D J Weisdorf

..In the absence of an HLA-matched sibling donor, autologous peripheral blood may provide acceptable alternative post-remission therapy for patients with acute myeloid leukemia in first complete remission...

..After MAC, GVHD has an adverse effect on TRM with early modest augmentation of GVHD-associated graft-versus-leukemia (GVL). With RIC, GVHD-associated GVL may be important in limiting both early and late leukemia recurrence...

..Improvements in peritransplantation disease control and additional measures to augment the allogeneic graft-versus-leukemia effect are still required...

..The hematology/oncology community is most suited to participate in such contingency planning, and the necessary elements for its success are reviewed...

..The BMT CTN organizational structure, current portfolio of studies, and scientific agenda are reviewed. Opportunities for investigators in any institution to propose trials and participate are outlined...

..Of most significance, however, is that the best donor is HLA-compatible, healthy, promptly available, and willing to give the requested product for HCT...

..This improved categorization of HLA matching status allows adjustment for donor-recipient HLA compatibility, and can standardize interpretations of prior URD HCT experience...

..This approach can thereby reduce investigator bias, facilitate comparison between centers, and perhaps eliminate the need for an expert PR. This technique should be used in future prospective studies of GVHD prophylaxis...

..In this analysis, greater histoincompatibility can augment GVHD, but does not improve protection against relapse; thus the best donor remains the most closely matched donor...

..Human leukocyte antigen (HLA) mismatch does not appear to augment the GVL effect, and increased GVHD does not necessarily lead to decreased relapse...

..Risks of relapse may differ based on the depth of remission, measurable minimal residual disease (MRD), or patient's performance status...

..Therefore, UCB should be considered an acceptable alternative to HLA-matched BM for pediatric patients...

..75 x 10(6) IU/m(2)/day. Fifteen women with stage IIIA/B or metastatic breast cancer underwent G-CSF mobilization alone and served as a control group...

..Continuous monitoring of renal function is necessary in allogeneic HCT survivors, and studies exploring prevention strategies are needed...

..Analysis of hematopoietic cell transplantation (HCT) for high-risk or recurrent acute lymphoblastic leukemia (ALL) using different donor sources is confounded by variable conditioning and supportive care...

..6 (95% CI 0.2-1.3) P=0.16) and with URD RR 0.4 (0.2-1.0) P=0.04). Older patients with advanced hematologic malignancies achieve satisfactory outcomes using either of these reduced intensity conditioning regimens...

..5 μg h/mL had 4.56 greater risk of TRM and significantly lower OS. These data suggest that clinical strategies are needed to optimize dosing of fludarabine to prevent overexposure and toxicity in HCT...

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..4; P=0.05) were independent factors associated with unit predominance. Taken together, these findings suggest that immune reactivity has a role in unit predominance, and should be considered during graft selection and graft manipulation...

..We suggest that imatinib be included in the peri-transplant management of all patients with Ph+ ALL...

..Allogeneic HCT may be suitable in younger patients, soon after diagnosis, and in those with chemosensitive disease...

..6 vs RIC). At least in the first few years after HCT, the risks for hypothyroidism are similar among patients receiving TBI-based MA and reduced-intensity regimens...

..Survival was 47% at 1 year. Despite safety of administration, IBMI of one of two UCB units did not shorten the time to neutrophil engraftment and offers no advantage over conventional double unit transplantation...

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..To test the use of unrelated donor bone marrow transplantation (URD BMT) to cure children with high-risk acute leukemias...

..UCB is feasible as an alternative donor source for reduced-intensity conditioning HCT among older patients with AML and MDS who do not have a suitable MSD...

..67). Our results suggest comparable outcomes for reduced-intensity allo-SCT using UCB or MSD in adults at high risk with advanced Hodgkin lymphoma...

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..In conclusion, we are introducing the MCI which may have higher discriminating and predictive power for overall survival and NRM. Validation of the HCT-CI and the MCI in larger and separate cohorts of HCT recipients is still needed...

..1% (95% CI 68-94)); P=0.1. This analysis, undertaken in a contemporary cohort of related donor recipients, indicates that the consensus guidelines are applicable to this population of CGVHD patients...

..Reducing the intensity of preparative regimen does not protect against post transplant alveolar hemorrhage. Alveolar hemorrhage occurring after RIC or MAC HCT has similar incidence, clinical presentation, and associated high mortality...

..Viremia was detected in two thirds of patients with CMV prior to the diagnosis of enteritis. Most treatment regimens included ganciclovir. The overall survival rate was 35% at 2 years following the onset of enteritis...

..These results support the notion that T cells in the graft affect NK cell reconstitution in vivo. Understanding these mechanisms may result in strategies to improve clinical outcomes from unrelated HCT...

..44). Thus, patients treated with imatinib either before or after myeloablative allo-HCT had no increase in cardiac toxicity...

..The poor clinical outcome of patients with difficult mobilization using either method identifies them as a high-risk group who might benefit from alternative therapies...

..A risk-adapted approach should be followed in determining treatment options for patients with PR REF and REL HL...

..4, 95% CI, 0.2-0.6, P < .01). When compared with URD:M, OS with UCB was better (RR 0.3, 95% CI, 0.1-0.7, P = .01), supporting the use of UCB as an alternative stem cell source for adults with ALL...

..These results suggest that the IPI-R predicts OS and PFS following auto HSCT for patients with aggressive NHL in CR 2 or PR 2. Patients with high-risk IPI-R should be considered for novel therapeutic approaches...

..Recipients of UCB have similar risks of CMV infection, responses to antiviral therapy, and survival following CMV infection as recipients of either marrow or PBSC...

..However, although post-transplant neutropenia is brief, infections remain a significant cause of morbidity...

..Because adoptive immunotherapy with donor lymphocytes is not an available option for recipients of unrelated-donor UCBT, new therapeutic strategies are needed, and rituximab appears promising...

..Recognition of a high-risk group should facilitate assignment of more intensified regimens. Better treatment regimens need to be identified to improve survival and limit toxicity of prolonged immunosuppression...

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..8; 95% CI, 1.0-3.1; P = .05). Our results do not support the selection of UCB units based on KIR-L status and suggest that KIR-L mismatching should be avoided in reduced intensity UCB transplantation...

..These data suggest that with appropriate pre-transplant clinical evaluation, high-dose cyclophosphamide and irradiation in the BMT preparative phase does not result in frequent, clinically relevant short-term cardiac toxicity...

..Two cycles of priming chemotherapy plus autologous transplantation yields survival rates similar to those in published reports, including those using tandem transplantation...

..We review here the background data on the utilization of UCB for the treatment of hematological malignancies, and discuss the current challenges and future directions in the field of UCB transplantation...

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..Ongoing immunocompromise and need for prophylaxis should be appreciated in patients with graft-versus-host disease.(ABSTRACT TRUNCATED AT 250 WORDS)..

..For patients without an available HLA matched donor, the use of 2 partially HLA-matched UCB units is a suitable alternative...

..This study is registered at (http://www.clinicaltrials.gov) under the identifiers NCT00305682 and NCT00309842...

..KIR genotyping of prospective donors, in addition to HLA typing, should be performed to identify HLA-matched donors with B KIR haplotypes...

..This trial was registered at http://clinicaltrials.gov as NCT00309842...

..We reviewed reduced-intensity hematopoietic cell transplantation for older patients in the context of recently published studies...

..These unique features of UCB transplantation must be considered in comparisons of the outcomes of UCB versus BM transplant recipients and in the design of prospective trials comparing URD sources...

..The HCT-CI, although a useful tool for capturing pretransplant comorbidity and risk-assessment, needs to be further validated prior to adopting it for routine clinical use...

..Future efforts should focus on improving the outcome for older BMT recipients, especially those with diagnoses other than CML...

..Modifications to refine patient assignment to the preferred conditioning intensity and reduce relapse risks with NMA approaches are needed...

..Improvements in URD and MSD transplantation are still needed, and results of newer, nontransplantation therapies should be evaluated against the established curative potential of URD and MSD marrow transplantation...

..Adopting this practice could result in superior disease-free survival for patients with AML...

..These data suggest that treatment with ATG can be an active therapy, especially in patients with skin GVHD and early signs of steroid resistance...

..These data demonstrate that 0-2 antigen mismatched UCB is sufficient to engraft most adults after reduced-intensity conditioning and is associated with a low incidence of severe acute GVHD...

..Better pre-HCT performance status predicted improved 2-year OS. CONCLUSION With these similar outcomes observed in older patients, we conclude that older age alone should not be considered a contraindication to HCT...

..Allogeneic hematopoietic-cell transplantation (HCT), although curative for some high-risk diseases, is a complex and costly procedure. The costs of transplantation among children have not been described previously...

..These findings suggest that SNPs in the BER pathway can be used as genetic biomarkers to predict individuals at high risk for TRM and disease relapse. Modulation of pretransplant conditioning may alter risk in these patients...

..These costs are primarily driven by severe posttransplant complications, graft failure, and prolonged inpatient stay. Strategies to enhance engraftment will decrease the costs of UCB transplantation...

..However, the utility and outcome associated with transplants from URDs compared with those from MSDs remains undefined...

..No other differences in response by donor source were observed. These data suggest that day 28 is the best early endpoint for acute GVHD therapeutic trials in predicting 2-year TRM...

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..01). For adults with ALL in CR, reduced intensity conditioning allografting results in modest TRM, limited risk of relapse, and promising leukemia-free survival. Clinical trial numbers are NCT00365287, NCT00305682, and NCT00303719...

..Based on our data, we conclude that a nonmyeloablative conditioning regimen followed by UCB transplantation is an effective treatment for patients with advanced lymphoid malignancies who lack a suitable sibling donor...

..A careful review of existing comorbidities is necessary when considering older patients for HCT...

..01) and use of 2 UCB units (P = .07). These findings support the use of UCB after a nonmyeloablative conditioning as a strategy for extending the availability of transplantation therapy, particularly for older patients...

..These findings suggest that haploidentical NK cells can persist and expand in vivo and may have a role in the treatment of selected malignancies used alone or as an adjunct to HCT...

..It is possible that there will be a benefit of NK cell alloreactivity if strategies of haploidentical transplantation are used: high stem cell doses, extensive T-cell depletion, and no postgrafting immune suppression...

..Herein is a report on the experience of clinical-scale, good manufacturing practices (GMPs) production of NK cells to treat advanced cancer...

..58, 95% CI 1.13-2.22; P = .008). These data support a genetically determined role for NK cells following unrelated HCT in myeloid leukemia...

..7 x 10(5) CD34(+) cells per kilogram of recipient's body weight. Therefore, graft selection should be based principally on CD34 cell dose when multiple UCB units exist with an HLA disparity of 2 or less...

..This prospective, multicenter, randomized clinical trial for steroid-resistant acute GVHD serves as a model for future evaluation of new agents...

..28). The pathogenesis of alveolar hemorrhage after HSCT is multifactorial, and we propose that IAH and DAH in HSCT recipients are related clinical syndromes with similar clinical presentation, risks, and associated high mortality...

..We conclude that palifermin was generally safe in allogeneic HSCTs but had no significant effect on engraftment, acute GVHD, or survival in this trial...

..Use of ATG in recipients of an NMA preparative regimen warrants close monitoring for evidence of EBV reactivation and potentially preemptive therapy with rituximab...

..Therefore, transplantation of 2 partially HLA-matched UCB units is safe, and may overcome the cell-dose barrier that limits the use of UCB in many adults and adolescents...

..However, adverse medical late effects with significant morbidity were uncommon. Chronic GVHD is the most important predictor of adverse medical late effects and poor overall health...

..2, P < 0.01) and decreased TRM (RR 0.1, P < 0.01). These data suggest that donor polymorphism in IL-1alpha and IL-1beta might influence survival after unrelated donor BMT, but does not alter risk of GVHD...

..In addition, progressive onset of cGVHD was a significant predictor of increased mortality in URD cohort. These data suggest that cGVHD following UCB transplant may be more responsive to therapy and also lead to a lower NRM...

..BrOb had high mortality rate of 55%, and pulmonary failure was the leading cause of death. More effective BrOb therapy is needed, especially for patients with unfavorable presentation...

..More effective prophylaxis and therapy for acute GVHD is needed for mismatched unrelated donor recipients and for those with severe GVHD...

..Because IL-2 is a proinflammatory cytokine, we hypothesized that recipients with high-producer genotypes would have increased frequency of GVHD after allogeneic bone marrow transplantation (BMT)...

..The purpose of this study was to examine the relationship between ethnicity and post-transplantation events and determine their net effect on survival...

..Structured exercise may have a positive impact on physical and emotional recovery following transplant therapy and may accelerate patients' return to health and function...

..This trial was registered at www.clinicaltrials.gov as no. NCT00303693 and www.cancer.gov/clinicaltrials as no. NCT00167180...

..With this dose and schedule of administration of IL-2, no improvement in patient disease outcomes was noted. Alternative strategies will be needed to exploit the immunotherapeutic potential of IL-2-activated NK cells...

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..02). None of the SNPs were associated with acute or chronic GvHD risk. These findings suggest that genetic variants in the vascular adhesion molecules may be used to identify patients at high risk for TRM...

..We conclude that FVII deficiency should be considered in the differential diagnosis of prolonged PT in patients who have recently undergone SCT. The mechanism of this acquired deficiency state remains to be defined...

..Rates of yeast colonization after neutrophil recovery were similar in patients treated with fluconazole or clotrimazole...

..End of abstract.) ..