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ABSTRACT: The Internet provides a widely accessible modality for meeting survivorship care needs of cancer survivors. In this paper, we describe the development and implementation of an Internet site designed as a base from which to conduct a randomized controlled trial to meet psycho-educational needs of hematopoietic stem cell transplantation (HSCT) survivors.
A cross-disciplinary team designed, wrote content, and programmed an Internet site for online study registration, consent, assessment, and study implementation. All survivors who were 3-18 years after HSCT for hematologic malignancy and treated at one transplant center were approached by mail for participation. All study activities could be conducted without study staff contact. However, participants had options for phone or email contact with study staff as desired.
Of 1,775 participants approached for the study, 775 (58% of those eligible) consented and completed baseline assessment. Mean age was 51.7 (SD, 12.5; age range, 18-79 years), with 56% male. Fifty-seven percent required staff contact one or more times; a majority were for minor technical issues or delays in completion of enrollment or baseline assessment.
This study demonstrated the potential for providing Internet-based survivorship care to long-term survivors of HSCT. Although building a survivorship Internet site requires a team with diverse expertise, once built, these resources can be implemented rapidly with large numbers of survivors.
While Internet-based services will not meet all the needs of cancer survivors, this methodology represents an important modality for augmenting onsite clinical services as a method for meeting psycho-educational, information, and resource needs of cancer survivors.
Journal of Cancer Survivorship 05/2011; 5(3):292-304. · 2.63 Impact Factor
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ABSTRACT: Recent advances in genotyping technologies have enabled genomewide association studies (GWAS) of many complex traits including autoimmune disease, infectious disease, cancer and heart disease. To facilitate interpretations and establish biological basis, it could be advantageous to identify alleles of functional genes, beyond just single nucleotide polymorphisms (SNPs) within or nearby genes. Leslie et al. ([2008] Am J Hum Genet 82:48–56) have proposed an Identity-by-Decent method (IBD-based) for predicting human leukocyte antigen (HLA) alleles (multiallelic and highly polymorphic) with SNP data, and predictions have achieved a satisfactory accuracy on the order of 97%. Building upon their success, we introduce a complementary method for predicting highly polymorphic alleles using unphased SNP data as the training data set. Due to its generality and flexibility, the new method is readily applicable to large population studies. Applying it to HLA genes in a cohort of 630 healthy individuals as a training set, we constructed predictive models for HLA-A, B, C, DRB1 and DQB1. Then, we performed a validation study with another cohort of 630 healthy individuals, and the predictive models achieved predictive accuracies for HLA alleles defined at intermediate or high resolution ranging as high as (100%, 97%) for HLA-A, (98%, 96%) for B, (98%, 98%) for C, (97%, 96%) for DRB1 and (98%, 95%) for DQB1, respectively. These preliminary results suggest the feasibility of predicting other polymorphic genetic alleles, since HLA loci are almost certainly among most polymorphic genes.
Genetic Epidemiology 02/2011; 35(2):85-92. · 3.44 Impact Factor
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ABSTRACT: We retrospectively analyzed transfusion requirements within the first 100 d among allogeneic haematopoietic cell transplantation (HCT) recipients with haematological malignancies given either myeloablative (n = 1353) or nonmyeloablative conditioning (n = 503). We confirmed that myeloablative recipients required more platelet and red blood cell (RBC) transfusions than nonmyeloablative recipients (P < 0.0001 for both). Myeloablative patients given peripheral blood stem cells required less platelet transfusions (P < 0.0001) than those given marrow while RBC transfusion requirements did not differ significantly. Subsequent analyses were restricted to nonmyeloablative recipients. Platelet and RBC transfusions were less frequent among related compared to unrelated recipients (P < 0.0001 for both), with comparable median numbers of transfused units. Major/bidirectionally ABO-mismatched recipients required more RBC transfusions than ABO-matched recipients (P = 0.006). Rates of graft rejection/failure, grades II-IV acute and chronic graft-versus-host-disease (GVHD), 2-year relapse, 3-year survivals and non-relapse mortality were comparable among ABO-matched, minor-mismatched, and major/bidirectionally mismatched recipients (P = 0.93, 0.72, 0.57, 0.36, 0.17 and 0.79, respectively). Times to disappearance of anti-donor IgG and IgM isohemagglutinins among major/bidirectionally ABO-mismatched recipients were affected by magnitude of pre-HCT titres (P < 0.001 for both) but not GVHD (P = 0.71 and 0.78, respectively). In conclusion, nonmyeloablative recipients required fewer platelet and RBC transfusions and among them, both unrelated and major/bidirectionally ABO-mismatched recipients required more RBC transfusions. ABO incompatibility did not affect nonmyeloablative HCT outcomes.
British Journal of Haematology 04/2010; 149(1):101-10. · 4.94 Impact Factor
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Fabrizio Carnevale-Schianca,
Wendy Leisenring,
Paul J Martin,
Terry Furlong, Gary Schoch,
Claudio Anasetti,
Frederick R Appelbaum,
Paul A Carpenter,
H Joachim Deeg,
Hans-Peter Kiem,
Rainer Storb,
George B McDonald,
Richard A Nash
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ABSTRACT: Because morbidity early after hematopoietic cell transplantation (HCT) results in large part from the development of acute graft-versus-host disease (GVHD), we previously proposed that a longitudinal assessment of morbidity involving the skin, liver, and gastrointestinal (GI) tract might provide a more complete, objective approach for comparing 2 arms of open-label randomized clinical trials for acute GVHD prevention. In this study, we determined both morbidity across time and GVHD across time in a retrospective analysis of a database from an open-label randomized clinical trial comparing tacrolimus/methotrexate and cyclosporine/methotrexate after myeloablative conditioning and marrow transplantation from HLA-matched unrelated donors. The results confirm differences in overall morbidity across time in patients with peak grade II-IV GVHD compared with those with grade 0-I GVHD, but no significant differences in morbidity associated with grade II GVHD compared with grade 0-I GVHD. We observed less skin morbidity and a trend toward less liver morbidity across time in the tacrolimus group (P = .04 and .09, respectively), but not for GI morbidity or overall morbidity, despite significantly decreased skin and liver stages and overall grades of GVHD across time in this group. Thus, our objective assessment of differences in morbidity (regardless of cause) as a measure of acute GVHD in a randomized clinical trial of acute GVHD prevention has only limited utility. The difficulty of demonstrating clinical benefits from objective parameters, such as survival and morbidity, and the subjectivity of grading acute GVHD emphasize the need for blinded assessments in clinical trials of GVHD prevention.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 07/2009; 15(6):749-56. · 3.15 Impact Factor
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ABSTRACT: Chronic kidney disease (CKD) is common after hematopoietic cell transplantation (HCT). We prospectively measured the urinary albumin:creatinine ratio (ACR) in 142 patients. Total (intact) monomeric albumin was determined by liquid chromatography of untreated urine samples collected weekly to day 100 after HCT. Albuminuria was defined as ACR (mg/g creatinine) > 30; proteinuria, as ACR >300. Cox and logistic regression analyses evaluated ACR as a risk factor for clinical events. The prevalence of albuminuria was 37% at baseline, 64% at day 100, and 50% at 1 year. Proteinuria occurred in 4% of patients at baseline, in 15% at day 100, and in 4% at 1 year. Characteristics associated with albuminuria include age, sex, donor type, hypertension, and sinusoidal obstruction syndrome (SOS). Albuminuria was associated with an increased risk of acute graft-versus-host disease (aGVHD) and bacteremia, but not acute kidney injury (AKI). Albuminuria at day 100 was associated with CKD at 1 year (odds ratio = 4.0; 95% confidence interval [CI] = 1.1 to 14.6). Nonrelapse mortality (NRM) risk was elevated (hazard ratio = 6.8; 95% CI = 1.1 to 41.5) in patients with overt proteinuria at day 100. Albuminuria occurs frequently after HCT and is correlated with aGVHD, bacteremia, hypertension, and progression of renal disease. Proteinuria at day 100 is associated with an 6-fold increased risk of NRM by 1 year after HCT.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2009; 14(12):1365-72. · 3.15 Impact Factor
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ABSTRACT: Survival after myeloablative therapy followed by hematopoietic cell transplant (HCT) is limited by substantial treatment-related toxicities. Acute renal failure (ARF) develops in 25% to 50% of patients after HCT.
One hundred forty-seven patients were followed prospectively from time of transplant. ARF was defined as a doubling of baseline serum creatinine at any time during the first 100 days post-transplant. We conducted a nested case-control study to identify precipitants of ARF. For each person who developed ARF, 2 controls were selected at random from patients who had not developed ARF as of that time. An exposure period was defined for each case as the 2 weeks prior to the day on which the matched case met the criteria for ARF. The risk of ARF in relation to demographic and anthropometric characteristics, and to types of treatment and comorbidity, was examined using univariable and multivariable conditional logistic regression models. Odds ratios for the associations with ARF were estimated, taking into account the matching.
Fifty-three patients (36%) developed ARF at a median of 33 days after transplant (range 1 to 97). Elevated risks were observed in patients who received liposomal amphotericin (OR 6.58; 95%CI 1.45-29.95) and conventional (OR 3.60; 95%CI 0.79-16.55), and in those patients with sinusoidal obstruction syndrome (SOS) (previously termed veno-occlusive disease) (OR 9.37; 95%CI 2.29-38.38). For every 0.1 mg/dL increase in baseline serum Cr, the risk of ARF decreased by 30%. Neither total body irradiation (TBI) dose, levels of metabolites of cyclophosphamide, sepsis, acute graft versus host disease (GVHD), nor cyclosporine (CSA) levels was associated with an increased risk of ARF.
The cumulative incidence of ARF after HCT remains high. Amphotericin use during the 2-week exposure period and presence of hepatic sinuosoidal injury increased the risk of ARF within the first 100 days after HCT. Higher levels of serum creatinine at baseline were associated with a lower risk of ARF.
Kidney International 02/2005; 67(1):272-7. · 6.61 Impact Factor
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ABSTRACT: Allogeneic marrow transplantation using related marrow donors for myelodysplasia (MDS) and acute myeloid leukaemia (AML) arising from MDS results in 35–56% actuarial disease-free survival. Because the use of unrelated donors has not been well-characterized, we report on the outcome of 52 patients with MDS or MDS-related AML consecutively treated between 1987 and 1993 with unrelated donor marrow transplantation. The median age was 33 (range 1–53) years. 33 patients received chemotherapy and total body irradiation and the remainder busulfan and cyclophosphamide. The donors were phenotypically identical at the HLA-A, B and Dw/DRB1 loci in 34 cases and mismatched for one HLA locus in 17 cases and two loci in one case. Marrow was non-T-cell depleted and methotrexate with cyclosporine or FK506 was used for postgrafting immunosuppression. The 2-year disease-free survival, relapse, and non-relapse mortality rates were 38%, 28% and 48%, respectively. One patient who relapsed survives disease-free after withdrawal of immunosuppressive therapy. 16/19 survivors have a performance status of 90–100%. Patients with MDS in transformation or with AML had a significantly higher risk of relapse than patients with less advanced disease (P = 0.0014). Increased non-relapse mortality was significantly associated with higher age, longer disease duration before transplant, lower neutrophil count on admission and, unexpectedly, being seronegative for cytomegalovirus. We conclude that the outcome with transplantation using unrelated donors is similar to reported results using related donors and that a meaningful proportion of eligible patients with an otherwise incurable disease may be cured with this treatment. However, mortality from the transplant procedure is high and future studies should focus on reducing toxicity.
British Journal of Haematology 10/2003; 93(1):59 - 67. · 4.94 Impact Factor
