt DNA binding and proline-, serine-, threonine-rich activation domains of CBFalpha. ELA2 transcript levels are up-regulated in bone marrow of an SCN patient with the -199 C to A substitution. Conversely, a mutation of the CBFalpha activation domain, found in a patient with familial platelet disorder with AML, fails to stimulate the ELA2 promoter in vitro, and bone marrow correspondingly demonstrates reduced ELA2 transcript. Observations in these complementary patients indicate that LEF-1 cooperates with CBFalpha to activate ELA2 in vivo and also suggest the possibility that up-regulating promoter mutations can contribute to SCN. Two hereditary AML predisposition syndromes may therefore intersect via LEF-1, potentially linking them to more generalized cancer mechanisms.

Purpura fulminans is a thrombotic disease that can occur during infections, disseminated intravascular coagulation or in the context of an acquired or congenital protein C or S deficiency. Here we report the case of a 4-year-old child who developed, 5 days after a chickenpox infection, large painful ecchymotic, necrotizing and retiform plaques on the lower extremities. Laboratory analyses revealed very low protein S levels as well as anticardiolipin antibodies. Aggressive treatment by low-molecular-weight heparin, steroids, intravenous immunoglobulins and fresh frozen plasma was able to prevent the extension of the lesions and to correct the coagulation abnormalities. No lesions required skin grafting. As in our patient, an acquired protein S deficiency is probably responsible for most cases of purpura fulminans occurring after varicella, but the concomitant presence of antiphospholipid antibodies may also play a role., (Copyright 2004 S. Karger AG, Basel)

The anaplastic large cell lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is a rare type of non-Hodgkin lymphoma which occurs in children mostly. The ALK protein is highly immunogenic and elicits both humoral and cellular immune responses. A 15-yr-old child presented with fever and adenopathy and did not respond to antibiotics. Biopsy of the enlarged lymph node contained almost no lymphoid element except for a few CD8-positive T cells, plasma cells and isolated CD30-positive blasts. The patient's condition improved following lymphadenectomy but relapse occurred 3 months later with multiple nodes, high fever and an abdominal mass. This time an ALK-positive ALCL was diagnosed and the retrospective analysis of the initial biopsy revealed rare, isolated ALK+ cells. Molecular analysis showed T-cell clones and oligoclonal B cells in both biopsies and peripheral blood of the patient. The tumour cells harbour a t(2;5) translocation, revealing a null phenotype by immunohistochemistry and no evidence for T-cell clonality by Southern blotting. The patient's serum contained anti-ALK antibodies. Our findings suggest that the T-cell clones and anti-ALK antibodies in this patient constitute an anti-tumour response that caused the hypocellularity of the initial lymph node. Hypocellular and oedematous lymph nodes occurring in a child with evocative symptoms should be tested for the presence of ALK.