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Sixteen adults were studied for the first 100 days after allogeneic bone marrow transplant to assess the pathogenic role of human herpesvirus-6 (HHV-6) infection in patients with unexplained febrile illnesses. HHV-6 was directly isolated from the blood of 6 patients. Analysis of the clinical courses of these 16 patients revealed otherwise unexplained posttransplant marrow suppression in 5 patients. Idiopathic marrow suppression occurred more frequently in patients with concurrent HHV-6 viremia (4/6) than in those from whom HHV-6 was not isolated from peripheral blood (1/10, P < .05). An etiologic role for the virus was also supported by isolation of HHV-6 from the bone marrow of all 4 patients at the time of marrow suppression and by in vitro colony-forming unit (cfu) assays that demonstrated that HHV-6 could inhibit cfu-granulocyte-macrophage and burst-forming unit-erythroid growth from human bone marrow. By restriction enzyme mapping, all clinical isolates were type B, suggesting that bone marrow transplant recipients may be preferentially infected with and reactivate this HHV-6 subtype. This study implicates HHV-6 as a novel cause of bone marrow suppression in marrow transplant recipients.

Summary:own is late or long-term renal toxicity. [2][3][4][5][6][7][8][9][10][11] The renal toxicity described consists of a group of clinical signs including hypertension, anemia, and decreased glomerular filThe purpose of this study was to evaluate the effect of partial renal shielding used in conjunction with total tration rate (GFR) with occasional proteinuria and microscopic hematuria, and edema. Biopsies of the affected body irradiation (TBI) on the incidence of bone marrow transplantation nephropathy (BMT Np) seen as a late kidneys have a unifying aspect in that there is extreme subendothelial widening of the basement membranes, with sequelae after transplantation. Of 402 patients who have undergone bone marrow transplantation (BMT) at the endothelial cell dropout, glomerular arteriolar intimal thickening and atrophic tubules. Whether all the changes seen Medical College of Wisconsin (MCW) 157 were greater than 18 years of age, received 14 Gy TBI and survived on biopsy relate to the 'BMT nephropathy' (BMT Np) previously described has yet to be determined. What is unquesat least 100 days post-transplant. The incidence of BMT nephropathy was evaluated in these patients by dose to tionably true of the data to date is that the use of TBI appears to play a significant role in the development of the the kidneys. In the 72 patients who received 14 Gy TBI with no renal shielding, the actuarial risk of developing syndrome. 5,7-11 Previously, our institution described the use of selective BMT Np at 2. years (30 months) post-BMT was 29 ± 7%. Sixty-eight patients received 14 Gy TBI with partial renal shielding in an effort to reduce the incidence of this late renal toxicity. 7 Here, we found an incidence of partial renal shielding of 15% (renal dose = 11.9 Gy), the actuarial risk of developing BMT Np was 14 ± 5%BMT nephropathy of 26% in the unshielded patients at 18 months vs 6% in the shielded patients (P Ͻ 0.05). Shielding at 2. years. Seventeen patients received 14 Gy TBI with renal shielding of 30% (renal dose = 9.8 Gy); none of utilized at that time was a 70% transmission posterior/ anterior (PA)-only shield that decreased the total renal dose this group have developed BMT Np despite a median follow-up of over 2. years (985 days). The trend of from 14 Gy to 11.9 Gy. Since the partial shielding appeared effective but we were still experiencing some level of late decreasing BMT Np with increasing shielding is statistically significant (P = 0.012). Prognostic factors such as renal toxicity we doubled the shielding to a 40% transmission PA-only block to decrease the dose to the kidneys age, type of transplant and good-risk vs poor-risk disease status were evaluated and were similar in each to 9.8 Gy. Results of this change as well as long-term follow-up of the initial cohort of patients both renally blocked cohort of patients described above. We conclude that given the statistically significant benefit seen here in the and unblocked are the focus of this manuscript. reduced incidence of BMT Np by the use of selectiv...

Eight patients who had hematologic relapse of chronic myelogenous leukemia (CML) after undergoing allogeneic bone marrow transplantation (BMT) were treated with leukocyte infusions from the original bone marrow donors. All patients had previously received marrow grafts from HLA-identical siblings. Six patients were in the accelerated phase of their disease and two were in blast crisis. Each patient received a predetermined T-cell dose within a narrow range of 2.5 to 5.0 x 10(8) T cells/kg. Three patients also received short courses of therapy with alpha interferon to control elevated white blood cell counts within the first several weeks after leukocyte transfusions. Seven of eight evaluable patients developed graft-versus-host disease (GVHD) at a median of 32 days after the initial infusion. One patient had fatal GVHD. A second patient had grade 3 acute GVHD, which has responded to immunosuppressive therapy. The remaining patients all had mild grade I GVHD. Six patients continue to require modest doses of prednisone more than 6 months after infusion. Four patients developed marrow aplasia, which in three patients required marrow boosts from the original donors. Two of these three patients have normal hematopoietic function, whereas the third patient remains growth factor and transfusion dependent. Both patients treated in blast crisis have died, one from GVHD and one from disease progression. All six patients in the accelerated phase are alive and in cytogenetic remission at a median of 42 weeks after infusion. Five of these six patients are in molecular remission. This study demonstrates that leukocyte infusions that administered a defined T-cell dose can exert a profound graft-versus- leukemia effect and are an effective form of salvage immunotherapy in allogeneic marrow transplant recipients. This therapeutic approach appears to be a viable alternative to existing chemotherapeutic and immunomodulatory strategies for the treatment of relapsed CML.

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