Although transplant practices have changed over the last decades there is no information on trends in incidence and outcome of cGVHD over time. This study utilized the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe the time trends for cGVHD incidence, non-relapse mortality, and the risk factors for cGVHD. The 12-year period was divided into three intervals: 1995-1999, 2000-2003, 2004-2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia and myelodysplastic syndrome. In the multivariate analysis, the incidence of cGVHD was shown to be increased in more recent years (odds ratio= 1.19, p<0.0001) and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, non-relapse mortality has decreased over time, but at 5-years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research.

The immunologic consequences of prolonged infusions of rIL-2 in doses that produce physiologic serum concentrations of this cytokine were investigated. rIL Invest. 1993. 91:123-132.)

We examined the efficacy of reducedintensity conditioning (RIC) and compared outcomes of 93 patients older than 16 years after RIC with 1428 patients receiving full-intensity conditioning for allografts using sibling and unrelated donors for Philadelphia-negative acute lymphoblastic leukemia (ALL) in first or second complete remission. RIC conditioning included busulfan 9 mg/kg or less (27), melphalan 150 mg/m 2 or less (23), lowdose total body irradiation (TBI; 36), and others (7). The RIC group was older (median 45 vs 28 years, P < .001) and more received peripheral blood grafts (73% vs 43%, P < .001) but had similar other prognostic factors. The RIC versus full-intensity conditioning groups had slightly, but not significantly, less acute grade II-IV graftversus-host disease (39% vs 46%) and chronic graft-versus-host disease (34% vs 42%), yet similar transplantation-related mortality. RIC led to slightly more relapse (35% vs 26%, P ‫؍‬ .08) yet similar age-adjusted survival (38% vs 43%, P ‫؍‬ .39). Multivariate analysis showed that conditioning intensity did not affect transplantation-related mortality (P ‫؍‬ .92) or relapse risk (P ‫؍‬ .14). Multivariate analysis demonstrated significantly improved overall survival with: Karnofsky performance status more than 80, first complete remission, lower white blood count, well-matched unrelated or sibling donors, transplantation since 2001, age younger than 30 years, and conditioning with TBI, but no independent impact of conditioning intensity. RIC merits further investigation in prospective trials of adult ALL. (Blood. 2010;116(3):366-374)

Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and B M from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 X I O 5 mononuclear cells. lmmunostained tumor cells were detected in 9.8% (1 3/133) PBSC specimens from 9/48 (1 8.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < ,005). IGH-DOSE chemotherapy followed by autologousH marrow infusion appears to be an effective treatment for some patients with locally advanced or metastatic breast cancer.I4 However, using sensitive immunocytochemical techniques, tumor cells can be observed in histologically normal bone marrow (BM) in 20% to 45% of patients with operable disease and in 20% to 70% of patients with metastatic breast cancer.'-* As a result, many patients who have multiple bone or BM metastases have not been considered eligible for autologous BM transplantation (BMT).Recently, peripheral blood stem collections (PBSC) have been used as an alternative to BM for hematopoietic support in patients with breast cancer or hematologic malignancies who have BM Several studies examining patients with neuroblastoma and lymphoma"-I3 suggest that PBSC collections are less likely to contain tumor cells than BM and thus may provide a less contaminated source of hematopoietic stem cell support after high-dose chemotherapy.The incidence and quantity of tumor cell contamination of PBSC collections in breast cancer patients has not been widely inve~tigated.'~,'' We prospectively examined the incidence of tumor cell contamination in paired samples of PBSC and BM collections from 48 advanced-stage breast cancer patients using a highly sensitive immunocytochemical technique. To determine whether these tumor cells were capable of clonogenic growth in vitro, tumor cell-specific clonogenic assays were performed on 58 BM or PBSC collections. MATERIALS AND METHODS Patient population andparticipating centers.Patients with histologically documented locally advanced or metastatic adenocarcinoma of the breast who were enrolled on high-dose chemotherapy programs at the participating treating institutions were eligible for this study. This protocol was approved by the Institutional Review Board for Human Investigation and each patient gave written in-The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/1 O5 mononuclear cells (range 0.33 to 2.0/105) compared with 22.9/105 mononuclear cells in BM (range 1 to 3,000/105, P < .0001). In culture experiments, clonogenic tumor colonies grew in 21 /26 immunocytochemically po...

Reports have shown a worse outcome for donor-recipient pairs mismatched for ABO blood groups in bone marrow transplantation (BMT). These studies, however, included small and heterogeneous study populations, and not all considered bidirectional ABO incompatibility separately. Because the issue remains controversial, we analyzed the effect of ABO mismatch on the overall survival, transplant-related mortality, and occurrence of acute and chronic graft-versus-host disease (GVHD) in a large homogenous group of patients undergoing allogeneic BMT. A total of 3103 patients with early-stage leukemia who underwent transplantation between 1990 and 1998 with bone marrow from an HLA-identical sibling and who were reported to the Center for International Blood and Marrow Transplant Research were studied. The median follow-up was 54 months. A total of 2108 (67.9%) donor-recipient pairs were ABO identical, 451 (14.5%) had a minor mismatch, 430 (13.9%) had a major mismatch, and 114 (3.7%) had a bidirectional ABO mismatch. The groups did not differ significantly in patient or donor characteristics except for more female-to-male sex mismatch in the bidirectional ABO mismatch group (P = .017). In multivariate models of overall survival, transplant-related mortality, and grade II to IV acute GVHD, there were no significant differences among the 4 groups. Bidirectional ABO mismatch was associated with a significantly higher risk of grade III or IV acute GVHD (hazard ratio, 1.869; 95% confidence interval, 1.192-2.93; P = .006). Patients with major ABO mismatch received red blood cell transfusions (P = .001) for a longer timer after transplantation and had a slightly slower neutrophil recovery (P < .001). There was no evidence of a substantial effect of ABO blood group incompatibility on the outcome of conventional BMT among patients with leukemia.

Several risk factors are associated with increased mortality in patients with chronic graft-versus-host disease (cGVHD), but there is considerable variability in the reported factors. Therefore, we evaluated patient, transplantation, and cGVHD characteristics to develop a risk score in 5343 patients with cGVHD. Ten variables were identified as being significant in multivariate analysis of overall survival and nonrelapse mortality (NRM): age, prior acute GVHD, time from transplantation to cGVHD, donor type, disease status at transplantation, GVHD prophylaxis, gender mismatch, serum bilirubin, Karnofsky score, and platelet count. These 10 variables were used to build a cGVHD risk score, and 6 risk groups (RGs) were identified. The 5-year NRM was 5% (1%-9%) in RG1, 20% (19%-23%) in RG2, 33% (29%-37%) in RG3, 43% (40%-46%) in RG4, 63% (53%-74%) in RG5, and 72% (59%-85%) in RG6. The 5-year overall survival was highest at 91% (95% confidence interval [CI]:85%-97%) in RG1, followed by 67% (65%-69%) in RG2, 51% (46%-55%) in RG3, 40% (37%-43%) in RG4, 21% (12%-30%) in RG5, and 4% (0%-9%) in RG6 (all P < .01). This analysis demonstrates the usefulness of data from a large registry to develop risk-score categories for major transplantation outcomes. Validation of this cGVHD risk score is needed in a different population to ensure its broad applicability. (Blood. 2011;117(24):6714-6720)

We compared the outcomes of unrelated donor (URD, n ‫؍‬ 358) with human leukocyte antigen (HLA)-matched sibling donor (MSD, n ‫؍‬ 226) transplantations in patients with acute myeloid leukemia (AML) in first complete remission (CR1) having unfavorable cytogenetics at diagnosis. Unfavorable cytogenetic abnormalities were: complex (> 3 abnormalities), 32%; and noncomplex involving chromosome 7, 25%; chromosome 5, 9%; 11q or MLL rearrangements, 18%; t(6;9), 5%; and other noncomplex, 10%.

As compared to the administration of HDPs, the administration of LDPs for prophylactic transfusion in hematopoietic progenitor cell transplant patients results in a lower platelet count increment, a lower likelihood of obtaining a posttransfusion platelet increment >20,000 per microL, a shorter transfusion-free interval, and a greater relative risk per day of requiring additional transfusions.