Showing papers by "Todd E. DeFor published in 2006"
TL;DR: Use of ATG in recipients of an NMA preparative regimen warrants close monitoring for evidence of EBV reactivation and potentially preemptive therapy with rituximab.
257 citations
TL;DR: Using a simple prognostic model, patients with high-risk disease who have predictably unfavorable outcome after ASCT and require novel therapeutic approaches can be identified and follow a risk-adapted approach in determining treatment options.
161 citations
TL;DR: It is concluded that palifermin was generally safe in allogeneic HSCTs but had no significant effect on engraftment, acute GVHD, or survival in this trial.
139 citations
TL;DR: The pathogenesis of alveolar hemorrhage after HSCT is multifactorial, and it is proposed that IAH and DAH in HSCT recipients are related clinical syndromes with similar clinical presentation, risks, and associated high mortality.
124 citations
TL;DR: The results suggest comparable outcomes for reduced-intensity allo-SCT using UCB or MSD in adults at high risk with advanced Hodgkin lymphoma.
99 citations
TL;DR: A regimen using fludarabine, cyclophosphamide, and anti‐thymocyte globulin followed by infusion of T‐cell depleted bone marrow or unmanipulated umbilical cord blood is developed to potentially reduce late effects of malignancy, chronic graft‐versus‐host disease (GVHD), endocrinopathy, and infertility in patients with Fanconi anemia undergoing HLA‐matched related donor hematopoietic cell transplantation.
Abstract: Background
To potentially reduce late effects of malignancy, chronic graft-versus-host disease (GVHD), endocrinopathy, and infertility in patients with Fanconi anemia (FA) undergoing HLA-matched related donor hematopoietic cell transplantation (HCT), we developed a regimen using fludarabine (FLU), cyclophosphamide (CY), and anti-thymocyte globulin (ATG) followed by infusion of T-cell depleted (TCD) bone marrow (BM) or unmanipulated umbilical cord blood (UCB). GVHD prophylaxis consisted of cyclosporine and short course methylprednisolone.
Procedure
Between April 2000 and June 2003, 11 patients (10 aplastic anemia (AA), 1 myelodysplastic syndrome (MDS)) underwent HCT using this regimen. Stem cell sources were BM and UCB in eight and three patients, respectively.
Results
All patients demonstrated primary engraftment. Median days to neutrophil and platelet engraftment were 11 days (range 9–21) and 38 days (range 19–381), respectively. No patient developed GVHD after primary HCT. The patient with MDS relapsed with AML and a maternal donor recipient experienced secondary graft failure. For the nine FA patients with AA who underwent HLA-identical sibling donor HCT, the Kaplan–Meier estimates of overall survival and event-free survival (EFS) at 2 years are 100% and 82%, respectively, at a median follow-up of 2.9 years (range 1.9–4.8).
Conclusions
In summary, a FLU-based, non-irradiation approach is effective for FA patients with AA undergoing HLA-identical sibling donor HCT. © 2005 Wiley-Liss, Inc.
78 citations
TL;DR: Data suggest that chemotherapy-induced lymphodepletion enhances activation of donor lymphocytes, the toxicity needs to be managed before testing whether better disease control can be achieved.
76 citations
TL;DR: The data justify continued investigation of ASCT as a consolidation therapy in patients with metastatic or relapsed ES and DSRCT, with patients with a diagnosis of Ewing's sarcoma or desmoplastic small round cell tumor having significantly better survival.
Abstract: The prognosis for many pediatric and young adult patients with solid tumors that have metastasized at the time of diagnosis or have relapsed after therapy remains very poor. The steep dose-response curve of many of these tumors to alkylating agents makes myeloablative chemotherapy followed by autologous stem cell transplantation (ASCT) an attractive potential therapy. The role of ASCT for these high-risk patients is yet to be conclusively determined. We have transplanted 36 patients on two consecutive protocols with a variety of histological diagnoses. Overall survival (OS) was 63% (95% CI: 47-79%) at 1 year and 33% (95% CI: 16-50%) at 3 years. Patients with a diagnosis of Ewing's sarcoma (ES) or desmoplastic small round cell tumor (DSRCT) had significantly better survival than those with other diagnoses with estimated 3-year OS of 54% (95% CI: 29-79%) for this group of patients (P = 0.03). There were two transplant-related deaths both attributable to hepatic veno-occlusive disease. Median follow-up among survivors is 3.5 years (range: 0.6-7.9 years). These data justify continued investigation of ASCT as a consolidation therapy in patients with metastatic or relapsed ES and DSRCT.
50 citations
TL;DR: The diagnostic yield versus complications from endoscopy in children after hematopoietic stem cell transplantation (HSCT) was determined and acute GVHD was diagnosed most commonly on sigmoid biopsy.
46 citations
TL;DR: The results suggest comparable outcomes for reduced-intensity allo-SCT using UCB or MSD in adults at high risk with advanced Hodgkin lymphoma.
41 citations
TL;DR: Alveolar hemorrhage occurring after RIC or MAC HCT has similar incidence, clinical presentation, and associated high mortality, and reducing the intensity of preparative regimen does not protect against post transplantal hemorrhage.
Abstract: Allogeneic hematopoietic cell transplantation (HCT) using reduced-intensity conditioning (RIC) has lower morbidity and mortality compared to transplantation using myeloablative conditioning (MAC). The syndrome of alveolar hemorrhage, a life-threatening pulmonary complication of HCT, has not been well described after RIC HCT. We reviewed prospectively collected data on 206 RIC and 1112 MAC HCT performed between 1995 and 2004 to study the impact of conditioning regimen on the clinical features and outcome of alveolar hemorrhage. Alveolar hemorrhage occurred in 18 RIC HCT recipients (cumulative incidence 8% (95% confidence intervals (CI), 5-11%)) and 85 MAC HCT recipients (cumulative incidence 7% (95% CI, 6-8%), P = 0.56). The clinical presentation of hemorrhage in both cohorts was similar. Survival at 60 days from the onset of hemorrhage was 28% (95% CI, 7-49%) for RIC group compared to 26% (95% CI, 17-35%) after MAC HCT (P = 0.56). 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.
TL;DR: It is hypothesized that UCB-derived NK cells may show better in vivo expansion than adult derived NK cells after cytoreduction and the triple UCBT strategy in patients with refractory relapsed AML who were tested.
TL;DR: Evaluating the safety and potential efficacy of TS in FA patients indicates that TS reduces the infection rate and potentially improves survival in patients with FA, and suggests that TS should be considered for other high risk populations (e.g. adults) and in those with other non malignant disorders.
TL;DR: It is hypothesized that UCB would increase the utilization of HSCT in patients with AML who lacked a HLA-matched, medically suitable sibling donor, and only disease risk group was associated with increased relative risk of relapse.
TL;DR: Risk of acute GVHD is significantly higher in recipients of two partially HLA matched UCB units, yet it does not appear to adversely effect TRM or survival, and ATG in the preparative therapy does not appears to reduce TRM despite its favorable association with reduced GV HD.
TL;DR: The successful use of Tomotherapy at delivering intensity modulated radiotherapy to the bone and bone marrow spaces along the entire axis of a patient and a dosimetric analysis of the total marrow irradiation (TMI) treatment are reported.
Abstract: Purpose: We report here the successful use of Tomotherapy at delivering intensity modulated radiotherapy to the bone and bone marrow spaces along the entire axis of a patient and describe a dosimetric analysis of the total marrow irradiation (TMI) treatment. This is part of a dose escalation trial to determine the maximum tolerated dose (MTD) of TMI when given prior to an alkylator‐intensive conditioning regimen for the treatment of high risk or relapsed solid tumors.Method and Materials: A patient enrolled in a dose escalation study trial received 600 cGy in 3 fractions. Two independent CTimage sets (upper and lower part of the body) were obtained. A helical tomotherapy treatment plan was created from this CTimage sets. The quality assurance was evaluated with the use of (a) ion chamber and (b) extended dose range film. The isorad‐p cylindrical diodes were used for in‐vivodosimetry.Results: The patient showed neutrophil engraftment on day 11 and platelet engraftment by day 58. He is currently well at 120 days post transplant with no evidence of disease. The patient developed nausea and vomiting after the first fraction of Tomotherapy TMI. Other than above there were no adverse effects of TMI. The planned radiation conformed to all bone marrow sites. Average doses to lungs,kidneys,heart, and eyes were 50–70% of the prescribed dose for TMI treatments. The dose delivery verifications (pretreatment and in vivodose measurement) were within ±3–5% of the expected dose calculated from the treatment planning station. Conclusions: We show that helical tomotherapy targeting the bone marrow of the whole body is clinically feasible. The clinical implementation of intensity modulated radiation to conform the radiation dose to all active bone marrow of the whole body opened up the possibility of a dose escalation study for high risk patients.
01 Jan 2006
TL;DR: It is concluded that palifermin was generally safe in allogeneic HSCT, but had no significant effect on engraftment, acute GVHD, or survival in this trial.
Abstract: Palifermin, a recombinant human keratinocyte growth factor, was tested for potential benefits on acute GVHD and hematopoietic recovery in allogeneic HSCT recipients. This randomized, double-blind, placebo-controlled, dose-escalation study assessed the safety and tolerability of palifermin (n=69) as compared to placebo (n=31) in patients conditioned with cyclophosphamide/fractionated total-body irradiation (Cy/TBI) or busulfan/cyclophosphamide and given methotrexate along with a calcineurin inhibitor (cyclosporine A, tacrolimus) for GVHD prophylaxis. All patients received 3 doses pre-conditioning and either 3 (cohort 1), 6 (cohort 2), or 9 (cohort 3) doses after HSCT. Palifermin doses were 40 mcg/kg/day (cohort 1 only) or 60 mcg/kg/day (all cohorts). Six patients (placebo=2, palifermin=4), experienced a total of 11 dose-limiting toxicities (most often skin, respiratory, or oral mucositis). The most common adverse events included edema, infection, skin pain, or rash. Times to neutrophil and platelet engraftment were similar. No significant differences in acute GVHD incidence or severity, survival, or day 100 relapse rates were observed between groups. Palifermin was associated with reduced incidence and mean severity of mucositis in patients conditioned with Cy/TBI but not Bu/Cy. We conclude that palifermin was generally safe in allogeneic HSCT, but had no significant effect on engraftment, acute GVHD, or survival in this trial. For personal use only. by guest on June 7, 2013. bloodjournal.hematologylibrary.org From
TL;DR: It is found that double umbilical cord blood transplant patients are at high risk of having a positive HHV-6 PCR assay compared to BM, PB and single UCBT patients, and the use of Fludarabine was not significantly different between myeloablative and non-myeloabative conditioning regimens in those patients who received a double UCBT.
TL;DR: It is hypothesized that FLU is the principal factor for improving engraftment, and that co-administration of two units speeds neutrophil recovery based on higher cell dose, and is now routinely prescribed for pts for whom an adequate single unit cannot be identified.