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Previous randomized graft-versus-host disease (GVHD)-prophylaxis trials have failed to demonstrate reduced incidence and severity of chronic GVHD (cGVHD).Here we reanalyzed and updated a randomized phase 3 trial comparing standard GVHD prophylaxis with or without pretransplantation ATG-Fresenius (ATG-F) in 201 adult patients receiving myeloablative conditioning before transplantation from unrelated donors. The cumulative incidence of extensive cGVHD after 3 years was 12.2% in the ATG-F group versus 45.0% in the control group (P < .0001). The 3-year cumulative incidence of relapse and of nonrelapse mortality was 32.6% and 19.4% in the ATG-F group and 28.2% and 33.5% in the control group (hazard ratio [HR] ‫؍‬ 1.21, P ‫؍‬ .47, and HR ‫؍‬ 0.68, P ‫؍‬ .18), respectively. This nonsignificant reduction in nonrelapse mortality without increased relapse risk led to an overall survival rate after 3 years of 55.2% in the ATG-F group and 43.3% in the control group (HR ‫؍‬ 0.84, P ‫؍‬ .39, nonsignificant). The HR for receiving immunosuppressive therapy (IST) was 0.31 after ATG-F (P < .0001), and the 3-year probability of survival free of IST was 52.9% and 16.9% in the ATG-F versus control, respectively. The addition of ATG-F to standard cyclosporine, methotrexate GVHD prophylaxis lowers the incidence and severity of cGVHD, and the risk of receiving IST without raising the relapse rate. ATG-F prophylaxis reduces cGVHD morbidity. (Blood. 2011; 117(23):6375-6382) IntroductionAllogeneic hematopoietic stem cell transplantation (HSCT) is increasingly used worldwide as a curative therapy for malignant and nonmalignant hematologic disorders. Chronic graft-versushost disease (cGVHD) is the leading cause of nontransplantation mortality and morbidity after allogeneic HSCT. 1-3 cGVHD is a multiorgan disease resembling autoimmune disorders, such as scleroderma or systemic lupus. 4,5 Its incidence and prevalence are rising because of transplantation practices known to be associated with increased risk of cGVHD. 4,6 Indeed, older patients now undergo HSCT, and more transplantations are being performed from unrelated donors and/or with peripheral blood stem cells instead of bone marrow. Furthermore, the reduced-intensity conditioning (RIC) regimens developed during recent years have also led to higher numbers of transplantations performed worldwide. 7,8 However, although the acute GVHD (aGVHD) rate appears lower after RIC, the incidence of cGVHD seems to be unaffected. 9 Altogether, cGVHD thus remains the most challenging complication after allogeneic HSCT. 10 The main risk factor for developing cGVHD is the previous occurrence of aGVHD. 11 Thus, transplantation physicians have focused on decreasing the rate of aGVHD to lower nonrelapse mortality (NRM) associated with both aGVHD and cGVHD. However, although calcineurin inhibitors (cyclosporine or tacrolimus) in association with methotrexate have proven to decrease the aGVHD rate in randomized studies and although new regimens, such as the association of rapamycin with tacrolimus, seem to l...

Summary:diagnostic procedures further decrease the natural resistance to infection. Finally, granulocytopenia compromises the first line of defense against bacterial, fungal and paraType, severity and incidence of infection during the neutropenic period after peripheral blood stem cell transsitic pathogens. Fever of unknown origin, bacteremia and pneumonia are the most frequent clinical manifestations of plantation (PBSCT) for treatment of malignant disease were studied in 66 patients treated at a single instiinfection in patients after chemotherapy. 3 Infections with both gram-positive and gram-negative bacteria as well as tution. Data of 34 female and 32 male patients with a median age of 43 years suffering from leukemia (12), fungi are common in these patients. In particular, staphylococci, streptococci, E.coli, klebsiella, pseudomonas, canlymphoma (35), multiple myeloma (six) or solid tumors (13) were retrospectively analyzed. All patients had dida and aspergillus species are frequently isolated from infectious sites in granulocytopenic patients. received at least 2.5 ؋ 10 6 CD34-positive cells for stem cell rescue after high-dose chemotherapy. Ninety-fourChemotherapeutic agents display a dose-response relationship in vivo and in vitro. 4,5 However, the application percent of the patients experienced at least one febrile episode during their post-transplant course. The of high-dose chemotherapy is limited by its toxic effects, in particular on the hematopoietic system. Stem cell rescue patients recovered quickly and defervesced after a median of 4 days. The incidence of bacteremia was 39%by autologous bone marrow transplantation has been applied to circumvent the dose-limiting hematopoietic toxand gram-positive cocci were the predominant pathogens. In contrast, severe organ infections were rare.icities. 6-8 Myeloablative therapies with autologous bone marrow transplantation, however, cause prolonged marrow Only 5% of the patients suffered from lung infiltrates. No invasive fungal infections were observed. No transaplasia accompanied by severe infectious complications. Autologous bone marrow transplantation caused a transplant-related deaths occurred in the 66 patients studied. We conclude that the severe, but shortlasting neutroplant-related mortality consistently in the range of 5-10%. 6-8 Mobilization of peripheral hematopoietic stem penia after peripheral blood stem cell transplantation is associated with a high incidence of bacterial infection.cells by chemotherapy and growth factors and leukapheresis yields higher numbers of hematopoietic stem cells than The severity of the majority of these infections is moderate. With appropriate anti-infective therapies these bone marrow harvesting. 9,10 Numerous reports have meanwhile confirmed the feasibility and effectiveness of transinfections can be managed and life-threatening infectious complications, in particular fungal infections, are plantation with peripheral blood stem cells (PBSCT) to mitigate the hematotoxic effects of myeloablative therrare. Empiric...