Minimal residual disease is more common in patients who have mixed T- cell chimerism after bone marrow transplantation for chronic myelogenous leukemia

Determining both lymphoid chimerism and the presence of minimal residual disease after allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML) could be helpful to the understanding of the biology of leukemic relapse in this disease. We prospectively investigated 32 patients with CML post-BMT by assessing T- cell chimerism and minimal residual disease using sensitive polymerase chain reaction (PCR) methodologies. Patients were studied between 1 and 24 months post-BMT. Thirty patients received a T-cell-depleted marrow grafts and 2 received unmanipulated marrow. All but 1 patient were conditioned with total body irradiation (TBI)+thiotepa+cyclophosphamide (Cy). The other patient received TBI+Cy as conditioning. The T cells were exclusively of donor origin in 12 of 16 patients who were tested at 1 month post-BMT, but were mixed chimeric in 11 of these patients by > or = 3 months. Once mixed T-cell chimerism was documented, no patient returned to having all donor T-cells. At a median follow-up of 12 months, minimal residual disease was present in 18 of 22 patients with mixed T-cell chimerism and in 3 of 10 patients with full donor chimerism. The actuarial molecular relapse rate at 24 months for the two groups is 91% and 33%, respectively (P < .02). The finding of BCR- ABL mRNA within the first 6 months of transplant or on two consecutive assays was highly predictive of subsequent cytogenetic or hematologic relapse (P = .032 and P < .02, respectively). Ten patients, 9 with mixed T-cell chimerism, have relapsed (4 clinical, 6 cytogenetic) at a median of 12 months post-BMT. These data suggest that mixed T-cell chimerism may be a marker for abrogation of graft-versus-leukemia activity that is thought to be pivotal in eradicating minimal residual disease after BMT for CML.     

H2M3wt-restricted, Listeria monocytogenes-immune CD8 T cells respond to multiple formylated peptides and to a variety of gram-positive and gram- negative bacteria

A subset of H2M3wt-restricted, Listeria monocytogenes (LM)-immune CD8 effectors recognize antigen-presenting cells (APC) preincubated with heat-killed LM. The responsible product, which we have previously designated heat-killed Listeria-associated antigen (HAA), is extremely hydrophobic and resistant to proteolytic degradation. Despite the protease resistance of HAA, we now report that HAA-immune clones are uniformly responsive to fMIGWII, a formylated oligopeptide derived from the recently described LM product, lemA. While fMIGWII was by far the most potent peptide tested, over half our clones also responded to the LM-derived peptide fMIVII and cross-reactive responses to two other unrelated formylated peptides at concentrations of <1 microM were frequently observed. One of these peptides (fBlaZ) did not share any amino acid in common with fMIGWII except N-formyl methionine at position 1. Unformylated variants of the same peptides were inactive. HAA-immune CD8 cells also responded in an H2M3wt-restricted manner to APC pretreated with heat-killed or live preparations of other gram- positive and gram-negative bacteria such as Streptococcus pyogenes (SP) and Proteus vulgaris (PV). Unlike fMIGWII which is water soluble and protease sensitive, the native antigens extracted from SP and PV, like HAA, were very hydrophobic and proteinase K resistant, presumably reflecting in each case the association of cross-reactive polypeptides with bacterial lipid or phospholipid. Thus, HAA/lemA-immune, H2M3wt- restricted effectors can respond to a variety of formylated peptides and bacterial antigens in vitro. Similar cross-reactions in vivo might have physiologically significant implications.      

Ergotism as a consequence of thromboembolic prophylaxis

Vasospasm related to ergot intoxication is unusual. The authors report the case of 15-year-old boy who developed vasospasm necessitating amputation, due to an ergot derivative prescribed for thromboembolic prophylaxis. The importance of prompt angiographic recognition and therapy is stressed.     

Aetiology of perforating eye injury

This study addresses the aetiology of perforating ocular injury in childhood and possible preventive measures. Data have been collected from the case notes of 143 patients presenting over a 10 year period to a single ophthalmic unit. Injuries occurred most often in a domestic setting (34%) or with a child at play (19%) and showed an overall four to one ratio of boys to girls. Sports injuries accounted for 15% and assault for 8% of all injuries. A changing pattern of ocular injury is evident: road traffic accidents constituted 6% of injuries, compared with 31% in a similar study published in 1976. The role of litigation is discussed, particularly with regard to firearms, which accounted for 8% of injuries. It is concluded that the most important factor in the prevention of perforating ocular trauma is parental awareness, 53% of injuries occurring with the child in a domestic setting or at play.     

Mediastinal lymph node metastases from bronchogenic carcinoma: detection with MR imaging and CT

Magnetic resonance (MR) imaging and computed tomography (CT) were compared in a prospective study of 48 patients for the detection of metastatic mediastinal lymphadenopathy from bronchogenic carcinoma. The images were interpreted by three experienced radiologists using a five-point rating scale, enabling receiver operating characteristic (ROC) analysis. Imaging results were evaluated against "truth" data based on analysis of surgical specimens from mediastinoscopy and thoracotomy. All MR images were cardiac gated to reduce cardiac motion artifacts in the mediastinum. MR and CT both performed well, as indicated by similar areas under the ROC curves of 0.779 +/- 0.039 for MR imaging and 0.781 +/- 0.038 for CT scanning. No strong correlation between nodal size and metastatic involvement could be found for either MR or CT results. As long as nodal size remains the sole criterion in the detection of metastatic mediastinal lymphadenopathy, MR imaging is unlikely to enable better interpretations than CT scanning.