CD40 activation of B-CLL cells is associated with augmented intracellular levels of CD79b and increased BCR expression in a subset of patients.
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Over the past decade considerable advances have been made in the sensitivity of detection of residual lymphoma and leukaemia cells. Assays based on the polymerase chain reaction (PCR) can detect one tumour cell in up to 10(5) to 10(6) normal cells. The identification and cloning of breakpoints associated with specific chromosomal translocations has made possible the application of these techniques to a variety of lymphoid malignancies. In parallel, B cell malignancies exhibit rearrangements of their immunoglobulin genes that are also suitable targets for PCR amplification to identify residual cells. Although these techniques provide a useful adjunct to standard methods of detection and diagnosis, their role in determining disease outcome remains investigational. There is confusion as to whether it is necessary to eradicate PCR-detectable lymphoma cells for cure, so it is not yet possible to determine whether the detection of residual lymphoma cells by PCR is an indication to continue therapy.
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BACKGROUND: We investigated the long-term outcome of allogeneic stem-cell transplantation after myeloablative conditioning regimen as treatment for patients with chronic lymphocytic leukemia. METHODS: Patients were eligible for our study if they were refractory or failed a prior response to fludarabine. The conditioning regimen consisted of high-dose CY 60 mg/kg daily for 2 days and fractionated TBI. One patient received BEAM because of prior radiation. GvHD prophylaxis consisted of CYA or tacrolimus and MTX in the majority of patients. RESULTS: Twenty eight patients were treated. nineteen had disease that was refractory to fludarabine. The median number of prior chemotherapy regimens per patient was 3. Twenty had HLA-identical donors and one had a one-Ag mismatched sibling donor. Seven patients had a matched unrelated transplant. The median follow-up time for the surviving patients was 66 months. By univariate analysis, chemosensitivity was the only factor that predicted a better outcome. For the chemosensitive patients, the overall survival was 78%, compared with 31% for those with refractory disease (P = 0.05). Progression-free survival at 5 years was 78% for the chemosensitive and 26% for those who were refractory to conventional chemotherapy at the time of transplantation (P = 0.03). Three patients (11%) died within 100 days of transplant. The actuarial risk of acute Grade II-IV GvHD was 49%. Only one patient developed acute Grade III GvHD. CONCLUSION: Allogeneic transplantation is probably curative for a subset of patients with chronic lymphocytic leukemia. Patients should be considered for clinical trials involving allogeneic transplantation at an earlier stage prior acquiring chemorefractoriness.
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Autolymphocytotoxic antibodies are found commonly in dialysis patients and these autoantibodies may be directed against T and B lymphocytes or just B lymphocytes. However, these autoantibodies react with a low frequency or not at all against chronic lymphocytic leukemia cells, and are not absorbed by autologous erythrocytes. Thus, a number of positive crossmatches between donor and recipient may be attributable to autoantibodies. Six renal transplants have been carried out in the presence of such a positive crossmatch against donor B lymphocytes, including one against donor T lymphocytes, with a successful graft outcome. Thus, the indications for renal transplantation in the presence of a positive crossmatch between donor and recipient are becoming better defined.