Search PubMed⌕ Search

Biomedical subjects

D J Weisdorf

Publications and source records attributed to D J Weisdorf.

At least 19 recordsLinked to original sources
PubMed2007

Fludarabine vs cladribine plus busulfan and low-dose TBI as reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation: a prospective randomized trial.

Purine analogs are often used for conditioning preceding allogeneic hematopoietic stem cell transplantation (HCT). We prospectively tested fludarabine (Flu) 40 mg/m(2)/day x 5 days vs cladribine (Clad) 10 mg/m(2)/day x 5 days plus oral busulfan (1 mg/kg q6 h x 2 days) and total body irradiation 200 cGy in 32 recipients of matched sibling and unrelated donor (URD) HCT. Patients were similar in age (median 52 years), diagnosis, extensive pre-HCT therapy (56 vs 63%), and high-risk disease status (81 vs 93%). Neutrophil engraftment was prompt (median 11 vs 12 days), but early graft failure using Clad halted randomization. Platelet recovery was prompt (median Flu 18 vs Clad 24 days). Graft-versus-host disease (GVHD) after Flu vs Clad was similar; (acute grade II/IV 56 vs 69%, P=0.26; chronic 50 vs 31%, P=0.27). Nonrelapse mortality (Flu 25 vs Clad 38%, P=0.47) and progression-free survival at 3 years were similar as well. Multivariate analyses showed slightly, but not significantly lower relative risk (RR) of neutrophil engraftment with Clad (RR 0.6 (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.

Adult↗
PubMed2006

Alveolar hemorrhage following allogeneic hematopoietic cell transplantation using reduced-intensity conditioning.

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.

Adolescent↗
PubMed2006

Prevalence of conception and pregnancy outcomes after hematopoietic cell transplantation: report from the Bone Marrow Transplant Survivor Study.

We conducted a retrospective study to describe the magnitude of compromise in reproductive function and investigate pregnancy outcomes in 619 women and partners of men treated with autologous (n=241) or allogeneic (n=378) hematopoietic cell transplantation (HCT) between 21 and 45 years of age, and surviving 2 or more years. Median age at HCT was 33.3 years and median time since HCT 7.7 years. Mailed questionnaires captured pregnancies and their outcomes (live birth, stillbirth, miscarriage). Thirty-four patients reported 54 pregnancies after HCT (26 males, 40 pregnancies; eight females, 14 pregnancies), of which 46 resulted in live births. Factors associated with reporting no conception included older age at HCT (> or =30 years: odds ratio (OR)=4.8), female sex (OR=3.0), and total body irradiation (OR=3.3). Prevalence of conception and pregnancy outcomes in HCT survivors were compared to those of 301 nearest-age siblings. Although the risk for not reporting a conception was significantly increased among HCT survivors (OR=36), survivors were not significantly more likely than siblings to report miscarriage or stillbirth (OR=0.7). Although prevalence of conception is diminished after HCT, if pregnancy does occur, outcome is likely to be favorable. Patients should be counseled prior to transplant regarding strategies to preserve fertility.

Adult↗
PubMed2005

Results of autologous and allogeneic hematopoietic cell transplant therapy for multiple myeloma.

We compared the results of autologous and allogeneic peripheral blood hematopoietic cell transplant (HCT) in 87 patients with multiple myeloma using myeloablative preparative regimen. Autologous transplant (n=70) led to a lower 100-day transplant-related mortality (TRM) of 4% [0-9%] compared to 18% [0-36%] in allogeneic recipients (P=0.02). More frequent complete responses were seen in allogeneic recipients (64% [37-91%] vs 34% [23-45%] in autologous recipients, P=0.09). In autologous recipients, survival at 1 year was 86% [80-95%] and, it fell to 50% [47-75%] at 4 years, whereas in allogeneic recipients, survival at 1 and 4 years remained at 64% [40-87%]. In patients surviving more than one year, 4-year survival was superior in allogeneic (100%) vs autologous recipients (58% [41-75%], P=0.02). A trend toward higher relapse was seen in autologous transplant patients (73% [55-90%] vs 37% [11-63%] in allogeneic transplant patients, P=0.1). We observed good tolerance of myeloablative conditioning regimen followed by either autologous or allogeneic transplant. Although autologous HCT is associated with lower TRM, allogeneic HCT has acceptable TRM, and is more likely to provide a sustained response. Allogeneic HCT may be suitable in younger patients, soon after diagnosis, and in those with chemosensitive disease.

Adult↗
PubMed2003

IL-2-based immunotherapy after autologous transplantation for lymphoma and breast cancer induces immune activation and cytokine release: a phase I/II trial.

We determined the safety, immune activating effects, and potential efficacy of i.v. infusion of ex vivo interleukin-2 (IL-2) activated natural killer (NK) cells (part I) or IL-2 boluses (part II) during daily s.c. IL-2 administration following hematopoietic recovery from autologous transplantation. In all, 57 patients with relapsed lymphoma (n=29) or metastatic breast cancer (n=28) were enrolled. In part I of the study, 34 patients were enrolled at three dose levels of ex vivo IL-2-activated NK cells. Lymphaphereses were performed on days 28 and 42 of s.c. IL-2 administration. Following overnight ex vivo IL-2 activation of the pheresis product, the cells were reinfused the following day. In part II, 23 patients were enrolled at three dose levels of supplemental i.v. IL-2 bolus infusions, given on days 28 and 35 during s.c. IL-2 administration. Toxicities were generally mild, and no patient required hospitalization. Lytic function was markedly enhanced for fresh peripheral blood mononuclear cells (PBMNCs) obtained 1 day postinfusion of either IL-2-activated cells or IL-2 boluses. IL-2 boluses transiently increased the levels of IL-6, IFN-gamma, TNF-alpha and IL1-beta, with increases in IL-6 and IFN-gamma being dose dependent. A total of 37 patients (19 patients with lymphoma, 18 with breast cancer) treated with an optimum dose of post-transplant immunotherapy (defined as having received 1.75 x 10(6) IU/m(2)/day of s.c. IL-2 plus at least one of the planned ex vivo IL-2-activated cell infusions/IL-2 boluses) could be matched with controls from the Autologous Blood and Marrow Transplant Registry database. The matched-pairs analysis demonstrated no improvement in disease outcomes of survival and relapse. We conclude that IL-2-activated cells/IL-2 boluses can be safely administered, generate PBMNCs with enhanced cytotoxicity against NK-resistant targets, and increase cytokine levels. 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.

Adult↗
PubMed2003

Autologous stem cell transplantation in multiple myeloma patients <60 vs >/=60 years of age.

The role of autologous stem cell transplantation (AuSCT) in older multiple myeloma patients is unclear. Using data from the Autologous Blood and Marrow Transplant Registry, we compared the outcome of 110 patients >/=the age of 60 (median 63; range 60-73) years, undergoing AuSCT with that of 382 patients <60 (median 52; range 30-59) years. The two groups were similar except that older patients had a higher beta(2)-microglobulin level at diagnosis (P=0.016) and fewer had lytic lesions (P=0.007). Day 100 mortality was 6% (95% confidence interval 4-9) and 1-year treatment-related mortality (TRM) was 9% (6-13) in patients <60 years, compared with 5% (2-10) and 8% (4-14), respectively, in patients >/=60 years. The relapse rate, progression-free survival (PFS) and overall survival (OS) in the two groups were also similar. Multivariate analysis of all patients identified only an interval from diagnosis to AuSCT >12 months and the use of two prior chemotherapy regimens within 6 months of AuSCT as adverse prognostic factors. Our results indicate that AuSCT can be safely performed in selected older patients: the best results were observed in patients undergoing AuSCT relatively early in their disease course.

Adult↗
PubMed2002

Acquired factor VII deficiency in hematopoietic stem cell transplant recipients.

Acquired factor VII (FVII) deficiency in the absence of vitamin K deficiency, oral anticoagulant therapy, synthetic liver dysfunction, or DIC is rare, with only a handful of cases thus far reported. In the period from 1990 to 1996 we identified eight patients with acquired FVII deficiency, all of whom presented with prolongation of the prothrombin time (PT) in the first 2 weeks following stem cell transplantation (SCT). The mean plasma FVII clotting activity (FVII:c) was 22% (range 8-35%) with an approximately equivalent reduction in FVII antigen (FVII:Ag) level. Mean plasma levels of fibrinogen and factors II, V, IX, and X were normal. Protein C activity was significantly depressed in only one of the three patients in whom it was measured. Several patients experienced bleeding complications, and hemorrhage directly accounted for death in two cases. Veno-occlusive disease of the liver developed in three patients. 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.

Adult↗
PubMed2002

Randomized clinical trial of ganciclovir vs acyclovir for prevention of cytomegalovirus antigenemia after allogeneic transplantation.

Cytomegalovirus (CMV) disease remains a major cause of morbidity following allogeneic stem cell transplantation (SCT). In a prospective randomized trial, we tested prophylactic therapy with ganciclovir or acyclovir for patients at high risk of disease. Ninety-one CMV seropositive recipients of related (n = 53) and unrelated (n = 38) donor transplants were enrolled. All patients received intravenous (i.v.) ganciclovir 5 mg/kg every 12 h days -7 to -2, followed by acyclovir 10 mg/kg i.v. every 8 h from day -1 until neutrophil engraftment. Patients were then randomly assigned to either ganciclovir (n = 45) or acyclovir (n = 46) until day 100 post transplant. Any degree of antigenemia was treated with ganciclovir 5 mg/kg i.v. twice a day for 2 weeks, followed by 5 mg/kg i.v. each weekday for 6 weeks. At day 100, the cumulative incidence of antigenemia was 31% (95% CI 17-45%) for ganciclovir and 41% (95% CI 26-56%) (P = 0.22) for acyclovir prophylaxis, respectively. The assigned prophylaxis cohort did not predict for CMV antigenemia. The cumulative incidence of CMV disease at 12 months was 13% (95% CI 3-23%) and 17% (95% CI 6-28%) (P = 0.59) for the ganciclovir- and acyclovir-treated groups, respectively. An absolute neutrophil count (ANC) <or=1500 x 10(6)/l at randomization (P < 0.01) and grade II-IV acute graft-versus-host-disease (P = 0.01), but not the assigned prophylaxis cohort (P = 0.62), were independent risk factors for CMV disease. The incidence of fungal infections and renal insufficiency was similar across treatment groups; however, bacterial infections and secondary neutropenia occurred more frequently in the ganciclovir group. With our study powered to detect a 60% reduction in antigenemia with ganciclovir prophylaxis, we did not find a statistically significant difference between ganciclovir and acyclovir when used as part of an overall strategy for prevention of CMV antigenemia and disease in SCT, although fewer side-effects occurred with acyclovir treatment.

Acyclovir↗
PubMed2001

Survival after transplantation of unrelated donor umbilical cord blood is comparable to that of human leukocyte antigen-matched unrelated donor bone marrow: results of a matched-pair analysis.

Umbilical cord blood (UCB) is being increasingly used for hematopoietic stem cell transplantation and has been associated with a reduced incidence of severe graft-versus-host disease (GVHD). To further investigate the relative merits of unrelated donor UCB versus bone marrow (BM), a matched-pair analysis comparing the outcomes of recipients of 0 to 3 human leukocyte antigen (HLA)-mismatched UCB and HLA-A, B, DRB1-matched BM was performed. UCB patients, who received cyclosporine (CSA) and methylprednisolone (MP), were matched for age, diagnosis, and disease stage with BM patients, who received either methotrexate (MTX) and CSA (26 pairs) or T-cell depletion (TCD) and CSA/MP (31 pairs). Patients were predominantly children (median age, 5 years) undergoing transplantation for malignancy, storage diseases, BM failure, and immunodeficiency syndromes between 1991 and 1999. Although neutrophil recovery was significantly slower after UCB transplantation, the probability of donor-derived engraftment at day 45 was 88% in UCB versus 96% in BM-MTX recipients (P =.41) and 85% in UCB versus 90% in BM-TCD recipients (P =.32), respectively. Platelet recovery was similar in UCB versus BM pairs. Furthermore, incidences of acute and chronic GVHD were similar in UCB and BM recipients, with 53% of UCB versus 41% of BM-MTX recipients alive (P =.40) and 52% of UCB versus 56% of BM-TCD recipients alive at 2 years (P >.80), respectively. These data suggest that despite increased HLA disparity, probabilities of engraftment, GVHD, and survival after UCB transplantation are comparable to those observed after HLA-matched BM transplantation. Therefore, UCB should be considered an acceptable alternative to HLA-matched BM for pediatric patients.

Adolescent↗
PubMed2001

Equivalent outcomes in patients with chronic myelogenous leukemia after early transplantation of phenotypically matched bone marrow from related or unrelated donors.

PURPOSE: To determine if the favorable outcomes after transplantation of matched sibling donor bone marrow in patients with chronic myelogenous leukemia can be achieved using bone marrow from an HLA-A,B/DRB1-matched unrelated donor. SUBJECTS AND METHODS: Between April 1983 and December 1997, 141 patients with chronic myelogenous leukemia in its first chronic phase received a bone marrow transplant from a matched sibling donor (n = 96) or an HLA-A,B/DRB1-matched unrelated donor (n = 45). The median age of matched sibling donor recipients was 38 years (range, 8 to 56 years) and of unrelated donor recipients was 35 years (range, 3 to 53 years; P = 0.03). The median follow-up was 6 years (range, 1 to 15 years) in matched sibling donor recipients and 5 years (range, 2 to 10 years) in unrelated donor recipients. RESULTS: There was no significant difference in the 5-year survival rates of matched sibling donor recipients [58%; 95% confidence interval (CI), 48% to 68%] and unrelated donor recipients (53%; 95% CI, 39% to 67%; P = 0.4). Among patients who underwent transplantation within 1 year after diagnosis, the 5-year survival rate of matched sibling donor recipients (76%; 95% CI, 65% to 87%) was not significantly different (P = 0.5) from that of unrelated donor recipients (70%; 95% CI, 52% to 88%). In multiple regression analysis, longer time from diagnosis to transplantation, T-cell depletion, and grades III or IV graft versus host disease were independently associated with poorer survival. Transplantation of unrelated donor bone marrow was not associated with mortality (relative risk, 1.1; 95% CI, 0.6 to 2.1; P = 0.7). CONCLUSIONS: Transplantation of bone marrow from a matched sibling donor or an HLA-A,B/DRB1-matched unrelated donor produces equivalent outcomes in patients with chronic myelogenous leukemia, particularly if the transplant takes place within 1 year after diagnosis.

Adolescent↗
PubMed2001

Serious cardiac complications during bone marrow transplantation at the University of Minnesota, 1977-1997.

Cardiac complications may result from high-dose chemotherapy or irradiation administered during the conditioning phase of bone marrow and blood stem cell transplantation (BMT). To assess the frequency of clinically serious cardiac toxicity related to the acute phase of BMT, we retrospectively examined life-threatening or fatal cardiotoxicity identified using the complications records of our transplant center clinical database. All serious cardiac toxicity events within 100 days of BMT except those attributable to septic shock, pneumonitis or multi-organ failure were reviewed. Of 2821 BMT patients at the University of Minnesota between 1977 and 1997, 26 were identified as having suffered major or fatal (n = 13) cardiotoxicity (0.9%, 19 adults and seven children). Rapidly progressive heart failure resulted in death of 11 patients, one patient had fatal pericardial tamponade, and one had an acute ventricular fibrillation arrest. The remaining 13 patients (50%) had life-threatening cardiotoxicity including four patients with pericardial tamponade and nine patients with cardiac arrhythmias. Overall, we observed that acute, major cardiotoxic events attributable to BMT are uncommon, occurring with a frequency of <1%. 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.

Adolescent↗
PubMed2001

Infections during mobilizing chemotherapy and following autologous stem cell transplantation.

Autologous peripheral blood stem cells (PBSC), for transplantation following high-dose chemotherapy, are collected using regimens containing cytokines with or without chemotherapy. The added period of neutropenia prior to stem cell transplantation (SCT) in patients receiving chemotherapy mobilization may increase the risk of infections following transplantation. We studied the incidence of culture-positive infections in 107 consecutive patients who were divided into three groups, according to whether they experienced extended neutropenia during chemotherapy for stem cell mobilization as well as post autotransplant. All the patients received antibiotic prophylaxis and hematopoietic growth factors during neutropenia. The total duration of pre-transplant neutropenia differed among the three mobilization schemes (growth factors alone; one cycle; or two cycles of chemotherapy plus growth factor for mobilization) at 0, 6 and 18 days, respectively (median). However the post-autograft time to myeloid engraftment was similar at 10 days (median). The incidence of culture-proven infections in all three groups was similar. Using fluconazole for yeast prophylaxis, 40% patients developed gastrointestinal colonization with yeast, and the majority of speciated isolates were Candida glabrata. Bacteremia developed in 22% and 9% of patients with S. epidermidis and Gram-negative organisms, respectively, while 11% developed C. difficile-associated diarrhea. In conclusion, treatment using none, one or two cycles of mobilizing chemotherapy pre-transplant does not influence the overall incidence of infections among autologous SCT recipients. However, although post-transplant neutropenia is brief, infections remain a significant cause of morbidity.

Adolescent↗
PubMed2001

Low incidence of Epstein-Barr virus-associated posttransplantation lymphoproliferative disorders in 272 unrelated-donor umbilical cord blood transplant recipients.

Umbilical cord blood (UCB) is being increasingly used for transplantation, but the ability of neonatal T cells to regulate Epstein-Barr virus (EBV)-associated lymphoproliferation is unknown. Because UCB transplantation (UCBT) is associated with a relatively low infused dose of donor T cells, frequent donor-recipient HLA disparity, and use of antithymocyte globulin during conditioning, we hypothesized that the risk of EBV-associated posttransplantation lymphoproliferative disorders (EVB-PTLD) after UCBT may be increased. To investigate the incidence of EBV-PTLD after UCBT, we analyzed 272 unrelated-donor UCBTs performed from August 1993 to December 1999 at Duke University Medical Center and the University of Minnesota. Five cases of EBV-PTLD were identified, with a cumulative incidence of 2% (95% confidence interval, 0.3%-3.7%) at 2 years. EBV-PTLD affected UCB recipients aged 1 to 49 years (median, 8 years), with 4 patients undergoing transplantation for leukemia and 1 for immunodeficiency. Patients received UCB grafts that were HLA matched (n = 1) or mismatched at 1 (n = 1) or 2 (n = 3) HLA loci. Diagnoses occurred at 4 to 14 months (median, 6 months) after UCBT, with 4 of 5 patients having preceding grade II to IV acute graft-versus-host disease and 1 being diagnosed at autopsy. Treatment of 4 patients consisted of withdrawal of immunosuppressive treatment and administration of rituximab, with 2 of 4 patients responding. Thus, the incidence of EBV-PTLD after unrelated-donor UCBT appears similar to that observed after transplantation using unrelated bone marrow (BM) and compares favorably with unrelated-donor T-cell-depleted BM transplantation. 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.

Adolescent↗
PubMed2001

Cytomegalovirus enteritis among hematopoietic stem cell transplant recipients.

Cytomegalovirus (CMV) is a cause of enteritis associated with hematopoietic stem cell transplantation (HSCT), but the natural history is rarely studied and hence poorly understood. CMV infection at this end-organ site is notably less frequent than is pneumonitis. To evaluate the spectrum of CMV enteritis after HSCT, we reviewed the database spanning 11.5 years of 2240 University of Minnesota transplantation patients for cases of gastrointestinal CMV. We identified 46 case-patients. The incidence of CMV enteritis at 2 years following HSCT averaged 2% over the 11.5-year study interval. The median time to diagnosis of CMV enteritis after HSCT was 91 days (range, 17-527 days). The methods used in diagnosis included histopathology (58%) and virology (61%). 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.

Adolescent↗