Summary:We investigated the use of 'prophylactic' donor lymphocyte infusions (DLI) containing 1 ؋ 10 7 CD3 ؉ cells, given at 30, 60 and 90 days post-allogeneic blood and marrow transplantation (BMT), following conditioning with fludarabine 30 mg/m 2 /4 days and melphalan 70 mg/m 2 /2 days. GVHD prophylaxis consisted of cyclosporin A (CsA) 2 mg/kg daily with early tapering by day 60. Our goals were the rapid achievement of chimerism and disease control, providing an immunological platform for DLIs to treat refractory patients with hematological malignancies. Twelve heavily pre-treated patients with life expectancy less than 6 months were studied; none were in remission. Diagnoses were AML (n ‫؍‬ 4), MDS (n ‫؍‬ 1), ALL (n ‫؍‬ 3), CML (n ‫؍‬ 3) and multiple myeloma (n ‫؍‬ 1). Response rate was 75%. Three patients are alive at a median of 450 days (range, 450-540). Two patients are in remission of CML in blast crisis and AML for more than 14 months. Median survival is 116 days (range, 25-648). Six patients received 12 DLIs; three patients developed acute GVHD after the first infusion and were excluded from further DLIs, but no GVHD occurred among patients receiving subsequent DLIs. One patient with CML in blast crisis went into CR after the first DLI. The overall incidence of acute GVHD was 70%. Primary causes of death were infections (n ‫؍‬ 3), acute GVHD (n ‫؍‬ 3), chronic GVHD (n ‫؍‬ 1) and disease relapse (n ‫؍‬ 2). We observed high response and chimerism rates at the expense of an excessive incidence of GVHD. DLI given at day ؉30 post BMT caused GVHD in 50% of the patients, and its role in this setting remains unclear. The therapeutic benefit of allogeneic BMT is in part related to an immunological graft-versus-leukemia (GVL) effect that frequently evolves in the context of graft-versus-host disease (GVHD). The ability of donor lymphocytes to induce remission in patients relapsing after allogeneic transplantation illustrates the potency of this effect.1 Establishing donor-recipient tolerance with less toxic regimens may provide the basis for further immunological manipulations in order to maximize the GVL effect. However, rapidly evolving diseases may not be amenable to this strategy, considering that the immune-mediated elimination of malignant cells may take weeks or months to occur. This fact suggests the need for strategies to reinforce the immune-mediated phenomena in the post-transplant period.Groups in Jerusalem and Houston pioneered the use of sub-lethal doses of fludarabine-based conditioning regimens. These regimens have been shown to be less toxic and to provide enough immunosuppression to prevent graft rejection and establish stable mixed or complete chimerism.2,3 The combination of melphalan and fludarabine has enabled allogeneic stem cell engraftment in the majority of patients treated, at least in the setting of HLA-identical transplantation. Patients with refractory relapses of advanced leukemias appear to benefit the least.

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Burkitt lymphoma/leukaemia (BL/L) is a heterogeneous disease with respect to epidemiological patterns and cell origin. The occurrence of BL/L with an immature phenotype raises the question whether this phenotype might be a consequence of early B-cell transformation or, alternatively, a secondary feature of transformed, mature B cells. It also poses important clinical questions regarding diagnosis and therapeutic procedures. Here we describe the case of a 4-yr-old child with BL/L and FAB L3 morphology, with phenotypic and genotypic characteristics of a CD10+ precursor B-cell acute lymphoid leukaemia (ALL) associated with t(8;14)(q24;q32). Molecular analysis showed expression of RAG1 and RAG2 and an unmutated VDJCmu immunoglobulin rearrangement coinciding with a lack of AICDA expression, indicating an immature B-cell origin. His clinical response suggested that FAB L3 ALL with MYC rearrangement and an aberrant precursor B-cell phenotype is clinically similar to BL/L. Moreover, short, intensive chemotherapeutic protocols seemed to be beneficial. This case also allowed us to refine the description of cellular and molecular variants of BL/L regarding the cell origin and pathogenesis of this biologically heterogeneous disease.

Impairment of natural cytotoxicity mediated by natural killer (NK) cells may play a role in the pathogenesis of penile carcinoma. The aim of this study was to examine the NK activity profile and its prognostic significance in patients with squamous cell carcinoma of the penis. The NK activity was measured in peripheral blood mononuclear cells (PBMCs) from 39 patients diagnosed histologically as having invasive squamous cell penile carcinoma and 4 patients with verrucous carcinoma of the penis. Of 39 patients with invasive squamous cell carcinoma, 4 had undergone previous penile amputation. According to the prognosis, the patients with invasive squamous cell carcinoma were divided into two groups: with metastasis and without metastasis. The patients were evaluated in relation to clinicopathologic variables using univariate analyses. NK cell activity was significantly decreased in all patients with penile carcinoma when compared with the control groups (p < 0.0001). There was no statistically significant difference between the groups with and without metastasis. We conclude that there is a decrease in NK activity in PBMCs from patients with penile carcinoma and that the presence of advanced disease or metastatic involvement is not responsible for this reduction.

Alterations involving the short arm of chromosome 17 (17p) during the progression of chronic myeloid leukemia (CML) have been described. This chromosomal region contains the tumor suppressor gene TP53 that may be an important factor in the evolution of this disease. In this study, we used flow cytometry and western blotting to assess p53 protein expression and single stranded conformational polymorphism to examine TP53 gene alterations in three patients with CML who showed alterations in 17p. Only the case with del(17)(p11) had p53 expression positive by flow cytometry and an abnormal migration pattern by SSCP analysis. The importance of the correlation between the results obtained with these techniques, as well as the clinical course of the patients, are discussed.

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CONTEXT AND OBJECTIVE: Following hematopoietic stem cell transplantation (HSCT), karyotyping is a valuable tool for monitoring engraftment and disease status. Few studies have examined the prognostic significance of karyotypes in patients who underwent HSCT for chronic myeloid leukemia (CML). The objective of this study was to evaluate the significance of pretransplantation cytogenetic status in relation to outcomes following HSCT in CML patients. DESIGN AND SETTING: Case series study at Instituto Nacional do Câncer (INCA), Rio de Janeiro, Brazil. METHODS: Cytogenetic analysis was performed by G banding on 39 patients treated with HSCT. RESULTS: Thirty-one patients were in the chronic phase and eight were in the accelerated phase. Prior to HSCT, additional chromosomal abnormalities on the Philadelphia (Ph) chromosome were found in 11 patients. The most frequent additional abnormality was a double Ph, which was observed in four cases. Following HSCT, full chimeras were observed in 31 patients (79.5%). Among these, 23 (82.3%) had presented Ph as the sole abnormality. Mixed chimeras were observed in seven patients, of which three had additional abnormalities. Only one case did not present any cytogenetic response. Five patients presented cytogenetic relapse associated with clinical relapse following HSCT. Twenty-seven patients are still alive and present complete hematological and cytogenetic remission. CONCLUSION: In our study, the presence of additional abnormalities was not associated with worse outcome and relapse risk. Also, no differences in survival rates were observed. Our study supports the view that classical cytogenetic analysis remains an important tool regarding HSCT outcome.